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11,300 | 27,165,970 | Based on the available evidence , weak recommendations are suggested for massage therapy , compared to active comparators for reducing pain intensity/severity and anxiety in patients undergoing surgical procedures . | OBJECTIVE Pain is multi-dimensional and may be better addressed through a holistic , biopsychosocial approach .
Massage therapy is commonly practice d among patients seeking pain management ; however , its efficacy is unclear . | OBJECTIVES To determine whether massage therapy improves postoperative mood , pain , anxiety , and physiologic measurements ; shortens hospital stay ; and decreases occurrence of atrial fibrillation . METHODS Two hundred fifty-two adults undergoing cardiac surgery were r and omized to usual postoperative care ( n=126 ) or usual care plus two massages ( n=126 ) . Assessment s of mood , depression , anxiety , pain , physiologic status , cardiac rhythm , and hospital length of stay were completed . Logistic and linear regressions were performed . RESULTS Preoperative pain , mood , and affective state scores were positively associated with postoperative scores ; however , there were no postoperative differences between groups for any measures ( P=.11 to .93 ) . There were no differences in physiologic variables except lower postoperative blood pressure after massage ( P = .01 ) . Postoperative atrial fibrillation occurrence ( P = .6 ) and median postoperative hospital length of stay ( P = .4 ) were similar between groups . CONCLUSION Massage therapy is feasible in cardiac surgical patients ; however , it does not yield therapeutic benefit . Nevertheless , it should be a patient-selected and -paid option BACKGROUND The conduct of r and omized , controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports . OBJECTIVE To develop an extension of the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement for trials of nonpharmacologic treatments . DESIGN A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses r and omized trials of nonpharmacologic treatments . To prepare for the meeting , a survey was conducted to identify the specific issues for discussion . SETTING Consensus meeting in Paris , France . PARTICIPANTS A total of 33 experts attended the meeting . The experts were method ologists ( n = 17 ) ; surgeons ( n = 6 ) ; editors ( n = 5 ) ; and clinicians involved in rehabilitation ( n = 1 ) , psychotherapy ( n = 2 ) , education ( n = 1 ) , and implantable devices ( n = 1 ) . MEASUREMENTS Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments . During a 3-day consensus meeting , all items were discussed and additional method ological issues related to nonpharmacologic research were identified . RESULTS The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials : item 1 ( title and abstract ) , item 3 ( participants ) , item 4 ( interventions ) , item 7 ( sample size ) , item 8 ( r and omization ) , item 11 ( blinding ) , item 12 ( statistical methods ) , item 13 ( participant flow ) , item 15 ( baseline data ) , item 20 ( discussion : interpretation ) , and item 21 ( generalizability ) . In addition , the meeting participants added 1 item related to implementation of the intervention . LIMITATION Evidence was not always available to support the inclusion of each checklist item . CONCLUSION The methods and processes used to develop this extension could be used for other reporting guidelines . The use of this extension to the CONSORT Statement should improve the quality of reporting r and omized , controlled trials assessing nonpharmacologic treatments OBJECTIVE To examine the effects of adjunctive postoperative massage and vibration therapy on short-term postsurgical pain , negative affect , and physiologic stress reactivity . DESIGN Prospect i ve , r and omized controlled trial . The treatment groups were : ( 1 ) usual postoperative care ( UC ) ; ( 2 ) UC plus massage therapy ; or ( 3 ) UC plus vibration therapy . SETTING The University of Virginia Hospital Surgical Units , Gynecology-Oncology Clinic , and General Clinical Research Center . SUBJECTS One hundred and five ( N = 105 ) women who underwent an abdominal laparotomy for removal of suspected cancerous lesions . INTERVENTIONS All patients received UC with analgesic medication . Additionally , the massage group received st and ardized 45-minute sessions of gentle Swedish massage on the 3 consecutive evenings after surgery and the vibration group received 20-minute sessions of inaudible vibration therapy ( physiotones ) on the 3 consecutive evenings after surgery , as well as additional sessions as desired . OUTCOME MEASURES Sensory pain , affective pain , anxiety , distress , analgesic use , systolic blood pressure , 24-hour urine free cortisol , number of postoperative complications , and days of hospitalization . RESULTS On the day of surgery , massage was more effective than UC for affective ( p = 0.0244 ) and sensory pain ( p = 0.0428 ) , and better than vibration for affective pain ( p = 0.0015 ) . On postoperative day 2 , massage was more effective than UC for distress ( p = 0.0085 ) , and better than vibration for sensory pain ( p = 0.0085 ) . Vibration was also more effective than UC for sensory pain ( p = 0.0090 ) and distress ( p = .0090 ) . However , after controlling for multiple comparisons and multiple outcomes , no significant differences were found . CONCLUSIONS Gentle Swedish massage applied postoperatively may have minor effects on short-term sensory pain , affective pain , and distress among women undergoing an abdominal laparotomy for removal of suspected malignant tissues This r and omized-controlled study examined the effects of foot massage on patients ' perception of care received following surgery . The sample of 59 women who underwent laparoscopic sterilization as day case patients were r and omly allocated into two groups . The experimental group received a foot massage and analgesia post-operatively , whilst the control group received only analgesia post-operatively . Each participant was asked to complete a question naire on the day following surgery . This examined satisfaction , memory and analgesia taken . The 76 % response rate was comparable with other patient satisfaction studies following day-case surgery . Statistical analysis showed no overall significant difference in the pain experienced by the two groups ; however , the mean pain scores recorded following surgery showed a significantly different pattern over time , such that the experimental group consistently reported less pain following a foot massage than the control group . This study has attempted to explore the use of foot massage in a systematic way and is therefore a basis for further study PURPOSE Cardiopulmonary resuscitation ( CPR ) during flight is challenging and has to be sustained for long periods . In this setting a mechanical-resuscitation-device ( MRD ) might improve performance . In this study we compared the quality of resuscitation of trained flight attendants practicing either st and ard basic life support ( BLS ) or using a MRD in a cabin-simulator . METHODS Prospect i ve , open , r and omized and crossover simulation study . Study participants , competent in st and ard BLS were trained to use the MRD to deliver both chest compressions and ventilation . 39 teams of two rescuers resuscitated a manikin for 12 min in r and om order , st and ard BLS or mechanically assisted resuscitation . Primary outcome was " absolute h and s-off time " ( sum of all periods during which no h and was placed on the chest minus ventilation time ) . Various parameters describing the quality of chest compression and ventilation were analysed as secondary outcome parameters . RESULTS Use of the MRD led to significantly less " absolute h and s-off time " ( 164±33 s vs. 205±42 s , p<0.001 ) . The quality of chest compression was comparable among groups , except for a higher compression rate in the st and ard BLS group ( 123±14 min(-1 ) vs. 95±11 min(-1 ) , p<0.001 ) . Tidal volume was higher in the st and ard BLS group ( 0.48±0.14 l vs. 0.34±0.13 l , p<0.001 ) , but we registered fewer gastric inflations in the MRD group ( 0.4±0.3 % vs. 16.6±16.9 % , p<0.001 ) . CONCLUSION Using the MRD result ed in significantly less " absolute h and s-off time " , but less effective ventilation . The translation of higher chest compression rate into better outcome , as shown in other studies previously , has to be investigated in another human outcome study Integrative therapies such as massage have gained support as interventions that improve the overall patient experience during hospitalization . Cardiac surgery patients undergo long procedures and commonly have postoperative back and shoulder pain , anxiety , and tension . Given the promising effects of massage therapy for alleviation of pain , tension , and anxiety , we studied the efficacy and feasibility of massage therapy delivered in the postoperative cardiovascular surgery setting . Patients were r and omized to receive a massage or to have quiet relaxation time ( control ) . In total , 113 patients completed the study ( massage , n=62 ; control , n=51 ) . Patients receiving massage therapy had significantly decreased pain , anxiety , and tension . Patients were highly satisfied with the intervention , and no major barriers to implementing massage therapy were identified . Massage therapy may be an important component of the healing experience for patients after cardiovascular surgery UNLABELLED Factors contributing to pain following surgery are poorly understood , with previous research largely focused on adults . With approximately 6 million children undergoing surgery each year , there is a need to study pediatric persistent postsurgical pain . The present study includes patients with adolescent idiopathic scoliosis undergoing spinal fusion surgery enrolled in a prospect i ve , multicentered registry examining postsurgical outcomes . The Scoliosis Research Society Question naire-Version 30 , which includes pain , activity , mental health , and self-image subscales , was administered to 190 patients prior to surgery and at 1 and 2 years postsurgery . A subset ( n = 77 ) completed 5-year postsurgery data . Pain prevalence at each time point and longitudinal trajectories of pain outcomes derived from SAS PROC TRAJ were examined using analyses of variance and post hoc pairwise analyses across groups . Thirty-five percent of patients reported pain in the moderate to severe range presurgery . One year postoperation , 11 % reported pain in this range , whereas 15 % reported pain at 2 years postsurgery . At 5 years postsurgery , 15 % of patients reported pain in the moderate to severe range . Among the 5 empirically derived pain trajectories , there were significant differences on self-image , mental health , and age . Identifying predictors of poor long-term outcomes in children with postsurgical pain may prevent the development of chronic pain into adulthood . PERSPECTIVE This investigation explores the prevalence of pediatric pain following surgery , up to 5 years after spinal fusion surgery . Five pain trajectories were identified and were distinguishable on presurgical characteristics of age , mental health , and self-image . This is the largest study to examine longitudinal pediatric pain trajectories after surgery INTRODUCTION : Poor sleep quality is common among patients following cardiopulmonary artery bypass graft surgery . Pain , stress , anxiety and poor sleep quality may be improved by massage therapy . OBJECTIVE : This study evaluated whether massage therapy is an effective technique for improving sleep quality in patients following cardiopulmonary artery bypass graft surgery . METHOD : Participants included cardiopulmonary artery bypass graft surgery patients who were r and omized into a control group and a massage therapy group following discharge from the intensive care unit ( Day 0 ) , during the postoperative period . The control group and the massage therapy group comprised participants who were subjected to three nights without massage and three nights with massage therapy , respectively . The patients were evaluated on the following mornings ( i.e. , Day 1 to Day 3 ) using a visual analogue scale for pain in the chest , back and shoulders , in addition to fatigue and sleep . Participants kept a sleep diary during the study period . RESULTS : Fifty-seven cardiopulmonary artery bypass graft surgery patients were enrolled in the study during the preoperative period , 17 of whom were excluded due to postoperative complications . The remaining 40 participants ( male : 67.5 % , age : 61.9 years ± 8.9 years , body mass index : 27.2 kg/m2 ± 3.7 kg/m2 ) were r and omized into control ( n = 20 ) and massage therapy ( n = 20 ) groups . Pain in the chest , shoulders , and back decreased significantly in both groups from Day 1 to Day 3 . The participants in the massage therapy group had fewer complaints of fatigue on Day 1 ( p = 0.006 ) and Day 2 ( p = 0.028 ) in addition , they reported a more effective sleep during all three days ( p = 0.019 ) when compared with the participants in the control group . CONCLUSION : Massage therapy is an effective technique for improving patient recovery from cardiopulmonary artery bypass graft surgery because it reduces fatigue and improves sleep BACKGROUND Opioid analgesia alone may not fully relieve all aspects of acute postoperative pain . Complementary medicine techniques used as adjuvant therapies have the potential to improve pain management and palliate postoperative distress . STUDY DESIGN This prospect i ve r and omized clinical trial compared pain relief after major operations in 202 patients who received one of three nursing interventions : massage , focused attention , or routine care . Interventions were performed twice daily starting 24 hours after the operation through postoperative day 7 . Perceived pain was measured each morning . RESULTS The rate of decline in the unpleasantness of postoperative pain was accelerated by massage ( p = 0.05 ) . Massage also accelerated the rate of decline in the intensity of postoperative pain but this effect was not statistically significant . Use of opioid analgesics was not altered significantly by the interventions . CONCLUSIONS Massage may be a useful adjuvant therapy for the management of acute postoperative pain . Its greatest effect appears to be on the affective component ( ie , unpleasantness ) of the pain The aim of this study was to determine the efficiency of foot and h and massage on reducing postoperative pain in patients who had cesarean operation . This pretest-posttest design study was planned as a r and omized controlled experimental study . In the light of the results , it was reported that the reduction in pain intensity was significantly meaningful in both intervention groups when compared to the control group . It was also noted that vital findings were measured comparatively higher before the massage in the test groups , and they were found to be relatively lower in the measurements conducted right before and after the massage , which was considered to be statistically meaningful . Foot and h and massage proved useful as an effective nursing intervention in controlling postoperative pain The purpose of this study was to examine the effects of relaxation techniques and back massage on postoperative pain , anxiety , and vital signs on postoperative days 1 - 3 in patients who had undergone total hip or knee arthroplasty ( THA , TKA ) . Sixty patients having a THA or TKA were r and omly assigned to either a experimental group or a control group . The McGill Pain Question naire Short Form ( MPQ-SF ) and State Anxiety Inventory ( SAI ) were used to measure pain and anxiety , respectively . Vital signs , including blood pressure ( systolic and diastolic ) , pulse , and respiratory rate , were also obtained . Statistically significant differences in pain intensity ( F = 14.50 ; p = .000 ) , anxiety level ( F = 19.13 ; p = .000 ) , and vital signs ( F = 169.61 , 9.14 , 14.23 , 65.64 ; p = .000 ) measured over time were found between the experimental and the control group . Results of this research provide evidence to support the use of relaxation techniques and back massage at bed rest times of patients to decrease pain and anxiety . The interventions helped them to forget about their pain for a while and improved their anxiety state . After an evaluation of the conclusions , use of these interventions should be implemented by nurses into routine plans of care for patients BACKGROUND Because of the widely presumed association between heart disease and psychological wellbeing , the use of so-called ' complementary ' therapies as adjuncts to conventional treatment modalities have been the subject of considerable debate . The present study arose from an attempt to identify a safe and effective therapeutic intervention to promote wellbe ing , which could be practicably delivered by nurses to patients in the postoperative recovery period following coronary artery bypass graft ( CABG ) surgery . Aim . To investigate the impact of foot massage and guided relaxation on the wellbeing of patients who had undergone CABG surgery . METHOD Twenty-five subjects were r and omly assigned to either a control or one of two intervention groups . Psychological and physical variables were measured immediately before and after the intervention . A discharge question naire was also administered . RESULTS No significant differences between physiological parameters were found . There was a significant effect of the intervention on the calm scores ( ANOVA , P=0.014 ) . Dunnett 's multiple comparison showed that this was attributable to increased calm among the massage group . Although not significant the guided relaxation group also reported substantially higher levels of calm than control . There was a clear ( nonsignificant ) trend across all psychological variables for both foot massage and , to a lesser extent , guided relaxation to improve psychological wellbeing . Both interventions were well received by the subjects . CONCLUSIONS These interventions appear to be effective , noninvasive techniques for promoting psychological wellbeing in this patient group . Further investigation is indicated AIM This article is a report of a r and omized controlled trial of the effects of ' M ' technique massage with or without m and arin oil compared to st and ard postoperative care on infants ' levels of pain and distress , heart rate and mean arterial pressure after major craniofacial surgery . BACKGROUND There is a growing interest in non-pharmacological interventions such as aromatherapy massage in hospitalized children to relieve pain and distress but well performed studies are lacking . METHODS This r and omized controlled trial allocated 60 children aged 3 - 36 months after craniofacial surgery from January 2008 to August 2009 to one of three conditions ; ' M ' technique massage with carrier oil , ' M ' technique massage with m and arin oil or st and ard postoperative care . Primary outcome measures were changes in COMFORT behaviour scores , Numeric Rating Scale pain and Numeric Rating Scale distress scores assessed from videotape by an observer blinded for the condition . RESULTS In all three groups , the mean postintervention COMFORT behaviour scores were higher than the baseline scores , but differences were not statistically significant . Heart rate and mean arterial pressure showed a statistically significant change across the three assessment periods in all three groups . These changes were not related with the intervention . CONCLUSIONS Results do not support a benefit of ' M ' technique massage with or without m and arin oil in these young postoperative patients . Several reasons may account for this : massage given too soon after general anaesthesia , young patients ' fear of strangers touching them , patients not used to massage OBJECTIVES To assess the role of massage therapy in the cardiac surgery postoperative period . Specific aims included determining the difference in pain , anxiety , tension , and satisfaction scores of patients before and after massage compared with patients who received st and ard care . DESIGN A r and omized controlled trial comparing outcomes before and after intervention in and across groups . SETTING Saint Marys Hospital , Mayo Clinic , Rochester , Minnesota . SUBJECTS Patients undergoing cardiovascular surgical procedures ( coronary artery bypass grafting and /or valvular repair or replacement ) ( N=58 ) . INTERVENTIONS Patients in the intervention group received a 20-minute session of massage therapy intervention between postoperative days 2 and 5 . Patients in the control group received st and ard care and a 20-minute quiet time between postoperative days 2 and 5 . OUTCOME MEASURES Linear Analogue Self- assessment scores for pain , anxiety , tension , and satisfaction . RESULTS Statistically and clinical ly significant decreases in pain , anxiety , and tension scores were observed for patients who received a 20-minute massage compared with those who received st and ard care . Patient feedback was markedly positive . CONCLUSIONS This pilot study showed that massage can be successfully incorporated into a busy cardiac surgical practice . These results suggest that massage may be an important therapy to consider for inclusion in the management of postoperative recovery of cardiovascular surgical patients & NA ; The purpose of this study was to determine the levels of change on st and ard pain scales that represent clinical ly important differences to patients . Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious . Differences between groups , as summarized by a change in mean values over time , can be difficult to apply to clinical care . Baseline scores vary widely and group mean differences could reflect large changes in a few patients , small changes in many patients , or any combination of these outcomes . Determination of the proportion of patients who have a clinical ly important improvement in their pain would provide a more interpretable result with direct clinical implication s. However , determining a clinical ly important outcome requires information about the degree of change over time that is clinical ly important . Data from the titration phase of a multiple cross‐over r and omized clinical trial of oral transmucosal fentanyl citrate ( OTFC ) for the treatment of cancer‐related breakthrough pain were re‐analyzed to examine the differences in pain scores between treatment episodes that did and did not yield adequate pain relief . The scales evaluated were absolute pain intensity difference ( PID , 0–10 scale ) , percentage pain intensity difference ( PID% , 0–100 % scale ) , pain relief ( PR , 0 ( none ) , 1 ( slight ) , 2 ( moderate ) , 3 ( lots ) , 4 ( complete ) ) , sum of the pain intensity difference ( SPID over 60 min ) , percentage of maximum total pain relief ( % Max TOTPAR over 60 min ) , and global medication performance ( 0 ( poor ) , 1 ( fair ) , 2 ( good ) , 3 ( very good ) , 4 ( excellent ) ) . Adequate relief was defined by the patient 's decision not to use another dose of opioid medication as a rescue , in addition to the study medication , to treat each painful episode . One hundred thirty OTFC naive patients contributed data on 1268 episodes of breakthrough pain . The scales that were converted to a percentage change yielded the best accuracy in predicting adequate relief , with balanced sensitivity and specificity . The best cut‐off point for both the % Max TOTPAR and the PID% was 33 % . The best cut‐off points for the absolute scales were absolute pain intensity difference of 2 , pain relief of 2 ( moderate ) , and SPID of 2 . The global medication performance of 2 ( good ) had excellent values as well . This study presents data ‐derived cut‐off points for the changes in several pain scales , each reflecting the clinical ly important improvement for patients treating breakthrough cancer pain episodes with OTFC . Confirmation in other patient population s and different pain syndromes will be needed . The use of consistent clinical ly important cut‐off points as the primary outcome in future pain therapy clinical trials will enhance their validity , comparability , and clinical applicability OBJECTIVE To determine if light pressure effleurage ( leg rubbing ) during genetic amniocentesis reduces procedure-related pain and anxiety . METHODS Two hundred women with singleton gestations undergoing genetic amniocentesis between 15 - 22 weeks recorded their level of anticipated pain and anxiety on a 10-cm linear visual analog scale prior to the amniocentesis . Subjects were then r and omized to receive effleurage or no effleurage by the assisting nurse during the procedure . Subjects were blinded to the effleurage nature of the study . Following the amniocentesis , subjects repeated the pain and anxiety scoring . RESULTS The two groups were similar with respect to subject and procedure characteristics , as well as anticipated pain or anxiety prior to amniocentesis . Postamniocentesis pain and anxiety scoring were similar in the two groups . The mean effleurage acceptance score was 8.3 + /- 1.8 ( out of 10 ) , and 90.2 % of subjects reported that they would want effleurage with future amniocenteses . CONCLUSIONS Although well accepted by women , light pressure effleurage during genetic amniocentesis does not reduce procedure-related pain or anxiety OBJECTIVES To determine whether massage significantly reduces anxiety , pain , and muscular tension and enhances relaxation compared with an equivalent period of rest time after cardiac surgery . The feasibility of delivering the treatment , effects on heart rate , blood pressure , and respiratory rate , and patient satisfaction were also assessed . METHODS Elective cardiac surgery patients were r and omized to receive massage or rest time at 2 points after surgery . Visual analog scales were used to measure pain , anxiety , relaxation , muscular tension , and satisfaction . Heart rate , respiratory rate , and blood pressure were measured before and after treatment . Focus groups and feedback were used to collect qualitative data about clinical significance and feasibility . RESULTS A total of 152 patients ( 99 % response rate ) participated . Massage therapy produced a significantly greater reduction in pain ( P = .001 ) , anxiety ( P < .0001 ) , and muscular tension ( P = .002 ) and increases in relaxation ( P < .0001 ) and satisfaction ( P = .016 ) compared to the rest time . No significant differences were seen for heart rate , respiratory rate , and blood pressure . Pain was significantly reduced after massage on day 3 or 4 ( P < .0001 ) and day 5 or 6 ( P = .003 ) . The control group experienced no significant change at either time . Anxiety ( P < .0001 ) and muscular tension ( P < .0001 ) were also significantly reduced in the massage group at both points . Relaxation was significantly improved on day 3 or 4 for both groups ( massage , P < .0001 ; rest time , P = .006 ) , but only massage was effective on day 5 or 6 ( P < .0001 ) . Nurses and physiotherapists observed patient improvements and helped facilitate delivery of the treatment by the massage therapists on the ward . CONCLUSIONS Massage therapy significantly reduced the pain , anxiety , and muscular tension and improves relaxation and satisfaction after cardiac surgery HYPOTHESIS Adjuvant massage therapy improves pain management and postoperative anxiety among many patients who experience unrelieved postoperative pain . Pharmacologic interventions alone may not address all of the factors involved in the experience of pain . DESIGN R and omized controlled trial . SETTING Department of Veterans Affairs hospitals in Ann Arbor , Michigan , and Indianapolis , Indiana . PATIENTS Six hundred five veterans ( mean age , 64 years ) undergoing major surgery from February 1 , 2003 , through January 31 , 2005 . INTERVENTIONS Patients were assigned to the following 3 groups : ( 1 ) control ( routine care ) , ( 2 ) individualized attention from a massage therapist ( 20 minutes ) , or ( 3 ) back massage by a massage therapist each evening for up to 5 postoperative days . Main Outcome Measure Short- and long-term ( > 4 days ) pain intensity , pain unpleasantness , and anxiety measured by visual analog scales . RESULTS Compared with the control group , patients in the massage group experienced short-term ( preintervention vs postintervention ) decreases in pain intensity ( P = .001 ) , pain unpleasantness ( P < .001 ) , and anxiety ( P = .007 ) . In addition , patients in the massage group experienced a faster rate of decrease in pain intensity ( P = .02 ) and unpleasantness ( P = .01 ) during the first 4 postoperative days compared with the control group . There were no differences in the rates of decrease in long-term anxiety , length of stay , opiate use , or complications across the 3 groups . CONCLUSION Massage is an effective and safe adjuvant therapy for the relief of acute postoperative pain in patients undergoing major operations CONTEXT Despite major advances in cancer treatment , many patients undergo painful procedures during treatment and suffer debilitating side effects as well as report a decrease in quality of life ( QOL ) . This problem is exacerbated for low-income , racial , and ethnic minorities with cancer . Minority cancer patients often enter care with larger tumors and with a more aggressive disease , increasing the risk of debilitating symptoms , such as pain and anxiety . Research ers have never assessed the feasibility and effectiveness of offering massage therapy for low-income , underserved cancer patients who are undergoing port insertion . OBJECTIVE This study examined the feasibility of conducting a r and omized , controlled trial ( RCT ) that would assess the use of massage therapy to reduce pain and anxiety in urban patients with cancer who undergo surgical placement of a vascular access device ( port ) . The study also assessed the effectiveness of the intervention in reducing perioperative pain and anxiety . DESIGN The research team conducted a 9-month RC T of 60 cancer patients undergoing port placement . The research team r and omly assigned patients in a 2:1 ratio to usual care with massage therapy ( intervention group ) versus usual care with structured attention ( control group ) . SETTING The study took place at Boston Medical Center ( BMC ) , which is an urban , tertiary-referral , safety-net hospital . PARTICIPANTS Participants were cancer patients undergoing port placement . Sixty-seven percent were racial or ethnic minorities , and the majority were female and unemployed , with annual household incomes < $ 30 000 and publicly funded health insurance coverage . INTERVENTION For the intervention , an expert panel developed a reproducible , st and ardized massage therapy intended for individuals undergoing surgical port insertion . Both groups received 20-minute interventions immediately pre- and postsurgery . The research team collected data on pain and anxiety before and after the preoperative and postoperative interventions as well as 1 day after the surgery . OUTCOME MEASURES With respect to feasibility , the study examined ( 1 ) data about recruitment -- time to complete enrollment and proportion of racial and ethnic minorities enrolled ; ( 2 ) participants ' retention ; and ( 3 ) adherence to treatment allocation . The efficacy outcomes included measuring ( 1 ) participants ' average pain level using an 11-point numerical rating scale ( 0 = no pain to 10 = worst possible pain ) and ( 2 ) participants ' situational anxiety using the State-Trait Anxiety Inventory ( STAI ) . RESULTS The research team assigned the 60 patients to the groups over 53 weeks . Sixty-seven percent of the participants were racial or ethnic minorities . A majority were female and unemployed , with annual household incomes < $ 30 000 and publicly funded health insurance coverage . Of the 40 patients allocated to massage therapy , the majority ( n = 33 ) received both the pre- and postoperative interventions . Massage therapy participants had a statistically significant , greater reduction in anxiety after the first intervention compared with individuals receiving structured attention ( -10.27 vs -5.21 , P = .0037 ) . CONCLUSIONS Recruitment of low-income , minority patients into an RCT of massage therapy for perioperative pain and anxiety is feasible . Both massage therapy and structured attention proved beneficial for alleviating preoperative anxiety in cancer patients undergoing port placement OBJECTIVES ( 1 ) To assess the efficacy of a 20 minute massage therapy session on pain , anxiety , and tension in patients before an invasive cardiovascular procedure . ( 2 ) To assess overall patient satisfaction with the massage therapy . ( 3 ) To evaluate the feasibility of integrating massage therapy into preprocedural practice s. Experimental pretest-posttest design using r and om assignment . Medical cardiology progressive care units at a Midwestern Academic Medical Center . Patients ( N=130 ) undergoing invasive cardiovascular procedures . The intervention group received 20 minutes of h and s on massage at least 30 minutes before an invasive cardiovascular procedure . Control group patients received st and ard preprocedural care . Visual analogue scales were used to collect verbal numeric responses measuring pain , anxiety , and tension pre- and postprocedure . The differences between pre- and postprocedure scores were compared between the massage and st and ard therapy groups using the Mann-Whitney Wilcoxon 's test . Scores for pain , anxiety , and tension scores were identified along with an increase in satisfaction for patients who received a 20-minute massage before procedure compared with those receiving st and ard care . This pilot study showed that massage can be incorporated into medical cardiovascular units ' preprocedural practice and adds validity to prior massage studies |
11,301 | 20,113,981 | These data provide , for the first time , evidence for improved management of children by use of paediatric formulations , and support the further development and use of paediatric ACTs | Paediatric formulations of artemisinin combination therapies ( ACTs ) have recently been developed for the treatment of children with falciparum malaria .
Compared with conventional tablet formulations , the new non-tablet preparations have shown equivalent efficacy , safety , and tolerability in individual trials .
We aim ed to investigate whether objective evidence supports the development and use of paediatric ACTs . | BACKGROUND Combination treatments , preferably containing an artemisinin derivative , are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance . Our aim was to show non-inferiority of a new dispersible formulation of artemether-lumefantrine to the conventional crushed tablet in the treatment of young children with uncomplicated malaria . METHODS We did a r and omised non-inferiority study on children weighing 5 - 35 kg with uncomplicated P falciparum malaria in Benin , Kenya , Mali , Mozambique , and Tanzania . The primary outcome measure was PCR-corrected 28-day parasitological cure rate . We aim ed to show non-inferiority ( with a margin of -5 % ) of dispersible versus crushed tablet . We constructed an asymptotic one-sided 97.5 % CI on the difference in cure rates . A computer-generated r and omisation list was kept central ly and investigators were unaware of the study medication administered . We used a modified intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00386763 . FINDINGS 899 children aged 12 years or younger were r and omly assigned to either dispersible ( n=447 ) or crushed tablets ( n=452 ) . More than 85 % of patients in each treatment group completed the study . 812 children qualified for the modified intention-to-treat analysis ( n=403 vs n=409 ) . The PCR-corrected day-28 cure rate was 97.8 % ( 95 % CI 96.3 - 99.2 ) in the group on dispersible formulation and 98.5 % ( 97.4 - 99.7 ) in the group on crushed formulation . The lower bound of the one-sided 97.5 % CI was -2.7 % . The most common drug-related adverse event was vomiting ( n=33 [ 7 % ] and n=42 [ 9 % ] , respectively ) . No signs of ototoxicity or relevant cardiotoxicity were seen . INTERPRETATION A six-dose regimen of artemether-lumefantrine with the new dispersible formulation is as efficacious as the currently used crushed tablet in infants and children , and has a similar safety profile Background Artemether/lumefantrine ( AL ) has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region . Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria . However , oral paediatric formulations are urgently needed , as the tablets are difficult to administer to young children , who can not swallow whole tablets or tolerate the bitter taste of the crushed tablets . Methods A r and omized , controlled , open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6–59 months , treated over three days with either six-dose of artemether/lumefantrine tablets ( Coartem ® ) or three-dose of artemether/lumefantrine suspension ( Co-artesiane ® ) for uncomplicated falciparum malaria in western Kenya . The children were followed-up with clinical , parasitological and haematological evaluations over 28 days . Results Ninety three percent ( 124/133 ) and 90 % ( 121/134 ) children in the AL tablets and AL suspension arms respectively completed followed up . A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0 % at Day 28 in the AL tablets group and 93.4 % in the AL suspension group , p = 0.40 . Both drugs effectively cleared gametocytes and were well tolerated , with no difference in the overall incidence of adverse events . Conclusion The once daily three-dose of artemether-lumefantrine suspension ( Co-artesiane ® ) was not superior to six-dose artemether-lumefantrine tablets ( Coartem ® ) for the treatment of uncomplicated malaria in children below five years of age in western Kenya . Trial registration Clinical Trials.gov ZusammenfassungPädiatrische Medikamentenformulierungen sind ein wichtiger Fortschritt in der Therapie von afrikanischen Kindern , die an Malaria tropica erkrankt sind . In dieser klinischen Studie wurde die Wirksamkeit , Sicherheit und Verträglichkeit einer neuen pädiatrischen Artesunat-Mefloquin Koformulierung i m Vergleich mit einer Tablettenformulierung evaluiert . Einundsiebzig pädiatrische Patienten am Albert Schweitzer Spital in Lambaréné , Gabun , die an unkomplizierter Malaria tropica litten , wurden nach Körpergewicht stratifiziert , um mit der pädiatrischen ( 10 – 20 kg ; n = 41 ) oder der Tabletten-Formulierung ( 20 – 40 kg ; n = 30 ) therapiert zu werden . Die PCR korrigierte Heilungsrate war 100 % am Tag 28 . Die häufigsten Nebenwirkungen waren Erbrechen ( 17 % ) , abdominelle Schmerzen ( 11 % ) und Cephalea ( 17 % ) . Diese Studie bestätigt die hervorragende Wirksamkeit und gute Verträglichkeit von Artesunat-Mefloquin zur Therapie pädiatrischer Patienten in Afrika . Summary Pediatric drug formulations of artemisinin combination therapies are urgently needed for improving the treatment of children suffering from uncomplicated malaria . The aim of this clinical trial was to evaluate the efficacy , safety and tolerability of a novel pediatric fixed-dose granule formulation of artesunate-mefloquine and a new co-blister tablet formulation . A total of 71 children aged 1–13 years suffering from uncomplicated falciparum malaria were stratified into two groups according to weight : 10–20 kg , pediatric group ( n = 41 ) ; 20–40 kg , tablet group ( n = 30 ) . All the children were treated once daily for three days : the pediatric group received the novel granule formulation , the tablet group received the co-blister tablets . The PCR-corrected cure rate on day 28 was evaluated . There was no reappearance of parasitemia during the follow-up period and the day-28 cure rate was therefore 100 % in per- protocol analysis . In intention-to-treat analysis the cure rates were 95 % in the pediatric group and 97 % in the tablet group . The most frequent adverse events were vomiting ( 17 % ) , abdominal pain ( 11 % ) and headache ( 17 % ) . This study confirms the excellent efficacy and favorable safety and tolerability profile of a novel pediatric artesunate-mefloquine formulation for treatment in African children AIMS To assess the haemodynamic , electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin ( Artekin ) fixed combination therapy in uncomplicated malaria . METHODS Sixty-two Cambodians ( 32 children and 30 adults ) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure , the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring . QT intervals were rate-corrected ( QTc ) using Bazett 's formula . RESULTS Artekin therapy was well tolerated and all patients responded to treatment . Average parasite and fever clearance times were 19 and 12 h , respectively . The pretreatment mean fall in systolic blood pressure on st and ing was 8 + /- 6 mmHg and 6-hourly measurements over 72 h showed no significant change ( P = 0.48 ) . There was a significant lengthening of the mean QTc to a maximum of 11 ms(0.5 ) ( 95 % confidence interval 4 - 18 ms(0.5 ) ) relative to baseline at 24 h ( P = 0.003 ) . The maximal QTc prolongation observed in any patient was 53 ms(0.5 ) . There was a mean 0.4 mmol l(-1 ) reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia ( plasma glucose < 3.0 mmol l(-1 ) ) were observed at any time . CONCLUSIONS Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults . Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine , no clinical ly significant cardiovascular or metabolic effects were observed OBJECTIVES Paediatric drug formulations of artemisinin combination therapies and pharmacokinetic data supporting their use in African children are urgently needed for the effective treatment of young children suffering from falciparum malaria in sub-Saharan Africa . PATIENTS AND METHODS In this study , the pharmacokinetic characteristics of a novel paediatric granule formulation of artesunate-mefloquine therapy were evaluated in comparison to the st and ard tablet formulation in the treatment of uncomplicated malaria in paediatric patients . Twenty-four patients were assigned to treatment according to body weight with either a fixed-dose paediatric granule co-formulation ( 10 - 20 kg body weight ) or a free-dose co-blister tablet formulation of artesunate-mefloquine ( > 20 - 40 kg body weight ) . RESULTS Median values for C(max ) ( 861 and 930 ng/mL ) , T(max ) ( 1.5 and 1.5 h ) and AUC(0-)(t ) ( 2,050 and 2,470 ng.h/mL ) were comparable for dihydroartemisinin in the two groups . Exploratory analysis of mefloquine plasma levels revealed a trend towards higher concentrations in the younger age group during the absorption phase ( 2,550 and 1,815 ng/mL , 54 h after initiation of treatment , respectively ) . Median mefloquine concentrations at day 28 were 197 and 343 ng/mL , respectively . CONCLUSIONS The pharmacokinetic characteristics of the two paediatric dosage forms , i.e. the novel fixed-dose co-formulation and the st and ard co-blister of artesunate-mefloquine show comparable results in the two treatment groups . The novel fixed-dose paediatric formulation is an interesting option for outpatient treatment of uncomplicated malaria in African children The bioavailability/pharmacokinetics of dihydroartemisinin and mefloquine following the oral doses of 4 mg/kg body weight artesunate ( Cambodian Pharmaceutical Enterprise ) given concurrently with 10 mg/kg body weight oral mefloquine artesunate ( Cambodian Pharmaceutical Enterprise ) were investigated in 15 healthy Cambodian male volunteers . Both formulations were generally well tolerated . Both produced satisfactory plasma/blood concentration-time profiles . Oral artesunate and mefloquine were rapidly absorbed from gastrointestinal tract with marked inter-individual variation . For the dihydroartemisinin , the median ( 95 % Cl ) Cmax of 748 ( 304 - 1,470 ) ng/ml was observed at 1.5 ( 0.3 - 3.0 ) hours ( tmax ) after drug administration . The median ( 95 % CI ) values for AUC0-infinity , lambda(z ) and tl/2z were 1.673 ( 1.08 - 2.88 ) microg.h/ml , 0.54(0.24 - 1.1)/hour and 1.3 ( 0.6 - 2.9 ) hours , respectively . For mefloquine , a median ( 95 % Cl ) Cmax of 1,000 ( 591 - 1,500 ) ng/ml was observed at 4 ( 2 - 6 ) hours ( tmax ) after drug administration . The median ( 95 % CI ) value for AUC0 - 168h was 3.92 ( 2.88 - 7.02 ) microg.h/ml The safety and efficacy of a novel combination of dihydroartemisinin ( DHA ) and piperaquine , Artekin ( Holleykin Pharmaceuticals ) , were assessed in 106 patients ( 76 children and 30 adults ) with uncomplicated falciparum malaria from 2 remote areas in Cambodia . Age-based doses were given at 0 , 8 , 24 , and 32 h. Mean total DHA and piperaquine doses were 9.1 and 73.9 mg/kg , respectively , for children and 6.6 and 52.9 mg/kg for adults . All patients became aparasitemic within 72 h. Excluding the results for 1 child who died on day 4 , there was a 96.9 % 28-day cure rate ( 98.6 % in children and 92.3 % in adults ) . Patients who had recrudescent infection received low doses of Artekin . Side effects were reported by 22 patients ( 21 % ) but did not necessitate premature cessation of therapy . Although Artekin is a promising and inexpensive option for antimalarial therapy , further efficacy and pharmacokinetic studies are needed , especially for its use in children |
11,302 | 22,110,781 | In conclusion , data summarized in this review support the concept that the vitamin D endocrine system ( VDES ) is of importance for pathogenesis and progression of MM and other types of skin cancer | Skin cancer is the most common cancer in humans .
There are several types of skin cancer that include basal cell carcinoma ( BCC ) , squamous cell carcinoma ( SCC ) and malignant melanoma ( MM ) .
The associations of vDr polymorphisms with skin cancer risk are not well characterized so far .
Only a few epidemiologic studies have directly addressed the relationship between VDR polymorphisms and the incidence and prognosis of MM . | Psoriasis is a genetically determined disease characterized by hyperproliferation and disordered maturation of the epidermis . Th1 lymphocytes are implicated in its pathogenesis . The vitamin D receptor ( VDR ) is a c and i date modifying gene , having immunosuppressive effects and being involved in anti-proliferative and pro-differentiation pathways in keratinocytes . There is suggestive evidence that the A allele of the A-1012 G polymorphism is associated with down-regulation of the Th1 response , via GATA-3 . The F and T alleles of Fok1 and Taq1 have been associated with increased VDR activity . The present study aim ed to test the hypothesis that the A allele of A-1012 G is protective for occurrence and severity of psoriasis and enhances therapeutic response to vitamin D analogues and that these effects would be additive to those of Fok1 and Taq1 . The study group comprised 206 psoriasis patients who had received topical calcipotriol treatment and 80 controls . There was no significant linkage disequilibrium between any pair of the three polymorphic sites ( P=0.3–0.8 ) . The A , F and T alleles were positively associated with calcipotriol response : AA genotype ( compared to AG/GG ) , odds ratio (OR)=2.18 ( P=0.04 ) ; TT , OR=1.97 ( P=0.03 ) ; AAFF genotype combination , OR=4.11 ( P=0.03 ) ; AATT , OR=5.64 ( P=0.005 ) ; and FFTT , OR=3.22 ( P=0.01 ) . Comparing patients without , to patients with , a family history of psoriasis , the A allele was under represented ( P=0.01 ) and the AAFF genotype combination even more so ( compared to residual genotypes ) ( OR=0.24 ; P=0.005 ) . AAFF was also under-represented in patients without a family history compared to controls ( OR=0.31 ; P=0.04 ) . There were no associations of family history with Fok1 and Taq1 . There were no associations of severity of psoriasis with any polymorphism . In conclusion , the A-1012 G , Fok1 and Taq1 VDR polymorphisms were associated with response to calcipotriol . A-1012 G and Fok1 were associated with susceptibility to non-familial psoriasis The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma ( MM ) , as predicted by tumour ( Breslow ) thickness , has been reported previously . We now report a novel adenine – guanine substitution −1012 bp relative to the exon 1a transcription start site ( A-1012 G ) , found following screening by single-str and ed conformational polymorphism of this promoter region . There was a total of 191 MM cases , which were stratified according to conventional Breslow thickness groups , cases being r and omly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area , and this population ( n=176 ) was compared to 80 controls . The A allele was over-represented in MM patients and , with GG as reference , odds ratio ( OR ) for AG was 2.5 , 95 % confidence interval ( CI ) 1.1–5.7 , ( P=0.03 ) and AA 3.3 , CI 1.4–8.1 , ( P=0.007 ) . The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis , the Kaplan – Meier estimates of the probability of metastasis at 5 years being : GG 0 % ; AG 9 % , CI 4–16 % ; AA 21 % , CI 12–36 % ; ( P=0.008 ) , and to thicker Breslow thickness groups ( P=0.04 ) . The effect on metastasis was independent of tumour thickness and A-1012 G may have predictive potential , additional to Breslow thickness . Neither the Fok 1 nor Taq 1 variants ( f and t ) were significantly related to the development of metastasis , although there was a strong relationship of fftt with the thickest Breslow thickness group ( P=0.005 ) . There was an interaction between the A-1012 G and Fok 1 polymorphisms ( P=0.025 ) and the Fok 1 variant enhanced the effect of the A allele of the A-1012 G polymorphism on metastasis , the probability of metastasis for AAff at 5 years follow-up being 57 % , CI 24–92 % Calcitriol , via its receptor ( VDR ) is a main regulator of PTH secretion and parathyroid cell proliferation . Recently , marked overrepresentation of the polymorphic VDR alleles b , a , and T was found in patients with primary hyperparathyroidism ( pHPT ) , which suggests pathogenic importance in the disease . Using the ribonuclease protection assay , relative VDR and PTH messenger ribonucleic acid ( mRNA ) levels of parathyroid adenomas from 42 patients with sporadic pHPT were related to these VDR polymorphisms . The tumors of patients homozygous for the b , a , or T alleles demonstrated significantly lower VDR and higher PTH mRNA levels than those exhibiting the BB , AA , or tt genotypes ( P < 0.0001 - 0.02 ) , whereas heterozygotes had intermediate values . A similar discrepancy was found when comparing the baT and non-baT haplotypes ( 0.042 + /- 0.005 vs. 0.064 + /- 0.004 for VDR ; 34.4 + /- 3.7 vs. 21.6 + /- 2.2 for PTH ; both P < 0.005 ) . The lower VDR mRNA levels associated with the b , a , and T alleles may affect the calcitriol-mediated control of parathyroid function and thereby contribute to the development of sporadic pHPT |
11,303 | 27,900,768 | Nonabsorbable nasal packing is no more effective than treatments without packing after septoplasty .
Septal splints and transseptal sutures reduce postoperative pain , headache , and synechia . | OBJECTIVES Septoplasty is one of the most frequently performed rhinologic surgeries .
Complications include nasal bleeding , pain , headache , septal hematoma , synechia , infection , residual septal deviation , and septal perforation .
In this study , we aim ed to compare complication rates among patients according to packing method . | SUMMARY The trans-septal suturing method has been developed in septoplasty as an alternative to packing . This study was carried out to compare the postoperative results of trans-septal suturing with the anterior Merocel packing technique . The study involved 697 patients who underwent septoplasty . Following surgery , patients were r and omly divided into two groups , one with trans-septal suturing and the other with Merocel packing . Patients were asked to record pain levels using a visual analogue scale . Postoperative symptoms and complications were compared . A total of 697 nasal operations were evaluated in the postoperative period considering pain , bleeding , haematoma , septal perforation synechiae and septal perforation . The results for haemorrhage , haematoma , synechiae and perforation were not statistically different ( p > 0.05 ) between groups . In contrast , the level of postoperative pain in patients undergoing trans-septal suturing was significantly less than in the group who received Merocel packing ( p < 0.05 ) . Patients with Merocel packing had significantly more pain and nasal discomfort when assessed 1 week after intervention . Therefore , the trans-septal suturing technique may be the preferred option to provide higher patient satisfaction Septoplasty is one of the most common otorhinolaryngologic surgical procedure . It is customary to place a pack in the nose as a part of nasal surgery to stop bleeding , enhance apposition of mucosal flaps , and stabilize the operated septal cartilage and bones . But nasal packing is not an innocuous procedure . The most common problem encountered by the patients after septoplasty with nasal pack is the pain and discomfort in post operative period . The study has been performed to compare the complications and outcome of septoplasty with or without nasal packing . Forty four patients were r and omly allocated into two groups , Group A ( n = 21 ) and Group B ( n = 23 ) . In Group A trans-septal suture and in Group B intranasal pack was used following septoplasty . Both groups were compared for postoperative pain , postoperative complications and surgical outcome . Among 44 patients 31 patients were male and 13 patients were female . Most of the patients ie 79.5 % were operated for nasal obstruction . Only one patient had postoperative nasal bleeding requiring nasal pack in Group A. Higher Postoperative pain score , longer hospital stay and more complications were observed in Group B patients . No difference was found in patients ' satisfaction after the operation . Septoplasty can be safely performed without postoperative nasal packing and is preferred to avoid postoperative pain , discomfort and other complications This r and omized study was conducted to evaluate the role of nasal packing following septorhinoplasty . Fifty septorhinoplasty patients were selected ( on a r and om basis ) to either receive or not receive nasal packing . Twenty-three of 25 patients with nasal packing and 22 of 25 patients without nasal packing were available for follow-up . This study suggests that patients with nasal packing are less likely to develop recurrent septal deviation and synechia and more likely to have improvement in the nasal airway . Only one of the patients with nasal packing found the removal of the packing the most uncomfortable part of the surgery . The most impressive and statistically significant finding , however , was the significant difference between the two groups in terms of airway improvement , which was 96 percent in the nasal packing group and 64 percent in the group without nasal packing . There was also a higher incidence of recurrent or residual septal deviation in the group without nasal packing ( 41 percent ) , while the group with nasal packing had only ( 13 percent ) recurrent or residual deviation OBJECTIVES /HYPOTHESIS 1 ) Study outcomes of revision septoplasty using a vali date d disease-specific question naire and a patient satisfaction survey ; 2 ) assess the effect of surgery on the use of medication to treat nasal congestion ; and 3 ) report on sites of persistent septal deviation identified at revision septoplasty . STUDY DESIGN Prospect i ve , single-center outcome study of patients with symptomatic nasal obstruction and persisting septal deviation despite prior septal surgery . METHODS The Nasal Obstruction Symptom Evaluation ( NOSE ) scale was administered preoperatively and at 3 and 6 months following revision surgery . Patients were also question ed regarding ease of breathing and medication use preoperatively and postoperatively , as well as satisfaction with the surgical outcome . Anatomic site(s ) of residual septal deviation were recorded intraoperatively . RESULTS Thirty-nine patients completed the study . Mean NOSE scores decreased significantly from 75.9 preoperatively to 14.9 3 months after revision surgery . Mean Ease-of-Breathing scores over this interval improved from 3/10 preoperatively to 8.5/10 . Both results were sustained at 6 months ( P < 0.0001 ) . Patient satisfaction was very high , and many patients required less medication to treat symptoms of nasal congestion postoperatively . Deviations persisting from prior surgery most commonly involved the dorsal or caudal septum . CONCLUSION In patients who experience ongoing nasal obstruction with a persistent septal deviation despite prior septoplasty , revision surgery significantly improves disease-specific quality of life , results in high patient satisfaction , and may diminish the need for nasal medications postoperatively . Caudal or dorsal deflections may be more difficult to correct , leading to the need for revision surgery . LEVEL OF EVIDENCE 2C The once-common practice of packing the nose after septoplasty was based on a desire to prevent postoperative complications such as bleeding , septal hematoma , and adhesion formation . However , it was since found that not only is nasal packing ineffective in this regard , it can actually cause these complications . Although the consensus in the world literature is that packing should be avoided , to the best of our knowledge , no truly r and omized study has been undertaken in Southwest Asia upon which to justify this recommendation here . Therefore , we conducted a prospect i ve r and omized comparison of the incidence of a variety of postoperative signs and symptoms in 88 patients , 15 years of age and older , who did ( n = 44 ) and did not ( n = 44 ) undergo nasal packing following septoplasty . We found that the patients who underwent packing experienced significantly more postoperative pain , headache , epiphora , dysphagia , and sleep disturbance on the night of surgery . Oral and nasal examinations 7 days postoperatively revealed no significant difference between the two groups in the incidence of bleeding , septal hematoma , adhesion formation , and local infection . Finally , the packing group reported a moderate to high level of pain during removal of the packing . Our findings confirm that nasal packing after septoplasty is not only unnecessary , it is actually a source of patient discomfort and other signs and symptoms Nasal packing may influence the mucociliary clearance of the nose in the postoperative healing phase . In an attempt to overcome some of this problem , a haemostatic septal suturing technique was conceived . In this prospect i ve study , we aim ed to investigate the effects of nasal packing and septal suturing technique on mucociliary clearance by rhinoscintigraphy . Forty-eight adult patients who had undergone septoplasty were included in the investigation . Preoperatively , the patients were allocated into three groups : group 1 , fingerstall packs filled with gauze and smeared with vaseline were used ( 11 male , 4 female ) ; group 2 , silicon septal splint packs were used ( 11 male , 4 female ) ; group 3 , haemostatic septal sutures were used ( 14 male , 4 female ) . Mucociliary clearance was measured by rhinoscintigraphy in all patients before surgery and 6 weeks after surgery . The nasal mucociliary clearance was presented as the velocity ( mm/min ) of nasal mucociliary transport of the 99mTc-MAA droplet . The mean velocity of nasal mucociliary clearances before and after surgery for group 1 , group 2 and group 3 were 1.85 ± 0.67 versus 2.43 ± 0.78 mm/min , 2.36 ± 0.80 versus 2.92 ± 0.96 mm/min and 2.03 ± 0.58 versus 2.62 ± 0.65 mm/min , respectively . A significant difference in nasal mucociliary clearance was observed after surgery in all groups ( p < 0.001 ) . No significant differences were found between the groups regarding mucociliary clearance before and after surgery . Patients with septal deviation have a prolonged mucociliary transit time as compared with postoperative . Nasal packing did not significantly influence the mucociliary clearance in the postoperative healing phase OBJECTIVE The most frequent complaint of patients after septoplasty is severe pain felt during removal of nasal packing placed on the operation . Various methods have been described to decrease pain and to increase patient comfort during removal of nasal packing . However , these methods are not practical . There has been an increase in the number of studies on pre-emptive analgesia use for postoperative pain relief . The aim of this study was to determine whether pre-emptive analgesia decreased pain during removal of Merocel packs placed in septoplasties . METHODS This is a double-blind r and omized , placebo-controlled study . The study included 121 patients who underwent elective septoplasty in our otorhinolaryngology clinic . The patients were r and omly assigned into two groups : study and placebo groups . The study and placebo groups received two tablets of diflunisal 500 mg and placebo , respectively , two and a half hours before removal of nasal packing . Visual analog scale ( VAS ) values immediately after and 5 min after removal of nasal packing , effects of the procedure on patient comfort and its side-effects were evaluated separately . RESULTS VAS values immediately after the removal of nasal packs significantly decreased in the study group ( p<0.001 ) , but there was no significant difference in VAS values obtained after the procedure between the study and placebo groups . Patient discomforts were significantly lower in the diflunisal group ( p<0.001 ) . CONCLUSIONS It can be concluded that pre-emptive analgesia decreases pain during removal of nasal packing placed in septoplasties and increases patient comfort Background : This study compared the effects of nasal packing and transseptal suturing after septoplasty by evaluating olfactory function , pain , and mucociliary clearance . Methods : The study enrolled 39 patients diagnosed with isolated septal deviation . The patients were r and omly assigned to 2 groups . In Group A ( n = 21 ) , transseptal sutures were placed for septal stabilization after the septoplasty . In Group B ( n = 18 ) , both nasal passages were packed with Merocel tampons after the septoplasty . It was made Sniffin Sticks test , sacchranirine test , and pain and discomfort scales preoperatively , 1 week postoperatively and 3 months postoperatively on all patients . Results : There was no postoperative bleeding , submucoperichondrial haematoma , or abscess formation in either group . The postoperative discomfort and pain scores were increased in Group B ( the packing group ) in our study , the mucociliary clearance improved after septoplasty in both groups , and there was no significant difference in mucociliary clearance between the 2 groups . The odor threshold , odor identification , and odor discrimination were significantly increased 3 months postoperatively , but not 1 week postoperatively . Conclusions : Nasal packing causes more discomfort and pain than transseptal suturing , while there was no significant difference in olfactory functions or the mucociliary clearance after septoplasty between nasal packing and transseptal suturing OBJECTIVE To discuss and compare the results of suturing the nasal septum after septoplasty with the results of nasal packing . METHODS A prospect i ve study , which was performed at Prince Hashem Military Hospital in Zarqa , Jordan and Prince Rashed Military Hospital in Irbid , Jordan between September 2005 and August 2006 included 169 consecutive patients that underwent septoplasty . The patients were r and omly divided into 2 groups . After completion of surgery , the nasal septum was sutured in the first group while nasal packing was performed in the second group . RESULTS Thirteen patients ( 15.3 % ) in the first group and 11 patients ( 13 % ) in the second group had minor oozing in the first 24 hours , 4 patients ( 4.8 % ) had bleeding after removal of the pack in the second group . Four patients ( 4.8 % ) developed septal hematoma in the second group . Two patients ( 2.4 % ) had septal perforation in the second group . One patient ( 1.1 % ) in the first group , and 5 patients ( 5.9 % ) in the second group had postoperative adhesions . Five patients ( 5.9 % ) were found to have remnant deviated nasal septum in each group . The operating time was 4 minutes longer in the first group . CONCLUSION Septal suturing after septoplasty offers the following advantages : elimination of discomfort for the patients , minimal complications , the outcome is almost the same as with nasal packing , and finally the hospital stay is less than with nasal packing . Therefore , suturing of the nasal septum after septoplasty should be a preferred alternative to nasal packing The need for nasal packing in septal surgery is not proven though its use is widespread . Post-operative complications , while uncommon , are frequently pack related . Consenting adults were prospect ively r and omized to one of the following : Vaseline gauze nasal packing or 30 Dexon mucosal suture . All patients were operated on by one surgeon who was made aware of the r and omization decision only when the corrective surgery was complete . Details of post-operative morbidity were collected and pain scored subjectively by a visual analogue scale the morning after surgery . The first 50 available pain scales illustrated a difference between the groups ( P less than 0.05 ) , means 4 and 3 in the pack and suture group respectively . There was no demonstrable difference in post-operative haemorrhage , adhesions , nasal crusting or mucosal atrophy . The need for nasal packing is not supported The objective of this study is to compare the nasal packing and the transseptal suturing techniques regarding the extubation difficulty evaluation scores , follow-up times in post-anaesthesia care unit ( PACU ) , pain scores , and postoperative complications . Two hundred patients who underwent septoplasty from January 2009 to October 2009 were r and omly assigned either to have nasal packs ( n : 100 ) or transeptal sutures ( n : 100 ) . In the transseptal suture group , extubation was easier and PACU follow-up times were shorter , when compared to the nasal packing group ( p < 0.001 ) . Patients with nasal packing had significantly higher pain scores ( p < 0.001 ) . Minor bleeding was significantly higher in the transseptal group with seven cases , compared to the nasal packing group without any bleeding cases ( p = 0.014 ) . There were two patients who had postoperative major bleeding , and two patients who had septal hematoma in the transseptal suture group . One patient with nasal packing had postoperative infection . Septal perforation was not seen in any of the cases . While patients in both groups experienced postoperative crusting , patients in the transseptal suture group also complained about foreign body sensation . Extubation was more comfortable ; post-anaesthesia monitorization duration was shorter , and postoperative pain was less , but minor bleeding was seen more with transseptal sutures . There was no significant difference in terms of major bleeding , hematoma , infection or perforation . Foreign body sensation was the main cause of postoperative discomfort in the transseptal suture group . Transseptal suturing might be a significantly comfortable , cost-effective and reliable alternative to nasal packing We conducted a prospect i ve , comparative , interventional study to evaluate the role of intranasal septal splints and to compare the results of this type of support with those of conventional nasal packing . Our study population was made up of 60 patients , aged 18 to 50 years , who had undergone septoplasty for the treatment of a symptomatic deviation of the nasal septum at our tertiary care referral hospital . These patients were r and omly divided into two groups according to the type of nasal support they would receive : 30 patients ( 25 men and 5 women , mean age : 23.3 yr ) received bilateral intranasal septal splints and the other 30 ( 26 men and 4 women , mean age : 22.4 yr ) underwent anterior nasal packing . Outcomes parameters included postoperative pain and a number of other variables . At 24 and 48 hours postoperatively , the splint group had significantly lower mean pain scores ( p < 0.05 ) . At 48 hours , the splint group experienced significantly fewer instances of nasal bleeding ( p < 0.01 ) , swelling over the face and nose ( p < 0.01 ) , watering of the eyes ( p < 0.01 ) , nasal discharge ( p = 0.028 ) , nasal obstruction ( p < 0.001 ) , and feeding difficulty ( p = 0.028 ) . Likewise , mean pain scores during splint or pack removal were significantly lower in the splint group ( p < 0.01 ) . At the 6-week follow-up , only 2 patients ( 6.7 % ) in the splint group exhibited a residual deformity , compared with 8 patients ( 26.7 % ) in the packing group ( p = 0.038 ) . Finally , no patient in the splint group had an intranasal adhesion at follow-up , while 4 ( 13.3 % ) in the packing group did ( p < 0.05 ) . We conclude that intranasal septal splints result in less postoperative pain without increasing postoperative complications , and thus they can be used as an effective alternative to nasal packing after septoplasty Nasal packing has evolved over the years . Though effective in preventing postoperative bleeding complications , they are associated with significant morbidity and pain . In recent years nasal splints have been used to reduce the duration of nasal packs . The aim of this study is to compare the postoperative results in 200 nasal surgeries where in nasal packing was replaced by trans-septal splint suturing . Two hundred cases of septoplasties were prospect ively studied over a period of 5 years at Adichunchanagiri Institute of Medical Sciences . In 100 cases ( group A ) nasal packing was done postoperatively whereas in other 100 ( group B ) trans-septal splint suturing was done . Post operatively patients were followed up in both groups regarding the presence of pain , bleeding , crusting and synechiae for a period of 6 months . Two hundred patients were prospect ively studied over a period of 5 years with a male – female ratio of 1.35:1 and the mean age was 31 . In group A out of 100 patients followed postoperatively , ten had mild bleeding on second day after pack removal none of which required repacking , 22 patients had mild pain on second and third day , 18 had moderate crusting on day 4 , 12 had synechiae after 2 weeks . In group B , out of 100 patients , minimal bleeding was noted in 13 patients on day 1 and 2 , mild discomfort was noted in the nose in 34 patients till day 7 ( day of splint removal ) , crusting was noted in six patients , synechiae was noted in one patient . Elimination of pain and discomfort for the patients and absence of complications like synechiae . Also the hospital stay is less than with nasal packing . Therefore , suturing of the nasal septum with a splint after septoplasty should be a preferred alternative to nasal packing A study was carried out to compare the effectiveness of nasal splints ( in preventing intranasal adhesions ) with the morbidity associated with their use in nasal surgery . One hundred and ten patients undergoing a routine nasal operation were r and omly allocated into two equal groups , one with splints and the other without . Post-operative pain and discomfort was assessed by a visual analogue scale at 48 hours and a week following surgery when either nasal suction ( non-splinted group ) or removal of splints was carried out . All patients were examined after six weeks for development of adhesions . Results showed that there was no significant difference in the incidence of adhesions between the splinted and non-splinted patient groups . However , the patients with splints had significantly more pain and nasal discomfort when assessed one week after surgery . It is concluded that the morbidity associated with nasal splints does not justify their use in routine nasal surgery if the aim is to prevent nasal adhesions , but they may still be indicated for enhancing the stability of the septum following septoplasty OBJECTIVES This study aims to compare pain , bleeding , nasal obstruction , crust and synechia formation , and anesthesia-related morbidity in patients with and without use of nasal packs after septoplasty . PATIENTS AND METHODS A total of 66 patients ( 32 women , 34 men ; mean age 24 years ; range 18 to 48 years ) who underwent Cottle 's septoplasty under general anesthesia were r and omly allocated to three groups in this prospect i ve cohort . Telfa nasal packs were used in sutures + telfa group ( n=22 ) and Merocell nasal packs in merocel alone group ( n=22 ) . No packs were administered in sutures alone group ( n=22 ) . Three groups were compared in terms of nasal obstruction , bleeding , pain , crust and synechia formation , as well as the amount of secretion , the need for oropharyngeal airway , the presence of laryngospasm , and effort for nasal breathing after anesthesia . RESULTS The amount of bleeding was higher with lower degree of nasal obstruction in sutures alone group . Pain and secretion were more remarkable in merocel alone group . After the first week , these differences were unable to be differentiated among the groups . There were no differences between three groups with respect to crust and synechia formation two weeks after septal surgery . CONCLUSION Nasal packs can be more useful in patients who suffer from bleeding-related morbidity , while septoplasty applied without nasal packs can be more suitable in patients with obstructive sleep apnea . The use of nasal packs in septoplasty should be determined on an individualized basis with respect to the characteristics of each patient OBJECTIVE The objective of this study was to evaluate the efficacy and subjective discomfort of one-day internal dressing compared to that of two-day in patients undergoing nasal septal surgery . STUDY DESIGN / METHODS Prospect i ve , r and omized , clinical trial conducted on 75 patients undergoing septoplasty in a tertiary ENT clinic . Discomfort caused by nasal dressings was evaluated by means of a visual analog scale . Postoperative complications were also compared . RESULTS Mean discomfort score for group A ( nasal packing for 48 hours ) was 3.5 ( SD 1.15 ) vs. 2.7 ( SD 1.52 ) for group B ( nasal packing for 24 hours ) . Significant lower discomfort is reported when the nasal packing is removed the first day instead of after two or more days . No increase in complication rate was noticed . CONCLUSION Our results point out that one-day internal nasal dressing is preferable to that of two or more days , because of less patient discomfort and increased cost-effectiveness without increasing immediate complications OBJECTIVE Nasal packing is used to control postoperative bleeding and wound healing , and it also exerts a very strong influence on the comfort of the patient . Sorbsan ( ® ) ( calcium alginate ) is an absorbent packing that shows a potent hemostatic effect and is able to maintain wound surfaces in a moist environment by absorbing and gelling the wound exu date . The aim of this study was to evaluate the early symptoms and QOL with Sorbsan ( ® ) versus Beschitin-F ( ® ) ( chitin-coated gauze ) for middle meatus packing after endoscopic sinus surgery ( ESS ) . METHODS We performed a cohort study of 40 patients who underwent ESS . Following ESS , the patients were r and omly allocated into two groups of 20 patients each who underwent insertion of either Sorbsan ( ® ) or Beschitin-F ( ® ) into the middle meatus . A daily diary was used to record the symptoms and QOL , measured using visual analogue scales , before the ESS and on each day thereafter . Postoperative bleeding and local infection were also recorded . RESULTS The scores for each of the symptoms of nasal pain , headache , nasal bleeding and postnasal drip were statistically significantly lower in the Sorbsan ( ® ) group . The scores for each of the QOL parameters , including the effect on their stay in the hospital and sleep disturbance , were also significantly lower in the Sorbsan ( ® ) group . There were no findings of postoperative hemorrhage or local infection in either group . CONCLUSION Sorbsan ( ® ) packing did not cause any major complications and has the potential to reduce nasal pain and suffering in post ESS patients compared with gauze packing Intranasal splints have been used to maintain septal stability and prevent intranasal adhesions following septal surgery . However , their efficacy and attendant morbidity have received surprisingly little attention . Our prospect i ve study of 100 adults was divided into patients undergoing septoplasty or submucous resection of the nasal septum alone ( n = 50 ) and those undergoing combined septal and inferior turbinate surgery ( n = 50 ) . All patients were r and omized to have paired silicon rubber splints inserted for 7 days or not at all . All noses were additionally packed with 2 pieces of Jelonet for 12 - 20 h and examined and cleaned at 1 and 6 weeks post-operatively . The position of the septum , patency of the airways , presence of adhesions and degree of discomfort were recorded . Statistical analysis of the 89 complete sets of results obtained indicated splints added significantly to post-operative discomfort in both groups , with no demonstrable benefit to the patient UNLABELLED Anterior nasal packing is carried out in a number of nasal surgeries , especially in septoplasty . However , it is not an innocuous procedure and for this its benefit has been challenged . OBJECTIVE To assess the need for anterior nasal packing and the quality of life of patients su bmi tted to septoplasty . METHOD Patients su bmi tted to septoplasty with or without inferior turbinoplasty were r and omized to receive or not anterior nasal packing postoperatively . We recorded and compared postoperative data ( pain and bleeding ) . Quality of life was assessed before and after surgery . This is a r and omized prospect i ve study . RESULTS We had 73 patients ( 37 packed and 36 who did not receive a nasal packing ) with a minimum follow-up of 3 months . Patients with nasal packing complained more of nasal pain and headache in the immediate postoperative period . Of these patients , 75.7 % reported moderate/intense pain upon nasal packing removal . Bleeding was more frequent in those patients who did not receive a nasal packing , and only 1 patient required packing . All the patients enjoyed an improvement in quality of life . CONCLUSION Septoplasty improves the quality of life of patients with septal deviation and nasal obstruction . Routine use of anterior nasal packing should be challenged for not presenting proven benefit This study was conducted to compare the outcome of septoplasty with or without Nasal packing . The study subjects were r and omly allocated into two groups . There was significant reduction in frequency of post operative pain , headache , discomfort and duration of hospital stay in patients who have undergone septoplasty without nasal packing . However there was no difference in post operative bleeding and septal perforation between two groups . Therefore after Septoplasty without nasal packing is preferred alternative to with nasal packing The aim of this study was to compare the efficacy of a trans-septum suturing technique with conventional nasal packing and intranasal splints in the classic septoplasty operation . The study is a prospect i ve , r and omized clinical trial . 114 patients underwent septoplasty for septal deviation and ensuing nasal obstruction . These patients were divided into two groups : packing ( using intranasal septal splints and antibiotic meshes at the end of the operation ) and non-packing ( using four separate trans-septum through and through horizontal mattress sutures without any mesh or intranasal splint insertion ) . R and omization was performed using the four block r and omization system . Patients who failed the regular follow-up were excluded , and the two groups were compared for postoperative bleeding , hematoma , perforation and synechiae . Patients were asked to record pain levels using a visual analogue scale . The authors found no significant statistical differences between the two groups in the parameters studied , but significantly higher pain levels were noted in the patients in the packing group . The final results confirmed that patients who underwent septoplasty , intranasal packing and septal splint insertion did not benefit more than those who had trans-septum through and through suturing |
11,304 | 26,315,477 | By meta-regression analysis , we found no independent effects of study characteristics on weighted mean difference between reference and tested methods .
Although the pooled bias was small , the mean pooled percentage error was in the gray zone of clinical applicability .
In the sub-group analysis , electrical cardiometry was the device that provided the most accurate measurement . | Abstract Several minimally-invasive technologies are available for cardiac output ( CO ) measurement in children , but the accuracy and precision of these devices have not yet been evaluated in a systematic review and meta- analysis . | Introduction Non-invasive hemodynamic monitoring may facilitate resuscitation in critically ill patients . Validation studies examining a transcutaneous Doppler ultrasound technology , USCOM-1A , using pulmonary artery catheter as the reference st and ard showed varying results . In this study , we compared non-invasive cardiac index ( CI ) measurements by USCOM-1A with transthoracic echocardiography ( TTE ) . Methods This study was a prospect i ve , observational cohort study at a university tertiary-care emergency department , enrolling a convenience sample of adult and pediatric patients . Paired measures of CI , stroke volume index ( SVI ) , aortic outflow tract diameter ( OTD ) , velocity time integral ( VTI ) were obtained using USCOM-1A and TTE . Pearson ’s correlation and Bl and –Altman analyses were performed . Results One-hundred and sixteen subjects were enrolled , with obtainable USCOM-1A CI measurements for 99 subjects ( 55 adults age 50 ± 20 years and 44 children age 11 ± 4 years ) in the final analysis . Cardiac , gastrointestinal and infectious illnesses were the most common presenting diagnostic categories . The reference st and ard TTE measurements of CI , SVI , OTD , and VTI in all subjects were 3.08 ± 1.18 L/min/m2 , 37.10 ± 10.91 mL/m2 , 1.92 ± 0.36 cm , and 20.36 ± 4.53 cm , respectively . Intra-operator reliability of USCOM-1A CI measurements showed a correlation coefficient of r = 0.79 , with 11 ± 22 % difference between repeated measures . The bias and limits of agreement of USCOM-1A compared to TTE CI were 0.58 ( −1.48 to 2.63 ) L/min/m2 . The percent difference in CI measurements with USCOM-1A was 31 ± 28 % relative to TTE measurements . Conclusions The USCOM-1A hemodynamic monitoring technology showed poor correlation and agreement to st and ard transthoracic echocardiography measures of cardiac function . The utility of USCOM-1A in the management of critically ill patients remains to be determined Objective . Assess outcome in children treated with inotrope , vasopressor , and /or vasodilator therapy for reversal of fluid-refractory and persistent septic shock . Design . Survey ; case series . Setting . Three pediatric hospitals . Patients . Fifty consecutive patients with fluid-refractory septic shock with a pulmonary artery catheter within 6 hours of resuscitation . Interventions . Patients were categorized according to hemodynamic state and use of inotrope , vasopressor , and /or vasodilator therapy to maintain cardiac index ( CI ) > 3.3 L/min/m2 and systemic vascular resistance > 800 dyne-sec/cm 5 /m 2 to reverse shock . Outcome Measures . Hemodynamic state , response to class of cardiovascular therapy , and mortality . Results . After fluid resuscitation , 58 % of the children had a low CI and responded to inotropic therapy with or without a vasodilator ( group I ) , 20 % had a high CI and low systemic vascular resistance and responded to vasopressor therapy alone ( group II ) , and 22 % had both vascular and cardiac dysfunction and responded to combined vasopressor and inotropic therapy ( group III ) . Shock persisted in 36 % of the children . Of the children in group I , 50 % needed the addition of a vasodilator , and in group II , 50 % of children needed the addition of an inotrope for evolving myocardial dysfunction . Four children showed a complete change in hemodynamic state and responded to a switch from inotrope to vasopressor therapy or vice versa . The overall 28-day survival rate was 80 % ( group I , 72 % ; group II , 90 % ; group III , 91 % ) . Conclusions . Unlike adults , children with fluid-refractory shock are frequently hypodynamic and respond to inotrope and vasodilator therapy . Because hemodynamic states are heterogeneous and change with time , an incorrect cardiovascular therapeutic regimen should be suspected in any child with persistent shock . Outcome can be improved compared with historical literature Objective : To vali date clinical ly cardiac output ( CO ) measurements using femoral artery thermodilution in ventilated children and infants by comparison with CO estimated from the Fick equation via a metabolic monitor . Design : Prospect i ve , comparison study . Setting : Paediatric intensive care unit of a university hospital . Patients : 24 ventilated infants and children , aged 0.3 to 175 months ( median age 19 months ) . Interventions : Oxygen consumption measurements were made and averaged over a 5-min period , at the end of which arterial and mixed venous blood sample s were taken and oxygen saturations measured by co-oximetry , with CO being calculated using the Fick equation . Over this 5-min period , five sets of femoral arterial thermodilution ( FATD ) measurements were made and averaged . One comparison of CO values was made per patient . Results : Mean Fick CO was 2.55 l/min ( range 0.24 to 8.71 l/min ) and mean FATD CO was 2.51 l/min ( range 0.28–7.96 l/min ) . The mean bias was 0.03 l/min ( 95 % confidence interval –0.07 to 0.14 l/min ) , with limits of agreement of –0.45 to 0.52 l/min . When indexed to body surface area , the mean Fick cardiac index became 3.51 l/min per m2 ( 1.52–6.98 l/min per m2 ) and mean FATD 3.49 l/min per m2 ( 1.74–6.84 l/min per m2 ) . The mean bias was 0.02 l/min per m2 ( 95 % confidence interval –0.11 to 0.15 l/min per m2 ) with limits of agreement of –0.57 to 0.61 l/min per m2 . The mean FATD coefficient of variation was 5.8 % ( SEM 0.5 % ) . Conclusions : FATD compares favourably with Fick derived CO estimates in infants and children and may represent an advance in haemodynamic monitoring of critically ill children Objective To compare the assessment of cardiac output ( CO ) in children using the noninvasive Ultrasound Cardiac Output Monitor ( USCOM ) with the invasive pulmonary artery catheter ( PAC ) thermodilution cardiac output measurement . Design and setting Prospect i ve observational study in a tertiary center for pediatric cardiology of a university children 's hospital . Patients Twenty-four pediatric patients with congenital heart disease without shunt undergoing cardiac catheterization under general anesthesia . Measurements and results CO was measured by USCOM using a suprasternal CO Doppler probe in children undergoing cardiac catheterization . USCOM data were compared to CO simultaneously measured by PAC thermodilution technique . Measurements were repeated three times within 5 min in each patient . A mean percentage error not exceeding 30 % was defined as indicating clinical useful reliability of the USCOM . CO values measured by PAC ranged from 1.3 to 5.3 l/min ( median 3.6 l/min ) . Bias and precision were −0.13 and 1.34 l/min , respectively . The mean percentage error of CO measurement by the USCOM compared to PAC thermodilution technique was 36.4 % for USCOM . Conclusions Our preliminary data demonstrate that cardiac output measurement in children using the USCOM does not reliably represent absolute CO values as compared to PAC thermodilution . Further studies must evaluate the impact of incorporating effective aortic valve diameters on CO measurement using the USCOM BACKGROUND It is currently uncertain which hemodynamic monitoring device reliably measures stroke volume and tracks cardiac output changes in pediatric cardiac surgery patients . OBJECTIVE To evaluate the difference between stroke volume index ( SVI ) measured by pressure recording analytical method ( PRAM ) and bioreactance and their ability to track changes after a therapeutic intervention . METHODS A single-center prospect i ve observational cohort study in children undergoing cardiac surgery with cardiopulmonary bypass ( CPB ) was conducted . Twenty children below 20 kg with median ( interquartile range ) weight of 5.3 kg ( 4.1 - 7.8 ) and age of 6 months ( 3 - 20 ) were enrolled . Data were collected after anesthesia induction , at the end of CPB , before fluid administration and after fluid administration . Overall , median-IQR PRAM SVI values ( 23 ml·m(-2 ) , 19 - 27 ) were significantly higher than bioreactance SVI ( 15 ml·m(-2 ) , 12 - 25 , P = 0.0001 ) . Correlation ( r(2 ) ) between the two methods was 0.15 ( P = 0.0003 ) . The mean difference between the measurements ( bias ) was 5.7 ml·m(-2 ) with a st and ard deviation of 9.6 ( 95 % limits of agreement ranged from -13 to 24 ml·m(-2 ) ) . Percentage error was 91.7 % . Baseline SVI appeared to be similar , but PRAM SVI was systematic ally greater than bioreactance thereafter , with the highest gap after the fluid loading phase : 13 ( 12 - 18 ) ml·m(-2 ) vs. 23 ( 19 - 25 ) ml·m(-2 ) , respectively , P = 0.0013 . A multivariable regression model showed that a significant independent inverse correlation with patients ' body weight predicted the CI difference between the two methods after fluid challenge ( β coefficient -0.12 , P = 0.013 ) . CONCLUSIONS Pressure recording analytical method and bioreactance provided similar SVI estimation at stable hemodynamic conditions , while bioreactance SVI values appeared significantly lower than PRAM at the end of CPB and after fluid replacement Background Intraoperative hypovolemia is common and is a potential cause of organ dysfunction , increased postoperative morbidity , length of hospital stay , and death . The objective of this prospect i ve , r and omized study was to assess the effect of goal -directed intraoperative fluid administration on length of postoperative hospital stay . Methods One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were r and omly assigned to a control group ( n = 50 ) that received st and ard intraoperative care or to a protocol group ( n = 50 ) that , in addition , received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume . Length of postoperative hospital stay and postoperative surgical morbidity were assessed . Results Groups were similar with respect to demographics , surgical procedures , and baseline hemodynamic variables . The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group . Patients in the protocol group had a shorter duration of hospital stay compared with the control group : 5 ± 3 versus 7 ± 3 days ( mean ± SD ) , with a median of 6 versus 7 days , respectively ( P = 0.03 ) . These patients also tolerated oral intake of solid food earlier than the control group : 3 ± 0.5 versus 4.7 ± 0.5 days ( mean ± SD ) , with a median of 3 versus 5 days , respectively ( P = 0.01 ) . Conclusions Goal -directed intraoperative fluid administration results in earlier return to bowel function , lower incidence of postoperative nausea and vomiting , and decrease in length of postoperative hospital stay OBJECTIVES To vali date a new device ( PiCCO system ; Pulsion Medical Systems , Munich , Germany ) , we compared cardiac index derived from transpulmonary thermodilution and from pulse contour analysis in pediatric patients after surgery for congenital heart disease . We performed a prospect i ve clinical study in a pediatric cardiac intensive care unit of a university hospital . METHODS Twenty-four patients who had had cardiac surgery for congenital heart disease ( median age 4.2 years , range 1.4 - 15.2 years ) were investigated in the first 24 hours after admission to the intensive care unit . A 3F thermodilution catheter was inserted in the femoral artery . Intracardiac shunts were excluded by echocardiography intraoperatively or postoperatively . Cardiac index derived from pulse contour analysis was documented in each patient 1 , 4 , 8 , 12 , 16 , 20 , and 24 hours after admission to the intensive care unit . Subsequently , a set of three measurements of thermodilution cardiac indices derived by injections into a central venous line was performed and calculated by the PiCCO system . RESULTS The mean bias between cardiac indices derived by thermodilution and those derived by pulse contour analysis over all data points was 0.05 ( SD 0.4 ) L x min x m(-2 ) ( 95 % confidence interval 0.01 - 0.10 ) . A strong correlation between thermodilution and contour analysis cardiac indices was calculated ( Pearson correlation coefficient r = 0.93 ; coefficient of determination r2 = 0.86 ) . CONCLUSIONS Pulse contour analysis is a suitable method to monitor cardiac index over a wide range of indices after surgery for congenital heart disease in pediatric patients . Pulse contour analysis allows online monitoring of cardiac index . The PiCCO device can be recalibrated with the integrated transpulmonary thermodilution within a short time frame OBJECTIVE ( S ) To evaluate the measurement of cardiac output ( CO ) using continuous electrical bioimpedance cardiography ( Physioflow ; Neumedx , Philadelphia , PA ) ( CO(PF ) ) with a simultaneous direct Fick measurement ( CO(FICK ) ) in children with congenital heart disease . DESIGN A prospect i ve cohort study comparing 2 methods of measurement of CO . SETTING A quaternary university-affiliated pediatric hospital . PARTICIPANTS Children undergoing cardiac catheterization for clinical care . INTERVENTIONS The Physioflow measured continuous real time CO in 15-second epochs and simultaneous measurement of cardiac output by direct Fick ( with mass spectrometry to assess VO(2 ) ) were acquired . MEASUREMENTS AND MAIN RESULTS Sixty-five patients were recruited , and data from 56 ( 25 males ) were adequate for analysis . The median age at study was 3.5 years ( range , 0.4 - 16.6 years ) , and the median body surface area was 0.62 m(2 ) ( range , 0.31 - 1.71 ) . There were 25 of 56 ( 45 % ) with univentricular physiology . A total of 19,228 Physioflow data points were available for the analysis of which 14,569 ( 76 % ) were valid ; 96 % of the invalid measurements were identified as artifacts by the device . The average cardiac index of valid measurements was 3.09 ± 0.72 L/min/m(2 ) . Compared with the Fick CO , the mean bias was -0.09 L/min , but the 95 % limits of agreement were -3.20 to + 3.01 L/min/m(2 ) . Consequently , only 20 of 56 ( 36 % ) of measurements were within 20 % , and 31 of 56 ( 55 % ) of measurements were within 30 % of each other . CONCLUSIONS Compared with measurements made by direct Fick , CO measured using the Physioflow device was unreliable in anesthetized children with congenital heart disease Objective : To compare the results of cardiac output measurements obtained by lithium dilution and transpulmonary thermodilution in paediatric patients . Design : A prospect i ve study .¶ Setting : Paediatric intensive care unit in a university teaching hospital.¶ Patients : Twenty patients ( age 5 days–9 years ; weight 2.6–28.2 kg ) were studied.¶ Interventions : Between two and four comparisons of lithium dilution cardiac output ( LiDCO ) and transpulmonary thermodilution ( TPCO ) were made in each patient.¶ Measurements and results : Results from three patients were excluded : in one patient there was an unsuspected right-to-left shunt , in two patients there was a problem with blood sampling through the lithium sensor . There were 48 comparisons of LiDCO and TPCO in the remaining 17 patients over a range of 0.4–6 l/min . The mean of the differences ( LiDCO – TPCO ) was –0.1 ± 0.3 ( SD ) l/min . Linear regression analysis gave LiDCO = 0.11 + 0.90 × TPCO l/min ( r2 = 0.96 ) . There were no adverse effects in any patient.¶ Conclusions : These results suggest that the LiDCO method can be used to provide safe and accurate measurement of cardiac output in paediatric patients . The method is simple and quick to perform , requiring only arterial and venous catheters , which will already have been inserted for other reasons in these patients BACKGROUND Transpulmonary thermodilution ( TPTD ) is an increasingly popular method used to monitor the complex hemodynamic changes in critically ill children . The purpose of our study was to examine the relationship between transthoracic echocardiographic ( TTE ) parameters and global hemodynamic variables derived from TPTD and those derived from conventional measurements in infants and neonates undergoing corrective cardiac surgery . METHODS After approval from the Ethics Committee of Gottsegen György Hungarian Institute of Cardiology and individual parental consent were obtained , patients were prospect ively enrolled . In parallel with continuous postoperative conventional monitoring , TPTD was measured four times daily , and TTE was performed once per day . Conventional hemodynamic , TPTD and TTE parameters were compared with weighted linear regression statistics and a Pearson correlation . RESULTS One hundred forty-five TPTD measurements and 35 TTE examinations of thirteen enrolled patients were analyzed . Global end-diastolic volume index ( GEDVI ) was correlated with the fractional shortening ( SF , r=0.67 , P=0.001 ) measured by TTE . Among the preload parameters , the percentage change of GEDVI between two consecutive time points showed a pertinent correlation with changes of cardiac index ( r=0.67 , P=0.001 ) and changes of stroke volume index ( r=0.57 , P=0.008 ) . Percentage changes in SF demonstrated a strong negative correlation with changes of left ventricular end-systolic diameter ( r=-0.86 , P<0.001 ) . There was no significant relationship between alterations in arterial or central venous pressure values with TTE or TPTD parameters . CONCLUSION Both TPTD and TTE may be used in the estimating volumetric preload parameters . The time course of TPTD-derived parameters may have clinical relevance in pediatric critical care practice Purpose To vali date a novel method of ultrasound dilution ( COstatus ® ; Transonic Systems , Ithaca , NY ) for measuring cardiac output in paediatric patients after biventricular repair of congenital heart disease . Methods Children undergoing biventricular repair of congenital heart disease were prospect ively identified . Patients with significant intracardiac shunts were excluded . Postoperative cardiac output was measured by ultrasound dilution ( COud ) and concurrently calculated by the Fick equation ( COrms ) using measured oxygen consumption by respiratory mass spectrometry . Results Thirty-five patients were studied generating 66 individual data sets . Subjects had a median ( interquartile range ) age of 147 days ( 11 , 216 ) , weight of 4.98 kg ( 3.78 , 6.90 ) and body surface area of 0.28 m2 ( 0.22 , 0.34 ) . Of the patients , 66 % had peripheral arterial catheters and 34 % had femoral cannulation ; peripheral arterial lines accounted for 6/8 of unsuccessful studies due to inability to generate sufficient flow . The site of the central venous cannula did not impact the feasibility of completing the study . A mean bias of 0.00 L/min [ 2 st and ard deviation ( SD ) ± 0.76 L/min ] between COud and COrms was found with a percentage error of 97 % . When comparing cardiac index , bias increased to 0.13 L/min/m2 ( 2SD ± 2.16 L/min/m2 ) . Conclusions Cardiac output by ultrasound dilution showed low bias with wide limits of agreement when compared to measurement derived by the Fick equation . Although measurements through central and peripheral arterial lines were completed with minimal difficulties in the majority of patients , the application of COstatus ® in neonates with low body surface area may be limited Objective To compare clinical assessment of cardiac performance with an invasive method of haemodynamic monitoring . Design and setting Prospect i ve observational study in a 16-bed tertiary paediatric intensive care unit . Patients and participants Infants and children undergoing cardiopulmonary bypass and surgical repair of congenital heart lesions . Interventions Based on physical examination and routinely available haemodynamic monitoring in the paediatric intensive care unit , medical and nursing staff assessed cardiac index , systemic vascular resistance index and volume status . Clinical assessment was compared with cardiac index , systemic vascular resistance index and global end diastolic volume index , obtained by femoral artery thermodilution . Measurements and results A total of 76 clinical estimations of the three parameters were made in 16 infants and children undergoing biventricular repair of congenital heart lesions . Agreement was poor between clinical and invasive methods of determining all three studied parameters of cardiac performance . Cardiac index was significantly underestimated clinical ly ; mean difference was 0.71 l min−1 m−2 ( 95 % range of agreement ±2.7 ) . Clinical estimates of systemic vascular resistance ( weighted κ=0.15 ) and volume status ( weighted κ=0.04 ) showed poor levels of agreement with measured values and were overestimated clinical ly . There was one complication related to a femoral arterial catheter and one device failure . Conclusions Routine clinical assessment of parameters of cardiac performance agreed poorly with invasive determinations of these indices . Management decisions based on inaccurate clinical assessment s may be detrimental to patients . Invasive haemodynamic monitoring using femoral artery thermodilution warrants cautious further evaluation as there is little agreement with clinical assessment which is presently st and ard accepted care in this patient population Objective : Cardiac output is a useful measure of myocardial performance . St and ard methods of determining cardiac output are not without risk and can be problematic in children . Arterial pulse wave analysis ( PulseCO ) , a novel , minimally invasive cardiac output determination technique , offers the advantage of continuous monitoring , convenience , and low risk . This technique has not been vali date d in children . The purpose of this study was to vali date PulseCO as an accurate means of noninvasively determining real-time cardiac output in children . Design : Prospect i ve , single-center evaluation . Setting : Children ’s hospital . Patients : Any child with a structurally normal heart , undergoing hemodynamic evaluation in the cardiac catheterization laboratory , was included . Interventions : A pro grade right heart catheterization was performed , and cardiac output was determined using the thermodilution technique , via placement of a pulmonary arterial catheter . Measurements and Main Results : Thermodilution results were compared with continuous real-time cardiac output measurements obtained with the PulseCO system , and they were then analyzed by st and ard correlation techniques and Bl and -Altman analysis . Twenty patients were evaluated with a median age of 10.5 yrs and a median weight of 25 kg . The mean thermodilution cardiac index was 3.3 ± 0.9 L/min/m2 , whereas the mean PulseCO cardiac index was 3.1 ± 0.9 L/min/m2 . St and ard Pearson correlation tests revealed a correlation coefficient of .94 ( p < .001 ) . Bl and -Altman analysis revealed excellent clinical agreement with a mean difference of 0.19 L/min/m2 and a precision of 0.28 L/min/m2 at 2 sd . Conclusions : Arterial pulse wave analysis by the PulseCO system provides a novel , minimally invasive method of determining real-time cardiac output in children Objective Electrical velocimetry ( EV ) is a non-invasive method of continuous left cardiac output monitoring based on measurement of thoracic electrical bioimpedance . The objective was to vali date EV by investigating the agreement in cardiac output measurements performed by EV and echocardiography . Design In this prospect i ve observational study , left ventricular output ( LVO ) was simultaneously measured by EV ( LVOev ) using Aesculon and by echocardiography ( LVOecho ) in healthy term neonates during the first 2 postnatal days . To determine the agreement between the two methods , we calculated the bias ( mean difference ) and precision ( 1.96 × SD of the difference ) . As LVOecho has its own limitations , the authors also calculated the ‘ true precision ’ of EV adjusted for echocardiography as the reference method . Results The authors performed 115 paired measurements in 20 neonates . LVOev and LVOecho were similar ( 534±105 vs 538±105 ml/min , p=0.7 ) . The bias and precision of EV were −4 and 234 ml/min , respectively . The authors found the true precision of EV to be similar to the precision of echocardiography ( 31.6 % vs 30 % , respectively ) . There was no difference in bias and precision between the measurements obtained in patients with or without a haemodynamically significant patent ductus arteriosus . Conclusions EV is as accurate in measuring LVO as echocardiography and the variation in the agreement between EV and echocardiography among the individual subjects reflects the limitations of both techniques Objective : To assess cardiac output in pediatric patients with the pressure recording analytical method ( PRAM ) and the Doppler echocardiography method . PRAM derives cardiac output from beat-by-beat analysis of the arterial pressure profile ( systolic and diastolic phase ) in the time domain . Design : A prospect i ve observational study . Setting : Pediatric intensive care unit at a tertiary care children ’s hospital . Patients : Forty-eight patients between the ages of 1 month and 18 yrs . Interventions : Femoral or radial artery catheterization and mechanical ventilation . Measurements and Main Results : Cardiac output was simultaneously estimated by Doppler echocardiography and PRAM . Cardiac output values obtained by Doppler echocardiography ( 2.7 ± 1.6 L/min , range 0.92–8.20 ) were significantly correlated with those estimated by PRAM ( 2.6 ± 1.7 L/min , range 0.89–7.48 ; r2 = .99 , p < .01 ) . The mean difference between the two estimates was 0.12 ± 0.27 L·min−1 ( 95 % confidence interval , −0.54 to 0.77 L·min−1 ) . Conclusions : In the range of ages evaluated , PRAM provides reliable estimates of cardiac output when compared with noninvasive techniques Objective : To compare measurements of cardiac output ( CO ) and cardiac index ( CI ) obtained by a recently developed noninvasive continuous cardiac output system , NICO ( CONICO ) , and transthoracic Doppler echocardiography ( COTTE ) in mechanically ventilated children . Design and Setting : Prospect i ve study in a university-affiliated tertiary pediatric intensive care unit . Patients : A total of 21 mechanically ventilated children , weighing > 15 kg , in stable respiratory and hemodynamic condition . Measurements : Sets of three successive measurements of CO with the NICO system and transthoracic Doppler echocardiography were obtained . Bl and –Altman analysis was used to compare the agreement between the two methods . Results : The mean ± sd CO values were 4.06 ± 1.43 L/min for CONICO and 4.67 ± 1.78 L/min for COTTE . Bias ± sd between the two methods was −0.61 ± 0.94 L/min . The variability of the difference between the two methods increased as the magnitude of the CO measurement increased . Similar results were obtained for cardiac index : 4.01 ± 1.40 L·min−1·m−2 for CINICO and 4.59 ± 1.48 L·min−1·m−2 for CITTE . Bl and –Altman analysis revealed a nonuniform relationship between CI difference and the magnitude ( y = −0.299 − 0.0655 × mean ) . The variability of the differences did not increase as the magnitude of the CO measurement increased ( sd of estimate was 0.827 L·min−1·m−2 ) . With both CONICO and CINICO , each measurement was highly repeatable , with coefficient of variation of only 2.88 % ± 2.31 % . Repeatability with Doppler echocardiography was 7.02 % ± 4.33 % . Conclusions : The NICO system is a new device that measures CO easily and automatically in mechanically ventilated children weighing > 15 kg . CO values obtained with this technique were in agreement with those obtained with Doppler echocardiography in children in respiratory and hemodynamic stable condition . The NICO system needs further investigation in children in unstable respiratory and hemodynamic condition BACKGROUND Postoperative organ failures commonly occur after major abdominal surgery , increasing the utilization of re sources and costs of care . Tissue hypoxia is a key trigger of organ dysfunction . A therapeutic strategy design ed to detect and reverse tissue hypoxia , as diagnosed by an increase of oxygen extraction ( O2ER ) over a predefined threshold , could decrease the incidence of organ failures . The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those r and omized to conventional vs a protocol ized strategy design ed to maintain O2ER < 27 % . METHODS A prospect i ve , r and omized , controlled trial was performed in nine hospitals in Italy . One hundred thirty-five high-risk patients scheduled for major abdominal surgery were r and omized in two groups . All patients were managed to achieve st and ard goals : mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h . The patients of the " protocol group " ( group A ) were also managed to keep O2ER < 27 % . MEASUREMENTS AND MAIN RESULTS In group A , fewer patients had at least one organ failure ( n = 8 , 11.8 % ) than in group B ( n = 20 , 29.8 % ) [ p < 0.05 ] , and the total number of organ failures was lower in group A than in group B ( 27 failures vs 9 failures , p < 0.001 ) . Length of hospital stay was significantly lower in the protocol group than in the control group ( 11.3 + /- 3.8 days vs 13.4 + /- 6.1 days , p < 0.05 ) . Hospital mortality was similar in both groups . CONCLUSIONS Early treatment directed to maintain O2ER at < 27 % reduces organ failures and hospital stay of high-risk surgical patients . Clinical trials.gov reference No. NCT00254150 Background : Cardiac output is a useful measure of myocardial performance . Cardiac output monitoring is frequently performed in critically ill adults to guide physicians ' treatment strategies . However , st and ard methods of determining cardiac output in children are not without risk and can be problematic secondary to their invasive nature and other technical problems . The COstatus system ( Transonic Systems , NY ) , which is based on ultrasound dilution technology , works off in situ catheters and uses an innocuous indicator to allow for routine measurements of cardiac output and blood volumes in pediatric patients . The purpose of this study was to vali date cardiac output measured by the COstatus system with those obtained by the clinical st and ard technique of pulmonary artery thermodilution . Methods : This was a prospect i ve evaluation performed at a single institution . Any child with a structurally normal heart undergoing hemodynamic evaluation in the cardiac catheterization laboratory was included . A pro grade right heart catheterization was performed , and cardiac output was first determined by using the pulmonary artery thermodilution technique . Thermodilution results were then compared with cardiac output measurements obtained using the COstatus system . The results were analyzed by st and ard correlation , Bl and -Altman , and Critchley and Critchley analyses . Results : Twenty-eight patients were evaluated with a median age of 8 yrs and a median weight of 31 kg . The mean thermodilution cardiac index = 3.18 L/min ( ± 1.35 L/min ) , and the mean COstatus system cardiac index = 3.17 L/min ( ± 1.31 L/min ) . St and ard Pearson correlation tests revealed an excellent correlation coefficient of 0.95 ( p < .0001 ) . Bl and -Altman analysis revealed good clinical agreement with a mean difference of −0.004 L/min with a precision of 0.8 L/min at 2 SD . A percentage error of 25.4 % was noticed in this study , which is less than the clinical ly acceptable limit . Conclusion : The ultrasound dilution technique of determining cardiac output using the COstatus system provides a less invasive method than the traditional pulmonary artery thermodilution for accurately determining cardiac output in children . This is the first validation of the COstatus system in pediatric patients . Further studies are required to establish its accuracy in pediatric patients with cardiac shunts and other hemodynamically unstable conditions Abstract Objective . To show the equivalence of the transpulmonary thermodilution method to the direct Fick principle in children . Design . Prospect i ve single-centre study . Setting . A 16-bed paediatric cardiac ICU and a cardiac catheterisation laboratory at an university affiliated centre for paediatric cardiology and congenital heart disease . Patients . We consecutively investigated 18 patients ( mean age 12.1±6.4 years ) during cardiac catheterisation and after corrective cardiac operation . Methods and results . We prospect ively defined limits of equivalence for cardiac index ( CI ) for both methods of + /–0.25 l/min·m2 . We measured oxygen consumption for determination of CI by Fick as the clinical " gold st and ard " and performed a set of three transpulmonary thermodilution measurements . The mean CIFick was 2.88±1.07 l/min·m2 ( range 1.10–4.62 l/min·m2 ) and CITPID was 2.85±1.03 l/min·m2 ( range 1.02–4.49 l/min·m2 ) . The mean difference between CIFick and CITPID was 0.030±0.168 l/min·m2 , and limits of agreement –0.306 to 0.366 l/min·m2 ( 90 % confidence interval –0.040 to 0.099 l/min·m2 ) . The regression equation was : CIFick=1.0244 × CITPID–0.040 , r2=0.976 , P < 0.0001 . The intraclass coefficient of reliability for three repeated measurements of CITPID was 0.97 , the corresponding lower limit of the 95 % confidence interval was 0.94 . Conclusion . We demonstrated the equivalence of CI measurement by transpulmonary thermodilution and the Fick principle in children . This new method may improve hemodynamic monitoring and management in seriously ill children Objectives : Non-invasive cardiac output monitoring is a potentially useful clinical tool in the neonatal setting . Our aim was to evaluate a new method of non-invasive continuous cardiac output ( CO ) measurement ( NICOM ™ ) based on the principle of bioreactance in neonates . Methods : In this prospect i ve observational study , 10 neonates underwent 97 paired NICOM and echocardiography ( echo ) assessment s of left ventricular output ( LVO ) . For each neonate , NICOM measurements of left ventricular stroke volume ( SV ) and LVO over a 2- to 4-hour period were correlated with blinded , simultaneous , discrete echo measurements of SV and LVO . The precision and accuracy of the NICOM monitor relative to echo during periods of steady state were assessed . Results : The infants ’ median birth weight was 2.72 kg ( IQR 1.56–3.23 kg , range 1.44–4.00 ) and their median gestation was 37 weeks ( IQR 31–40 weeks , range 31–41 ) . Median NICOM SV and LVO readings were consistently lower than echo ( 2.6 ml [ IQR 1.4–3.2 , range 0.6–5.3 ] vs. 3.5 ml [ IQR 2.1–4.4 , range 1.1–6.8 ] , and 400 ml/min [ IQR 233–476 ] vs. 559 ml/min [ IQR 386–652 ] , p < 0.001 ) . The NICOM LVO readings were lower than the echo readings by a mean of 153 ± 56 ml/kg . NICOM consistently under-read LVO by 31 ± 8 % , and this systematic difference was constant across the range of LVOs obtained . There was a strong correlation between NICOM and echo measurements of LVO ( r = 0.95 , p < 0.001 ) . Conclusion : Non-invasive cardiac output monitoring is feasible in neonates . Further validation studies in neonatal animal experimental models and human neonates need to be conducted before routine clinical use BACKGROUND Electrical cardiometry ( EC ) is a continuous noninvasive method for measuring cardiac output ( CO ) , but there are limited data on premature infants . We evaluated the utility of EC monitoring by comparing the results obtained using EC to measurements of CO and systemic blood flow using echocardiography ( ECHO ) . METHODS In this prospect i ve observational study , 40 preterm neonates underwent 108-paired EC and ECHO measurements . RESULTS There were correlations between EC-CO and left ventricular output ( LVO , p < 0.005 ) and right ventricular output ( RVO , p < 0.005 ) but not with superior vena cava ( r = 0.093 , p = 0.177 ) . Both RVO and LVO correlated with EC with and without a hemodynamically significant ductus arteriosus ( p = 0.001 and 0.008 , respectively ) . The level of agreement was decreased in infants ventilated by high-frequency oscillation ventilators ( HFOV ) . The bias in HFOV was also positive compared with the negative biases found in other modes of ventilation . CONCLUSION Given the correlation of EC with LVO , RVO , and lack of confounding effects of the ductus , our results suggest that EC has promise for trending CO in the preterm infant . However , given the limitations with mode of ventilation and the lack of correlation at low LVO values , further study is needed before this technology can be for routine use Purpose A continuous cardiac output monitor based on arterial pressure waveform ( FloTrac ™ /Vigileo ™ ; Edwards Lifesciences , Irvine , CA ) is now approved for use in adults but not in children . This device is minimally invasive , calculates cardiac output continuously and in real time , and is easy to use . Our study sought to vali date the FloTrac ™ with the pulmonary artery catheter ( PAC ) intermittent thermodilution technique in pediatric cardiac patients . Methods This was a prospect i ve pilot study comparing cardiac output measurements obtained via the FloTrac ™ and arterial pressure waveform analysis with intermittent thermodilution . Subjects carried the diagnosis of pulmonary hypertension or cardiomyopathy , or were in the postoperative course after orthotopic heart transplantation . Results Enrolled in the study were 31 subjects , and 136 data points were obtained . The age range was 8 months to 16 years . The mean body surface area ( BSA ) was 1.1 m2 . Bl and -Altman plots for the mean cardiac outputs of all subjects with a BSA ≥1 m2 showed limits of agreement of −2.7 to 8.0 l/min ( ±5.4 l/min ) . Patients with a BSA ≤1 m2 demonstrated even wider limits of agreement ( ±8.5 l/min ) . The intraclass correlation for the PAC was 0.929 and 0.992 for the FloTrac ™ . Conclusion There was poor agreement between the PAC and FloTrac ™ in measuring cardiac output in a population of children with pulmonary hypertension or cardiomyopathy , or after cardiac transplantation . This is in contrast to adult studies published thus far . This suggests that the utility of the FloTrac ™ and measurements obtained from arterial pulse wave analysis in children is uncertain at this time Objective To assess ( 1 ) agreement between the ultrasonic cardiac output monitor ( USCOM ) 1A device for measurement of cardiac output in newborn infants and conventional echocardiography ( ECHO ) , ( 2 ) repeatability of USCOM measurements and ( 3 ) agreement between novice and expert users of the USCOM . Design A prospect i ve observational study . Setting The Neonatal Unit at the Royal Children 's Hospital , Melbourne , Australia . Patients 56 term and near-term infants , with no evidence of structural or functional cardiovascular disease , or haemodynamic shunts . Measurements Agreement between ECHO and USCOM was assessed by paired measurements of ventricular outputs by a single experienced user . Repeatability was assessed using five repeated measurements in 10 infants . Agreement between five novices and one expert user was assessed by paired USCOM measurements over 30 training measurements . Results Agreement between USCOM and ECHO for left ventricular output ( LVO ) was ( bias , ±limits of agreement , mean % error ) : 14 , ±108 ml/kg/min , 43 % , and for right ventricular output ( RVO ) : −59 , ±160 , ml/kg/min , 57 % . Intra-observer repeatability was 6.7 % for USCOM LVO and 3.6 % for ECHO LVO . After five training measurements , the mean difference between USCOM measures of LVO by novice and expert users was less than 50 ml/kg/min , but with variability . Conclusions Repeatability of USCOM measures is high in newborn infants . New users can be trained quickly , but with high inter-user variability . Agreement between USCOM and conventional ECHO is broad , and worse for RVO and LVO . Further studies are required to assess the ability of the device to detect clinical ly significant changes in infant cardiac output Cardiac output ( CO ) is an important hemodynamic measure that helps to guide the therapy of critically ill patients . Invasive CO assessment in infants and children is often avoided because of the inherent risks . A noninvasive CO monitor that uses partial rebreathing has been recently developed to determine CO via the Fick principle for carbon dioxide . There have been no clinical studies confirming its accuracy in pediatric patients . This is a prospect i ve observational study of 37 children < 12 yr of age who underwent cardiac catheterization . Under general anesthesia via an endotracheal tube without a leak , we made multiple CO measurements using thermodilution and compared them with noninvasively determined CO measurements . Paired measurements were analyzed for bias , precision , and correlation via Bl and -Altman plot and linear regression . Noninvasive measurements showed a linear correlation with thermodilution CO assessment with an r value of 0.83 ( P < 0.03 ) . Bl and -Altman analysis yielded a bias of −0.27 L/min and a precision ±1.49 L/min . Cardiac index measurements demonstrated a decreased r value of 0.67 ( P = 0.15 ) and a bias of −0.18 L · min−1 · m−2 and precision of ±2.13 L · min−1 · m−2 . Differences between partial rebreathing measurements and thermodilution measurements were largest in children with a body surface area of ≤0.6 m2 ventilated with tidal volumes < 300 mL. Based on these findings , noninvasive CO measurement using partial rebreathing may be clinical ly acceptable in children with > 0.6 m2 body surface area and > 300 mL tidal volume Objective : To vali date cardiac output measurements by ultrasound dilution technology ( COstatus monitor ) against those obtained by a transit-time ultrasound technology with a perivascular flow probe and to investigate ultrasound dilution ability to estimate pulmonary to systemic blood flow ratio in children . Design : Prospect i ve observational clinical trial . Setting : Pediatric cardiac operating theater in a university hospital . Material and Methods : In 21 children ( 6.1 ± 2.6 kg , mean ± SD ) undergoing heart surgery , cardiac output was simultaneously recorded by ultrasound dilution ( extracorporeal arteriovenous loop connected to existing arterial and central venous catheters ) and a transit-time ultrasound probe applied to the ascending aorta , and when possible , the main pulmonary artery . The pulmonary to systemic blood flow ratio estimated from ultrasound dilution curve analysis was compared with that estimated from transit-time ultrasound technology . Results : Bl and -Altman analysis of the whole cohort ( 90 pairs , before and after surgery ) showed a bias between transit-time ultrasound ( 1.01 ± 0.47 L/min ) and ultrasound dilution technology ( 1.03 ± 0.51 L/min ) of –0.02 L/min , limits of agreement –0.3 to 0.3 L/min , and percentage error of 31 % . In children with no residual shunts , the bias was –0.04 L/min , limits of agreement –0.28 to 0.2 L/min , and percentage error 19 % . The pooled co efficient of variation was for the whole cohort 3.5 % ( transit-time ultrasound ) and 6.3 % ( ultrasound dilution ) , and in children without shunt , it was 2.9 % ( transit-time ultrasound ) and 4 % ( ultrasound dilution ) , respectively . Ultrasound dilution identified the presence of shunts ( pulmonary to systemic blood flow ≠ 1 ) with a sensitivity of 100 % and a specificity of 92 % . Mean pulmonary to systemic blood flow ratio by transit-time ultrasound was 2.6 ± 1.0 and by ultrasound dilution 2.2 ± 0.7 ( not significant ) . Conclusion : The COstatus monitor is a reliable technique to measure cardiac output in children with high sensitivity and specificity for detecting the presence of shunts OBJECTIVE --To compare cardiac output measurements in critically ill infants by the dual beam Doppler and thermodilution techniques . DESIGN -- Prospect i ve direct comparison of the two techniques . For statistical evaluation one r and omly assigned paired measurement of every patient was used . SETTING --Paediatric intensive care unit in a university hospital . PATIENTS --18 infants after open heart surgery aged 4 - 25 months ( weight 4 - 10 kg ) . INTERVENTIONS --Cardiac output measurements by dual beam Doppler and thermodilution techniques were performed within 10 minutes of each other and without knowledge of the results of the other methods . Multiple measurements were performed on some patients with a pharmacological or electrophysiological intervention or with a minimum of six hours between each pair of measurements . MEASUREMENTS AND MAIN RESULTS --Three patients were excluded because of an inadequate Doppler signal or a significant residual shunt . Cardiac output measurements ranged from 0.4 to 2.2 l/min for the thermodilution technique and from 0.5 to 2.1 l/min for the dual beam Doppler technique . Agreement between both methods was acceptable . The mean difference between the two methods was 0.026 l/min with two st and ard deviations ranging from -0.20 to 0.26 l/min . CONCLUSION --The dual beam Doppler technique was shown to have promise for the non-invasive determination of cardiac output in critically ill infants Objective To evaluate the clinical utility of a new device for continuous noninvasive cardiac output monitoring ( NICOM ) based on chest bio-reactance compared with cardiac output measured semi-continuously by thermodilution using a pulmonary artery catheter ( PAC-CCO ) . Design Prospect i ve , single-center study . Setting Intensive care unit . Patients Consecutive adult patients immediately after cardiac surgery . Interventions Cardiac output measurements obtained from NICOM and thermodilution were simultaneously recorded minute by minute and compared in 110 patients . We evaluated the accuracy , precision , responsiveness , and reliability of NICOM for detecting cardiac output changes . Tolerance for each of these parameters was specified prospect ively . Measurements and results A total of 65,888 pairs of cardiac output measurements were collected . Mean reference values for cardiac output ranged from 2.79 to 9.27 l/min . During periods of stable PAC-CCO ( slope < ± 10 % , 2SD/mean < 20 % ) , the correlation between NICOM and thermodilution was R = 0.82 ; bias was + 0.16 ± 0.52 l/min ( + 4.0 ± 11.3 % ) , and relative error was 9.1 % ± 7.8 % . In 85 % of patients the relative error was < 20 % . During periods of increasing output , slopes were similar with the two methods in 96 % of patients and intra-class correlation was positive in 96 % . Corresponding values during periods of decreasing output were 90 % and 84 % , respectively . Precision was always better with NICOM than with thermodilution . During hemodynamic challenges , changes were 3.1 ± 3.8 min faster with NICOM ( p < 0.01 ) and amplitude of changes did not differ significantly . Finally , sensitivity of the NICOM for detecting significant directional changes was 93 % and specificity was 93 % . Conclusion Cardiac output measured by NICOM had most often acceptable accuracy , precision , and responsiveness in a wide range of circulatory situations BACKGROUND Cardiac function , including cardiac index ( CI ) , traditionally has been measured by a pulmonary artery catheter ( PAC ) . A noninvasive alternative for measuring cardiac function would offer obvious advantages . METHODS A prospect i ve study of trauma and nontrauma patients was performed in a surgical intensive care unit over a 3-month period . CI was determined using both a st and ard PAC and a continuous-wave Doppler ultrasound ( UTS ) . The study had 2 phases : phase I was nonblinded and phase II was blinded ; the correlation between UTS- and PAC-derived CI was assessed . RESULTS A total of 120 paired measurements of CI were observed in 31 patients . The UTS-derived CI measurements showed agreement with PAC measurements in both phase I and phase II of the study with a bias of .06 L/min/m(2 ) + /- .4 L/min/m(2 ) . Paired measurements correlated well in both phase I ( r = .97 , R2 = .95 , P < .0001 ) and phase II ( r = .93 , R2 = .86 , P < .0001 ) of the study . CONCLUSIONS Doppler UTS correlates well with PAC measurements of CI . This noninvasive modality is an accurate and safe alternative to PAC BACKGROUND : Goal -directed fluid therapy ( GDFT ) is associated with improved outcomes after surgery . The esophageal Doppler monitor ( EDM ) is widely used , but has several limitations . The NICOM , a completely noninvasive cardiac output monitor ( Cheetah Medical ) , may be appropriate for guiding GDFT . No prospect i ve studies have compared the NICOM and the EDM . We hypothesized that the NICOM is not significantly different from the EDM for monitoring during GDFT . METHODS : One hundred adult patients undergoing elective colorectal surgery participated in this study . Patients in phase I ( n = 50 ) had intraoperative GDFT guided by the EDM while the NICOM was connected , and patients in phase II ( n = 50 ) had intraoperative GDFT guided by the NICOM while the EDM was connected . Each patient ’s stroke volume was optimized using 250-mL colloid boluses . Agreement between the monitors was assessed , and patient outcomes ( postoperative pain , nausea , and return of bowel function ) , complications ( renal , pulmonary , infectious , and wound complications ) , and length of hospital stay ( LOS ) were compared . RESULTS : Using a 10 % increase in stroke volume after fluid challenge , agreement between monitors was 60 % at 5 minutes , 61 % at 10 minutes , and 66 % at 15 minutes , with no significant systematic disagreement ( McNemar P > 0.05 ) at any time point . The EDM had significantly more missing data than the NICOM . No clinical ly significant differences were found in total LOS or other outcomes . The mean LOS was 6.56 ± 4.32 days in phase I and 6.07 ± 2.85 days in phase II , and 95 % confidence limits for the difference were −0.96 to + 1.95 days ( P = 0.5016 ) . CONCLUSIONS : The NICOM performs similarly to the EDM in guiding GDFT , with no clinical ly significant differences in outcomes , and offers increased ease of use as well as fewer missing data points . The NICOM may be a viable alternative monitor to guide GDFT |
11,305 | 27,712,544 | There was a large effect on generic outcome measures and a moderate effect on comorbidities .
When compared to disorder-specific treatments there were no differences on anxiety and quality of life outcomes , however there were differences in depression outcomes .
Transdiagnostic and tailored iCBT are effective interventions for anxiety disorders and depression . | Abstract Anxiety and depressive disorders are often comorbid .
Transdiagnostic and tailored treatments seem to be promising approaches in dealing with comorbidity .
Although several primary studies have examined the effects of Internet-delivered cognitive behavior therapy ( iCBT ) for anxiety and depression , no meta- analysis including different types of iCBT that address comorbidity has been conducted so far . | UNLABELLED There is preliminary support for internet-delivered cognitive behaviour therapy ( iCBT ) as a way of improving access to treatment among older adults with anxiety . The aim of this r and omized controlled trial ( RCT ) was to examine the efficacy , long-term outcomes , and cost-effectiveness of an iCBT program for adults over 60 years of age with anxiety . Successful applicants were r and omly allocated to either the treatment group ( n=35 ) or the waitlist control group ( n=37 ) . The online treatment course was delivered over 8 weeks and provided with brief weekly contact with a clinical psychologist via telephone or secure email . Eighty-four percent of participants completed the iCBT course within the 8 weeks and 90 % provided data at posttreatment . Significantly lower scores on measures of anxiety ( Cohen 's d=1.43 ; 95 % CI : 0.89 - 1.93 ) and depression ( Cohen 's d=1.79 ; 95 % CI : 1.21 - 2.32 ) were found among the treatment group compared to the control group at posttreatment . These lower scores were maintained at 3-month and 12-month follow-up and the treatment group rated the iCBT treatment as acceptable . The treatment group had slightly higher costs ( $ 92.2 ; 95 % CI : $ 38.7 to $ 149.2 ) and Quality -Adjusted Life-Years ( QALYs=0.010 ; 95 % CI : 0.003 to 0.018 ) than the control group at posttreatment and the intervention was found to have a greater than 95 % probability of being cost-effective . The results support iCBT as an efficacious and cost-effective treatment option for older adults with symptoms of anxiety . TRIAL REGISTRATION TRIAL REGISTRATION Australian and New Zeal and Clinical Trials Registry : ACTRN12611000929909 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12611000929909 Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala , which can be normalized by effective treatment like cognitive behavior therapy ( CBT ) . Mechanisms underlying the brain ’s adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations , but multimodal neuroimaging studies addressing structure – function interactions are currently missing . Here , we examined treatment-related changes in brain structure ( gray matter ( GM ) volume ) and function ( blood – oxygen level dependent , BOLD response to self-referential criticism ) in 26 participants with social anxiety disorder r and omly assigned either to CBT or an attention bias modification control treatment . Also , 26 matched healthy controls were included . Significant time × treatment interactions were found in the amygdala with decreases both in GM volume ( family-wise error ( FWE ) corrected PFWE=0.02 ) and BOLD responsivity ( PFWE=0.01 ) after successful CBT . Before treatment , amygdala GM volume correlated positively with anticipatory speech anxiety ( PFWE=0.04 ) , and CBT-induced reduction of amygdala GM volume ( pre – post ) correlated positively with reduced anticipatory anxiety after treatment ( PFWE⩽0.05 ) . In addition , we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants , as compared with controls ( PFWE=0.029 ) , before but not after CBT . Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment ( P=0.007 ) . Thus , our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala , which could be essential for achieving anxiety reduction with CBT Background Major depression and depressive symptoms are common in patients with a recent myocardial infa rct ion ( MI ) , and depression is associated with adverse cardiovascular outcomes . Anxiety post-MI is less studied , but occurs commonly in patients with heart disease , and is also considered a risk factor for recurrence of cardiac events . Cognitive behavior therapy ( CBT ) is an established therapy for depression and anxiety disorders . To the best of our knowledge , there have not been any studies to determine if internet-based CBT ( iCBT ) can reduce the symptoms of depression and anxiety in patients with a recent MI . The main aim of the U-CARE Heart trial is to evaluate an iCBT intervention for patients with a recent MI . Methods / design This is a r and omized , controlled , prospect i ve study with a multicenter design . A total of 500 participants will be r and omized at a 1:1 ratio , around two months after an acute MI , to either iCBT or to a control group . Both groups will receive an optimal st and ard of care according to guidelines . The intervention consists of a self-help program delivered via the internet with individual online support from a psychologist . Treatment duration is 14 weeks . The primary outcome is change in patients ’ self-rated anxiety and depression symptoms from baseline to end of treatment . An internal pilot study was conducted indicating sufficient levels of study acceptability and engagement in treatment . Discussion The present study is design ed to evaluate an iCBT intervention targeting symptoms of depression and anxiety in a post-MI population . If effective , iCBT has several advantages , and will potentially be implemented as an easily accessible treatment option added to modern st and ard of care . Trial registration This trial was registered with Clinical trials.gov ( identifier : NCT01504191 ) on 19 December 2011 Background Symptoms of anxiety and depression are prevalent in older adults . Aims To compare clinician-guided and self-guided versions of a transdiagnostic internet-delivered cognitive – behavioural therapy ( iCBT ) intervention for adults aged 60 years and above . Method Adults ( n=433 ) with symptoms of anxiety and depression were r and omly allocated to : ( 1 ) clinician-guided treatment ( n=153 ) ; ( 2 ) initial clinician interview followed by self-guided treatment ( n=140 ) ; or ( 3 ) self-guided treatment without interview ( n=140 ) . Results Large reductions ( d ≥1.00 ) in symptoms of depression and anxiety were observed across groups , and sustained at follow-up . No differences were observed in clinical outcomes or satisfaction ratings . Age did not affect outcomes . Conclusions Carefully developed iCBT interventions may significantly reduce symptoms of anxiety and depression in older adults when delivered in either clinician-guided or self-guided formats . Declaration of interest N.T. and B.F.D. developed the Wellbeing Plus Course but derive no financial benefit from it . Copyright and usage © 2016 The Royal College of Psychiatrists . This is an open access article distributed under the terms of the Creative Commons Non-Commercial , No Derivatives ( CC BY-NC-ND ) licence Background Previous studies on Internet-based treatment with minimal therapist guidance have shown promising results for several specific diagnoses . Objective To ( 1 ) investigate the effects of a tailored , therapist-guided , Internet-based treatment for individuals with reoccurring panic attacks , and ( 2 ) to examine whether people in different age groups ( 18–30 years and 31–45 years ) would respond differently to the treatment . Methods We recruited 149 participants from an online list of individuals having expressed an interest in Internet treatment . Screening consisted of online question naires followed by a telephone interview . A total of 57 participants were included after a semistructured diagnostic interview , and they were r and omly assigned to an 8-week treatment program ( n = 29 ) or to a control condition ( n = 28 ) . Treatment consisted of individually prescribed cognitive behavior therapy text modules in conjunction with online therapist guidance . The control group consisted of people on a waitlist who later received treatment . Results All dependent measures improved significantly immediately following treatment and at the 12-month follow-up . The between-group effect size on the primary outcome measure , the Panic Disorder Severity Scale , was d = 1.41 ( 95 % confidence interval 0.81–1.95 ) at posttreatment . The within-group effect size from pretreatment to 12-month follow-up was d = 1.66 ( 95 % confidence interval 1.14–2.35 ) . Age group had no effect , suggesting that age did not influence the outcome . Conclusions Tailoring an Internet-based treatment can be a feasible approach in the treatment of panic symptoms and comorbid anxiety and depressive symptoms . Younger adults benefit as much as adults over 30 years and up to 45 years of age . Trial Registration Clinical trials.gov NCT01296321 ; http://www . clinical trials.gov/ct2/show/NCT01296321 ( Archived by WebCite at http://www.webcitation.org/65wddsqlL BACKGROUND To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders . Four groups were compared according to sociodemographic- , vulnerability- and clinical factors : single anxiety disorder , anxiety-anxiety comorbidity , anxiety-depressive comorbidity and " double " comorbidity ( i.e. anxiety and depressive comorbidity ) . METHODS Data were obtained from the Netherl and s Study of Anxiety and Depression ( NESDA ) . A sample of 1004 participants with a current anxiety disorder was evaluated . RESULTS As compared with single anxiety , anxiety-anxiety comorbidity was associated with higher severity , greater chronicity and more treatment . Anxiety-anxiety comorbidity was associated with an earlier age of onset and a more chronic course compared with anxiety-depressive comorbidity , while anxiety-depressive comorbidity was associated with more severe symptoms and more impaired functioning than anxiety-anxiety comorbidity . " Double " comorbidity was associated with higher severity , greater chronicity , more treatment and increased disability . Sociodemographic and vulnerability factors were comparable among the four groups . Limitations A prospect i ve design would be more appropriate to study the outcome . In this study no distinction was made between whether depression or anxiety disorder preceded the current anxiety disorder . CONCLUSIONS It is clinical relevant to diagnose and treat comorbidity among anxiety disorders as it is associated with higher severity and more chronicity . Whereas anxiety-anxiety comorbidity has an earlier age of onset and a more chronic course , anxiety-depressive comorbidity leads to more treatment and impaired functioning . " Double " comorbidity leads to even more severity , chronicity and impairment functioning compared with both anxiety-anxiety and anxiety-depressive comorbidity Transdiagnostic cognitive behaviour therapy ( TD-CBT ) aims to target the symptoms of multiple disorders whereas disorder-specific CBT ( DS-CBT ) targets the symptoms of principal disorders . This study compared the relative benefits of internet-delivered TD-CBT and DS-CBT when provided in clinician-guided ( CG-CBT ) and self-guided ( SG-CBT ) formats for people with a principal diagnosis of Panic Disorder ( PD ) . Participants ( n=145 ) were r and omly allocated to receive TD-CBT or DS-CBT and CG-CBT or SG-CBT . Large reductions in symptoms of PD ( Cohen 's d ≥ 0.71 ; avg . reduction ≥ 36 % ) and moderate-to-large reductions in symptoms of comorbid depression ( Cohen 's d ≥ 0.71 ; avg . reduction ≥ 33 % ) , generalised anxiety disorder ( Cohen 's d ≥ 0.91 ; avg . reduction ≥ 34 % ) and social anxiety disorder ( Cohen 's d ≥ 0.50 ; avg . reduction ≥ 15 % ) were found over the 24-month follow-up period . Highlighting their efficacy and acceptability , no marked and consistent differences were observed between TD-CBT and DS-CBT or CG-CBT and DS-CBT 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 Clinician-guided Internet-based cognitive behavioural therapy ( iCBT ) programs are clinical ly effective at treating specific anxiety disorders . The present study examined the efficacy of a transdiagnostic Internet-based cognitive behavioural treatment ( iCBT ) program to treat more than one anxiety disorder within the same program ( the Anxiety Program ) . Eighty six individuals meeting diagnostic criteria for generalized anxiety disorder ( GAD ) , panic disorder , and /or social phobia were r and omly assigned to a treatment group , or to a waitlist control group . Treatment consisted of CBT based online educational lessons and homework assignments , weekly email or telephone contact from a clinical psychologist , access to a moderated online discussion forum , and automated emails . An intention-to-treat model using the baseline-observation-carried-forward principle was employed for data analyses . Seventy-five percent of treatment group participants completed all 6 lessons within the 8 week program . Post-treatment data was collected from 38/40 treatment group and 38/38 control group participants , and 3-month follow-up data was collected from 32/40 treatment group participants . Relative to controls , treatment group participants reported significantly reduced symptoms of anxiety as measured by the Generalized Anxiety Disorder - 7 Item , Social Phobia Screening Question naire , and the Panic Disorder Severity Rating Scale - Self Report Scale , but not on the Penn State Worry Question naire , with corresponding between-groups effect sizes ( Cohen 's d ) at post-treatment of 0.78 , 0.43 , 0.43 , and 0.20 , respectively . The clinician spent a total mean time of 46min per person over the program , participants rated the procedure as moderately acceptable , and gains were sustained at follow-up . Modifications to the Anxiety program , based on post-treatment feedback from treatment group participants , were associated with improved outcomes in the control group . These results indicate that transdiagnostic programs for anxiety disorders may be successfully administered via the Internet Background and Aims Major depression can be treated by means of cognitive behavior therapy , delivered via the Internet as guided self-help . Individually tailored guided self-help treatments have shown promising results in the treatment of anxiety disorders . This r and omized controlled trial tested the efficacy of an Internet-based individually tailored guided self-help treatment which specifically targeted depression with comorbid symptoms . The treatment was compared both to st and ardized ( non-tailored ) Internet-based treatment and to an active control group in the form of a monitored online discussion group . Both guided self-help treatments were based on cognitive behavior therapy and lasted for 10 weeks . The discussion group consisted of weekly discussion themes related to depression and the treatment of depression . Methods A total of 121 participants with diagnosed major depressive disorder and with a range of comorbid symptoms were r and omized to three groups . The tailored treatment consisted of a prescribed set of modules targeting depression as well as comorbid problems . The st and ardized treatment was a previously tested guided self-help program for depression . Results From pre-treatment to post-treatment , both treatment groups improved on measures of depression , anxiety and quality of life . The results were maintained at a 6-month follow-up . Subgroup analyses showed that the tailored treatment was more effective than the st and ardized treatment among participants with higher levels of depression at baseline and more comorbidity , both in terms of reduction of depressive symptoms and on recovery rates . In the subgroup with lower baseline scores of depression , few differences were seen between treatments and the discussion group . Conclusions This study shows that tailored Internet-based treatment for depression is effective and that addressing comorbidity by tailoring may be one way of making guided self-help treatments more effective than st and ardized approaches in the treatment of more severe depression . Trial Registration Clinical trials.gov Disorder-specific ( DS-CBT ) and transdiagnostic ( TD-CBT ) cognitive behaviour therapy have both been used to treat social anxiety disorder ( SAD ) . This study compared internet-delivered DS-CBT and TD-CBT for SAD across clinician-guided ( CG-CBT ) and self-guided ( SG-CBT ) formats . Participants with SAD ( n=233 ) were r and omly allocated to receive internet-delivered TD-CBT or DS-CBT and CG-CBT or SG-CBT . Large reductions in symptoms of SAD ( Cohen 's d≥1.01 ; avg . reduction≥30 % ) and moderate-to-large reductions in symptoms of comorbid depression ( Cohen 's d≥1.25 ; avg . reduction≥39 % ) , generalised anxiety disorder ( Cohen 's d≥0.86 ; avg . reduction≥36 % ) and panic disorder ( Cohen 's d≥0.53 ; avg . reduction≥25 % ) were found immediately post-treatment and were maintained or further improved to 24-month follow-up . No marked differences were observed between TD-CBT and DS-CBT or CG-CBT and SG-CBT highlighting the potential of each for the treatment of SAD and comorbid disorders UNLABELLED A significant proportion of the general population suffers from anxiety disorders , often with comorbid psychiatric conditions . Internet-delivered cognitive behavior therapy ( ICBT ) has been found to be a potent treatment for patients with specific psychiatric conditions . The aim of this trial was to investigate the effectiveness and cost-effectiveness of ICBT when tailoring the treatment to address comorbidities and preferences for primary -care patients with a principal anxiety disorder . One hundred participants were recruited through their primary -care contact and r and omized to either treatment or an active control group . The treatment consisted of 7 - 10 weekly individually assigned modules guided by online therapists . At post-treatment , 46 % of the treatment group had achieved clinical ly significant improvement on the primary outcome measure ( CORE-OM ) and between-group effect sizes ranged from d = 0.20 to 0.86 , with a mean effect of d = 0.59 . At one-year follow-up , within-group effect sizes varied between d = 0.53 to 1.00 . Cost analysis showed significant reduction of total costs for the ICBT group , the results were maintained at one-year follow-up and the incremental cost-effectiveness ratio favored ICBT compared to control group . Individually tailored ICBT is an effective and cost-effective treatment for primary -care patients with anxiety disorders with or without comorbidities . TRIAL REGISTRATION Clinical trials.gov : NCT01390168 Background Anxiety disorders share common vulnerabilities and symptoms . Disorder-specific treatment is efficacious , but few access evidence -based care . Administering transdiagnostic cognitive-behavioral therapy via the internet ( iCBT ) may increase access to evidence -based treatment , with a recent r and omized controlled trial ( RCT ) providing preliminary support for this approach . This study extends those findings and aims to answer three questions : Is a transdiagnostic iCBT program for anxiety disorders efficacious and acceptable ? Does it result in change for specific disorders ? Can good clinical outcomes be obtained when guidance is provided via a Coach rather than a Clinician ? Method RCT ( N = 131 ) comparing three groups : Clinician-supported ( CL ) vs. Coach-supported ( CO ) vs. waitlist control ( Control ) . Individuals met DSM-IV criteria for a principal diagnosis of generalized anxiety disorder ( GAD ) , social phobia ( SP ) or panic disorder with or without agoraphobia ( Pan/Ag ) . Treatment consisted of an 8-lesson/10 week iCBT program with weekly contact from a Clinician or Coach , and follow-up at 3-months post-treatment . Results Outcomes for the pooled treatment groups ( CL+CO ) were superior to the Control group on measures of anxiety , depression and disability , were associated with medium to large effect sizes ( Cohen 's d = .76 – 1.44 ) ( response rate = 89–100 % ) , and were maintained at follow-up . Significant reductions were found on disorder-specific outcomes for each of the target diagnoses , and were associated with large effect sizes . CO participants achieved similar outcomes to CL participants at post-treatment , yet had significantly lower symptom severity scores on general anxiety , panic-disorder , depression and disability at follow-up ( d = .45 – .46 ) . Seventy-four percent of CO and 76 % of CL participants completed the program . Less than 70 minutes of Clinician or Coach time was required per participant during the program . Discussion This transdiagnostic iCBT course for anxiety appears to be efficacious , associated with significant change for three target disorders , and is efficacious when guided by either a Clinician or Coach . Trial Registration Australian New Zeal and Clinical Trials Registry Anxiety , depression and stress , often co-occurring , are the psychological problems for which university students most often seek help . Moreover there are many distressed students who can not , or choose not to , access professional help . The present study evaluated the efficacy of an internet-based guided self-help program for moderate anxiety , depression and stress . The program was based on st and ard cognitive behavior therapy principles and included 5 core modules , some of which involved options for focusing on anxiety and /or depression and /or stress . Trained student coaches provided encouragement and advice about using the program via e-mail or brief weekly phone calls . Sixty-six distressed university students were r and omly assigned to either Immediate Access or a 6-week Delayed Access condition . Sixty-one percent of Immediate Access participants completed all 5 core modules , and 80 % of all participants completed the second assessment . On the Depression , Anxiety and Stress Scales-21 , Immediate Access participants reported significantly greater reductions in depression ( ηp(2)=. 07 ) , anxiety ( ηp(2)=. 08 ) and stress ( ηp(2)=. 12 ) in comparison to participants waiting to do the program , and these improvements were maintained at a six month follow-up . The results suggest that the provision of individually-adaptable , internet-based , self-help programs can reduce psychological distress in university students Objective : Social phobia can be treated by brief Internet-based cognitive behaviour therapy ( CBT ) . Most people with social phobia , however , meet criteria for another mental disorder ; this comorbidity is associated with significant disability , and cases of comorbidity may be more difficult to treat . The present study examined the impact of the Shyness programme , an Internet-based treatment programme for social phobia , on comorbid symptoms of depression and generalized anxiety disorder . Method : Data from three r and omized controlled trials using the Shyness programme to treat social phobia were reanalysed . The 211 subjects , all of whom met DSM-IV criteria for social phobia , were divided into four groups : ( i ) social phobia only ; ( ii ) social phobia with elevated symptoms of depression ; ( iii ) social phobia with elevated symptoms of generalized anxiety ; and ( iv ) social phobia with elevated symptoms of both generalized anxiety and depression . The improvement in social phobia , depression and anxiety following Internet-based treatment for social phobia was measured . Results : Improvement in social phobia was seen in all groups , whether comorbid or not . Significant improvements in comorbid symptoms of depression and generalized anxiety occurred even though the treatment was focused on the social phobia . Conclusions : Brief Internet-based CBT can reduce both the target disorder as well as comorbid symptoms . These findings are consistent with evidence that unified or transdiagnostic programmes may reduce the severity of comorbid disorders and symptoms , indicating an important direction for future research Previous studies on Internet-based treatment with minimal to moderate therapist guidance have shown promising results for a number of specific diagnoses . The aim of this study was to test a new approach to Internet treatment that involves tailoring the treatment according to the patient 's unique characteristics and comorbidities . A total of 54 participants , regardless of specific anxiety diagnosis , were included after an in-person , semi-structured diagnostic interview and r and omized to a 10 week treatment program or to a control group . Treatment consisted of a number of individually-prescribed modules in conjunction with online therapist guidance . Significant results were found for all dependent measures both immediately following treatment and at 1 and 2 year intervals . Mean between-group effect size including measures of anxiety , depression and quality of life was Cohen 's d = 0.69 at post-treatment , while the mean within-group effect size was d = 1.15 at post-treatment and d = 1.13 and d = 1.04 at 1 and 2 year follow-up respectively . The tentative conclusion drawn from these results is that tailoring the Internet-based therapy can be a feasible approach in the treatment of anxiety in a homogeneous population BACKGROUND AND OBJECTIVES Many individuals with anxiety disorders do not receive professional treatment . Internet interventions have shown to be effective in the treatment of anxiety . The present r and omized controlled trial was design ed to examine the effectiveness of a short-term ( 4-week ) Internet intervention in treating panic disorder , agoraphobia , social anxiety disorder , and specific phobias ( ' ConfID ' ) . We addressed the questions of whether this transdiagnostic program would affect these disorders to varying degrees and whether there would be moderators of effectiveness . METHODS Adults who were recruited in online forums for anxiety underwent an online baseline assessment ( N = 179 ) and were r and omized either to the intervention group ( ConfID ) or the control group ( care as usual ) . Online post- assessment took place 4 weeks later . The primary outcome was assessed with the Beck Anxiety Inventory ( BAI ) ; the secondary outcomes targeted the disorder-specific symptoms , depression , and somatization . RESULTS Participants in the intervention group showed a significantly stronger anxiety reduction compared to participants receiving care as usual ( small-to-medium effect size between groups in intention-to-treat analysis ) . The treatment effect was similar for the different disorders and was moderated by participants ' attitudes towards Internet interventions . Secondary outcomes yielded effect sizes in the medium range . LIMITATIONS Moderate treatment adherence , lack of measures beyond online self-reports , and unavailability of long-term results . CONCLUSIONS The study provides further evidence that transdiagnostic Internet interventions are promising in reducing the existing treatment gap in individuals with panic disorder and phobias . Results extend previous findings by showing that significant effects can also be reached by comprehensive short-term programs and that the effects might be moderated by participants ' attitudes towards Internet interventions Internet-delivered self-help with minimal therapist guidance has shown promising results for a number of diagnoses . Most of the evidence comes from studies evaluating st and ardized disorder-specific treatments . A recent development in the field includes transdiagnostic and tailored Internet-based treatments that address comorbid symptoms and a broader range of patients . This study evaluated an Internet-based tailored guided self-help treatment , which targeted symptoms of social anxiety disorder , panic disorder with or without agoraphobia , and generalized anxiety disorder . The tailored treatment was compared both with st and ardized disorder-specific Internet-based treatment and with a wait-list control group . Both active treatment conditions were based on cognitive-behavioral therapy and lasted for 8 weeks . A total of 132 individuals meeting diagnostic criteria for at least one of the anxiety disorders were r and omly assigned to 1 of the 3 conditions . Both treatment groups showed significant symptom reductions as compared with the wait-list control group on primary disorder-unspecific measures of anxiety , depression , and general symptomatology and on secondary anxiety disorder-specific measures . Based on the intention-to-treat sample , mean between-group effect sizes were d = 0.80 for the tailored treatment and d = 0.82 for the st and ardized treatment , versus wait-list controls . Treatment gains were maintained at 6-month follow-up . No differences were found between the 2 active treatment conditions on any of the measures , including a telephone-administered diagnostic interview conducted at posttreatment . The findings suggest that both Internet-based tailored guided self-help treatments and Internet-based st and ardized treatments are promising treatment options for several anxiety disorders Disorder-specific cognitive behavioural therapy programs delivered over the internet ( iCBT ) with clinician guidance are effective at treating specific anxiety disorders and depression . The present study examined the efficacy of a transdiagnostic iCBT protocol to treat three anxiety disorders and /or depression within the same program ( the Wellbeing Program ) . Seventy-seven individuals with a principal diagnosis of major depression , generalised anxiety disorder , panic disorder , and /or social phobia were r and omly assigned to a Treatment or Waitlist Control group . Treatment consisted of CBT-based online educational lessons and homework assignments , weekly email or telephone contact from a clinical psychologist , access to a moderated online discussion forum , and automated emails . Eighty one percent of Treatment group participants completed all 8 lessons within the 10 week program . Post-treatment data were collected from 34/37 Treatment group and 35/37 Control group participants , and 3-month follow-up data were collected from 32/37 Treatment group participants . Relative to Controls , Treatment group participants reported significantly reduced symptoms of anxiety and depression as measured by the Depression Anxiety and Stress Scales-21 item , Patient Health Question naire-9 item , and Generalised Anxiety Disorder-7 item scales , with corresponding between-groups effect sizes ( Cohen 's d ) at post treatment of.56,.58 , and .52 , respectively . The clinician spent a mean time of 84.76 min ( SD=50.37 ) per person over the program . Participants rated the procedure as highly acceptable , and gains were sustained at follow-up . These results provide preliminary support for the efficacy of transdiagnostic iCBT in the treatment of anxiety and depressive disorders Disorder-specific cognitive behavior therapy ( DS-CBT ) is effective at treating major depressive disorder ( MDD ) while transdiagnostic CBT ( TD-CBT ) addresses both principal and comorbid disorders by targeting underlying and common symptoms . The relative benefits of these two models of therapy have not been determined . Participants with MDD ( n=290 ) were r and omly allocated to receive an internet delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided ( CG-CBT ) or self-guided ( SG-CBT ) formats . Large reductions in symptoms of MDD ( Cohen 's d≥1.44 ; avg . reduction≥45 % ) and moderate-to-large reductions in symptoms of comorbid generalised anxiety disorder ( Cohen 's d≥1.08 ; avg . reduction≥43 % ) , social anxiety disorder ( Cohen 's d≥0.65 ; avg . reduction≥29 % ) and panic disorder ( Cohen 's d≥0.45 ; avg . reduction≥31 % ) were found . No marked or consistent differences were observed across the four conditions , highlighting the efficacy of different forms of CBT at treating MDD and comorbid disorders Background Depression and anxiety are common , disabling and chronic . Self-guided internet-delivered treatments are popular , but few people complete them . New strategies are required to realise their potential . Aims To evaluate the effect of automated emails on the effectiveness , safety , and acceptability of a new automated transdiagnostic self-guided internet-delivered treatment , the Wellbeing Course , for people with depression and anxiety . Method A r and omised controlled trial was conducted through the website : www.ecentreclinic.org . Two hundred and fifty seven people with elevated symptoms were r and omly allocated to the 8 week course either with or without automated emails , or to a waitlist control group . Primary outcome measures were the Patient Health Question naire 9-Item ( PHQ-9 ) and the Generalized Anxiety Disorder 7-Item ( GAD-7 ) . Results Participants in the treatment groups had lower PHQ-9 and GAD-7 scores at post-treatment than controls . Automated emails increased rates of course completion ( 58 % vs. 35 % ) , and improved outcomes in a sub sample with elevated symptoms . Conclusions The new self-guided course was beneficial , and automated emails facilitated outcomes . Further attention to strategies that facilitate adherence , learning , and safety will help realise the potential of self-guided interventions . Trial Registration Australian and New Zeal and Clinical Trials Registry Generalized anxiety disorder ( GAD ) can be treated effectively with either disorder-specific cognitive behavior therapy ( DS-CBT ) or transdiagnostic CBT ( TD-CBT ) . The relative benefits of DS-CBT and TD-CBT for GAD and the relative benefits of delivering treatment in clinician guided ( CG-CBT ) and self-guided ( SG-CBT ) formats have not been examined . Participants with GAD ( n=338 ) were r and omly allocated to receive an internet-delivered TD-CBT or DS-CBT intervention delivered in either CG-CBT or SG-CBT formats . Large reductions in symptoms of GAD ( Cohen 's d ≥ 1.48 ; avg . reduction ≥ 50 % ) and comorbid major depressive disorder ( Cohen 's d ≥ 1.64 ; avg . reduction ≥ 45 % ) , social anxiety disorder ( Cohen 's d ≥ 0.80 ; avg . reduction ≥ 29 % ) and panic disorder ( Cohen 's d ≥ 0.55 ; avg . reduction ≥ 33 % ) were found across the conditions . No substantive differences were observed between DS-CBT and TD-CBT or CG-CBT and SG-CBT , highlighting the public health potential of carefully developed TD-CBT and SG-CBT BACKGROUND Major depressive disorder ( MDD ) and generalized anxiety disorder ( GAD ) have the highest co-morbidity rates within the internalizing disorders cluster , yet no Internet-based cognitive behavioural therapy ( iCBT ) programme exists for their combined treatment . METHOD We design ed a six-lesson therapist-assisted iCBT programme for mixed anxiety and depression . Study 1 was a r and omized controlled trial ( RCT ) comparing the iCBT programme ( n = 46 ) versus wait-list control ( WLC ; n = 53 ) for patients diagnosed by structured clinical interview with MDD , GAD or co-morbid GAD/MDD . Primary outcome measures were the Patient Health Question naire nine-item scale ( depression ) , Generalized Anxiety Disorder seven-item scale ( generalized anxiety ) , Kessler 10-item Psychological Distress scale ( distress ) and 12-item World Health Organization Disability Assessment Schedule II ( disability ) . The iCBT group was followed up at 3 months post-treatment . In study 2 , we investigated the adherence to , and efficacy of the same programme in a primary care setting , where patients ( n = 136 ) completed the programme under the supervision of primary care clinicians . RESULTS The RCT showed that the iCBT programme was more effective than WLC , with large within- and between-groups effect sizes found ( > 0.8 ) . Adherence was also high ( 89 % ) , and gains were maintained at 3-month follow-up . In study 2 in primary care , adherence to the iCBT programme was low ( 41 % ) , yet effect sizes were large ( > 0.8 ) . Of the non-completers , 30 % experienced benefit . CONCLUSIONS Together , the results show that iCBT is effective and adherence is high in research setting s , but there is a problem of adherence when translated into the ' real world ' . Future efforts need to be placed on developing improved adherence to iCBT in primary care setting |
11,306 | 28,905,362 | Of the comparisons , we had planned to explore , we were only able to undertake a quantitative synthesis for TENS versus sham TENS .
In this review , we reported on the comparison between TENS and sham TENS .
The quality of the evidence was very low meaning we were unable to confidently state whether TENS is effective for pain control in people with neuropathic pain . | BACKGROUND Neuropathic pain , which is due to nerve disease or damage , represents a significant burden on people and society .
It can be particularly unpleasant and achieving adequate symptom control can be difficult .
Non-pharmacological methods of treatment are often employed by people with neuropathic pain and may include transcutaneous electrical nerve stimulation ( TENS ) .
This review supersedes one Cochrane Review ' Transcutaneous electrical nerve stimulation ( TENS ) for chronic pain ' ( Nnoaham 2014 ) and one withdrawn protocol ' Transcutaneous electrical nerve stimulation ( TENS ) for neuropathic pain in adults ' ( Claydon 2014 ) .
This review replaces the original protocol for neuropathic pain that was withdrawn .
OBJECTIVES To determine the analgesic effectiveness of TENS versus placebo ( sham ) TENS , TENS versus usual care , TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults . | BACKGROUND Chronic pain is a common consequence of spinal cord injury ( SCI ) . No therapeutic drugs or drug groups are proven to be superior for neuropathic pain and treatments only aim to convert pain from dull to tolerable levels and not to remove it . OBJECTIVE This study was planned to compare the effect of visual illusion ( VI ) and transcutaneous electrical nerve stimulation ( TENS ) on pain intensity , pain quality and functional capacity in SCI patients with neuropathic pain . METHODS Twenty-four patients were included and r and omly categorized into two groups . In the first group ( n= 12 ) , visual illusion was applied for first two weeks , 1 week wash out period and then TENS was applied for 2 weeks . In second group ( n= 12 ) , TENS was applied firstly , 1 week wash out and then % visual illusion VI were applied . Pain severity , pain quality , and functional capacity were assessed with the visual analog scale ( VAS ) , the neuropathic pain scale ( NPS ) , and the brief pain inventory ( BPI ) , respectively . A pre-post-treatment and cross over design was used . RESULTS Wilcoxon signed-rank tests were used for within group analyses . Mann-Whitney U tests were used for analyses that compared different groups . It was observed that pain intensity decrease immediately after both applications ( VI : p= 0.07 , TENS : p= 0.08 ) . After TENS application for 2 weeks , it was observed that significant decrease in most ( p= 0.04 ) and less ( p= 0.02 ) pain intensity ; while there was no significant decrease in pain intensity after 2 weeks for VI ( p > 0.05 ) . When findings of NPS were analyzed , hot ( p= 0.047 ) , sharp ( p= 0.02 ) , unpleasant ( p= 0.03 ) and deep items ( p= 0.047 ) decreased after VI application . When the results of BPI were detected , they were observed that the negative effect of pain on moving ability ( p= 0.04 ) after visual illusion application and the negative effect of pain on mood ( p= 0.03 ) , relationships with others ( p= 0.04 ) and sleep ( p= 0.04 ) after TENS application decreased significantly . CONCLUSION TENS and VI therapies can be successfully used in clinical practice as an alternative treatment or as a supportive method separetely or together Sciatica is a common pain problem and current pharmacologic therapies have proven inadequate for many patients . The objective of this sham-controlled investigation was to compare a novel non-pharmacologic technique , percutaneous electrical nerve stimulation ( PENS ) , to transcutaneous electrical nerve stimulation ( TENS ) in the management of the radicular pain associated with sciatica . Sixty-four consenting patients with sciatica due to lumbar disc herniation were treated with PENS , TENS and sham-PENS according to a r and omized , single-blinded , cross-over study . All patients had been maintained on a stable oral non-opioid analgesic regimen for at least 6 weeks prior to entering the study . Each treatment modality was administered for a period of 30 min three times per week for 3 weeks , with 1 week ' off ' between each modality . Both PENS and TENS treatments were administered using a stimulation frequency of 4 Hz . The pre-treatment assessment included the health status survey short form ( SF-36 ) , as well as visual analog scales ( VAS ) for radicular pain , physical activity and quality of sleep . The pain VAS was also repeated after each treatment session . At the end of each 3-week treatment block , the SF-36 was repeated . After receiving all three treatment modalities , a global assessment question naire was completed . Both PENS ( 42 % ) and TENS ( 23 % ) were significantly more effective than the sham ( 8 % ) treatments in decreasing VAS pain scores . The daily oral analgesic requirements were also significantly reduced compared to the pre-treatment values with PENS ( P<0.01 ) and TENS ( P<0.05 ) . However , PENS was significantly more effective than TENS ( and sham-PENS ) in improving physical activity and quality of sleep . The SF-36 evaluation confirmed the superiority of PENS ( versus TENS and sham-PENS ) with respect to post-treatment functionality . In the overall assessment , 73 % of the patients reported that PENS was the most desirable modality ( versus 21 % for TENS and 6 % for sham-PENS ) . Finally , 71 % of the patients stated that they would be willing to pay extra to receive PENS therapy compared to 22 % and 3 % for TENS and sham-PENS , respectively . In this sham-controlled study , we concluded that PENS was more effective than TENS when administered at a stimulation frequency of 4 Hz in providing short-term pain relief and improved functionality in patients with sciatica AIM The aim of the study was to compare LASER versus transcutaneous electrical nerve stimulation ( TENS ) in reducing pain and paraesthesia ; and in improving motor and sensory median nerve conduction parameters in mild to moderate carpal tunnel syndrome ( CTS ) . DESIGN R and omised blinded pilot study . Patients and staff administered treatments and outcome measures were blinded . SETTING Outpatient ; Research and Care Rehabilitation Institute . PARTICIPANTS Twenty CTS symptomatic patients . INTERVENTIONS Fifteen sessions of : 1 ) 100 Hz TENS ( 30 minutes ; rectangular waves ; 80 ms width , intensity below muscle contraction ) ; 2 ) combined 830 - 1064 nm LASER ( radiating dose : 250 J cm-2 delivered to the skin overlying the course of the median nerve at the wrist for 100 s at 25 W ( 18 W [ 1064 nm ] + 7 W [ 830 nm ] ) via a fiber-optic probe with a spot size of ~1 cm2 ) . Outcome measures . Visual analogue scale ( VAS ) for pain and paresthesia ; median nerve distal motor latency and sensory nerve conduction velocity . RESULTS LASER improved both positive and negative sensory symptoms . TENS induced clinical improvement but this was not statistically significant and was limited to pain reduction . LASER but not TENS favourably modified the neurophysiological parameters . CONCLUSION High-intensity combined LASER wavelengths of 830 nm and 1064 nm , which produce a better transparency with less scattering and a high energy transfer , are better than TENS in improving both pain and paraesthesia as well as neurophysiological parameters in CTS UNLABELLED Transcutaneous electrical nerve stimulation ( TENS ) is an electrophysical modality used for pain management . This study investigated the dose response of different TENS intensities on experimentally induced pressure pain . One hundred and thirty TENS naïve healthy individuals ( 18 - 64 years old ; 65 males , 65 females ) were r and omly allocated to 5 groups ( n = 26 per group ) : Strong Non Painful TENS ; Sensory Threshold TENS ; Below Sensory Threshold TENS ; No Current Placebo TENS ; and Transient Placebo TENS . Active TENS ( 80 Hz ) was applied to the forearm for 30 minutes . Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds ( PPT ) were recorded from 2 points on the h and and forearm before and after TENS to measure hypoalgesia . There were significant differences between groups at both the h and and forearm ( ANOVA ; P = .005 and .002 ) . At 30 minutes , there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to : Below Sensory Threshold TENS , No Current Placebo TENS and Transient Placebo TENS groups ( P < .0001 ) at the forearm ; Transient Placebo TENS and No Current Placebo TENS groups at the h and ( P = .001 ) . There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups . The area under the curve for the changes in PPT significantly correlated with the current amplitude ( r(2 ) = .33 , P = .003 ) . These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes . PERSPECTIVE This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect ; thus , we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief [ Purpose ] To investigate the effects of transcutaneous electrical nerve stimulation ( TENS ) on pain in patients with spinal cord injury . [ Subjects and Methods ] Fifty-two spinal cord injury patients with central pain were r and omly allocated into two groups TENS and control with 26 subjects per group . The patients in TENS and control groups were treated with TENS and sham TENS for 20 min ( three times a week ) for 12 consecutive weeks , respectively . The two group ’s pain was assessed using visual analog scale ( VAS ) and the McGill Pain Question naire ( including pain rating index-total , pain rating index-affective , pain rating index-sensory , present pain intensity , and number of words chosen ) before and after the treatment . [ Results ] After the intervention , we found significant differences in VAS , pain rating index-total , pain rating index-affective , pain rating index-sensory , present pain intensity , and number of words chosen between the TENS group and the control group . [ Conclusion ] Our results suggest that TENS effectively decreases pain in patients with spinal cord injury Summary Pain and fatigue during movement , but not at rest , are reduced by a onetime 30‐m treatment with active transcutaneous electrical nerve stimulation ( TENS ) in individuals with fibromyalgia . Abstract Because transcutaneous electrical nerve stimulation ( TENS ) works by reducing central excitability and activating central inhibition pathways , we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition . The current study used a double‐blinded r and omized , placebo‐controlled cross‐over design to test the effects of a single treatment of TENS with people with fibromyalgia . Three treatments were assessed in r and om order : active TENS , placebo TENS and no TENS . The following measures were assessed before and after each TENS treatment : pain and fatigue at rest and in movement ; pressure pain thresholds , 6‐m walk test , range of motion ; 5‐time sit‐to‐st and test , and single‐leg stance . Conditioned pain modulation was completed at the end of testing . There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS . Pressure pain thresholds increased at the site of TENS ( spine ) and outside the site of TENS ( leg ) when compared to placebo TENS or no TENS . During active TENS , conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS . No changes in functional tasks were observed with TENS . Thus , the current study suggests TENS has short‐term efficacy in relieving symptoms of fibromyalgia while the stimulator is active . Future clinical trials should examine the effects of repeated daily delivery of TENS , similar to the way in which TENS is used clinical ly on pain , fatigue , function , and quality of life in individuals with fibromyalgia Background : Painful diabetic peripheral neuropathy ( DPN ) is a long-term complication of type 1 and type 2 diabetes that majorly impacts quality of life . Its prevalence increases with age and duration of diabetes . It is more common in patients who have suboptimal glycemic control over several years . Because DPN may be resistant to conventional treatments , it is common for patients to only have partial pain relief . Therefore , new therapeutic options are needed for the condition . Objectives : The aim of the present study was to compare the efficacy of transcutaneous electrical nerve stimulation ( TENS ) and pulsed radiofrequency ( PRF ) lumbar sympathectomy in treating painful DPN . Patients and Methods : Sixty-five patients with painful DPN refractory to conventional treatment were r and omly and evenly assigned to either the TENS or PRF lumbar sympathectomy groups . Pain evaluations were based on the 10-point numerical rating scale ( NRS ) . Subjects were followed for three months and had a total of four study visits ( baseline and 1 week , 1 month , and 3 months after treatment ) . Results : Sixty patients completed all study visits . In both groups , the NRS rating significantly decreased after treatment , with a marked pain reduction observed at the first follow-up evaluation . In the PRF group , the NRS decreased from 6.46 at baseline to 2.76 at the 1 week visit . One and 3 months after treatment , the NRS was 4.30 and 5.13 , respectively ( P < 0.0001 ) . In the TENS group , the NRS decreased from 6.10 at baseline to 3.96 at the 1 week visit . One and 3 months after treatment , the NRS was 5.23 and 5.90 , respectively ( P < 0.0001 ) . Unfortunately , the NRS steady increased almost back to baseline levels in the TENS group . The NRS only slightly increased during the follow-up period in the PRF group , but did not reach baseline levels . Conclusions : Both TENS and PRF lumbar sympathectomy are promising pain relief treatments for painful DNP . However , PRF lumbar sympathectomy seems to have a superior efficacy . Further studies with a larger sample size and a longer follow-up period are needed Study design : Prospect i ve , r and omized and controlled study . Objectives : The aim of the study was to investigate the effect of low-frequency transcutaneous electrical nerve stimulation ( LF-TENS ) in the treatment of neuropathic pain in patients with spinal cord injury ( SCI ) . Methods : A total of 33 SCI patients with neuropathic pain were included in the study . History , duration , localization and characteristics of pain were recorded . Visual analog scale ( VAS ) was used to investigate the effect of LF-TENS four times during the day . Patients were r and omly assigned to study and control groups . The study group was treated with 30 min of LF-TENS daily for 10 days while the placebo group with 30 min of sham TENS . Results : The mean age of the patients was 36.55±10.36 years . Out of 33 patients , 7 were tetraplegic and 26 were paraplegic . Twenty-three patients had complete SCI while 10 patients had incomplete injuries . Two groups were similar with respect to age , gender , duration , level and severity of injury . In the LF-TENS treatment group , a statistically significant reduction of the VAS values was observed , however , such an effect was not evident in the control group . Conclusion : This study revealed that in treatment of neuropathic pain of SCI patients , LF-TENS may be effective . Perspective : This article presents LF-TENS may effectively complement pharmacological treatment in patients with SCI and neuropathic pain & NA ; Previous human studies have shown that the analgesic effect of high‐frequency TENS could not be reversed by low doses of naloxone . The aim of the present study was to reinvestigate the possible contribution of opioid receptors to high‐frequency TENS analgesia by using low ( 0.02 mg/kg ) and high ( 0.14 mg/kg ) doses of naloxone . Naloxone ( high and low doses ) and saline were administered intravenously to young healthy adults using a triple‐blind r and omized cross‐over design . For each visit , TENS ( 100 Hz , 60 & mgr;s ) was applied for 25 min to the external surface of the left ankle . TENS intensity was adjusted to obtain strong but comfortable ( innocuous ) paresthesias . Experimental pain was evoked with a 1 cm2 thermode applied on the lateral aspect of the left heel . Subjective pain scores were obtained before , during and after TENS . Because preliminary analyses showed that the order of presentation affected the pattern of results , only the first visit of every participant could be analyzed without fear of contamination from possible carry‐over effects . These revealed that TENS maintained its analgesic properties following the injection of saline ( p < .001 ) and the injection of a low dose of naloxone ( p < .05 ) . However , when a high dose of naloxone was administered , TENS analgesia was completely blocked ( p = .20 ) . These results suggest that high‐frequency TENS involves opioid receptors . An insufficient amount of opioid antagonist likely prevented previous human studies from discovering the importance of opioid receptors in producing high‐frequency TENS analgesia We studied the effect of transcutaneous electrical nerve stimulation ( TENS ) on stump healing and postoperative and late phantom pain after major amputations of the lower limb . A total of 51 patients were r and omised to one of three postoperative treatment regimens : sham TENS and chlorpromazine medication , sham TENS only , and active low frequency TENS . There were fewer re-amputations and more rapid stump healing among below-knee amputees who had received active TENS . Sham TENS had a considerable placebo effect on pain . There were , however , no significant differences in the analgesic requirements or reported prevalence of phantom pain between the groups during the first four weeks . The prevalence of phantom pain after active TENS was significantly lower after four months but not after more than one year Objective . Pain is a patient-important outcome , but current reporting in r and omized controlled trials and systematic review s is often suboptimal , impeding clinical interpretation and decision making . Methods . A working group at the 2014 Outcome Measures in Rheumatology ( OMERACT 12 ) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic review s. Results For individual trials , authors should report , in addition to mean change , the proportion of patients achieving 1 or more thresholds of improvement from baseline pain ( e.g. , ≥ 20 % , ≥ 30 % , ≥ 50 % ) , achievement of a desirable pain state ( e.g. , no worse than mild pain ) , and /or a combination of change and state . Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation . When pooling data for meta analysis , authors should consider converting all continuous measures for pain to a 100 mm visual analog scale ( VAS ) for pain and use the established , minimally important difference ( MID ) of 10 mm , and the conventionally used , appreciably important differences of 20 mm , 30 mm , and 50 mm , to facilitate interpretation . Effects ≤ 0.5 units suggest a small or very small effect . To further increase interpretability , the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference . This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups . Conclusion . Presentation of relative effects regarding pain will facilitate interpretation of treatment effects Aims /hypothesisDiabetic distal symmetrical sensory polyneuropathy ( DSP ) affects 20–30 % of diabetic patients . Transcutaneous electrical nerve stimulation ( TENS ) and electrical spinal cord stimulation have been proposed as physical therapies . We performed a controlled , r and omised pilot trial to compare the effects of high-frequency external muscle stimulation ( HF ) with those of TENS in patients with symptomatic DSP . Methods Patients with type 2 diabetes and DSP ( n=41 ) were r and omised to receive treatment with TENS or HF using strata for non-painful ( n=20 ) and painful sensory symptoms ( n=21 ) . Both lower extremities were treated for 30 min daily for three consecutive days . The patients ’ degree of symptoms and pain were grade d daily on a scale of one to ten , before , during and 2 days after treatment termination . Responders were defined by the alleviation of one or more symptoms by at least three points . Results The two treatment groups were similar in terms of baseline characteristics , such as age , duration of diabetes , neurological symptoms scores and neurological disability scores . The responder rate was significantly higher ( p<0.05 ) in the HF group ( 80 % , 16 out of 20 ) than in the TENS group ( 33 % , seven out of 21 ) . Subgroup analysis revealed that HF was more effective than TENS in relieving the symptoms of non-painful neuropathy ( HF : 100 % , seven out of seven ; TENS : 44 % , four out of nine ; p<0.05 ) and painful neuropathy ( HF : 69 % , nine out of 13 ; TENS : 25 % , three out of 12 ; p<0.05 ) . The responders did not differ in terms of the reduction in mean symptom intensity during the trial . Conclusions /interpretationThis pilot study shows , for the first time , that HF can ameliorate the discomfort and pain associated with DSP , and suggests that HF is more effective than TENS . External muscle stimulation offers a new therapeutic option for DSP OBJECTIVE To compare therapeutic effects of electroacupuncture and TENS on senile radical sciatica . METHODS One hundred and thirty-nine cases were r and omly divided into 2 groups , electroacupuncture group ( n=70 ) and TENS group ( n=69 ) . The electroacupuncture group was treated with electroacupuncture at main points Qihaishu ( BL 24 ) , Dachangshu ( BL 25 ) , Guanyuanshu ( BL 26 ) , etc . and the TENS group was treated with skin electrode sticking at the pressure pain point of the nerve trunk which was connected with pulse current . Their therapeutic effects were observed and compared . RESULTS At the end of the first course , the cured rate was 41.4 % in the electroacupuncture group and 29.0 % in the TENS group with a significant difference between the two groups ( P < 0.05 ) , and at the end of second course , their cured rates were 80.0 % and 44.9 % , respectively , with a very significant difference between the two groups ( P < 0.005 ) . CONCLUSION The therapeutic effect of electroacupuncture on senile radical sciatica is significantly better than TENS & NA ; This study evaluated the effects of varying frequency , intensity and stimulation site , of transcutaneous electrical nerve stimulation ( TENS ) in an experimental model of pain . In a double‐blind design 240 volunteers were r and omised to one of six experimental TENS groups , a sham TENS or control ( n=30 per group ; gender balanced ) . Two TENS frequencies ( 110 or 4 Hz ) and two intensities ( strong but comfortable or highest tolerable ) at a fixed pulse duration ( 200 & mgr;s ) were applied at three sites relative to the measurement site ( segmentally , extrasegmentally or a combination of these ) , for 30 min . Pressure pain thresholds ( PPT ) were measured using a pressure algometer , in the first dorsal interosseous muscle , every 10 min , during stimulation and for a further 30 min . The high frequency , high intensity segmental , and combined stimulation groups , showed rapid onset and significant hypoalgesic effects . This effect was sustained for 20 min post‐stimulation in the high frequency segmental group . All other TENS intervention groups showed hypoalgesic responses similar to the sham TENS group , and none of these groups reached a clinical ly significant hypoalgesic level . Conclusions : The role of TENS frequency , intensity and site are pivotal to achieving optimal hypoalgesic effects , during and after stimulation . Clinical applications of these parameter combinations require further investigations A prospect i ve phase 2 study was conducted to evaluate the clinical utility of acupuncture-like transcutaneous nerve stimulation ( ALTENS ) for the treatment of chemotherapy-induced peripheral neuropathy ( CIPN ) . Eligible cancer patients had a < 2 ECOG performance score , received neurotoxic chemotherapy , and developed CIPN symptoms for > two months . R and omization was used to eliminate bias in patient selection for ALTENS and was not to compare the effectiveness between the two treatments . ALTENS treatments were delivered using Codetron units . Bilateral acupuncture points included LI4 and LIV3 , plus LI11 or ST36 were stimulated . Acupuncture treatments were administered to CV6 , SP6 , ST6 , LI11 , Bafeng , Baxie and selective Jing points bilaterally . Twelve treatments were delivered twice weekly over 6 to 8 weeks . The Modified Total Neuropathy Score ( mTNS ) , Numbness Score , and Edmonton Symptom Assessment Score ( ESAS ) were assessed at baseline , treatment completion , plus at 3 and 6 months follow-up . The primary study endpoint was mTNS score at 6 months . We planned to recruit 23 patients into each group . After 30 patients were recruited , 2 were lost to follow-up at 3 months in the ALTENS group and 3 in the acupuncture group . The research team decided to recruit all remaining consecutive patients only to the ALTENS group to ensure an adequate evaluation of ALTENS , the primary object of evaluation . There were 27 patients in the ALTENS group , with an average symptom duration of 10 months after chemotherapy . Twenty four and 23 patients completed the 3 and 6 month follow-up respectively . The median mTNS scores were 7.1 , 4.0 , 3.6 and 3.1 at baseline , treatment completion , 3 and 6 months follow-up , respectively . One-way ANOVA analysis showed a significant improvement in mTNS scores ( p<0.001 ) at 6 months . Numbness scores were also significantly improved at 6 months . ESAS pain scores and perception of well-being scores analyses were inconclusive . There were no significant reported side effects of ALTENS . There were only 13 patients in the acupuncture group and the number was insufficient for either an independent or a comparative analysis . The results of this study suggests that ALTENS significantly reduces the mTNS scores and numbness in patients suffering from CIPN symptoms OBJECTIVE To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Thirty-one patients with symptoms and signs of peripheral neuropathy were r and omized to the electrotherapy or sham treatment ( control ) group . The electrostimulation was given by a portable unit ( H-Wave machine ) than generated a biphasic , exponentially decaying waveform ( pulse width 4 ms , 25–35 V , ≥ 2 Hz ) . Patients treated each of their lower extremities for 30 min daily for 4 weeks at home . Nine patients from the sham-treatment group participated for a second period , during which all of them received the active electrotherapy . Patient 's degree of pain and discomfort was grade d on a scale of 0 to 5 . RESULTS In the sham-treated group ( n = 13 ) , the neuropathic symptoms improved in five ( 38 % ) patients , and the pain score declined from 2.92 ± 0.13 to 2.38 ± 0.26 ( P < 0.04 ) , suggesting a procedure-related placebo effect . In the electrotherapy group ( n = 18 ) , symptomatic improvement was seen in 15 ( 83 % ) cases , 3 of which were completely asymptomatic ; the pain score declined from 3.17 ± 0.12 to 1.44 ± 0.25 ( P < 0.01 ) and the posttreatment pain scores were considerably lower ( P < 0.03 ) , indicating a substantial treatment effect over and above any placebo influence . Patients in the electrotherapy group reported greater reduction in symptoms ( 52 ± 7 % vs. 27 ± 10 % in control subjects , P < 0.05 ) on an analog scale . Moreover , the electrotherapy decreased pain scores ( from 3.0 ± 0.62 to 1.56 ± 0.32 , P < 0.02 ) in nine patients who had received sham treatment earlier . CONCLUSIONS A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy . This novel modality offers a potential non-pharmacological treatment option A double-blind trial was done using a stimulator and a placebo device on patients who had chronic pain to determine the effectiveness of transcutaneous electrical stimulation in controlling pain . Ninety-three patients were studied , and 83 of these completed the Minnesota Multiphasic Personality Inventory ( MMPI ) . Thirty-three patients had low-back pain and 24 had neuropathies . The stimulator was more effective than the placebo during treatment when used over the center of pain ( P less than .005 ) or over an unrelated nerve trunk ( P less than .01 ) and after treatment over the center of pain ( P less than .05 ) . The stimulator was significantly more effective than the placebo in neuropathies when stimulating over the related nerve trunk ( P less than .005 ) , where the stimulator response was nearly three times better than that of the placebo . The duration of subsequent relief was not significantly different after treatment with the stimulator or with the placebo device . Follow-up showed significant declines in the use and effect of the stimulator with the greatest decline noted by the depressed group Bloodworth DM , Nguyen BN , Garver W , Moss F , Pedroza C , Tran T , Chiou-Tan FY : Comparison of stochastic vs. conventional transcutaneous electrical stimulation for pain modulation in patients with electromyographically documented radiculopathy . Am J Phys Med Rehabil 2004;83:584–591 . Objective : To determine if a transcutaneous electrical stimulation ( TENS ) unit modified to deliver electrical impulses at r and om ( R ) or stochastic frequency , called TENS-R , provided better pain relief than conventional TENS . Design : A prospect i ve , r and omized , double-blinded , placebo-controlled study at an urban teaching hospital . A total of 13 adult subjects with radiculopathy on electromyogram and chronic radicular pain rated pain before and after walking 100 feet with proximal ( axial ) placement of TENS leads with r and omized setting s on conventional TENS , placebo , or TENS-R and , subsequently , with distal ( limb ) placement of TENS leads with r and omized setting s , all on the same day . The pain measures used were the McGill Pain Question naire , parts 1 and 2 , and the Visual Analog Scale . The functional measure was speed of walking . Results : Four men and seven women completed the study pain scores , measured by McGill Pain Question naire part 2 , significantly improved when the patient used TENS-R vs. conventional TENS ( P = 0.006 , analysis of variance ) . Placement of TENS electrodes on the back significantly decreased pain compared with lead placement on the legs for McGill Pain Question naire part 1 ( P = 0.007 ) , McGill Pain Question naire part 2 ( P = 0.042 ) , and the Visual Analog Scale ( P = 0.026 ) measures . Conclusions : Qualitative pain scores significantly improved when the patient used TENS-R vs. conventional TENS . Lead placement of any TENS modality over the back vs. over the leg improved all pain scores UNLABELLED This study compared a new transient sham transcutaneous electrical nerve stimulation ( TENS ) that delivers current for 45 seconds to an inactive sham and active TENS to determine the degree of blinding and influence on pain reduction . Pressure-pain thresholds ( PPT ) , heat-pain thresholds ( HPT ) , and pain intensities to tonic heat and pressure were measured in 69 healthy adults before and after r and omization . Allocation investigators and subjects were asked to identify the treatment administered . The transient sham blinded investigators 100 % of the time and 40 % of subjects compared to the inactive sham that blinded investigators 0 % of the time and 21 % of subjects . Investigators and subjects were blinded only 7 % and 13 % of the time , respectively , with active TENS . Neither placebo treatment result ed in significant changes in PPT , HPT , or pain intensities . Subjects using higher active TENS amplitudes ( > or = 17 mAs ) had significantly higher PPTs and lower pain intensities to tonic pressure than subjects using lower amplitudes ( < 17 mAs ) . HPTs and pain intensities to tonic heat were not significantly changed . The transient TENS completely blinds investigators to treatment and does not reduce pain , thereby providing a true placebo treatment . PERSPECTIVE This article presents the benefits of a new transient sham TENS device for use in prospect i ve , r and omized , clinical trials . This device facilitates blinding of subjects and investigators to eliminate expectation bias and determine the true efficacy of TENS for use in clinical population Abstract We assessed the effectiveness of interferential current ( IFC ) and transcutaneous electrical nerve stimulation ( TENS ) therapies in the management of carpal tunnel syndrome ( CTS ) compared with splint therapy , a st and ard treatment modality for CTS . This was a prospect i ve , single-blinded , single-center , r and omized , three-group parallel intervention study of 3 weeks duration . Efficacy was examined in the third week after the end of treatments . Subjects were assigned r and omly to one of three groups : group I patients received splint therapy , group II patients received TENS applied on the palmar surface of the h and and the carpal tunnel , and group III patients underwent IFC therapy applied on the palmar surface of the h and and the volar surface of the forearm . TENS and ICF treatments were applied five times weekly for a total of 15 sessions . Group 1 patients were stabilized with volar wrist splints for 3 weeks . The efficacy of the therapies was assessed before initiation of therapy and at 3 weeks after completion of therapy using a visual analog scale ( VAS ) , a symptom severity scale , the functional capacity scale of the BCTQ , and measurement of median nerve motor distal latency ( mMDL ) and median sensory nerve conduction velocity ( mSNCV ) . Groups were compared pairwise using the Mann – Whitney U test to identify the source of differences between groups . The Wilcoxon test was used to analyze changes in variables over time within a group . In the VAS , BCTQ , MDL , and mSNCV , no significant difference was observed between the groups ( p > 0.05 ) . In the VAS , BCTQ , and mSNCV , statistically significant improvements were detected in all groups ( p < 0.05 ) . There was no statistically significant difference between TENS and splint therapy with respect to improvement in clinical scores , whereas IFC therapy provided a significantly greater improvement in VAS , mMDL , and mSNCV values than splint therapy ( VAS : 4.80 ± 1.18 and 6.37 ± 1.18 ; p = 0.001 , mMDL : 3.89 ± 0.88 and 4.06 ± 0.61 ; p = 0.001 , mSNCV : 41.80 ± 1.76 and 40.75 ± 1.48 ; p = 0.010 ) . IFC therapy provided a significantly greater improvement in VAS , symptom severity , functional capacity , and mMDL and mSNCV values than TENS therapy ( VAS : 4.80 ± 1.18 and 6.68 ± 1.42 ; p < 0.001 , symptom severity : 2.70 ± 1.03 and 3.37 ± 1.21 ; p = 0.015 , functional capacity : 1.90 ± 1.21 and 2.50 ± 0.78 ; p = 0.039 , mMDL : 3.89 ± 0.88 and 4.06 ± 0.88 ; p = 0.003 , and mSNCV : 41.80 ± 1.76 and 41.38 ± 1.78 ; p = 0.021 ) . IFC may be considered a new and safe therapeutic option for the treatment of CTS Summary Background Post-herpetic neuralgia ( PHN ) is the most common complication of herpes zoster ( HZ ) and is difficult to treat . The role of antiviral agents and nonpharmacologic procedures in preventing PHN is not entirely clear . Recent retrospective study showed that transcutaneous electrical nerve stimulation ( TENS ) may completely prevent PHN . The aim of our study was to identify predictors for PHN and evaluate the treatment with antiviral agents and TENS . Methods We conducted a multicenter prospect i ve , r and omized intervention study in patients with a new onset of HZ . Immunocompromised patients were excluded . Patients were r and omly assigned to four groups ( TENS , Antiviral agents , TENS and Antiviral agents , and Control Group ) . At the inclusion , the following criteria were recorded : age , gender , duration of pain before the onset of the rash , the number of efflorescence , the intensity of pain , and the analgesic prescribed . During the follow-up , we recorded a spontaneous pain sensation , pain intensity , and presence of allodynia , hyperalgesia , or paraesthesia . Results With each additional year of age , the odds for the presence of PHN with unchanged values of other predictors increase ( odds ratio ( OR ) = 1.03 [ 1.01 ; 1.05 ] , p = 0.001 ) . The same is true for the initial intensity of the pain ( OR = 1.25 [ 1.09 ; 1.43 ] , p = 0.002 ) . The odds for acute and subacute herpetic neuralgia are greater than for PHN . The odds for subacute herpetic neuralgia are the lowest in the group treated with TENS ( OR = 0.15 [ 0.05 ; 0.47 ] , p = 0.001 ) . Conclusions PHN can not be completely prevented . TENS as a single therapy was found the most successful among the tested treatments in reducing the incidence of subacute herpetic neuralgia . ZusammenfassungGrundlagenPost-Zoster-Neuralgie ( PZN ) ist die häufigste Komplikation des Herpes Zoster ( HZ ) und ist schwer zu beh and eln . Die Rolle von antiviralen Mitteln und nicht- pharmakologischen Verfahren bei der Verhinderung von PZN ist nicht umfassend geklärt . Eine aktuelle retrospektive Studie hat gezeigt , dass Transkutane Elektrische Nervenstimulation ( TENS ) PZN vollständig verhindern kann . Das Ziel unserer Studie war es , Prädiktoren für PZN zu identifizieren und die Beh and lung mit antiviralen Mitteln und TENS zu bewerten . Method ikWir haben eine multizentrische , prospek-tive r and omisierte Interventions studie bei Patienten mit neuem Auftreten eines HZ durchgeführt . Immunsupprimierte Patienten wurden ausgeschlossen . Die Patienten wurden r and omisiert vier Gruppen ( TENS , antivirale Mittel , TENS und antivirale Mittel , Kontrollgruppe ) zugeordnet . Die Auswertung erfolgte anh and folgender Kriterien : Alter , Geschlecht , Dauer der Schmerzen vor dem Einsetzen des Hautausschlags , die Anzahl von Ausblühungen , die Intensität von Schmerzen und die Anzahl verschriebener schmerzstillender Mittel . Während des Follow-up verzeichneten wir spontane Schmerzempfindungen , Schmerzintensität und das Vorh and ensein von Allodynia , Hyperalgesie oder Parästhesie . ErgebnisseMit jedem Lebensjahr steigen die Chancen für das Vorh and ensein von PZN mit unveränderten Werten and erer Prädiktoren ( OR = 1,03 [ 1,01 ; 1,05 ] , p = 0,001 ) . Das gleiche gilt für die anfängliche Intensität des Schmerzes ( OR = 1,25 [ 1,09 ; 1,43 ] , p = 0,002 ) . Die Chancen für eine akute und subakute Zoster-Neuralgie sind größer als für PZN . Die Chancen für eine subakute Zoster-Neuralgie sind am niedrigsten in der Gruppe , die mit TENS ( OR = 0,15 [ 0,05 ; 0,47 ] , p = 0,001 ) beh and elt wurde . SchlussfolgerungenPZN kann nicht vollständig verhindert werden . TENS als Einzeltherapie ist die erfolgreichste unter den getesteten Beh and lungen bei der Verringerung der Häufigkeit von subakuter Neuralgie Objective : To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation ( TENS ) upon low back pain ( LBP ) in people with multiple sclerosis ( MS ) . Design : A r and omized double-blind placebo controlled clinical pilot study . Subjects and setting : Fifteen people with MS were recruited and r and omly allocated to one of the following groups under double blind conditions ( n = 5 per group ) : TENS 1 ( 4 Hz , 200 µs ) , TENS 2 ( 110 Hz , 200 µs ) , placebo TENS . Interventions : Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up . Outcome measures : The following outcome measures were taken at weeks 1 , 6 , and 10 : visual analogue scale ( VAS ) ( for current LBP , right leg pain , left leg pain ) ; Leeds Multiple Sclerosis Quality of Life Question naire ; Rol and Morris Disability Question naire ; Short Form-36 ( SF-36 ) Version 1 ; and the McGill Pain Question naire ( MPQ ) . VAS for current LBP , right and left leg pain were also taken before and after treatment , and once a week during the follow-up period . Results : Analysis showed no statistically significant effects for any of the data . However , both active treatment groups showed a trend of improvement in the majority of the outcome measures . Conclusion : Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant . Further work in this area is warranted and should include a larger number of participants in the form of a r and omized controlled clinical trial to determine the efficacy of this modality BACKGROUND AND PURPOSE Phantom limb pain ( PLP ) can be disabling for nearly two thirds of amputees . Hence , there is a need to find an effective and inexpensive treatment that can be self administered . Among the non-pharmacological treatment for PLP , transcutaneous electrical nerve stimulation ( TENS ) applied to the contralateral extremity and mirror therapy are two promising options . However , there are no studies to compare the two treatments . The purpose of this study is to evaluate and compare mirror therapy and TENS in the management of PLP in subjects with amputation . METHODS The study was an assessor blinded r and omized controlled trial conducted at Physiotherapy Gymnasium of Physical Medicine and Rehabilitation Department , Christian Medical College , Vellore . Twenty-six subjects with PLP consented to participate . An initial assessment of pain using visual analogue scale ( VAS ) and universal pain score ( UPS ) was performed by a therapist blinded to the treatment given . R and om allocation into Group I-mirror therapy and Group II-TENS was carried out . After 4 days of treatment , pain was re-assessed by the same therapist . The mean difference in Pre and Post values were compared among the groups . The change in pre-post score was analyzed using the paired t test . RESULTS Participants of Group I had significant decrease in pain [ VAS ( p = 0.003 ) and UPS ( p = 0.001 ) ] . Group II also showed a significant reduction in pain [ VAS ( p = 0.003 ) and UPS ( p = 0.002 ) ] . However , no difference was observed between the two groups [ VAS ( p = 0.223 and UPS ( p = 0.956 ) ] . DISCUSSION Both Mirror Therapy and TENS were found to be effective in pain reduction on a short-term basis . However , no difference between the two groups was found . Substantiation with long-term follow-up is essential to find its long-term effectiveness . Copyright © 2015 John Wiley & Sons , This study examined the clinical effectiveness of high-frequency transcutaneous electrical nerve stimulation for reducing hypersensitivity of the h and . Nineteen patients suffering from h and hypersensitivity were r and omly assigned into either a treatment or a placebo group . A visual analogue scale and the Downey H and Centre H and Sensitivity Test were used to measure the tactile tolerance of the h and . Grip strength was assessed by a grip dynamometer . Daily applications of electrical stimulation were provided for 2 weeks . Significantly lower pain scores were found in the treatment group than in the placebo group by Day 7 and Day 11 . The ranking of ten dowel textures of the Downey H and Centre H and Sensitivity Test in the treatment group was significantly higher than in the placebo group by Day 7 and Day 11 . However , no significant intergroup difference was found in grip strength Introduction It is cl aim ed that transcutaneous electrical nerve stimulation ( TENS ) operates via a segmental mechanism by reducing ongoing transmission and sensitization of nociceptive dorsal horn neurons . Hence , TENS electrodes are usually placed at the site of pain . Objective This study compared TENS administered at the site of experimentally induced ischemic pain ( ipsilateral forearm ) with TENS administered at a location not related to pain ( contralateral lower leg ) . Methods Ten healthy , pain free volunteers took part in a cross-over study during which ischemic pain was induced in the nondominant arm using a modified version of submaximal effort tourniquet technique . Pain intensity was taken at 1-minute interval/s for 5 minutes while receiving TENS either at the ipsilateral arm or contralateral leg . Results There were no statistically significant differences in pain intensity or McGill Pain Question naire ratings between TENS given at the arm compared with the leg . Discussion Taken at face value , the findings suggest that TENS effects were nonspecific and that electrode location does not affect outcome . However , this study should be seen as a call for further research rather than a definitive conclusion The present paper evaluates the efficacy of low frequency , high intensity auricular transcutaneous electrical nerve stimulation ( TENS ) for the relief of phantom limb pain . Auricular TENS was compared with a no-stimulation placebo condition using a controlled crossover design in a group of amputees with ( 1 ) phantom limb pain ( Group PLP ) , ( 2 ) nonpainful phantom limb sensations ( Group PLS ) , and ( 3 ) no phantom limb at all ( Group No PL ) . Small , but significant , reductions in the intensity of nonpainful phantom limb sensations were found for Group PLS during the TENS but not the placebo condition . In addition , 10 min after receiving auricular TENS , Group PLP demonstrated a modest , yet statistically significant decrease in pain as measured by the McGill Pain Question naire . Ratings of mood , sleepiness , and anxiety remained virtually unchanged across test occasions and sessions , indicating that the decrease in pain was not mediated by emotional factors . Further placebo-controlled trials of auricular TENS in patients with phantom limb pain are recommended in order to evaluate the importance of electrical stimulation parameters such as pulse width and rate , and to establish the duration of pain relief OBJECTIVES Diabetes is a common health care problem in western countries . Painful diabetic neuropathy ( PDN ) might be one of the consequences of long ongoing diabetes ; it is estimated that approximately 20 % of European diabetic patients suffer from PDN . Transcutaneous electrical nerve stimulation ( TENS ) is often used as additional pain treatment . However , recent studies show inconsistent results . We aim ed to assess the effect of micro-TENS in reducing neuropathic pain in patients with PDN in a placebo-controlled , single-blinded , and r and omized design . DESIGN / SETTING / PATIENTS / OUTCOME MEASURES : 22 diabetic patients have been treated with a micro-TENS therapy and 19 patients have been treated with a placebo therapy . Treatment duration was 4 weeks with three therapeutical setting s per week . St and ardized question naires ( Pain Disability Index [ PDI ] , neuropathic pain score [ NPS ] , Center for Epidemiologic Studies Depression Scale [ CES-D ] ) were used to assess pain intensity , pain disability , as well as quality of life at baseline at the end of the treatment period and 4 weeks after treatment termination . RESULTS Patients with a minimum of 30 % reduction in NPS were defined as therapy responders . After 4 weeks of treatment , 6/21 patients in the verum group vs 10/19 patients in the placebo group responded to therapy . The median PDI score after 4 weeks of treatment showed a reduction of 23 % in the verum vs 25 % in the placebo group . The differences did not reach statistical significance . CONCLUSIONS The pain reduction with the applied transcutaneous electrotherapy regimen is not superior to a placebo treatment Objective Postherpetic neuralgia ( PHN ) is responsible for one of the most common types of neuropathic pain , described as a burning pain that shakes , hits , and tightens and includes allodynia and paresthesia . Aim of the Study To evaluate the efficacy of Pregabalin when used during transcutaneous electric nerve stimulation ( TENS ) in patients with PHN and to analyze any changes in physical activity and sleep quality . Methods Patients aged 50 to 80 years were included in this r and omized study . We enrolled 15 male ( average age 65±8.6 y ) and 15 female patients ( average age 64±8.2 y ) . The male patients had a history of neuropathic pain lasting 15.6±8.8 months whereas the female patients had a history of neuropathic pain lasting about 14.9±8.6 months . We began with 1 week of patient screening followed by a week of Pregabalin titration . Then , we established the dose of Pregabalin for each patient to obtain visual analog scale ( VAS ) of less than 60 mm . The eligible patients were r and omly divided into 2 groups receiving Pregabalin + TENS or Pregabalin+TENS placebo for the following 4 weeks . Patients underwent 8 outpatient visits during which they completed VAS , SF-McGill Pain Question naire , and sleep interference question naire . Results The result ing data showed that Pregabalin administration associated with TENS reduced pain in patients with PHN . At the end of the treatment , all the observed groups presented a reduction of mean VAS . The group treated with Pregabalin 300 (P300)+TENS had a reduction of pain of 30 % and the group treated with Pregabalin 600 (P600)+TENS had a reduction of pain of 40 % . The comparison between group P300+TENS versus group P300+TENS placebo showed a statistically significant reduction of VAS ( P300+TENS 25±0.67 vs. P300+TENS placebo 39±1.19 P<0.02 ) . Moreover , the comparison between group P600+TENS versus group P600+TENS placebo has shown a statistically significant reduction of VAS ( P600+TENS 23±0.78 vs. P600+TENS placebo 32±0.81 P<0.02 ) . At the end of the study , all groups showed a statistically significant difference in terms of sleep interference , Short-Form McGill Pain Question naire total score , and Short-Form McGill Pain Question naire Present Pain Intensity . Conclusions These data support the conclusion that Pregabalin gives better results when combined with TENS therapy , which is an analgesic nonpharmacologic procedure . Therefore , a multidisciplinary treatment should be considered for this kind of pain In a double blind , r and omised study , 19 patients suffering from mild-to-moderate symptomatic diabetic neuropathy ( Total Symptom Score , NTSS 4 - 16 ) received either treatment with the new transcutaneous electrical nerve stimulation ( TENS ) device " Salutaris " ( verum group ) or a placebo treatment with an identical but electrically inactive device ( placebo group ) . Stimulation pads were placed at the anatomical localisation of the peroneal nerve and stimulation was performed using a low frequency mode . At baseline ( V1 ) , after 6 ( V2 ) , and 12 ( V3 ) wk of treatment , the patients ' symptoms were registered using the new total symptom score ( NTSS-6 ) and a visual analogue scale ( VAS ) . In addition , sensory nerve thresholds ( temperature , vibration , pain ) and microvascular function were measured at the lower limb at baseline and after 12 wk of treatment . Active TENS-treatment result ed in a significant improvement in NTSS-6 score after 6 wk ( -42 % ) and after 12 wk ( -32 % ) of treatment ( baseline : 10.0+/-3.3 , 6 wk : 5.8+/-5.0 , p<0.05 ; 12 wk : 6.8+/-3.9 , p=0.05 ; placebo group : baseline : 7.6+/-3.1 ; 6 wk : 8.1+/-5.1 , n.s . ; 12 wk : 6.5+/-6.1 , n.s . ) . Sub analysis of the different qualities of the NTSS-score revealed an improvement in numbness ( 2.2+/-1.0 to 1.6+/-1.3 ; p<0.03 ) ; lancinating pain ( 1.6+/-1.1 to 0.6+/-0.9 ; p<0.02 ) and allodynia ( 1.4+/-1.6 to 0.5+/-1.0 ; p<0.05 ) . Also , a significant improvement in the VAS rating was found after 6 wk of TENS therapy ( 19.8+/-5.0 to 14.4+/-9.6 ; p<0.05 ) , while no change was observed in the placebo arm . In conclusion , our study indicates that the new TENS device " Salutaris " is a convenient , non-pharmacological option for primary or adjuvant treatment of painful diabetic neuropathy Objective This study was design ed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation ( TENS ) on chronic low-back pain ( LBP ) in a multiple sclerosis ( MS ) population . Methods Ninety participants with probable or definite MS ( aged 21 to 78 y ) presenting with chronic LBP were recruited and r and omized into 3 groups ( n=30 per group ) : ( 1 ) low-frequency TENS group ( 4 Hz , 200 μs ) ; ( 2 ) high-frequency TENS group ( 110 Hz , 200 μs ) ; and ( 3 ) placebo TENS . Participants self-applied TENS for 45 minutes , a minimum of twice daily , for 6 weeks . Outcome measures were recorded at weeks 1 , 6 , 10 , and 32 . Primary outcome measures included : Visual Analog Scale for average LBP and the McGill Pain Question naire . Secondary outcome measures included : Visual Analog Scale for worst and weekly LBP , back and leg spasm ; Rol and Morris Disability Question naire ; Barthel Index ; Rivermead Mobility Index ; Multiple Sclerosis Quality of Life-54 Instrument , and a daily logbook . Data were analyzed blind using parametric and nonparametric tests , as appropriate . Results Results indicated a statistically significant interactive effect between groups for average LBP ( P=0.008 ) ; 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied ( P>0.05 ) . However , clinical ly important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods . Discussion Although not statistically significant , the observed effects may have implication s for the clinical prescription and the use of TENS within this population In two groups of 30 patients pain relief due to transcutaneous nerve stimulation was compared with a placebo , under similar external conditions . The two groups were approximately similar in age , sex , and the origin of pain . Only patients with continuous pain of the limbs or trunk were included in the investigation . There was no statistically significant difference in the success rate of the two groups INTRODUCTION It is estimated that about 80 % of the general population occasionally experience spinal pain , with as many as 50 % reporting pain in the cervical spine . The aim of this study was to determine the effectiveness of treatment of cervical spine pain with the Saunders traction device and transcutaneous electrical nerve stimulation ( TENS ) by assessing their impact on the cervical spine range of motion in the sagittal , coronal and horizontal planes . MATERIAL AND METHODS A total of 39 patients aged 26 to 62 years took part in the study . All patients reported chronic cervical spine pain caused by overload and postural insufficiency . The participants were r and omly divided into three experimental groups . The first group was treated with Saunders traction where the traction force was administered so that the patient would experience noticeable but painless traction . The second group received traction as well as classic transcutaneous electrical nerve stimulation , whereas the third group received only TENS . Each patient attended 10 treatment sessions not more than three days apart . Measurements of the range of motion were performed with the CROM instrument before and after the first session , after the fifth and tenth session and about three weeks after completion of rehabilitation . RESULTS The study revealed the greatest ROM improvement in the coronal and horizontal planes and for the extension motion . CONCLUSIONS The best therapeutic effect was obtained by combining traction with transcutaneous electrical nerve stimulation OBJECTIVE To evaluate the efficacy of combining electrotherapy with amitriptyline for the management of chronic painful peripheral neuropathy in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Patients ( n = 26 ) with peripheral neuropathy were treated with amitriptyline . After 4 weeks , those patients ( n = 23 ) who failed to respond to amitriptyline or who only had partial relief were r and omized between a sham treatment group ( control ) or an electrotherapy group . Transcutaneous electrotherapy was given for 12 weeks by a portable unit ( H-wave machine ) that generated a biphasic exponentially decaying waveform ( pulse width 4 ms , 25–35 V , ≥ 2 Hz ) . The degree of pain and discomfort was grade d on a scale of 0–5 . An analog scale was used to record the overall change in symptoms . RESULTS Amitriptyline produced some degree of symptomatic relief in 15 ( 60 % ) of the 26 patients by the 4th week ; pain scores decreased from 3.8 ± 0.1 to 2.9 ± 0.2 ( P < 0.1 ) and the overall reduction in pain was 26 ± 5 % on an analog scale . In the amitriptyline plus sham treatment group ( n = 9 ) , pain scores declined from 2.8 ± 0.3 to 1.9 ± 0.5 ( P < 0.03 ) and the overall reduction in pain was 55 ± 12 % , suggesting a procedure-related placebo effect . In the group receiving combined electrotherapy and amitriptyline ( n = 14 ) , symptomatic improvement occurred in 12 ( 85 % ) patients . Five ( 36 % ) of the patients in this group became asymptomatic . Pain scores declined from 3.2 ± 0.2 to 1.4 ± 0.4 ( P < 0.01 ) and the overall reduction in pain was 66 ± 10 % . The degree of reduction in pain scores and the incremental relief ( above the amitriptyline effect ) were significantly greater ( P < 0.03 ) with electrotherapy as compared with sham treatment . The outcomes indicate a substantial beneficial effect of electrotherapy over and above any placebo influence . CONCLUSIONS Our clinical observations suggest that transcutaneous electrotherapy is effective in reducing the pain associated with peripheral neuropathy . This form of therapy may be a useful adjunctive modality when it is combined with a pharmacological agent , such as amitriptyline , to augment symptomatic relief OBJECTIVE To see the efficacy of Transcutaneous Electrical Nerve Stimulation therapy and its different modes in trigeminal neuralgia , refractory or partially responsive to drug therapy and to find out the comparative effectiveness of different modes of TENS therapy in these cases . METHODS This was a prospect i ve analytical study , conducted at Rabia Moon Institute of Neurological Sciences over a period of one year . Thirty one patients diagnosed as suffering from trigeminal neuralgia according to International Headache Society Criteria , either Classic Trigeminal Neuralgia ( CTN ) or Symptomatic Trigeminal Neuralgia ( STN ) were r and omly subjected to two different modes of Transcutaneous Electrical Nerve Stimulation ( TENS ) therapy . Severity of pain was assessed on visual analogue scale prior to treatment and fifteen days after therapy and results were than compared . RESULTS Out of 31 patients , 20 females and 11 males , with a mean age of 50.1 + /- 11 years , 26 ( 83.7 % ) improved significantly with application of TENS , only 5 ( 16.3 % ) patients remained unresponsive to this form of therapy . Study also showed a better efficacy of constant mode of therapy over burst mode . CONCLUSION Transcutaneous electrical nerve stimulation is an effective , easy to use therapy with minimal side effects in patients suffering from trigeminal neuralgia not responding to conventional treatment . Constant mode of this therapy was a slightly better option than burst mode therapy Abstract Low back pain is one of the most significant medical and socioeconomic problems in modern society . International guidelines call for evidence -based management for the pain and disability associated with musculoskeletal disorders . The purpose of this r and omized controlled trial is to address the question of efficacy and appropriateness of vertebral axial decompression ( VAX-D ) therapy , a new technology that has been shown in clinical research to create negative intradiscal pressures , and has been shown to be effective in treating patients presenting with chronic low back pain ( > 3 months duration ) with associated leg pain . Successful outcome was defined as a 50 % reduction in pain utilizing a 10 cm Visual Analog Pain Scale and an improvement in the level of functioning as measured by patient-nominated disability ratings . Patients were r and omly assigned to VAX-D or to TENS which was used as a control treatment or placebo . The TENS treatment demonstrated a success rate of 0 % , while VAX-D demonstrated a success rate of 68.4 % ( p < 0.001 ) . A statistically significant reduction in pain and improvement in functional outcome was obtained in patients with chronic low back pain treated with VAX-D. [ Neurol Res 2001 ; 23 : 780 - 784 & NA ; Transcutaneous electrical nerve stimulation ( TENS ) is an easy to use non‐invasive analgesic intervention applied for diverse pain states . However , effects in man are still inconclusive , especially for chronic pain . Therefore , to explore the factors predicting result of TENS treatment in chronic pain we conducted a prospect i ve , r and omized , placebo‐controlled trial ( n = 163 ) , comparing high frequency TENS ( n = 81 ) with sham TENS ( n = 82 ) . Patients ’ satisfaction ( willingness to continue treatment ; yes or no ) and pain intensity ( VAS ) were used as outcome measures . The origin of pain and cognitive coping strategies were evaluated as possible predictors for result of TENS treatment . Results : Fifty‐eight percent of the patients in the TENS group and 42.7 % of the sham‐TENS group were satisfied with treatment result ( chi square = 3.8 , p = 0.05 ) . No differences were found for pain intensity . Patients diagnosed with osteoarthritis and related disorders ( especially of the vertebral column ) or peripheral neuropathic pain were less satisfied with high frequency TENS ( OR = 0.12 ( 95 % CI 0.04–0.43 ) and 0.06 ( 95 % CI 0.006–0.67 ) , respectively ) . Injury of bone and soft tissue ( especially postsurgical pain disorder ) provided the best results . Treatment modality or interactions with treatment modality did not predict intensity of pain as a result of treatment . We conclude , that predicting the effect of high frequency TENS in chronic pain depends on the choice of outcome measure . Predicting patients ’ satisfaction with treatment result is related to the origin of pain . Predicting pain intensity reflects mechanisms of pain behavior and perceived control of pain , independent of treatment modality . Pain catastrophizing did not predict TENS treatment outcome Postherpetic neuralgia remains a therapeutic challenge for the clinician . Many modalities have been utilized with limited success . In this pilot r and omized study of patients who were refractory to previous medicinal treatment , the patients were treated with transcutaneous nerve stimulation with a biofeedback capability . After every two treatments with the sham and true device , the patients were required to fill out a st and ard neuropathic pain scale score . The patients were allowed to select the other device after three consecutive treatments if they felt an inadequate decrease in their pain . The true device was chosen over the sham device by all patients . The majority of these patients treated by the true device reported a statistically significant decrease in pain scores ( P < 0.001 ) . Further investigation of this Food and Drug Administration , class 2 accepted , electronic device for relief of pain is warranted for patients with a history of recalcitrant postherpetic neuralgia Objective The aim of this study was to evaluate the relative efficacy of nortriptyline and self-applied transcutaneous electrical nerve stimulation ( TENS ) in the treatment of pain and /or sensory complaints of the upper extremities in people with multiple sclerosis ( MS ) . Methods A r and omized clinical trial conducted from September 2005 to September 2006 . Fifty-nine people with clinical ly definite MS aged 15 to 50 years were r and omly allocated to receive an 8-week treatment course of either nortriptyline ( 10 mg daily increment over 1 week to 50 mg ) or self-applied TENS . Response to treatment was assessed at 2 , 4 , and 8 weeks after commencement of the intervention . Results TENS seemed to be equivalent in efficacy to nortriptyline . A significant decrease in visual analog scale scores of pain and /or sensory complaints of the upper extremities occurred in both groups . Of the 29 people treated with TENS , the mean ( SD ) intensity of pain and /or sensory complaints decreased from 5.3 ( 1.6 ) at baseline to 2.8 ( 1.5 ) at 8 weeks follow-up ( P<0.001 ) . Correspondingly in the 30 people treated with nortriptyline , the mean ( SD ) intensity of pain and /or sensory complaints decreased from 4.9 ( 1.9 ) to 3.3 ( 2.1 ) ( P<0.001 ) . The mean difference in visual analog scale score at 8 weeks follow-up was not significant between the 2 groups ( mean difference −0.5 ; 95 % confidence interval , −1.5 - 0.5 ) . Discussion This study demonstrates that both nortriptyline and TENS can be effective in reducing the intensity of pain and /or sensory complaints in the upper extremities of people with MS . However given the side-effect profile of nortriptyline , TENS may have some benefits over nortriptyline . This modest reduction in the intensity of pain and /or sensory complaints suggests that physicians should carefully weigh the risk and benefits of nortriptyline and TENS in people with MS with pain and /or sensory complaints UNLABELLED Evidence from recent animal studies indicates that the analgesic effect of low-frequency transcutaneous electrical nerve stimulation ( TENS ) is reduced in opioid-tolerant animals . The aim of the present study was to compare the analgesic effect of conventional ( high frequency ) and acupuncture-like ( low frequency ) TENS between a group of opioid-treated patients and a group of opioid-naive patients in order to determine if this cross-tolerance effect is also present in humans . Twenty-three chronic pain patients ( 11 who took opioids and 12 who did not ) participated in the study . Participants were assigned in a r and omized crossover design to receive alternately conventional and acupuncture-like TENS . There was a significant reduction in pain during and after conventional TENS when compared to baseline for both the opioid and nonopioid group ( P < .01 ) . For acupuncture-like TENS however , the analgesic effect of TENS was only observed in the nonopioid group ( P < .01 ) , with opioid-treated patients showing no change in pain scores during and after TENS when compared to baseline ( P > .09 ) . The reduced analgesic effect of acupuncture-like TENS in opioid-treated patients is coherent with previous animal studies and suggests that conventional TENS should be preferred in patients taking opioids on a regular basis . PERSPECTIVE This study shows that patients taking opioids on a regular basis are less susceptible to benefit from acupuncture-like TENS . This phenomenon is probably attributable to the fact that the analgesia induced by acupuncture-like TENS and opioids are mediated by the same receptors ( ie , μ opioid receptors ) |
11,307 | 24,249,145 | Despite the limited evidence for their effectiveness , GC are frequently prescribed in SSc patients , mostly in those with the diffuse subset . | Glucocorticoids ( GC ) represent a mainstay in the therapeutical strategies of many autoimmune diseases , but their role in systemic sclerosis ( SSc ) is controversial .
The main objective of this review is to assess the extent of and the factors associated with GC use in SSc patients , taking into account data from cohort studies and registries . | Abstract : Until recently , renal crisis was the most significant cause of morbidity and mortality in patients with scleroderma ( SSc ) . Nowadays , following the introduction of angiotensin-converting enzyme inhibitors used in renovascular hypertension , pulmonary fibrosis and pulmonary hypertension have become the most common causes of death in SSc . Consequently , the early diagnosis and treatment of pulmonary fibrosis is essential to improve morbidity and mortality in SSc patients . The aim of this study was to investigate the effect of intravenous cyclophoshamide pulse therapy in patients with SSc and evidence of active alveolitis assessed on a high resolution computed tomographic ( H RCT ) scan , and to compare the effect of cyclophosphamide pulse therapy with oral therapy . Sixteen consecutive patients with SSc were allocated alternately to the two treatment groups . Eight patients were treated with monthly cyclophoshamide pulse therapy ( 750 mg/m2 ) for 12 months ; the other eight patients were treated with oral cyclophosphamide ( 2–2.5 mg/kg/day ) for the same period . All patients received concurrently prednisone ( 10 mg/day ) . Pulmonary function tests and H RCT scans were performed before therapy and at 6 and 12 months . In the oral cyclophosphamide group , three patients with a grade I pattern showed regression of disease extent . In the other five patients ( one with grade II and four with grade III ) the pattern and extent of disease remained stable during the study . No statistical differences were found in forced expiratory volume in 1 s , forced vital capacity and total lung capacity during the study period . The diffusing capacity for carbon monoxide increased significantly between baseline and 12 months ( p= 0.043 ) . In the cyclophosphamide pulse therapy group , seven patients with a grade I pattern showed regression of disease extent at 6 months ( p= 0.018 ) and 12 months ( p= 0.012 ) . One patient with grade III remained stable during the study . In both groups the regression of the extent of disease estimated on H RCT was due to a decrease in the ground glass appearance . The extent of the reticular appearance remained stable throughout the study . Our results indicate that cyclophosphamide pulse therapy is effective in suppressing active alveolitis ( ground glass appearance ) . Although in this study it is not possible to compare pulse therapy with oral therapy because of the different pattern seen on H RCT between the two groups , it seems that oral therapy is also effective in suppressing active alveolitis . Neither regimen improved pulmonary involvement when the reticular appearance predominated over the ground glass appearance on H RCT . It is concluded that either pulse or oral cyclophosphamide therapy may improve the outcome of SSc patients Interstitial lung disease ( ILD ) is a noteworthy condition in the treatment of systemic sclerosis ( SSc ) because of its associated mortality and morbidity ; however , the efficacy of various treatments for ILD has been controversial in previous reports . In this study , we examined the efficacy and safety of intravenous cyclophosphamide ( IVCY ) pulse therapy with prednisolone ( PSL ) for the treatment of ILD with SSc . A total of 121 patients with SSc were screened and evaluated for ILD , using high-resolution computed tomography of the chest , pulmonary function testing , and bronchoalveolar lavage . Thirteen patients with active ILD were enrolled in this study . The treatment protocol for ILD was 0.4 g/m2 of body surface area of IVCY monthly plus 0.8 mg/kg of body weight of PSL daily . Two to six doses of IVCY were administered , depending on the remission of ILD . Initial PSL doses were maintained for a month and then gradually tapered to 10 mg daily . An activity index of ILD showed improvements in all patients in the 12 months after the initial intervention ; however , four patients experienced recurrence of ILD after 24 months , and one additional patient had recurrence of ILD after 36 months . Seven patients reached the 48-month point with no recurrence of ILD . This long observational study for 48 months showed the efficacy of IVCY with PSL for active alveolitis in the first year . However , because five patients had recurrence of ILD more than 1 year after the treatment , it would be necessary to consider maintenance therapy for ILD beyond 1 year OBJECTIVE To evaluate the safety and efficacy of monthly intravenous pulses of cyclophosphamide ( CP ) in combination with low or high doses of prednisolone in patients with systemic sclerosis ( SSc ) related interstitial lung disease ( ILD ) with FVC < 70 % of predicted . METHODS An open label , non-parallel arm study , performed in the rheumatology outpatient clinic of a university hospital . Twenty-eight patients with SSc related ILD were evaluated . Endpoint evaluations included the evolution of high resolution computed tomography , pulmonary function tests , skin involvement and dyspnea over 12 months . Patients were treated with monthly IV CP in combination with prednisolone at low ( < 10 mg/day ; n = 12 ) or high doses ( 1 mg/kg/day for 4 weeks , then reducing the prednisolone by 5 mg/day on alternating days each 2 weeks ; n = 16 ) . RESULTS In the low dose steroid group , no improvement was seen for any endpoint at 6 and 12 months of followup . In the high dose steroid group , at 12 months there was significant improvement in the percentage of " ground glass " parenchymal lung involvement ( -5.7 % ; p = 0.003 ) , as well as in the percentage of predicted FVC ( 12.4 % ; p < 0.001 ) , the percentage of predicted DLCO ( 7.3 % ; p = 0.029 ) , the percentage of skin involvement ( -5.4 % ; p = 0.01 ) , and the severity of dyspnea ( p = 0.012 ) . Substantial improvement was seen as early as 6 months . One patient ( low dose group ) died from ILD . CONCLUSION A combination of IV pulse CP with high doses of prednisolone shows promising efficacy in improving the clinical , physiological , and radiological evolution of SSc related ILD with reversal of the underlying alveolitis Lung involvement constitutes nowadays the major cause of morbidity and mortality in scleroderma patients . Pulmonary fibrosis in systemic sclerosis ( SSc ) is thought to be the consequence of interstitial inflammation . Early diagnosis and treatment of active alveolitis is essential to prevent the deterioration of pulmonary function , improving outcome in SSc patients . The aim of the study was to investigate the effect of 1-year treatment with oral cyclophosphamide ( CYC ) on the evolution of interstitial lung disease in scleroderma patients with a diagnosis of active alveolitis . An open-label one-arm monocenteric study was conducted on 33 scleroderma patients with active alveolitis — defined as the presence of areas of ‘ ground-glass attenuation ’ on high-resolution computed tomography and a recent deterioration in lung function — treated with oral CYC 2 mg kg−1 day−1 for 1 year and medium-low dose steroids ( prednisone 25 mg for 3 months and then tapered to 5 mg/day ) . Results showed that diffusing capacity for carbon monoxide ( DLco ) values remained stable after 6 months of treatment and significantly increased after 12 months ( 2.06±1.38 , 2.21±1.62 and 2.39±1.64 mmol/min/kPa , at baseline/6/12 months , respectively ; p<0.001 12th month vs baseline ) vital capacity ( VC ) values slightly increased ( i.e. stabilised ) in the same time frame ( 2.46±0.71 , 2.41±0.76 and 2.56±0.75 l ) . Accordingly , the vast majority of our patients ( n=29 , 87.9 % ) presented a DLco and /or a VC improvement or stabilisation with respect to baseline . Favourable results were more likely to be observed in patients with a lower Wells ’ radiological grade ( grade I ) . In 25 patients followed up for further 12 months after the interruption of therapy , VC and DLco remained stable . Thus , long-term therapy with oral CYC is effective in ameliorating and /or stabilising lung function in scleroderma patients with active alveolitis , with beneficial effects lasting up to 1 year after interruption . The higher efficacy in those patients with an early pulmonary disease stage and a lower radiological grade underlies the importance of an early diagnosis and intervention Thirty-five patients with diffuse systemic sclerosis were studied in a r and omized , placebo-controlled , double-blind study . Seventeen patients received intravenous dexamethasone “ pulse ” therapy , while 18 patients received placebo . Each “ pulse ” consisted of 100 mg dexamethasone in 250 ml 5 % dextrose infused intravenously over 1 h. Pulse therapy was repeated every month for 6 months . Assessment of disease status with various parameters was done at entry and at completion of trial , i.e. after 6 months . Significant improvement in skin involvement was seen in the study group , with the total skin score ( TSS ) decreasing from 28.5±12.2 to 25.8±12.8 , while in the control group , TSS increased from 30.6±13.2 to 34.7±10 . Similarly , significant improvement was noted in the flexion index . Other parametres that included extension index , maximum oral opening , range of movement of joints , functional disability score , Raynaud 's phenomenon ( frequency and duration ) , ESR , proteinuria , chest X-ray , ECG , lung function tests , barium swallow and antinuclear antibody were unchanged . Adverse effects of therapy were limited to an increased incidence of minor chest infections . It is concluded that intravenous pulse dexamethasone may be useful in the treatment of diffuse systemic sclerosis OBJECTIVE The lack of r and omized controlled trials ( RCTs ) in pulmonary fibrosis in systemic sclerosis ( SSc ) has hampered an evidence -based approach to treatment . This RCT was undertaken to investigate the effects of intravenous ( IV ) cyclophosphamide ( CYC ) followed by azathioprine ( AZA ) treatment in pulmonary fibrosis in SSc . METHODS Forty-five patients were r and omized to receive low-dose prednisolone and 6 infusions ( monthly ) of CYC followed by oral AZA , or placebo . Primary outcome measures were change in percent predicted forced vital capacity ( FVC ) and change in single-breath diffusing capacity for carbon monoxide ( DLCO ) . Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores . An intent-to-treat statistical analysis was performed . RESULTS At baseline , there were no significant group differences in factors linked to outcome , including severity of pulmonary fibrosis and autoantibody status . Sixty-two percent of the patients completed the first year of treatment . Withdrawals included 9 patients ( 6 from the placebo group ) with significant decline in lung function , 2 with treatment side effects ( both from the active treatment group ) , and 6 with non-trial-related comorbidity . No hemorrhagic cystitis or bone marrow suppression was observed . Estimation of the relative treatment effect ( active treatment versus placebo ) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19 % ; this between-group difference showed a trend toward statistical significance ( P = 0.08 ) . No improvements in DLCO or secondary outcome measures were identified . CONCLUSION This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo . However , for FVC there was a trend toward statistical significance between the 2 groups . This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease . Therapy was well tolerated with no increase in serious adverse events Objective : Interstitial lung disease ( ILD ) frequently complicates systemic sclerosis ( SSc ) . Cyclophosphamide ( CYC ) is a promising immunosuppressive therapy for SSc-related ILD . Our objective was to investigate the effectiveness of an intravenous CYC ( iv CYC ) pulse regime in SSc-related ILD during treatment and thereafter . Methods : In a prospect i ve observational study ten consecutive patients with SSc-related ILD were treated with iv CYC in a pulse regime lasting from 6 to 24 months . Clinical status , pulmonary functional testing ( PFT ) and high resolution computed tomography ( H RCT ) of the chest were evaluated at enrolment and 6 , 12 and 24 months thereafter . After treatment withdrawal , patients were followed up every 6 months with PFT and chest H RCT to monitor lung disease . Results : Clinical improvement was apparent in 8 out of 10 patients . The median values of forced vital capacity ( FVC ) , forced expiratory volume in the first second ( FEV1 ) and diffusion lung capacity for carbon monoxide ( DLCO ) as well as ground-glass pattern on H RCT did not change significantly after 6 , 12 and 24 months of therapy . The follow-up continued in 8 out of 10 patients after treatment withdrawal for a median of 26.5 months ( range : 12 - 48 months ) . The final median FVC was 54.5 % of predicted value ( interquartile range , IQR= 31.6%-94 % ) . Only one patient suffered a FVC deterioration greater than 10 % , even though less than 160 ml . The final median DLCO was 68 % of predicted value ( IQR=38.3 - 83.6 % ) . Only 2 patients who developed pulmonary arterial hypertension deteriorated their DLCO values of more than 15 % . Conclusions : An iv CYC pulse regimen over 24 months may stabilize pulmonary activity in patients with SSc-related ILD during the course of treatment and for a median of 26.5 months thereafter BACKGROUND & AIM Disease-related malnutrition is known to negatively affect clinical outcomes . The aim of the present study was to evaluate the prevalence of malnutrition in a cohort of out patients affected by Systemic Sclerosis ( SSc ) and its association with clinical variables . METHODS One hundred sixty SSc patients were consecutively evaluated . The following clinical variables were assessed : disease duration , activity and severity , treatments , functional status , gastrointestinal involvement . Nutritional assessment included : body mass index ( BMI ) , weight loss ( WL ) history , nutritional intakes and serum prealbumin . Malnutrition was defined as BMI < 20 kg/m² and /or previous 6-month WL ≥ 10 % . RESULTS Prevalence of malnutrition was 15 % ( 10 - 21 % ) . Logistic regression showed that malnutrition was independently associated with disease activity ( OR 3.72 ; p < 0.001 ) and low serum prealbumin ( OR 8.58 ; p < 0.001 ) . The association with gastrointestinal involvement was not statistically significant , although a trend was detected ( OR 1.88 ) . CONCLUSION Malnutrition is common in SSc out patients . It appears associated with disease activity and not influenced by nutritional intakes ; gastrointestinal involvement might contribute to its development over time . Serum prealbumin could be an early marker of malnutrition in SSc , whose role should be confirmed by further longitudinal investigations . Prospect i ve studies are also required to clarify the clinical significance of the association between malnutrition and disease activity in SSc Current therapeutic modalities for the treatment of systemic sclerosis ( SSc ) have significant limitations . The window of opportunity to prevent tissue fibrosis and irreversible damage occurs during the early inflammatory phase of this condition . A drug that we believe has promise to exert a desired effect in early SSc is cyclophosphamide ( CYC ) . However , there are only a few published reports regarding the use of cytotoxic immunosuppressive medications at the onset of the illness . The goal of this study was to test the efficacy and toxicity of CYC in patients with early diffuse SSc . The study design was a r and omized , unblinded , 18 months per patient trial with a comparison group that received azathioprine ( AZ ) . Thirty patients were assigned to receive oral CYC ( 2 mg/ kg daily for 12 months and then maintained on 1 mg/kg daily ) and 30 patients were assigned to receive oral AZ ( 2.5 mg/kg daily for 12 months and then maintained on 2 mg/kg daily ) . During first 6 months of the trial , the patients also received prednisolone , which was started at a dosage of 15 mg daily and tapered to zero by the end of the sixth month . After treatment there was a statistically significant improvement in the modified Rodnan skin score ( MRSS ) , attack frequency of Raynaud ’s phenomenon ( RP ) , and erythrocyte sedimentation rate ( ESR ) in the CYC-group , but not in the AZ-group . The forced vital capacity ( FVC ) and carbon monoxide diffusing capacity ( DLCO ) did not change after treatment in the CYC-group , but statistically significantly worsened in the AZ-group . No life-threatening or irreversible adverse reactions were observed in either group . This study showed that CYC is a promising disease modifying medication for SSc as it exhibited a positive influence on the evolution of disease Objective : To investigate the efficacy of a treatment with low‐dose intravenous cyclophosphamide ( CYC ) and low‐dose prednisone in early diffuse cutaneous systemic sclerosis ( dcSSc ) . Methods : Patients with dcSSc and a disease duration < 24 months consecutively admitted to a tertiary centre underwent a prospect i ve 1‐year study . They were treated with i.v . CYC 500 mg/pulses , 10 mg prednisone equivalent , and supportive therapy . Modified Rodnan skin score ( mRss ) , Health Assessment Question naire – Disability Index ( HAQ‐DI ) , forced vital capacity ( FVC ) , and diffusing lung capacity for CO ( DLCO ) were assessed as outcome measures . In addition , the nine Medsger severity scale scores were evaluated . Results : mRss and DLCO significantly improved at both 6 ( p = 0.002 and 0.012 , respectively ) and 12 months ( p = 0.002 and 0.003 , respectively ) . HAQ‐DI showed a nearly significant reduction at 12 months ( p = 0.06 ) . Medsger 's severity scores also improved for general condition ( p = 0.001 ) , peripheral vascular ( p = 0.05 ) , skin ( p = 0.02 ) , joint/tendon ( p = 0.001 ) , muscle ( p = 0.05 ) , and lung ( p = 0.02 ) . No treatment interruption was needed . Conclusions : This preliminary study suggests a role for low‐dose i.v . CYC in the treatment of early dcSSc . Controlled studies are warranted Objectives Systemic sclerosis ( SSc ) is a rare disease requiring multicentre collaboration to reveal comprehensive details of disease-related causes for morbidity and mortality . Methods The European League Against Rheumatism ( EULAR ) Scleroderma Trials and Research ( EUSTAR ) group initiated a data base to prospect ively gather key data of patients with SSc using a minimal essential data set that was reorganised in 2008 introducing new items . Baseline visit data of patients who were registered between 2004 and 2011 were analysed using descriptive statistics . Results In June 2011 , 7655 patients ( 2838 with diffuse cutaneous ( dc ) and 4481 with limited cutaneous ( lc ) SSc who fulfilled the American College of Rheumatology diagnostic criteria had been registered in 174 centres , mainly European . The most prominent hallmarks of disease were Raynaud 's phenomenon ( 96.3 % ) , antinuclear antibodies ( 93.4 % ) and a typical capillaroscopic pattern ( 90.9 % ) . Scleroderma was more common on fingers and h and s than on any other part of the skin . Proton pump inhibitors ( 65.2 % ) , calcium channel blockers ( 52.7 % ) , and corticosteroids ( 45.3 % ) were most often prescribed . Among the immunosuppressant agents , cyclophosphamide was used more often in dcSSc than in lcSSc . Conclusions The EUSTAR data base provides an abundance of information on the true clinical face of SSc that will be helpful in improving the classification of SSc and its subsets and for developing more specific therapeutic recommendations OBJECTIVE This pilot study was aim ed at evaluating the efficacy and safety of a protocol -based treatment strategy combining mycophenolate mofetil ( MMF ) , intravenous ( IV ) methylprednisolone ( MP ) pulses and low-dose glucocorticoids ( GC ) in early systemic sclerosis ( SSc ) patients suffering from either active interstitial lung disease ( ILD ) or extensive skin disease . PATIENTS AND METHODS Sixteen SSc patients were recruited in the study , 9 based on the severity of their skin involvement ( modified Rodnan total skin score [ TSS ] > or= 15 ) and 7 based on the presence of active ILD . Patients received 3 consecutive daily IV MP pulses , followed by 5 additional monthly IV MP pulses . MMF ( 0.5 g bid for one week ; then , 1 g bid ) and low-dose ( 5 - 10 mg/day ) oral prednisolone were prescribed for one year . Patients were assessed at baseline , month 6 and 12 . Statistics were by ANOVA . RESULTS TSS and Health Assessment Question naire significantly improved over time . In ILD patients , the vital capacity , forced expiratory volume in one second and carbon monoxide diffusing capacity significantly improved . Although the difference was not statistically significant , ground glass lesions decreased , based on semi-quantitative planimetry analyses performed on chest high-resolution computerized tomography . Toxicity was low and none of the patients suffered from renal crisis . CONCLUSION The results of this pilot study suggest that the combination of MMF , IV MP and low-dose GC might achieve good clinical , functional and radiological results in patients suffering from severe early SSc INTRODUCTION Interstitial lung disease ( ILD ) as part of systemic sclerosis ( SS ) is a leading cause of morbidity and mortality . OBJECTIVES To evaluate the use of intravenous pulse cyclophosphamide combined with low and high doses of prednisone in the treatment of ILD in SS is equally effective . METHOD An experimental , exploratory and r and omized single-blind clinical trial was conducted at Hermanos Ameijeiras Clinical Surgical Hospital from September 2006 to December 2009 , including 23 patients with SS and ILD . Two treatment schedules were evaluated and r and omly assigned . Group A was composed of 13 patients with a monthly dose of cyclophosphamide ( ev ) for 6 months and a twice-monthly dose for the remaining 6 months , prednisone ( 1 mg × kg × day ) 4 weeks and then the dose was lowered to 5 mg every 2 weeks up to 10 mg . Group B : 10 patients with cyclophosphamide ( ev ) , oral prednisone 10 mg daily . RESULTS There are significant differences at onset of CVF and the honeycomb pattern between both groups , where the high dose group was at a disadvantage . At the end of treatment the low dose group achieved improvement of radiologic lesions and the Warrick index , unlike the high dose group . The remaining variables experienced improvement in both groups without marked ine quality . Similarly , slight adverse reactions were present in both groups . Two patients dropped out of the study . CONCLUSIONS A combination of low dose steroids with cyclophosphamide is effective in interstitial lung disease treatment especially in active disease , and results did not showe differences regarding the high dose group but the sample size and the evolutionary severity of high dose patients oblige other studies to verify this data OBJECTIVE This retrospective observational study attempted to determine whether any of the therapies used in the management of systemic sclerosis ( SSc ) patients held potential benefit for patients with interstitial lung disease . METHODS All patients with SSc who had a pulmonary function test ( PFT ) showing a forced vital capacity ( FVC ) of < 70 % predicted and an additional PFT at least 4 months later were grouped according to the treatment they received . Changes in pulmonary function were analyzed by the mean percent predicted FVC from the initial and the final test , and by the rate of percent change in FVC ( ml/year ) in the first 2 years after therapy . Bronchoalveolar lavage was performed in a subset of these patients . RESULTS Of 363 SSc patients who had an FVC < 70 % predicted , 122 had a second PFT and fulfilled the criteria for one of the following drug groups : high-dose prednisone ( n = 21 ) , immunosuppressive other than cyclophosphamide ( CYC ) ( n = 16 ) , CYC ( n = 14 ) , D-penicillamine ( n = 37 ) , or no drug ( n = 34 ) . In both analyses , the CYC-treated group showed significantly more improvement in FVC than did the other groups . Patients with early disease had the greatest likelihood of responding to any drug . CONCLUSION This retrospective study shows that patients treated with CYC had a significant improvement in FVC over time . Prospect i ve controlled studies of CYC treatment in early disease are necessary to determine if it can significantly alter the natural history of interstitial lung disease OBJECTIVE The endothelial damage of microvascular structures in systemic sclerosis ( SSc ; scleroderma ) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines , including E-selectin and thrombomodulin . Although there is still no ideal specific pharmacologic therapy for SSc , cyclophosphamide has result ed in clinical improvement in patients with SSc-related active alveolitis . This study was design ed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc , and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients ' clinical outcomes . METHODS Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide ( 2 - 2.5 mg/kg/day ) and methylprednisolone ( 30 mg/every other day ) for 1 year . The outcomes were determined as clinical ( skin score ) and laboratory parameters ( including the erythrocyte sedimentation rate , complete blood cell count , levels of C-reactive protein , antinuclear antibody , anti-double-str and ed DNA , rate of creatinine clearance , and findings on pulmonary function tests , esophageal manometry , and echocardiography ) . The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum sample s from the SSc patients and from 12 healthy adults as controls . RESULTS In the patients with early diffuse SSc , pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml ( range 34.2 - 135.5 ) and 33.4 ng/ml ( range 23 - 62.5 ) , respectively ( P = 0.01 ) , and those of thrombomodulin were 82 ng/ml ( range 35.8 - 120.5 ) and 74.6 ng/ml ( range 23.3 - 91.3 ) , respectively ( P = 0.016 ) . Clinical and laboratory parameters ( the skin score and measures of pulmonary function [ forced vital capacity and diffusing capacity for carbon monoxide ] ) were also improved ( P < 0.05 for each ) at the end of the followup period . CONCLUSION Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc . Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and /or activation , but also could be a useful marker to monitor the disease activity in SSc OBJECTIVE To find an effective , safe immunosuppressive regimen as an alternative to cyclophosphamide ( Cy ) for the treatment of clinical ly evident diffuse scleroderma (dSSc)-associated alveolitis of recent onset . METHODS Five consecutive patients with dSSc and recent-onset alveolitis were enrolled and treated with mycophenolate mofetil ( MMF ) and small ( < or = 10 mg/day ) doses of predinisolone in this open-label trial . One patient with long-st and ing fibrosing alveolitis was later added to our cohort . Pulmonary function tests [ carbon monoxide diffusing capacity ( DLCO ) and forced vital capacity ( FVC ) ] , pulmonary high-resolution computed tomography ( H RCT ) scans and clinical assessment were performed before and at specified time-points after enrolment . Cases of significant infections , leucopenia and abdominal pain were recorded . RESULTS After 4 - 6 months of MMF therapy , DLCO improved significantly compared with pre-treatment ( mean DLCO 75.4 % vs 64.2 % of predicted value , respectively , P = 0.033 ) . Values of FVC also improved , with the difference almost reaching levels of statistical significance ( mean FVC 76.2 % vs 65.6 % of predicted value , P = 0.057 ) . Ground glass opacities cleared in three of four patients with recent-onset alveolitis and were reduced in one patient after 6 - 8 months of treatment . Breathlessness and cough improved by 3 months . A possible treatment failure was seen in one patient . However , in five patients functional and clinical improvement was sustained during the study period . No adverse events were recorded in this ongoing clinical trial . CONCLUSION Our preliminary data suggest that in patients with dSSc and recent , clinical ly apparent alveolitis , early treatment with MMF and small doses of corticosteroids ( CS ) may represent an effective , well-tolerated and safe alternative therapy The purpose of the study was to examine prospect ively the efficacy and safety of the combination of intravenous pulses of cyclophosphamide and methylprednizolone , in the treatment of scleroderma lung disease . Thirteen patients were treated with the above combination for up to 24 months . Prior to this treatment , they underwent a pulmonary function evaluation and high resolution computed tomography ( H RCT ) . Carbon monoxide diffusion lung capacity and forced vital capacity were repeated at 6 , 12 , 24 and 48 months . H RCT was repeated at the end of the treatment period , but in between and afterwards in some patients , as well . A significant percentage of patients ( 66.6 % ) showed stabilization or improvement of their pulmonary function . Patients with already seriously compromised function , before treatment , were the least likely to exhibit this evolution pattern . There was a tendency in some individuals to deteriorate on later evaluations , off treatment , although they had stabilized at the end of the treatment . There was rather a poor correlation between functional evolution and H RCT appearance . Finally , the regimen was well tolerated . Our results suggest that the employed combination is safe and effective , mainly in stabilizing the respiratory function of the patients . This goal is more realistic when treatment is given before significant functional compromise has ensued . The need for long-term immunosuppression to maintain the initial favorable response is suggested OBJECTIVES There is currently no consensus on best practice in systemic sclerosis ( SSc ) . To determine if variability in treatment and investigations exists , practice s among Canadian Sclerodermia Research Group ( CSRG ) centres were compared . METHODS Prospect i ve clinical and demographic data from adult SSc patients are collected annually from 15 CSRG treatment centres . Laboratory parameters , self-reported socio-demographic question naires , current and past medications and disease outcome measures are recorded . For centres with > 50 patients enrolled , treatment practice s were analysed to determine practice variability . RESULTS Data from 640 of 938 patients within the CSRG data base met inclusion criteria , where 87.3 % were female , the mean ± SEM age was 55.3±0.5 , 48.9 % had limited SSc and 47.8 % had diffuse SSc ( and 3.3 % uncharacterised ) . Some investigation and treatment practice s were inconsistent among 6 centres including proportion receiving : PDE5 ( phosphodiesterase type 5 ) inhibitors for Raynaud 's phenomenon ( p=0.036 ) ; cyclophosphamide ( p=0.037 ) and azathioprine ( p=0.037 ) for treatment of ILD ; and current use of D-penicillamine , although uncommon , varied among sites . Annual echocardiograms and PFTs were frequently done and did not vary among sites but the rate of pulmonary arterial hypertension ( PAH ) was directly related to site size and this was not the case for other organ involvement . CONCLUSIONS Despite routine tests within a data base , site variation in SSc with respect to investigations and management among CSRG centres exists suggesting a need for a st and ardised approach to the investigation and treatment of SSc . One can speculate that larger centres are more export in detecting PAH OBJECTIVE Cyclophosphamide ( CYC ) is generally considered the most promising agent available today for systemic sclerosis (SSc)-related interstitial lung disease ( ILD ) . However , the optimal dosage and length of treatment are still undetermined . Our objective was to evaluate the effect of an 18-month long protocol with intravenous ( iv ) CYC . METHODS In a single-centre , prospect i ve , observational study , 13 patients with SSc and active alveolitis were given 8 iv pulses in a 6-months period ( CYC 750 mg + 6-methylprednisolone 125 mg every three weeks ) , as an induction therapy . Patients received maintenance therapy with further cycles at 4 ( 3 pulses ) , 6 ( 3 pulses ) and 9 weeks ( 3 pulses ) interval . Total CYC dosage was 12.75 g in an 18-month period . End-points were modifications of lung function test ( LFT ) . RESULTS During the first 6 months of treatment with CYC an increase in Forced Vital Capacity ( FVC ; p = 0.005 ) and in diffusion lung capacity for carbon monoxide ( DLCO ; p = 0.10 ) was observed ; during the maintenance therapy , there was a stabilization in FVC and a mild , non significant decline in DLCO . Treatment was well tolerated . CONCLUSION iv CYC can induce an initial improvement in LFT ( particularly , in FVC ) in the first six months , but no further improvement was observed during the maintenance phase OBJECTIVE To document the effectiveness , including the longterm effect , of a course of intravenous ( IV ) pulses of methylprednisolone ( MP ) and cyclophosphamide ( CYC ) in patients with scleroderma ( SSc ) who had evidence of lung inflammation on high resolution computer tomographic ( H RCT ) scan of the chest . METHODS Fourteen consecutive patients with SSc and lung involvement were treated with 6 pulses of IV MP ( 10 mg/kg ) and IV CYC ( 15 mg/kg ) given at 3 - 4 weekly intervals . H RCT scans and lung function tests were performed at baseline and after the 6th pulse . Further lung function tests were repeated at 12 months and annually thereafter . RESULTS Modified Rodnan skin scores improved significantly by 35 % from a median baseline score of 17 ( IQR 14 - 26.5 ) to a posttreatment score of 13 ( IQR 10.5 - 18.5 ; p = 0.0058 ) . H RCT scan scores improved significantly ( p = 0.04 ) . Twelve of 13 patients experienced either improvement or stabilization of the H RCT score . Median DLCO and lung volumes remained stable during the first 12 months . After a median followup of 26 months ( IQR 19 - 43 ) , 67 % of patients experienced deterioration in DLCO . Median deterioration was 23 % ( IQR 44 - 0.6 ) , with the median rate of deterioration of the predicted value of the DLCO/month being 0.87 % ( IQR 1.24 - 0.02 ) . The treatment was safe and well tolerated . CONCLUSION This IV regimen stabilized lung disease in patients with SSc . When treatment was stopped , or reduced in intensity , a deterioration in lung function occurred in the majority of patients . Rate of deterioration of DLCO may be a useful marker for determining the intensity of treatment . These findings have implication s for treating lung disease and design ing clinical trials in patients with SSc Fourteen patients with systemic sclerosis ( SSc , scleroderma ) and interstitial lung disease were treated with oral cyclophosphamide ( 1 - 2 mg/kg/day ) and low dose prednisone ( < 10 mg/day ) . There was a significant improvement in FVC after 6 months compared to entry values ( 2.21 + /- 0.19 l vs. 2.03 + /- 0.15 l , p < 0.02 ) . Improvement was maintained at 12 months ( 2.27 + /- 0.27 l , p < 0.05 ) and 18 - 24 months ( 2.60 + /- 0.28 l , p < 0.001 ) . In 12 cases followed for 18 - 24 months , FVC was stable or improved . No significant improvement or decline was noted for the DLCO . Side effects included cytopenia ( 2 ) , infection ( 1 ) , and hemorrhagic cystitis ( 2 ) , and one possible related malignancy . A controlled prospect i ve trial of cyclophosphamide is warranted in patients with SSc and active interstitial lung disease Aim : Currently , therapy for interstitial lung disease in patients with systemic sclerosis is unsatisfactory . A prospect i ve open label study was conducted in a North Indian tertiary Institute to assess the efficacy of intermittent pulse cyclophosphamide ( CYC ) and high‐dose prednisolone in systemic sclerosis (SSc)‐related interstitial lung disease ( ILD ) |
11,308 | 20,442,592 | However , we found no evidence for superior performance by the FACT-G compared with the SF-36 or EORTC and FACIT disease-specific modules versus the QLQ-C30 and FACT-G. There was also little evidence to favor EORTC versus FACIT question naires or vice versa .
The evidence we review ed offered little support for the hypothesis that disease- , symptom- , or treatment-specific instruments are more sensitive and responsive than cancer-specific or generic question naires . | OBJECTIVES Research ers wishing to assess the health-related quality of life ( HRQoL ) of women with gynecologic cancers have a range of question naires to choose from .
In general , disease- , treatment- , or symptom-specific question naires are assumed to be better able to identify between-group differences ( sensitivity ) and changes over time ( responsiveness ) than are cancer-specific or generic question naires .
However , little work has tested this assumption in oncology .
We set out to ( a ) identify all multidimensional HRQoL question naires used in studies with women with gynecologic cancer and ( b ) evaluate their track records in identifying minimal clinical ly important differences ( MCIDs ) , with a view to making recommendations . | OBJECTIVE This study was undertaken to prospect ively evaluate the effect of early stage endometrial cancer , age , and obesity on quality of life ( QOL ) . STUDY DESIGN Women undergoing surgery for endometrial cancer or an adnexal mass determined at surgery to be benign ( controls ) were enrolled preoperatively and followed for 6 months . RESULTS Seventy-nine women completed the study . Functional Assessment of Cancer Therapy ( FACT-G ) scores increased significantly in all women ; however , significant differences by patient weight and age were obtained . Obesity was associated with decreased physical FACT-G and SF-36 scores . Older women had lower SF-36 physical scores , higher emotional scores , and less change over time . CONCLUSION Women with early endometrial cancer had similar changes in QOL as those who received surgery for benign disease . Obese and elderly women had domain alterations . Given the aging population and rising incidence of obesity , these results emphasize the need for QOL interventions in postoperative gynecologic care of these patients OBJECTIVE This study was undertaken to compare the quality of life ( QoL ) in women with early stage endometrial cancer treated with 2 different surgical approaches . STUDY DESIGN Eighty-four women with clinical stage I endometrial cancer were enrolled in a prospect i ve r and omized controlled trial design and treated with laparoscopic or laparotomic approach . Another 40 women matched for demographic characteristics were studied as controls . In patients , before and after surgery , and in their matched controls , QoL was evaluated by using the Short-Form Healthy Survey ( SF-36 ) and the climacteric symptoms using the Kupperman Index ( KI ) . RESULTS After r and omization , no difference was detected in data recorded between the groups . At entry , QoL was similar in both treatment groups but significantly ( P < .05 ) worse in comparison with controls . Throughout the study , QoL was significantly ( P < .05 ) higher in laparoscopic group versus laparotomic group . After KI adjustment our data did not change . CONCLUSION In early stage endometrial cancer , the laparoscopic approach provides significant benefits compared with laparotomy in terms of In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials The objective of this study was to examine and compare two core measures of Quality Of Life ( QOL ) used in cancer clinical trials : the European Organisation for Research and Treatment of Cancer QOL Core Question naire 30 ( EORTC QLQ-30 ) and the Functional Assessment of Chronic Illness Therapy ( FACIT ) , in order to identify which one patients have the strongest preference for using . 68 patients suffering from Carcinomas of an Unknown Primary site ( CUP ) were recruited in a multicentric study ; all of them completed both question naires , administered in a r and omised manner . The criteria were the percentage of preferences , and four indicators of acceptability . The results indicated that an equal proportion of patients preferred the QLQ-C30 ( 19 % ) and FACIT ( 19 % ) . 54 % of patients felt both question naires were acceptable . All the indicators of acceptability favoured the QLQ-C30 . Analysis of open-ended questions shed light on the difficulties encountered by the patients . As no significant preference was observed for one of the question naires , the QLQ-C30 was chosen on the basis of its significantly better acceptability criteria PURPOSE The value of palliative chemotherapy in women with refractory and recurrent ovarian cancer is difficult to quantify , and little is known about patient expectations from these treatments . We evaluated in the current prospect i ve study patient expectations , palliative outcomes of chemotherapy , and the inherent re source utilization in patients undergoing second- or third-line chemotherapy for recurrent or refractory advanced ovarian cancer . METHODS The European Organization for Research and Treatment of Cancer Quality -of-Life Question naire C30 ( EORTC QLQ C30 ) and Functional Assessment of Cancer Therapy-Ovarian ( FACT-O ) question naires were used to assess palliative benefit and an in-house question naire was used to gauge patient expectations . The minimal clinical ly important difference ( MCID ) was calculated by asking women to make a global rating of change and correlating this to the EORTC QLQ C30 . Re source use was recorded and costs were calculated . RESULTS Twenty-seven patients were accrued . Objective response was documented on seven of 27 . The median survival was 11 months . Sixty-five percent of women expected that chemotherapy would make them live longer and 42 % that it would cure them . After two cycles , quality -of-life ( QL ) improvement was seen particularly in global function ( 11 of 21 ) and emotional function ( 13 of 21 ) with EORTC QLQ C-30 . Improvement was sustained for a median of 2 and 3 months , respectively , in these categories . The MCID was calculated to be 0.39 on a seven-point scale for physical function and 0.13 for global function . The mean total cost per patient for the study period was Can $ 12,500 . CONCLUSION Patient expectations from these treatments are often unrealistic . Although objective responses are low , active palliation with chemotherapy is associated with substantive improvement in patients ' emotional function and global QL , with overall costs that seem relatively modest OBJECTIVES To assess the reliability and validity of the Functional Assessment of Cancer Therapy-Vulvar ( FACT-V ) . METHODS Seventy-seven patients treated between January 1996 and January 2001 for cancer of the vulva completed the FACT-V , the Eastern Cooperative Oncology Group Performance Status Rating ( ECOG-PSR ) and the Hospital Anxiety and Depression Scale ( HADS ) once , 20 consecutive patients treated between February 2001 and October 2001 completed the question naires twice , once before surgery and at 2 months follow-up . The FACT-V scores were compared by patients ' performance status , FIGO stage , recurrence , and age , and correlated to the HADS scores . Changes in the FACT-V from baseline to 2 months follow-up were evaluated to establish FACT-V 's responsiveness to change . RESULTS The FACT-V 's internal consistency was adequate ( Chronbach 's alpha range , 0.75 to 0.92 ) . Patients with lower performance status , higher FIGO-stage or recurrent disease received lower FACT-V scores , indicating discriminant validity . The correlation between the FACT-V and the HADS were in the expected direction , indicating convergent and divergent validity . From pre- to post-surgery , scores in nine out of fifteen items of the vulvar cancer-specific subscale improved , while those of five items declined , indicating sensitivity of the vulvar cancer specific items to changes in patients ' well-being . CONCLUSIONS The newly developed FACT-V provides a reliable and valid assessment of the quality of life of women with vulvar cancer . It can be used as a short measure of quality of life within research studies , and to facilitate communication about quality of life issues in clinical practice The purpose of this study was to vali date the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group — Neurotoxicity ( FACT/GOG-Ntx ) question naire . The FACT/GOG-Ntx is the FACT-G plus an eleven-item subscale ( Ntx subscale ) that evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy . Two groups of women with ovarian cancer completed the FACT/GOG-Ntx : one group with known neurotoxicities and one group of chemotherapy-naive women newly diagnosed with ovarian cancer . Levels of patient neuropathy , severity of toxicity , and patient quality of life from diagnosis of ovarian cancer to 12 months post-diagnosis were assessed . The Ntx subscale significantly differentiated the two groups at baseline and 3- and 6-month follow-ups , demonstrating significantly fewer problems among chemotherapy-naive patients than among patients with known neuropathy . The FACT/GOG-Ntx is a reliable and valid instrument for assessing the impact of neuropathy on health-related quality of life . The Ntx subscale demonstrated sensitivity to meaningful clinical distinctions and change over time PURPOSE To compare self-reported quality of life ( QOL ) in patients who did versus did not undergo interval secondary cytoreduction after initial surgery and combination chemotherapy for advanced ovarian cancer and to assess the association between baseline QOL scores and survival . PATIENTS AND METHODS Consenting patients participating in a Gynecologic Oncology Group ( GOG ) phase III treatment trial ( GOG 152 ) completed the Functional Assessment of Cancer Therapy-Ovarian ( FACT-O ) question naire and treatment-specific supplemental questions at the third and sixth chemotherapy cycles and at 6 and 12 months after starting treatment . RESULTS For all patients , QOL decreased approximately 1 unit from the first to second assessment . Significant improvement observed at 6 months ( P < .001 ) was sustained at 12 months , with no appreciable between-group difference . The baseline FACT-O score was associated with overall survival ( P = .048 ) but not progression-free survival . Less neurotoxicity was reported among patients who did ( 38.4 % ) versus did not ( 54.0 % ) undergo interval secondary cytoreduction at the third assessment ( P = .005 ) , and older patients experienced more long-term effects . CONCLUSION This is the first multicenter r and omized trial in ovarian cancer to longitudinally examine self-reported QOL and establish a predictive value of baseline QOL on survival , attributed primarily to the lowest-scoring quartile . Although interval secondary cytoreduction result ed in no notable long-term difference , a clinical ly significant improvement was seen in both arms at 6 and 12 months after starting therapy . Interestingly , there were fewer complaints of neurotoxicity at 6 months among patients who did versus did not undergo interval secondary cytoreduction Objective To prospect ively compare quality of life ( QOL ) outcomes in patients with advanced endometrial cancer treated with whole abdominal irradiation ( WAI ) or doxorubicin-cisplatin ( AP ) chemotherapy . Methods Using the Fatigue Scale ( FS ) , Assessment of Peripheral Neuropathy ( APN ) , Functional Alterations due to Changes in Elimination ( FACE ) , and Functional Assessment of Cancer Therapy-General ( FACT-G ) , QOL was measured at : pre-treatment , end of treatment ( EOT ) , and 3 and 6 months post-treatment . Results 317 of 396 eligible patients provided a baseline QOL assessment . The AP arm produced a statistically significant survival benefit along with greater toxicities , including peripheral neuropathy persisting up to 6 months . WAI patients reported worse FS ( p<0.001 ) and FACE ( p<0.001 ) scores at EOT and poorer FACE scores 3 months post-treatment ( p = 0.004 ) compared to AP patients . APN scores were significantly worse among AP patients at EOT , and 3 and 6 months post-treatment ( p<0.001 for all ) . There is no indication that FACT-G scores differed between the two arms at any assessment point . Conclusions The trade-off for increased survival with AP is its potential for clinical ly significant peripheral neuropathy . This should be discussed with patients , particularly those who work with their h and s or on their feet , in weighing therapeutic choices . Further research is needed to manage side effects having an enduring impact on QOL PURPOSE A Gynecologic Oncology Group ( GOG ) r and omized phase III trial ( GOG 172 ) in optimal stage III epithelial ovarian cancer showed that intravenous ( IV ) paclitaxel plus intraperitoneal ( IP ) cisplatin and paclitaxel significantly lengthened progression-free survival and overall survival compared with IV paclitaxel and cisplatin . The purpose of this report is to comprehensively evaluate the patient-reported outcomes associated with IP versus IV therapy . PATIENTS AND METHODS Four hundred fifteen eligible women were enrolled onto GOG 172 at member institutions . The Functional Assessment of Cancer Therapy-Trial Outcome Index ( FACT-TOI ; which includes physical , functional , and ovarian subscales ) and neurotoxicity ( Ntx ) and abdominal discomfort ( AD ) subscales were used to assess patient-reported outcomes . Assessment s were completed before r and om assignment , before cycle 4 , and 3 to 6 weeks and 12 months after treatment . RESULTS Physical and functional well-being and ovarian cancer symptoms were significantly worse in the IP arm before cycle 4 ( P < .001 ) and 3 to 6 weeks after treatment ( P = .001 for FACT-TOI ) . Patients in the IP arm also reported significantly worse AD before cycle 4 ( P < .001 ) and significantly worse Ntx 3 to 6 weeks ( P = .001 ) and 12 months ( P = .003 ) after completing IP treatment . In general , however , the quality of life of both groups improved over time . CONCLUSION During active treatment , patients on the IP arm experienced more health-related quality -of-life disruption , AD , and Ntx compared with patients receiving conventional IV therapy . However , only Ntx remained significantly greater for IP patients 12 months after treatment . This trade-off should be included when discussing treatment options with patients . Future studies to mitigate the added burden associated with IP therapy are planned PURPOSE To compare the variability and sample size requirements of the global quality -of-life ( QOL ) scores of the following three major QOL instruments : the Functional Assessment of Cancer Therapy-General ( FACT-G ) , Functional Living Index-Cancer ( FLIC ) , and European Organisation for Research and Treatment of Cancer Core Quality of Life Question naire C30 ( EORTC QLQ-C30 ) . PATIENTS AND METHODS Cancer patients were r and omly assigned to answer two of the three instruments using an incomplete block design ( n = 1,268 ) . The instruments were compared in terms of coefficient of variation , effect size in detecting a difference between patients with different performance status , and correlation coefficient between scores at baseline and follow-up . RESULTS The FACT-G and FLIC had significantly smaller coefficients of variation than the EORTC QLQ-C30 ( both P < .05 ) . The FLIC also had significantly larger correlation coefficients between scores at baseline and follow-up than the EORTC QLQ-C30 ( P < .05 ) . The FACT-G and the FLIC had a larger effect size in a cross-sectional and longitudinal setting , respectively , than the EORTC QLQ-C30 in differentiating patients with different performance status ( both P < .05 ) . CONCLUSION In some aspects , the FACT-G and FLIC global QOL scores had smaller variability and larger discriminative ability than the EORTC QLQ-C30 . Further research using other criteria to compare the three instruments is recommended PURPOSE This analysis of data from a r and omized trial of chemotherapy in epithelial ovarian cancer sought to determine whether a relationship exists between the presence and severity of the most commonly observed toxic effects and the corresponding quality of life ( QOL ) items . PATIENTS AND METHODS One hundred fifty-two eligible patients accrued from Canada by the National Cancer Institute of Canada Clinical Trials Group on a r and omized trial of paclitaxel and cisplatin versus cyclophosphamide/cisplatin were included in the analysis . Toxicity to the chemotherapeutic treatments was subjectively evaluated using a trial-specific checklist for ovarian cancer and the European Organization for Research and Treatment of Cancer QLQ C30 + 3 question naire . Assessment s were conducted at baseline , before each cycle of treatment ( 3 weeks ) , and at each 3-month follow-up during the next 2 years ( or until progression ) . RESULTS The most frequently observed symptoms experienced during or shortly following chemotherapy were neurosensory loss , lethargy , nausea , vomiting , and alopecia . Regression analyses revealed that change scores of QOL items related to motor weakness and gastrointestinal pain were common predictors for the change global QOL score during protocol treatment ; and change scores of QOL items related to lethargy or fatigue and change toxicity grade of mood predicted the change global QOL score after patients were off treatment . CONCLUSION The use of the European Organization for Research and Treatment of Cancer QLQ C30 + 3 and trial-specific checklist was able to assess the effect of expected toxicities on patient ' s QOL during and following treatment , and so may be useful in addressing the concerns regarding method ological issues that have limited the acquisition of prospect i ve , longitudinal treatment-related toxicity data This study defines the psychometric properties of the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life ( QOL ) question naire design ed to measure the QOL of patients with ovarian cancer . The ovarian cancer module ( EORTC QLQ-OV28 ) was developed to supplement the EORTC QLQ-C30 . The core question naire and the QLQ-OV28 were prospect ively administered to 368 ovarian cancer patients after they had been treated with radical or debulking surgery followed by chemotherapy . The QLQ-OV28 module assesses abdominal/gastrointestinal symptoms , peripheral neuropathy , other chemotherapy side-effects , hormonal/menopausal symptoms , body image , attitude to disease/treatment and sexual functioning . Question naires were well accepted by patients , baseline compliance rates were 86 % , 72 % provided a second assessment , less than 3 % of the items had missing data . Multi-trait scaling analyses confirmed the hypothesised scales . All hypothesised scales exhibited good psychometric properties . These results support the clinical and psychometric validity of the EORTC QLQ-OV28 module as a supplement to the EORTC QLQ-C30 OBJECTIVES Lack of exercise and excess body weight may exacerbate treatment-related declines in quality of life ( QoL ) in endometrial cancer survivors . The primary purpose of this study was to examine the associations among exercise , body weight , and QoL in a population -based sample of endometrial cancer survivors . METHODS Participants were 386 endometrial cancer survivors residing in Alberta , Canada who completed a mailed survey that assessed self-reported exercise , height , and weight to calculate body mass index ( BMI ) and QoL using the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) scale . RESULTS Descriptive data indicated that 70 % of the sample were not meeting public health exercise guidelines and 72 % were overweight or obese . Multivariate analyses of variance demonstrated that endometrial cancer survivors meeting public health guidelines for exercise and body weight reported significantly better QoL than survivors not meeting guidelines . The differences in QoL between the groups were clinical ly meaningful and were not altered when controlling for important demographic and medical variables . There were no interactions between exercise , BMI , age , or time since diagnosis . Lastly , multiple regression analysis identified that both exercise ( beta = .21 ; P < .001 ) and BMI ( beta = -.17 ; P < .001 ) were independently associated with QoL. CONCLUSIONS These results suggest that exercise and body weight are important independent correlates of QoL in endometrial cancer survivors . R and omized controlled trials design ed to test the causal effects of exercise and /or weight loss on QoL in endometrial cancer survivors are warranted OBJECTIVE To evaluate the impact of treatment for genital cancer on quality of life and body image to determine patients ' therapy-related needs for quality improvement of medical care before and after surgery . METHODS We started to evaluate women with cervical cancer planned for pelvic exenteration in 1993 and integrated women planned for a Wertheim-Meigs surgery in 1995 before surgery , 4 and 12 months after surgery . Thanks to funding since 1999 , more than 400 patients with a diagnosis of genital ( n = 185 ) or breast ( n = 217 ) cancer participated in this prospect i ve study until July 2003 . In this paper , we will focus on n = 129 women with cervical cancer . The assessment protocol included objective question naires for quality of life and body image ( CARES ; EORTC ; Body image by Strauss and Appelt ) . The evaluation of quality of life incorporated five dimensions : physical and psychosocial health , marital and sexual status , and medical interaction . RESULTS Before surgery , women with a Wertheim 's procedure indicated significantly less problems concerning the quality of life global score ( P = 0.002 ) and several subscales compared to women with a pelvic exenteration . After surgery , both groups indicated their sexual problems to be the greatest restriction in terms of quality of life , especially in women with non-reconstructive surgery as well as in women with adjuvant radio and /or chemotherapy . Concerning body image , attractiveness or self-confidence was significantly reduced postoperatively compared to the preoperative status for both groups ( P = 0.000 ) , and also worsened with the extent of treatment . Worries about the patient 's family persisted over time and represented the most important item about all questions concerning quality of life as well as the fear of recurrence . CONCLUSION This on-going study demonstrates the interferences between the treatment modality and the patient 's quality of life , especially about sexuality and body image . Our results suggest not only to provide reconstructive surgery if possible , but also to integrate psychosocial information aspects on future quality of life outcome before surgery as well as to offer psychosocial support related to the extent of treatment modality after surgery OBJECTIVES To prospect ively evaluate quality of life ( QoL ) , use of complementary and alternative medicine ( CAM ) , and diet/exercise changes in ovarian cancer patients during the first 6 months following diagnosis . METHODS Patients with newly diagnosed ovarian cancer were enrolled pre- or post-operatively and surveyed at 3 and 6 months . The Functional Assessment of Cancer Therapy ( FACT-G ) , Medical Outcomes Survey ( SF-36 ) , and CAM/diet/exercise question naires were used . Independent sample s t test and repeated measures ANOVA were used . RESULTS Forty-two patients underwent surgical debulking and staging prior to chemotherapy . Patients completing the initial surveys post-operatively had significantly lower physical FACT-G and SF-36 physical scores compared to patients completing the surveys pre-operatively . In patients completing the baseline survey pre-operatively , there was a decrease in physical scores at 3 months ( after surgery and during chemotherapy ) . There was no change observed at 3 months relative to baseline when patients completed the baseline survey post-operatively . Increases in physical and functional well-being were seen at 6 months relative to 3 months . There were no changes in emotional or social scores over time . CAM use increased over time ; main reasons were to improve QoL and relieve symptoms . Alterations in diet and exercise were not seen . CONCLUSIONS These data highlight the need to conduct assessment s before and after surgery to identify effects due to surgery and /or chemotherapy . Patients may be using CAM during chemotherapy to deal with symptoms and compensate for decreased QoL. Intervention trials should be implemented to increase QoL following surgery and during adjuvant chemotherapy BACKGROUND The addition of hexamethylmelamine to therapy with cisplatin , cyclophosphamide , and doxorubicin significantly enhanced outcomes of patients with advanced ovarian cancer . Hexamethylmelamine , also known as altretamine , has potent antineoplastic activity when used as a single agent in patients who have failed to respond to both platinum-based and paclitaxel therapy . We have conducted a pilot study to evaluate the efficacy and safety of adding this drug to the popular ovarian cancer regimen of paclitaxel plus carboplatin . METHODS Patients with advanced ovarian , fallopian tube , or primary peritoneal cancer ( International Federation of Gynecology and Obstetrics stages IIA , IIIC , and IV ) were prospect ively enrolled to receive six cycles , repeated every 4 weeks , of paclitaxel ( 150 mg/m2 i.v . , day 1 ) , carboplatin ( AUC 5.0 i.v . , day 1 ) , and hexamethylmelamine ( 150 mg/m2 p.o . , days 2 - 15 ) . Colony stimulating factors were prohibited . Response and toxicity were monitored by use of Eastern Cooperative Oncology Group criteria . RESULTS Twenty patients were enrolled , 18 with ovarian cancer , one with fallopian tube cancer , and one with peritoneal cancer ; 17 of these patients were evaluable for response and toxicity . At a median follow-up of 6.5 months , 13 of the patients had a complete response ( 76 % ) , and four had progressive disease . Three of those with a complete response had a recurrence within 1 year of completing treatment . Toxicity was acceptable , with myelosuppression the most severe adverse effect ; one patient had grade 3 anemia , one patient had grade 4 thrombocytopenia , and 12 patients had grade 4 neutropenia . Quality of life showed improvement over the course of therapy , particularly in the physical well-being subscale . CONCLUSION The addition of hexamethylmelamine to paclitaxel and carboplatin is a well-tolerated multidrug combination for women with advanced ovarian cancer that deserves further testing in a phase III study PURPOSE Formal quality -of-life ( QOL ) assessment s may contribute important information on patient symptoms . Despite many trials of systemic chemotherapy in ovarian cancer , reports of its effect on QOL are few . PATIENTS AND METHODS QOL was assessed in an Intergroup r and omized trial comparing paclitaxel plus cisplatin to cyclophosphamide plus cisplatin in women with advanced ovarian cancer . One hundred fifty-two eligible patients accrued in Canada completed the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 and a trial-specific checklist at baseline ( after surgical debulking ) and at regular intervals during and after chemotherapy . Mean change scores over time in the two arms were calculated . RESULTS Compliance with QOL question naire completion was excellent ( 81 % to 93 % ) . In general , deterioration was seen in the QOL domains immediately after chemotherapy ( day 8 of cycle 1 ) , followed by clinical ly meaningful improvements compared with baseline ( change scores > or = 10 ) in both arms during the treatment period in a number of domains and items , including global QOL , emotional function , social function , fatigue , pain , sleep , constipation , appetite , abdominal swelling , and abdominal cramps . Improvements in global QOL persisted for the duration of follow-up . More neurosensory effects and myalgia were documented in the paclitaxel arm ; however , this did not adversely affect global or other domains of QOL and improved once chemotherapy was completed . CONCLUSION Improvement from baseline in QOL measures was seen in both treatment arms . The greater neurologic and muscle toxicity of paclitaxel did not adversely influence QOL . QOL data can contribute useful information on the experience of symptoms and their time course , which may assist patients and physicians in their discussion about the anticipated effects of therapy |
11,309 | 23,575,990 | DE-CMR has a higher sensitivity , whereas LDD-CMR has a higher specificity for the detection of viable stunned myocardium following myocardial infa rct ion . | BACKGROUND Myocardial stunning is an important sequela of acute coronary syndromes and its determination might affect decisions on defibrillator implantation and assist devices after myocardial infa rct ion ( AMI ) .
The aim of the study was to evaluate and compare the sensitivity , specificity , negative predictive value ( NPV ) , and positive predictive value ( PPV ) of cardiac magnetic resonance imaging ( CMR ) assessing myocardial stunning after acute myocardial infa rct ion using low-dose dobutamine ( LDD ) , end-diastolic wall thickness , and contrast delayed enhancement ( DE ) . | Background — The incretin hormone glucagon-like peptide-1 ( GLP-1 ) has been shown to have cardioprotective properties in animal models of ischemia and infa rct ion due to promotion of myocardial glucose uptake and suppression of apoptosis . We investigated whether GLP-1 protected the heart from dysfunction caused by supply ischemia during percutaneous coronary intervention ( PCI ) . Methods and Results — Twenty patients with normal left ventricular ( LV ) function and single-vessel coronary disease within the left anterior descending artery undergoing elective PCI were studied . A conductance catheter was placed into the LV through the femoral artery , and pressure-volume loops were recorded at baseline and during a 1-minute low-pressure balloon occlusion at the site of the stenosis . The patients were r and omized to receive an infusion of either GLP-1(7–36 ) amide at 1.2 pmol/kg per minute or saline immediately after the first balloon occlusion . Coronary balloon occlusion caused LV stunning in the control group with cumulative LV dysfunction on subsequent occlusion that was not seen in the GLP-1 group . GLP-1 improved recovery of LV systolic and diastolic function at 30 minutes after balloon occlusion compared with control ( delta dP/dtmax from baseline , −1.6 % versus −12.2 % ; P=0.02 ) and reduced the LV dysfunction after the second balloon occlusion ( delta dP/dtmax , −13.1 % versus −25.3 % ; P=0.01 ) . Conclusions — In this pilot study , infusion of GLP-1 has been demonstrated to reduce ischemic LV dysfunction after supply ischemia during coronary balloon occlusion in humans and mitigates stunning . The findings require confirmation in a larger scale clinical trial . Clinical Trial Registration — URL : http://www.is rct n.org . Unique identifier : IS RCT N 77442023 BACKGROUND Although poststress myocardial stunning is regarded as a marker for severe coronary artery disease ( CAD ) , no study has yet compared the diagnostic value of poststress stunning with transient ischemic dilation ( TID ) of the left ventricle ( LV ) for detecting multivessel CAD . METHODS AND RESULTS A total of 271 patients with suspected or known CAD underwent adenosine triphosphate ( ATP ) loading and at-rest gated single-photon emission computed tomography . We assessed myocardial perfusion with a 20-segment model , and analyzed the changes in LV volumetric analysis induced by ATP and an automatically derived TID ratio . In 147 patients with multivessel CAD , the prevalence of multi-territorial ischemia was higher , and the post-ATP increase in end-systolic volume ( ESV ) and TID ratio were greater , than in the 124 with insignificant or single-vessel CAD ( P<0.0001 , for all cases ) . The receiver-operating characteristic curves analysis revealed cutoff values for ESV of 5 ml and a TID ratio of 1.11 . Multivariate logistic regression analysis revealed that the combination of a poststress increase in ESV of ≥5 ml and multi-territorial ischemia best identified multivessel CAD , with a sensitivity of 78 % and a specificity of 84 % , whereas the TID ratio was not shown to be an independent predictor . CONCLUSIONS Post-ATP stress myocardial stunning is superior to the TID ratio for detecting multivessel CAD Background Postischemic global and regional left ventricular ( LV ) dysfunction on stressgated single photon emission computed tomography ( SPECT ) imaging is attributed widely to myocardial stunning . We sought to determine the specificity of gated SPECT for the detection of myocardial stunning after ischemic stress . Methods and Results Twenty-seven patients with an ischemic response to stress on dual-isotope exercise SPECT were enrolled prospect ively . Transthoracic echocardiography was performed just before stress gated SPECT for assessment of regional wall motion and quantitative LV ejection fraction ( LVEF ) . The 17 myocardial segments for each patient were scored for myocardial perfusion by stress gated SPECT , and regional wall motion by stress gated SPECT and echo . Of the 459 myocardial segments , 41 % had perfusion defects , 15 % had stress gated SPECT regional wall motion abnormality , 4.8 % had poststress echo regional wall motion abnormality , and 3.9 % had baseline regional wall motion abnormality . Overall , a stress gated SPECT regional wall motion abnormality had a sensitivity of 100 % and a specificity of 89 % . Among reversible perfusion defects of moderate severity or more , a stress gated SPECT regional wall motion abnormality had a specificity of 41 % and a positive predictive value of 8 % . Stress gated SPECT LVEF was similar to poststress echo LVEF for all patients , but significantly lower in patients with reversible perfusion defects of moderate severity or more . Conclusion Post-stress gated SPECT imaging overestimates global and regional myocardial stunning . Caution should be exercised in interpreting poststress global or regional LV function on stress gated SPECT in scans with reversible ischemia AIMS To prospect ively compare the agreement of left ventricular volumes and ejection fraction by M-mode echocardiography ( echo ) , 2D echo , radionuclide ventriculography and cardiovascular magnetic resonance performed in patients with chronic stable heart failure . It is important to know whether the results of each technique are interchangable , and thereby how the results of large studies in heart failure utilizing one technique can be applied using another . Some studies have compared cardiovascular magnetic resonance with echo or radionuclude ventriculography but few contain patients with heart failure and none have compared these techniques with the current fast breath-hold acquisition cardiovascular magnetic resonance . METHODS AND RESULTS Fifty two patients with chronic stable heart failure taking part in the CHRISTMAS Study , underwent M-mode echo , 2D echo , radionuclude ventriculography and cardiovascular magnetic resonance within 4 weeks . The scans were analysed independently in blinded fashion by a single investigator at three core laboratories . Of the echocardiograms , 86 % had sufficient image quality to obtain left ventricular ejection fraction by M-mode method , but only 69 % by 2D Simpson 's biplane analysis . All 52 patients tolerated the radionuclude ventriculography and cardiovascular magnetic resonance , and all these scans were analysable . The mean left ventricular ejection fraction by M-mode cube method was 39+/-16 % and 29+/-15 % by Teichholz M-mode method . The mean left ventricular ejection fraction by 2D echo Simpson 's biplane was 31+/-10 % , by radionuclude ventriculography was 24+/-9 % and by cardiovascular magnetic resonance was 30+/-11 . All the mean left ventricular ejection fractions by each technique were significantly different from all other techniques ( P<0.001 ) , except for cardiovascular magnetic resonance ejection fraction and 2D echo ejection fraction by Simpson 's rule ( P=0.23 ) . The Bl and -Altman limits of agreement encompassing four st and ard deviations was widest for both cardiovascular magnetic resonance vs cube M-mode echo and cardiovascular magnetic resonance vs Teichholz M-mode echo at 66 % each , and was 58 % for radionuclude ventriculography vs cube M-mode echo , 44 % for cardiovascular magnetic resonance vs Simpson 's 2D echo , 39 % for radionuclide ventriculography vs Simpson 's 2D echo , and smallest at 31 % for cardiovascular magnetic resonance-radionuclide ventriculography . Similarly , the end-diastolic volume and end-systolic volume by 2D echo and cardiovascular magnetic resonance revealed wide limits of agreement ( 52 ml to 216 ml and 11 ml to 188 ml , respectively ) . CONCLUSION These results suggest that ejection fraction measurements by various techniques are not interchangeable . The conclusions and recommendations of research studies in heart failure should therefore be interpreted in the context of locally available techniques . In addition , there are very wide variances in volumes and ejection fraction between techniques , which are most marked in comparisons using echocardiography . This suggests that cardiovascular magnetic resonance is the preferred technique for volume and ejection fraction estimation in heart failure patients , because of its 3D approach for non-symmetric ventricles and superior image quality OBJECTIVES We sought to evaluate the usefulness of a comprehensive assessment of four cardiovascular magnetic resonance imaging (CMR)-derived myocardial viability indexes in the setting of myocardial stunning . BACKGROUND Cardiovascular magnetic resonance imaging allows the simultaneous assessment of several viability indexes . METHODS We studied 40 patients with a first ST-segment elevation myocardial infa rct ion ( MI ) and an open infa rct -related artery . At the first week , using CMR , wall motion ( WM ) , and four viability indexes were determined : wall thickness , WM improvement with low-dose dobutamine , perfusion , and transmural extent of necrosis . We created a comprehensive score based on the presence and the relative power of these viability indexes for predicting normal WM at the sixth month . RESULTS Of 153 dysfunctional segments at the first week , 59 ( 39 % ) exhibited normal WM at the sixth month . According to the odds ratio of viability indexes for predicting normal WM , we developed a five-level predictive score . The proportions of segments showing normal WM at sixth month were as follows ; Level 1 ( 0 indexes ) : 0 of 13 ( 0 % ) ; Level 2 ( normal thickness and /or perfusion ) : 14 of 82 ( 17 % ) ; Level 3 ( dobutamine response ) : 5 of 11 ( 45 % ) ; Level 4 ( non-transmural necrosis ) : 20 of 26 ( 77 % ) ; Level 5 ( non-transmural necrosis and dobutamine response ) : 20 of 21 ( 95 % ) , p < 0.0001 for the trend . These proportions were similar in a matched prospect i ve validation group comprising 16 patients ( 0 % , 18 % , 62 % , 77 % , and 90 % for levels 1 to 5 , respectively , p < 0.0001 for the trend ) . CONCLUSIONS A comprehensive analysis of the four more widely used CMR-derived viability indexes is useful for predicting late systolic function after myocardial infa rct ion Background Reperfusion strategies salvage myocardium at risk in acute myocardial infa rct ion ( MI ) . This clinical study was performed to determine whether areas without evidence of delayed MRI contrast enhancement in MI correspond to viability by means of percent systolic wall thickening ( % SWT ) and enddiastolic wall thickness ( EDWT ) in chronic infa rct ion . Methods Twenty MRI studies were performed in ten patients within 6 days of MI and 3 months post-MI . On a segmental basis the percentage of viable myocardium as defined by contrast-enhanced MRI ( no delayed MRI contrast enhancement ) in acute MI was measured and was compared with % SWT and EDWT in chronic MI . Results Of the 1718 segments in acute infa rct ion in which the percentage of viable myocardium was measured 1333 were found to be completely viable by means of contrast-enhanced MRI ( no delayed MRI contrast enhancement ) . All of these segments revealed % SWT on day 90 post-MI , and 97 % of segments were viable by means of an EDWT of more than 5.5 mm . In 85 segments the proportion of viable myocardium was 50–99 % ( mean 56±8 % ) , with 92 % segments found to be viable by means of % SWT and 92 % by EDWT , and of 156 segments with viable myocardium between 1–49 % ( 36±8 % ) 79 % were found to be viable by means of % SWT and 82 % by EDWT . Corresponding proportions of 144 segments with transmural delayed MRI contrast enhancement in acute MI were 45 % and 17 % . Conclusions In acute reperfused MI viable myocardium as delineated by contrast-enhanced MRI is correlated with clinical parameters of viability . Delayed MRI contrast enhancement resolves nontransmural MI and may become a valuable clinical tool when planning revascularization procedures |
11,310 | 11,687,029 | The studies illustrate that a wide range of approaches are being employed by physiotherapists to treat Parkinson 's disease .
This was confirmed by the UK survey of physiotherapists . | BACKGROUND Despite optimal medical and surgical therapies for Parkinson 's disease , patients develop progressive disability .
The role of the physiotherapist is to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person .
OBJECTIVES To compare the efficacy and effectiveness of physiotherapy with placebo or no interventions in patients with Parkinson 's disease . | OBJECTIVES The effectiveness of an exercise intervention for people in early and midstage Parkinson 's disease ( stages 2 and 3 of Hoehn and Yahr ) in improving spinal flexibility and physical performance in a sample of community-dwelling older people is described . DESIGN AND SETTING Fifty-one men and women , aged 55 - 84 years , identified through advertisement , local support groups , and local neurologists were enrolled into a r and omized , controlled trial . Subjects were assigned r and omly to an intervention or a usual care arm ( i.e. , no specific exercise ) . Of the original 51 participants , 46 completed the r and omized , controlled trial . Participants in the exercise arm ( n = 23 ) received individual instruction three times per week for 10 weeks . Participants in the usual care arm ( n = 23 ) were " wait listed " for intervention . MEASUREMENTS Changes over 10 weeks in spinal flexibility ( i.e. , functional axial rotation ) and physical performance ( i.e. , functional reach , timed supine to st and ) were the primary outcome measures . RESULTS MANOVA conducted for the three primary outcome variables demonstrated significant differences ( P < or = .05 ) between the two groups . Further analysis using ANOVA demonstrated significant differences between groups in functional axial rotation and functional reach for the intervention compared with the control group . There was no significant difference in supine to sit time . CONCLUSION Study results demonstrate that improvements in axial mobility and physical performance can be achieved with a 10-week exercise program for people in the early and midstages of PD The purpose of this study was to determine if a balance and strength training program could improve equilibrium and strength in persons with stage I-III Parkinsonism . Subjects were pre-tested on strength and balance ( EquiTest ) and r and omized into either a treatment or a control group . The treatment subjects participated in 10 weeks of lower limb strength training and balance exercises design ed to challenge a stable posture and increase limits of stability . Both groups were then posttested on balance , knee flexion , knee extension , and ankle inversion strength . Subjects who received strength and balance training demonstrated significantly improved equilibrium and modest gains in knee flexion and extension strength , while the control group showed no improvement in conditions of destabilizing balance environments and significant declines in strength . Results indicate that 10 weeks of balance and strength training lead to improved equilibrium by producing positive changes in two different control mechanisms . One , training altered the ability to control the motor system when vestibular cues had to be the primary source of reliable feedback ; and two , training helped subjects to override faulty proprioceptive feedback and utilize reliable visual or vestibular cues Objective : To determine whether the Alex and er Technique , alongside normal treatment , is of benefit to people disabled by idiopathic Parkinson 's disease . Design : A r and omized controlled trial with three groups , one receiving lessons in the Alex and er Technique , another receiving massage and one with no additional intervention . Measures were taken pre and post-intervention , and at follow-up , six months later . Setting : The Polyclinic at the University of Westminster , Central London . Subjects : Ninety-three people with clinical ly confirmed idiopathic Parkinson 's disease . Interventions : The Alex and er Technique group received 24 lessons in the Alex and er Technique and the massage group received 24 sessions of massage . Main outcome measures : The main outcome measures were the Self- assessment Parkinson 's Disease Disability Scale ( SPDDS ) at best and at worst times of day . Secondary measures included the Beck Depression Inventory and an Attitudes to Self Scale . Results : The Alex and er Technique group improved compared with the no additional intervention group , pre-intervention to post-intervention , both on the SPDDS at best , p = 0.04 ( confidence interval ( CI ) –6.4 to 0.0 ) and on the SPDDS at worst , p = 0.01 ( CI –11.5 to –1.8 ) . The comparative improvement was maintained at six-month follow-up : on the SPDDS at best , p = 0.04 ( CI –7.7 to 0.0 ) and on the SPDDS at worst , p = 0.01 ( CI –11.8 to –0.9 ) . The Alex and er Technique group was comparatively less depressed post-intervention , p = 0.03 ( CI –3.8 to 0.0 ) on the Beck Depression Inventory , and at six-month follow-up had improved on the Attitudes to Self Scale , p = 0.04 ( CI –13.9 to 0.0 ) . Conclusions : There is evidence that lessons in the Alex and er Technique are likely to lead to sustained benefit for people with Parkinson 's disease BACKGROUND Baseline data collected on each patient at r and omisation in controlled clinical trials can be used to describe the population of patients , to assess comparability of treatment groups , to achieve balanced r and omisation , to adjust treatment comparisons for prognostic factors , and to undertake subgroup analyses . We assessed the extent and quality of such practice s in major clinical trial reports . METHODS A sample of 50 consecutive clinical -trial reports was obtained from four major medical journals during July to September , 1997 . We tabulated the detailed information on uses of baseline data by use of a st and ard form . FINDINGS Most trials presented baseline comparability in a table . These tables were often unduly large , and about half the trials inappropriately used significance tests for baseline comparison . Methods of r and omisation , including possible stratification , were often poorly described . There was little consistency over whether to use covariate adjustment and the criteria for selecting baseline factors for which to adjust were often unclear . Most trials emphasised the simple unadjusted results and covariate adjustment usually made negligible difference . Two-thirds of the reports presented subgroup findings , but mostly without appropriate statistical tests for interaction . Many reports put too much emphasis on subgroup analyses that commonly lacked statistical power . INTERPRETATION Clinical trials need a predefined statistical analysis plan for uses of baseline data , especially covariate-adjusted analyses and subgroup analyses . Investigators and journals need to adopt improved st and ards of statistical reporting , and exercise caution when drawing conclusions from subgroup findings The aim of this study was to evaluate the effects of orofacial physiotherapeutic treatment ( OPT ) on the facial mobility of Parkinson 's disease ( PD ) sufferers . Sixteen participants with PD were allocated r and omly to either the Treatment group or the Control group . A short interview between the physiotherapist and each subject was videotaped , and 10 r and om frames of the videotape were selected to be used in the facial expression assessment . The quantification of facial expressions was achieved by using an objective microcomputer-based measurement system , based on a mathematical model of the face ( FACEM ) . A facial outline is obtained , as well as 12 facial measures , which represent distances between key facial l and marks . The facial assessment was performed on 3 separate occasions , that is , baseline ( pretreatment ) , posttreatment , and follow-up ( 4 weeks later ) . A repeated measures analysis of variance ( MANOVA ) revealed a significant main effect of Time and a significant interaction effect between Time and Group for the Mouth-Opening Measure , suggesting that after treatment , members of the Treatment group opened their mouths to a greater degree than members of the Control group . Within the Treatment group , significant differences between pretreatment and posttreatment scores ( MANOVA ) were found for Mouth-Opening Measure and Mid-Top-Lip Measure . Similarly , Mouth-Opening Measure , Mid-Top-Lip Measure , Lower-Lip Thickness Measure , Top Eyelid/Iris Intersect Measure and Lower Eyelid/Iris Intersect Measure were significant across time from baseline to follow-up in the Treatment group only . No significant differences were found on any of the facial measures during the same period for members of the Control group . These findings suggest that OPT can improve facial movement and that this benefit extends in time , beyond the period of OPT itself . Such an increase in facial mobility can be expected to modify the " Parkinsonian facies " and facilitate the display of facial expressions Rhythmic auditory stimulation ( RAS ) was used as a pacemaker during a 3-week home-based gait-training program for Parkinson 's disease ( PD ) patients ( n = 15 ) . Electromyogram ( EMG ) patterns and stride parameters were assessed before and after the test without RAS to evaluate changes in gait patterns . Data were compared with those of two control groups ( n = 11 ) , who either did not participate in any gait training or who participated in an internally self-paced training program . RAS consisted of audiotapes with metronome-pulse patterns embedded into the on/off beat structure of rhythmically accentuated instrumental music . Patients who trained with RAS significantly ( p < 0.05 ) improved their gait velocity by 25 % , stride length by 12 % , and step cadence by 10 % more than self-paced subjects who improved their velocity by 7 % and no-training subjects whose velocity decreased by 7 % . In the RAS-group , timing of EMG patterns changed significantly ( p < 0.05 ) in the anterior tibialis and vastus lateralis muscles . Evidence for rhythmic entrainment of gait patterns was shown by the ability of the RAS group to reproduce the speed of the last training tape within a 2 % margin of error without RAS Objectives : To accurately establish the incidence of falls in Parkinson 's disease ( PD ) and to investigate predictive risk factors for fallers from baseline data . Methods : 109 subjects with idiopathic PD diagnosed according to the brain bank criteria underwent a multidisciplinary baseline assessment comprising demographic and historical data , disease specific rating scales , physiotherapy assessment , tests of visual , cardiovascular and autonomic function , and bone densitometry . Patients were then prospect ively followed up for one year using weekly prepaid postcards along with telephone follow up . Results : Falls occurred in 68.3 % of the subjects . Previous falls , disease duration , dementia , and loss of arm swing were independent predictors of falling . There were also significant associations between disease severity , balance impairment , depression , and falling . Conclusions : Falls are a common problem in PD and some of the major risk factors are potentially modifiable . There is a need for future studies to look at interventions to prevent falls 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 Abstract We studied prospect ively the epidemiology , clinical impact and prediction of falls in 59 moderately affected patients with Parkinson 's disease ( PD ) ( mean UPDRS motor score 31.5 ; mean age 61 years ) and 55 controls ( mean age 60 years ) . At baseline , balance and gait were evaluated extensively . The retropulsion test ( response to sudden shoulder pull ) was executed first unexpectedly and five more times following prior warning . All persons used st and ardised scoring forms to document their falls during six months . Thirty patients ( 50.8 % ) and eight controls ( 14.5 % ) fell at least once ( relative risk [ RR ] 6.1 ; 95 % confidence interval [ CI ] 2.5–15.1 , p < 0.001 ) . Recurrent ( ≥ 2 ) falls occurred in 15 patients ( 25.4 % ) , but in only two controls ( RR 9.0 ; 95 % CI 2.0–41.7 ; p=0.001 ) . Recurrent falls were more common among persons taking benzodiazepines ( RR 5.0 ; 95 % CI 1.6–15.5 ; p < 0.01 ) . Sixty-two percent of the falls in patients caused soft tissue injuries , but no fractures occurred . A fear of future falls was common ( 45.8 % of patients ) and was accompanied by restriction of daily activities ( 44.1 % of patients ) . Seventy percent of falls reported by patients were ‘ intrinsic ’ ( due to patient-related factors ) , but falls in controls were mainly ( 50 % ) ‘ extrinsic ’ ( due to environmental factors ) . None of the baseline posture and gait variables predicted falls adequately . The first ‘ unexpected ’ retropulsion test was more often abnormal than all subsequent ( predictable ) tests . Irrespective of its method of execution , the retropulsion test did not predict falls . A combination of asking for prior falls , disease severity and the Romberg test yielded the best overall diagnostic utility ( sensitivity 65 % and specificity 98 % ) . Recurrent fallers were best predicted by disease severity ( RR for Hoehn and Yahr stage 3 was > 100 ; 95 % CI 3.1–585 ) and asking for prior falls ( RR 5.0 ; 95 % CI 1.2–20.9 ) . We conclude that falls are common and disabling , even in relatively early stage PD . Recurrent fallers were best predicted by disease severity and presence of prior falls . Strategies to prevent falls in PD should particularly focus at intrinsic ( patient-related ) factors , such as minimising the use of benzodiazepines 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 |
11,311 | 29,860,722 | No r and omised controlled trials have compared the effectiveness and risks of continuous antibiotic therapy versus intermittent antibiotic therapy for bronchiectasis .
High- quality clinical trials are needed to establish which of these interventions is more effective for reducing the frequency and duration of exacerbations , antibiotic resistance and the occurrence of serious adverse events | BACKGROUND Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection , inflammation and tissue damage .
Antibiotics are a main treatment for bronchiectasis .
The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load , but bacteria may become resistant to the antibiotic , leading to a loss of effectiveness .
On the other h and , intermittent prophylactic antibiotics , given over a predefined duration and interval , may reduce antibiotic selection pressure and reduce or prevent the development of resistance .
This systematic review aim ed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy , the emergence of resistance and serious adverse events .
OBJECTIVES To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis , using the primary outcomes of exacerbations , antibiotic resistance and serious adverse events . | 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 ) The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis ( NCFB ) are to reduce the number of exacerbations , and improve quality of life . However , currently no therapies are licensed for this . Ciprofloxacin Dry Powder for Inhalation ( Ciprofloxacin DPI ) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients . The RESPIRE programme consists of two international phase III prospect i ve , parallel-group , r and omized , double-blinded , multicentre , placebo-controlled trials of the same design . Adult patients with idiopathic or post-infectious NCFB , a history of ≥2 exacerbations in the previous 12months , and positive sputum culture for one of seven pre-specified pathogens , undergo stratified r and omization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5 mg or placebo using a pocket-sized inhaler in one of two regimens : 28days on/off treatment or 14days on/off treatment . The treatment period is 48weeks plus an 8-week follow-up after the last dose . The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation . Secondary endpoints , including frequency of events using different exacerbation definitions , microbiology , quality of life and lung function will also be evaluated . The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI . The strict entry criteria and stratified r and omization , the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy . Additionally RESPIRE will increase underst and ing of NCFB treatment and could lead to an important new therapy for sufferers . TRIAL REGISTRATION The RESPIRE trials are registered in Clinical Trials.gov , ID number NCT01764841 ( RESPIRE 1 ; date of registration January 8 , 2013 ) and NCT02106832 ( RESPIRE 2 ; date of registration April 4 , 2014 ) RATIONALE Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency , a more rapid decline in lung function , and increased mortality in patients with bronchiectasis . OBJECTIVES To perform a r and omized placebo-controlled study assessing the efficacy and safety of inhaled colistin in patients with bronchiectasis and chronic P. aeruginosa infection . METHODS Patients with bronchiectasis and chronic P. aeruginosa infection were enrolled within 21 days of completing a course of antipseudomonal antibiotics for an exacerbation . Participants were r and omized to receive colistin ( 1 million IU ; n = 73 ) or placebo ( 0.45 % saline ; n = 71 ) via the I-neb twice a day , for up to 6 months . MEASUREMENTS AND MAIN RESULTS The primary endpoint was time to exacerbation . Secondary endpoints included time to exacerbation based on adherence recorded by the I-neb , P. aeruginosa bacterial density , quality of life , and safety parameters . All analyses were on the intention-to-treat population . Median time ( 25 % quartile ) to exacerbation was 165 ( 42 ) versus 111 ( 52 ) days in the colistin and placebo groups , respectively ( P = 0.11 ) . In adherent patients ( adherence quartiles 2 - 4 ) , the median time to exacerbation was 168 ( 65 ) versus 103 ( 37 ) days in the colistin and placebo groups , respectively ( P = 0.038 ) . P. aeruginosa density was reduced after 4 ( P = 0.001 ) and 12 weeks ( P = 0.008 ) and the St. George 's Respiratory Question naire total score was improved after 26 weeks ( P = 0.006 ) in the colistin versus placebo patients , respectively . There were no safety concerns . CONCLUSIONS Although the primary endpoint was not reached , this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection . Clinical trial registered with http://www.is rct n.org/ ( IS RCT N49790596 ) Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use . However , little is known about the wider , potentially adverse impacts of these treatments . Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation , while increases in macrolide resistance carriage would represent a serious public health concern . Using sample s from a r and omized controlled trial , we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota . We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance . Determining the clinical significance of these changes , relative to treatment benefit , now represents a research priority . ABSTRACT Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis . However , little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance . We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis , enrolled in the Bronchiectasis and Low-dose Erythromycin Study ( BLESS ) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate ( 400 mg ) . Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR , respectively . Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae ( P = 0.041 ) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae ( P = 0.024 ) and Actinomyces odontolyticus ( P = 0.027 ) . Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp . ( P = 0.046 ) . Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A ) , erm(B ) , erm(C ) , erm(F ) , mef(A/E ) , and msrA macrolide resistance genes . However , the abundance of erm(B ) and mef(A/E ) gene copies within carriers who had received erythromycin increased significantly ( P < 0.05 ) . Our findings indicate that changes in oropharyngeal microbiota composition result ing from long-term erythromycin treatment are modest and are limited to a discrete group of taxa . Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance . IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use . However , little is known about the wider , potentially adverse impacts of these treatments . Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation , while increases in macrolide resistance carriage would represent a serious public health concern . Using sample s from a r and omized controlled trial , we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota . We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance . Determining the clinical significance of these changes , relative to treatment benefit , now represents a research priority IMPORTANCE Macrolide antibiotics have been shown beneficial in cystic fibrosis ( CF ) and diffuse panbronchiolitis , and earlier findings also suggest a benefit in non-CF bronchiectasis . OBJECTIVE To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis . DESIGN , SETTING , AND PARTICIPANTS The BAT ( Bronchiectasis and Long-term Azithromycin Treatment ) study , a r and omized , double-blind , placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherl and s among 83 out patients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year . INTERVENTIONS Azithromycin ( 250 mg daily ) or placebo for 12 months . MAIN OUTCOME MEASURES Number of infectious exacerbations during 12 months of treatment . Secondary end points included lung function , sputum bacteriology , inflammatory markers , adverse effects , symptom scores , and quality of life . RESULTS Forty-three participants ( 52 % ) received azithromycin and 40 ( 48 % ) received placebo and were included in the modified intention-to-treat analysis . At end of study , the median number of exacerbations in the azithromycin group was 0 ( interquartile range [ IQR ] , 0 - 1 ) , compared with 2 ( IQR , 1 - 3 ) in the placebo group ( P < .001 ) . Thirty-two ( 80 % ) placebo-treated vs 20 ( 46 % ) azithromycin-treated individuals had at least 1 exacerbation ( hazard ratio , 0.29 [ 95 % CI , 0.16 - 0.51 ] ) . In a mixed-model analysis , change in forced expiratory volume in the first second of expiration ( percent of predicted ) over time differed between groups ( F1,78.8 = 4.085 , P = .047 ) , with an increase of 1.03 % per 3 months in the azithromycin group and a decrease of 0.10 % per 3 months in the placebo group . Gastrointestinal adverse effects occurred in 40 % of patients in the azithromycin group and in 5 % in the placebo group ( relative risk , 7.44 [ 95 % CI , 0.97 - 56.88 ] for abdominal pain and 8.36 [ 95 % CI , 1.10 - 63.15 ] for diarrhea ) but without need for discontinuation of study treatment . A macrolide resistance rate of 88 % was noted in azithromycin-treated individuals , compared with 26 % in the placebo group . CONCLUSIONS AND RELEVANCE Among adults with non-CF bronchiectasis , the daily use of azithromycin for 12 months compared with placebo result ed in a lower rate of infectious exacerbations . This could result in better quality of life and might influence survival , although effects on antibiotic resistance need to be considered . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00415350 RATIONALE Although airway microbiota composition correlates with clinical measures in non-cystic fibrosis bronchiectasis , these data are unlikely to provide useful prognostic information at the individual patient level . A system enabling microbiota data to be applied clinical ly would represent a substantial translational advance . OBJECTIVES This study aims to determine whether stratification of patients according to the predominant microbiota taxon can provide improved clinical insight compared with st and ard diagnostics . METHODS The presence of bacterial respiratory pathogens was assessed in induced sputum from 107 adult patients by culture , quantitative PCR , and , in 96 sample s , by ribosomal gene pyrosequencing . Prospect i ve analysis was performed on sample s from 42 of these patients . Microbiological data were correlated with concurrent clinical measures and subsequent outcomes . MEASUREMENTS AND MAIN RESULTS Microbiota analysis defined three groups : Pseudomonas aeruginosa dominated ( n = 26 ) , Haemophilus influenzae dominated ( n = 34 ) , and other taxa dominated ( n = 36 ) . Patients with P. aeruginosa- and H. influenzae-dominated communities had significantly worse lung function , higher serum levels of C-reactive protein ( CRP ) , and higher sputum levels of IL-8 and IL-1β . Predominance of P. aeruginosa , followed by Veillonella species , was the best predictor of future exacerbation frequency , with H. influenzae-dominated communities having significantly fewer episodes . Detection of P. aeruginosa was associated with poor lung function and exacerbation frequency , irrespective of analytical strategy . Quantitative PCR revealed significant correlations between H. influenzae levels and sputum IL-8 , IL-1β , and serum CRP . Genus richness was negatively correlated with 24-hour sputum weight , age , serum CRP , sputum IL-1β , and IL-8 . CONCLUSIONS Stratification of patients with non-cystic fibrosis bronchiectasis on the basis of predominant bacterial taxa is more clinical ly informative than either conventional culture or quantitative PCR-based analysis . Further investigation is now required to assess the mechanistic basis of these associations RATIONALE There are no risk stratification tools for morbidity and mortality in bronchiectasis . Identifying patients at risk of exacerbations , hospital admissions , and mortality is vital for future research . OBJECTIVES This study describes the derivation and validation of the Bronchiectasis Severity Index ( BSI ) . METHODS Derivation of the BSI used data from a prospect i ve cohort study ( Edinburgh , UK , 2008 - 2012 ) enrolling 608 patients . Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up . The score was vali date d in independent cohorts from Dundee , UK ( n = 218 ) ; Leuven , Belgium ( n = 253 ) ; Monza , Italy ( n = 105 ) ; and Newcastle , UK ( n = 126 ) . MEASUREMENTS AND MAIN RESULTS Independent predictors of future hospitalization were prior hospital admissions , Medical Research Council dyspnea score greater than or equal to 4 , FEV1 < 30 % predicted , Pseudomonas aeruginosa colonization , colonization with other pathogenic organisms , and three or more lobes involved on high-resolution computed tomography . Independent predictors of mortality were older age , low FEV1 , lower body mass index , prior hospitalization , and three or more exacerbations in the year before the study . The derived BSI predicted mortality and hospitalization : area under the receiver operator characteristic curve ( AUC ) 0.80 ( 95 % confidence interval , 0.74 - 0.86 ) for mortality and AUC 0.88 ( 95 % confidence interval , 0.84 - 0.91 ) for hospitalization , respectively . There was a clear difference in exacerbation frequency and quality of life using the St. George 's Respiratory Question naire between patients classified as low , intermediate , and high risk by the score ( P < 0.0001 for all comparisons ) . In the validation cohorts , the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88 . CONCLUSIONS The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality , hospitalization , and exacerbations across healthcare systems This phase II , r and omised , double-blind , multicentre study ( NCT00930982 ) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation ( DPI ) in patients with non-cystic fibrosis bronchiectasis . Adults who were culture positive for pre-defined potential respiratory pathogens ( including Pseudomonas aeruginosa and Haemophilus influenzae ) were r and omised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days ( with 56 days of follow-up ) . Bacterial density in sputum ( primary end-point ) , pulmonary function tests , health-related quality of life and safety were monitored throughout the study . 60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo . Subjects on ciprofloxacin DPI had a significant reduction ( p<0.001 ) in total sputum bacterial load at the end of treatment ( -3.62 log10 CFU·g−1 ( range -9.78–5.02 log10 CFU·g−1 ) ) compared with placebo ( -0.27 log10 CFU·g−1 ( range -7.96–5.25 log10 CFU·g−1 ) ) ; the counts increased thereafter . In the ciprofloxacin DPI group , 14 ( 35 % ) out of 40 subjects reported pathogen eradication at end of treatment versus four ( 8 % ) out of 49 in the placebo group ( p=0.001 ) . No abnormal safety results were reported and rates of bronchospasm were low . Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis BACKGROUND The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in r and omised controlled trials . We aim ed to assess safety and efficacy of aztreonam for inhalation solution ( AZLI ) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation . METHODS AIR-BX1 and AIR-BX2 were two double-blind , multicentre , r and omised , placebo-controlled phase 3 trials , which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms . Patients were r and omly assigned to receive either AZLI or placebo ( 1:1 ) . R and omisation was done without stratification and the code was generated by a Gilead design ee . In both studies , two 4-week courses of AZLI 75 mg or placebo ( three-times daily ; eFlow nebulizer ) were each followed by a 4-week off-treatment period . Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores ( QOL-B-RSS ) at 4 weeks . These trials are registered with Clinical Trials.gov , numbers are NCT01313624 for AIR-BX1 and NCT01314716 for AIR-BX2 . FINDINGS We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2 ; studies were done between April 25 , 2011 , and July 1 , 2013 . In AIR-BX1 , of the 348 patients screened , 134 were r and omly assigned to receive AZLI and 132 to receive placebo . In AIR-BX2 , of the 404 patients screened , 136 were r and omly assigned to receive AZLI and 138 to receive placebo . The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RSS was not significant at 4 weeks ( 0.8 [ 95 % CI -3.1 to 4.7 ] , p=0.68 ) in AIR-BX1 , but was significant ( 4.6 [ 1.1 to 8.2 ] , p=0.011 ) in AIR-BX2 . The 4.6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinical ly significant . In both studies , treatment-related adverse events were more common in the AZLI group than in the placebo group , as were discontinuations from adverse events . The most commonly reported treatment-emergent adverse events were dyspnea , cough , and increased sputum . Each was more common for AZLI-treated than for placebo-treated patients , but the incidences were more balanced in AIR-BX2 . INTERPRETATION AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis , as measured by QOL-B-RSS , suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder . FUNDING Gilead Sciences Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients . There have been no previous international guidelines . The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature . A multidisciplinary group representing respiratory medicine , microbiology , physiotherapy , thoracic surgery , primary care , methodology and patients considered the most relevant clinical questions ( for both clinicians and patients ) related to management of bronchiectasis . Nine key clinical questions were generated and a systematic review was conducted to identify published systematic review s , r and omised clinical trials and observational studies that answered these questions . We used the GRADE approach to define the quality of the evidence and the level of recommendations . The result ing guideline addresses the investigation of underlying causes of bronchiectasis , treatment of exacerbations , pathogen eradication , long term antibiotic treatment , anti-inflammatories , mucoactive drugs , bronchodilators , surgical treatment and respiratory physiotherapy . These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes . The publication of the first ERS guidelines for bronchiectasis BACKGROUND The burden of disease in children with non-cystic fibrosis ( non-CF ) bronchiectasis is unknown . Our study aim ed to identify the determinants of quality of life ( QOL ) and parental mental health in this group of patients and their parents and to evaluate the effect of exacerbations on these parameters . METHODS Parents of 69 children ( median age 7 years ) with non-CF bronchiectasis prospect ively completed two question naires ( parent-proxy cough-specific quality of life [ PC-QOL ] and the Depression , Anxiety , and Stress Scale [ DASS ] ) at stable and exacerbation states . Data on clinical , investigational , and lung function parameters were also collected . RESULTS During the stable state , the median interquartile range ( IQR ) PC-QOL score was 6.5 ( 5.3 - 6.9 ) and the DASS 21-item question naire score was 6 ( 0 - 20 ) . Being of a young age correlated with a worse QOL ( r(5 ) = 0.242 , P = .04 ) but radiologic extent , lung function , underlying cause , environmental tobacco smoke exposure , and chronic upper-airway disease did not influence these scores . Exacerbations caused significant worsening in the PC-QOL scores ( median [ IQR ] , 4.6 [ 3.8 - 5.4 ] ; P = .001 ) and DASS scores ( median [ IQR ] , 22 [ 9 - 42 ] ; P < .001 ; 38 % with elevated anxiety , 54 % with abnormal depression/stress scores during exacerbation ) . The presence of viral infection , hypoxia , and hospitalization did not influence the exacerbation PC-QOL and DASS scores . CONCLUSIONS There is a significant burden of disease , especially during exacerbation , on parents of children with bronchiectasis . Prevention , early detection , and appropriate treatment of exacerbations are likely to reduce psychologic morbidity in this group BACKGROUND Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties . We tested the hypothesis that azithromycin would decrease the frequency of exacerbations , increase lung function , and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis . METHODS We undertook a r and omised , double-blind , placebo-controlled trial at three centres in New Zeal and . Between Feb 12 , 2008 , and Oct 15 , 2009 , we enrolled patients who were 18 years or older , had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year , and had a diagnosis of bronchiectasis defined by high-resolution CT scan . We r and omly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio , with a permuted block size of six and sequential assignment stratified by centre . Participants , research assistants , and investigators were masked to treatment allocation . The co primary endpoints were rate of event-based exacerbations in the 6-month treatment period , change in forced expiratory volume in 1 s ( FEV(1 ) ) before bronchodilation , and change in total score on St George 's respiratory question naire ( SGRQ ) . Analyses were by intention to treat . This study is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12607000641493 . FINDINGS 71 patients were in the azithromycin group and 70 in the placebo group . The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period ( rate ratio 0·38 , 95 % CI 0·26 - 0·54 ; p<0·0001 ) . Prebronchodilator FEV(1 ) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group , but the difference was not significant ( 0·04 L , 95 % CI -0·03 to 0·12 ; p=0·251 ) . Additionally , change in SGRQ total score did not differ between the azithromycin ( -5·17 units ) and placebo groups ( -1·92 units ; difference -3·25 , 95 % CI -7·21 to 0·72 ; p=0·108 ) . INTERPRETATION Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year . FUNDING Health Research Council of New Zeal and and Auckl and District Health Board Charitable Trust 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 Fluoroquinolones are broad spectrum antimicrobial agents with excellent in vitro activity against Gram-negative pathogens , and variable activity against Gram-positive organisms and some intracellular pathogens such as chlamydia.[l ] Levofloxacin , the i-isomer of ofloxacin , is a new fluoroquinolone demonstrating greater activity and tolerability than ofloxacin ( fig. 1 ) . In vitro , the activity oflevofloxacin is equal to , or up to 4 times greater than , that of ofloxacin against a wide range of Gram-positive , Gram-negative , and anaerobic organismsPl As a single iso ~ er , it is believed that , in addition to the advantages pffered by its racemic predecessor ofloxacin ( such as excellent tolerability , no interactions with theqphylline , and a pharmacokinetic profile enabling a once-daily dosage schedule ) , levofloxacin requires only half the dose of ofloxacin to achieve equal efficacy . Levofloxacin has also been reported to have more potent microbiological activity than other currently marketed quinolonesPl The activity of levofloxacin against Enterobacteriaceae , Pseudomonas aeruginosa and Gram-positive organisms is lapproximately twice that reported for ofloxacinPl The purpose of this study was to evaluate the clinical efficacy and tolerability of orallevofloxacin I ~ n patients with difficult-to-treat respiratory tract infections and compare the 2 different levofloxacin dosage schedules ( 300 mg/day and 600 mg/day ) . Patients in this study had either diffuse panbronchiolitis ( DPB ) or bronchiectasis caused by Pseudomonas aeruginosa Aims : To prospect ively estimate the incidence of bronchiectasis among New Zeal and ( NZ ) children , to consider aetiology and severity , and to evaluate regional and ethnic variation . Methodology : NZ paediatricians were surveyed monthly for new cases of bronchiectasis during 2001 and 2002 via the NZ paediatric surveillance unit ( with coverage of > 94 % of NZ paediatricians ) . Notified cases had their computed tomography scans review ed and scored for severity . Confirmed cases were followed up by postal question naire one year after diagnosis . Demographic , aetiological , and severity data were collected . Results : Ninety nine notifications were received . Sixty five cases were confirmed . An overall incidence of 3.7 per 100 000 under 15 year old children per year was estimated . Incidence was highest in Pacific children at 17.8 compared with 4.8 in Maori , 1.5 in NZ European , and 2.4 other per 100 000 per year . Incidence varied significantly by region . The median age at diagnosis was 5.2 years ; the majority had symptoms for more than two years . Eighty three per cent had bilateral disease , with a median of three lobes affected , mean FEV1 of 77 % predicted , and modified Bhalla H RCT score of 18 . Conclusions : The incidence of bronchiectasis is high in NZ children , nearly twice the rate for cystic fibrosis and seven times that of Finl and , the only other country reporting a childhood national rate . Incidence varied substantially between ethnicities . Most cases developed disease in early childhood and had delayed diagnosis Summary Two different oral ofloxacin regimens , daily single-dose treatment with 200 mg ( Regimen I ) and every two week multidose treatment with 3 × 200 mg/day ( Regimen II ) , were compared to evaluate the efficacy of quinolone regimens in controlling acute exacerbations of chronic respiratory tract infections . Fifty-one patients were evaluated in the study : 28 in Regimen I and 23 in Regimen II . The corrected mean incidence of exacerbation per case during the six months before and during the study was reduced from 2.45 to 0.48 in Regimen I , and from 2.79 to 1.0 in Regimen II . The development of resistant strains was not found to be a problem . We conclude that the long-term administration of new quinolones , especially the daily single-dose regimen with 200 mg of ofloxacin , is useful in controlling acute exacerbations of chronic respiratory tract infections . ZusammenfassungZur Kontrolle akuter Exazerbationen chronischer Atemwegserkrankungen wurde Ofloxacin in zwei verschiedenen Therapieprotokollen eingesetzt ; dabei wurden entweder täglich 200 mg als Einmaldosis oder alle zwei Wochen dreimal täglich 200 mg oral verabreicht . Von den 51 auswertbaren Patienten erhielten 28 das erstgenannte Protokoll I , 23 Protokoll II . In einer Beobachtungszeit von sechs Monaten vor der Studie hatte i m Vergleich zur Studienphase bei Patienten der Gruppe I die Inzidenz der Exazerbationen i m Mittel von 2,45 auf 0,48 und in Gruppe II von 2,79 auf 1 abgenommen . Probleme durch Resistenzentwicklung traten nicht auf . Unserer Ansicht nach ist die Langzeitanwendung neuer Chinolone , vor allem bei täglicher Einnahme von 200 mg , eine wirksame Method e zur Prävention akuter Exazerbationen chronischer Atemwegsinfektionen |
11,312 | 28,752,414 | The studies indicate that mindfulness- and relaxation-based eHealth interventions can have positive effects on patients ’ general health and psychological well-being .
No effects were found for stress or mindfulness .
Conclusion There is some evidence that mindfulness- and relaxation-based eHealth interventions for medical conditions can have positive effects on health outcomes .
Therefore , such interventions might be a useful addition to st and ard medical care . | Purpose This systematic review aims to summarize eHealth studies with mindfulness- and relaxation-based interventions for medical conditions and to determine whether eHealth interventions have positive effects on health . | The aim of this study was to investigate if cognitive behavior therapy ( CBT ) based on exposure and mindfulness exercises delivered via the Internet would be effective in treating participants with irritable bowel syndrome ( IBS ) . Participants were recruited through self-referral . Eighty-six participants were included in the study and r and omized to treatment or control condition ( an online discussion forum ) . One participant was excluded after r and omization . The main outcome measure was IBS-symptom severity and secondary measures included IBS-related quality of life , GI-specific anxiety , depression and general functioning . Participants were assessed at pre-treatment , post-treatment and 3 month follow-up ( treatment condition only ) . Four participants ( 5 % of total sample ) in the treatment condition did not participate in post-treatment assessment . Participants in the treatment condition reported a 42 % decrease and participants in the control group reported a 12 % increase in primary IBS-symptoms . Compared to the control condition , participants in the treatment group improved on all secondary outcome measures with a large between group effect size on quality of life ( Cohen 's d = 1.21 ) . We conclude that CBT-based on exposure and mindfulness delivered via the Internet can be effective in treating IBS- patients , alleviating the total burden of symptoms and increasing quality of life Acceptance and commitment therapy ( ACT ) interventions for persons with chronic pain have recently received empirical support . ACT focuses on reducing the disabling influences of pain through targeting ineffective control strategies and teaches people to stay in contact with unpleasant emotions , sensations , and thoughts . The aim of the present study was to investigate the effect of a guided internet-delivered ACT intervention for persons with chronic pain . A total of 76 patients with chronic pain were included in the study and r and omized to either treatment for 7 weeks or to a control group that participated in a moderated online discussion forum . Intent-to-treat analyses showed significant increases regarding activity engagement and pain willingness . Measurements were provided with the primary outcome variable Chronic Pain Acceptance Question naire which was in favour of the treatment group . Reductions were found on other measures of pain-related distress , anxiety and depressive symptoms . A six month follow-up showed maintenance of improvements . We conclude that an acceptance based internet-delivered treatment can be effective for persons with chronic pain Background : Although mindfulness meditation interventions have recently shown benefits for reducing stress in various population s , little is known about their relative efficacy compared with relaxation interventions . Purpose : This r and omized controlled trial examines the effects of a 1-month mindfulness meditation versus somatic relaxation training as compared to a control group in 83 students ( M age=25 ; 16 men and 67 women ) reporting distress . Method : Psychological distress , positive states of mind , distractive and ruminative thoughts and behaviors , and spiritual experience were measured , while controlling for social desirability . Results : Hierarchical linear modeling reveals that both meditation and relaxation groups experienced significant decreases in distress as well as increases in positive mood states over time , compared with the control group ( p<.05 in all cases ) . There were no significant differences between meditation and relaxation on distress and positive mood states over time . Effect sizes for distress were large for both meditation and relaxation ( Cohen ’s d=1.36 and .91 , respectively ) , whereas the meditation group showed a larger effect size for positive states of mind than relaxation ( Cohen ’s d=.71 and .25 , respectively ) . The meditation group also demonstrated significant pre-post decreases in both distractive and ruminative thoughts/behaviors compared with the control group ( p<.04 in all cases ; Cohen ’s d=.57 for rumination and .25 for distraction for the meditation group ) , with mediation models suggesting that mindfulness meditation ’s effects on reducing distress were partially mediated by reducing rumination . No significant effects were found for spiritual experience . Conclusions : The data suggest that compared with a no-treatment control , brief training in mindfulness meditation or somatic relaxation reduces distress and improves positive mood states . However , mindfulness meditation may be specific in its ability to reduce distractive and ruminative thoughts and behaviors , and this ability may provide a unique mechanism by which mindfulness meditation reduces distress Background Internet-based cognitive behavior therapy ( ICBT ) has shown promising effects in the treatment of irritable bowel syndrome ( IBS ) . However , to date no study has used a design where participants have been sample d solely from a clinical population . We aim ed to investigate the acceptability , effectiveness , and cost-effectiveness of ICBT for IBS using a consecutively recruited sample from a gastroenterological clinic . Methods Sixty-one patients were r and omized to 10 weeks of ICBT ( n = 30 ) or a waiting list control ( n = 31 ) . The ICBT was guided by an online therapist and emphasized acceptance of symptoms through exposure and mindfulness training . Severity of IBS symptoms was measured with the Gastrointestinal symptom rating scale - IBS version ( GSRS-IBS ) . Patients in both groups were assessed at pre- and post-treatment while only the ICBT group was assessed 12 months after treatment completion . Health economic data were also gathered at all assessment points and analyzed using bootstrap sampling . Results Fifty of 61 patients ( 82 % ) completed the post-treatment assessment and 20 of 30 patients ( 67 % ) in the ICBT group were assessed at 12-month follow-up . The ICBT group demonstrated significantly ( p < .001 ) larger improvements on the IBS-related outcome scales than the waiting list group . The between group effect size on GSRS-IBS was Cohen 's d = 0.77 ( 95 % CI : 0.19 - 1.34 ) . Similar effects were noted on measures of quality of life and IBS-related fear and avoidance behaviors . Improvements in the ICBT group were maintained at 12-month follow-up . The ICBT condition was found to be more cost-effective than the waiting list , with an 87 % chance of leading to reduced societal costs combined with clinical effectiveness . The cost-effectiveness was sustained over the 12-month period . Conclusions ICBT proved to be a cost-effective treatment when delivered to a sample recruited from a gastroenterological clinic . However , many of the included patients dropped out of the study and the overall treatment effects were smaller than previous studies with referred and self-referred sample s. ICBT may therefore be acceptable and effective for only a subset of clinical patients . Study dropout seemed to be associated with severe symptoms and large impairment . Objective and empirically vali date d criteria to select which patients to offer ICBT should be developed . Trial Registration Clinical Trials.gov : Decentering has been proposed as a potential mechanism of mindfulness-based interventions but has received limited empirical examination to date in experimental studies comparing mindfulness meditation to active comparison conditions . In the present study , we compared the immediate effects of mindful breathing ( MB ) to two alternative stress-management techniques : progressive muscle relaxation ( PMR ) and loving-kindness meditation ( LKM ) to test whether decentering is unique to mindfulness meditation or common across approaches . Novice meditators ( 190 female undergraduates ) were r and omly assigned to complete one of three 15-min stress-management exercises ( MB , PMR , or LKM ) presented by audio recording . Immediately after the exercise , participants completed measures of decentering , frequency of repetitive thoughts during the exercise , and degree of negative reaction to thoughts . As predicted , participants in the MB condition reported greater decentering relative to the other two conditions . The association between frequency of repetitive thought and negative reactions to thoughts was relatively weaker in the MB condition than in the PMR and LKM conditions , in which these two variables were strongly and positively correlated . Consistent with the construct of decentering , the relative independence between these two variables in the MB condition suggests that mindful breathing may help to reduce reactivity to repetitive thoughts . Taken together , results help to provide further evidence of decentering as a potential mechanism that distinguishes mindfulness practice from other credible stress-management approaches Background Irritable Bowel Syndrome ( IBS ) is highly prevalent and is associated with a substantial economic burden . Cognitive behavior therapy ( CBT ) has been shown to be effective in treating IBS . The aim of this study was to evaluate the cost-effectiveness of a new treatment alternative , internet-delivered CBT based on exposure and mindfulness exercises . Methods Participants ( N = 85 ) with IBS were recruited through self-referral and were assessed via a telephone interview and self-report measures on the internet . Participants were r and omized to internet-delivered CBT or to a discussion forum . Economic data was assessed at pre- , post- and at 3-month and 1 year follow-up . Results Significant cost reductions were found for the treatment group at $ 16,806 per successfully treated case . The cost reductions were mainly driven by reduced work loss in the treatment group . Results were sustained at 3-month and 1 year follow-up . Conclusions Internet-delivered CBT appears to generate health gains in IBS treatment and is associated with cost-savings from a societal perspective Behavioral training ( BT ) is recommended as a supplementary preventive treatment for migraine . Online interventions have been successful in promoting health behavior change , the evidence for online BT in migraine is limited , however . This r and omized controlled trial aim ed to determine the post-treatment effectiveness of online BT ( n = 195 ) compared to a waitlist control group ( WLC ; n = 173 ) on migraine attack frequency ( primary outcome ) , headache self-efficacy and locus of control ( secondary outcomes ) . BT aims to counteract attacks in the prodromal stage through early detection of prodromal features and self-management via physical relaxation and cognitive behavioral regulation , and was offered with minimal e-mail support in eight online lessons . Results showed that 120 ( 62 % ) participants completed BT . A decrease of 20 - 25 % in migraine attack frequency was found in both conditions without a between-group difference ( ES = 0.02 , p = .71 ) . BT participants improved more than WLC participants on migraine related self-efficacy ( ES = 0.86 , p < .001 ) , developed more internal ( ES = 0.57 , p < .001 ) , and less external control ( ES = 0.78 , p < .001 ) . To conclude , results at post-training did not corroborate that improvements in migraine attack frequency were due to online BT , the waitlist control group improved accordingly . However , positive effects of BT on self-efficacy and locus of control were established . We have to await the long term effects to see if improvements in psychological variables translate to a reduction in migraine headache Mindfulness-based Cognitive Therapy ( MBCT ) has been shown to effectively prevent relapse and reduce residual depressive symptoms ( RDS ) , yet it faces barriers to dissemination . The present study examined Mindful Mood Balance ( MMB ) , the first web-based approach to deliver the core content of MBCT . Of the 107 recurrently depressed individuals screened , 100 elected to enroll in the study and received MMB in an 8-session open trial with 6-month follow-up . Outcomes included depressive symptom severity , rumination and mindful awareness , and program engagement . A quasi-experimental comparison between MMB participants and propensity matched case-controls receiving usual depression care ( UDC ) ( N = 100 ) also was conducted . The full sample and the subgroup with residual depressive symptoms ( N = 42 ) showed significantly reduced depressive severity , which was sustained over six months , and improvement on rumination and mindfulness . Examination of acceptability of MMB indicated that 42 % of participants within the full sample and 36 % of the RDS subgroup completed all 8 sessions and 53 % within the full sample and 50 % within the RDS subgroup completed at least 4 sessions , and that participants engaged with daily mindfulness practice . MMB also was associated with significant reduction in RDS severity as compared to quasi-experimental propensity matched controls . Although the use of a non-r and omized design , with potential unmeasured differences between groups , and short interval of clinical follow-up were limitations , findings from this study support the web-based delivery of MBCT and suggest clinical benefits for participants with histories of depression and with RDS , relative to those receiving usual care alone BACKGROUND AND AIMS In the past decade , a large body of research has demonstrated that internet-based interventions can have beneficial effects on depression . However , only a few clinical trials have compared internet-based depression therapy with an equivalent face-to-face treatment . The primary aim of this study was to compare treatment outcomes of an internet-based intervention with a face-to-face intervention for depression in a r and omized non-inferiority trial . METHOD A total of 62 participants suffering from depression were r and omly assigned to the therapist-supported internet-based intervention group ( n=32 ) and to the face-to-face intervention ( n=30 ) . The 8 week interventions were based on cognitive-behavioral therapy principles . Patients in both groups received the same treatment modules in the same chronological order and time-frame . Primary outcome measure was the Beck Depression Inventory-II ( BDI-II ) ; secondary outcome variables were suicidal ideation , anxiety , hopelessness and automatic thoughts . RESULTS The intention-to-treat analysis yielded no significant between-group difference ( online vs. face-to-face group ) for any of the pre- to post-treatment measurements . At post-treatment both treatment conditions revealed significant symptom changes compared to before the intervention . Within group effect sizes for depression in the online group ( d=1.27 ) and the face-to-face group ( d=1.37 ) can be considered large . At 3-month follow-up , results in the online group remained stable . In contrast to this , participants in the face-to-face group showed significantly worsened depressive symptoms three months after termination of treatment ( t=-2.05 , df=19 , p<.05 ) . LIMITATIONS Due to the small sample size , it will be important to evaluate these outcomes in adequately-powered trials . CONCLUSIONS This study shows that an internet-based intervention for depression is equally beneficial to regular face-to-face therapy . However , more long term efficacy , indicated by continued symptom reduction three months after treatment , could be only be found for the online group Background Complementary therapies ( CT ) , such as relaxation technique , massage , guided imagery , and accupuncture have shown to benefit patients undergoing surgery . The aim of this study was to determine the feasibility of using audio relaxation technique ( ART ) , music intervention ( MI ) , nature video application with music ( NVAM ) , and nature video application without music ( NVA ) delivered via mobile technologies in a clinical setting . Secondary , the effects of ART , MI , NVAM and NVA on patients ’ state anxiety , pain perception , and perceived self-efficacy in healing were determined . Methods A r and omized clinical trial ( RCT ) involving 105 same day surgery ( SDS ) patients , who were assigned to an ART ( n = 25 ) , MI ( n = 25 ) , NVAM ( n = 15 ) , NVA ( n = 16 ) , or a control group ( n = 24 ) were assessed for state anxiety , self-reported pain , and self-efficacy four days prior to surgery , immediately prior and following a surgical intervention , and day five post-operative . Results ANOVA found no statistically significant differences in anxiety scores ; pain , or perceived self-efficacy between the five groups . Matched pairs t-Test revealed all participants had an increase in anxiety from pre-op to day 10 follow-up ; a significant change in pain levels from pre-op to day 10 follow-up ; and all participants had a significant increase in general self-efficacy from pre-op to day 10 follow-up . Mean pain level scores from day 1 to pre-op showed a significant decrease in pain for the ART group and NVAM group . Matched pairs t-Test for self-efficacy scores indicated the MI group and the NVA group had significant increases in self-efficacy . A significant decrease in anxiety from pre-op to day 10 for participants reporting a prior history of anxiety and for those reporting prior history of taking anti-anxiety medications . Conclusions Despite the non-significant findings between the five groups , at any measurement point , there were valuable trends toward significance and confirmed feasibility in a clinical setting . Among the groups there were statistically significant findings for all interventions on anxiety , pain , and self-efficacy . The feasability of the implementation of novel interventions of NVAM and NVAM adds to clinical practice and the CT literature .Trial registration Clinical Trials.gov Identifier : NCT02236455 ( September 4 , 2014 Background Mindfulness has been shown to be effective in treating various medical and mental problems . Especially its incorporation in cognitive-behavioural interventions has improved long-term outcomes of those treatments . It has also been shown , that brief mindfulness-based trainings are effective in reducing distress . There have been few web-based interventions incorporating mindfulness techniques in their manual and it remains unclear whether a brief web-based mindfulness intervention is feasible . Methods Out of 50 adults ( different distress levels ; exclusion criteria : < 18 years , indication of psychotic or suicidal ideation in screening ) who were recruited via e-mail and screened online , 49 were r and omized into an immediate 2-weeks-treatment group ( N = 28 ) or a waitlist-control group ( N = 21 ) , starting with a 2-week delay . Distress ( BSI ) , perceived stress ( PSQ ) , mindfulness ( FMI ) , as well as mood and emotion regulation ( PANAS/SEK-27 ) were measured at pre- , post- and 3-month follow-up ( 3MFU ) . Intention-to-treat analyses using MI for missing data and per- protocol analyses ( ≥ 50 % attendance ) were performed . Results 26 participants of the treatment group completed post- measures . Most measures under ITT- analysis revealed no significant improvement for the treatment group , but trends with medium effect sizes for PSQ ( d = 0.46 ) and PANASneg ( d = 0.50 ) and a small , non-significant effect for FMI ( d = 0.29 ) . Per- protocol analyses for persons who participated over 50 % of the time revealed significant treatment effects for PSQ ( d = 0.72 ) and PANASneg ( d = 0.77 ) . Comparing higher distressed participants with lower distressed participants , highly distressed participants seemed to profit more of the training in terms of distress reduction ( GSI , d = 0.85 ) . Real change ( RCI ) occurred for PSQ in the treatment condition ( OR = 9 ) . Results also suggest that participants continued to benefit from the training at 3MFU . Conclusion This study of a brief web-based mindfulness training indicates that mindfulness can be taught online and may improve distress , perceived stress and negative affect for regular users . Although there were no significant improvements , but trends , for most measures under ITT , feasibility of such a program was demonstrated and also that persons continued to use techniques of the training in daily life . Trial Registration German Clinical Trials Register ( DRKS ) : An internet-delivered cognitive behavioral treatment ( ICBT ) based on systematic exposure exercises has previously shown beneficial effects for patients with irritable bowel syndrome ( IBS ) . Exposure exercises may be perceived as difficult for patients to perform because of the elicited short-term distress and clinicians may be reluctant to use these interventions . The aim of this study was to compare ICBT with the same protocol without systematic exposure ( ICBT-WE ) to assess if exposure had any incremental value . This r and omized controlled dismantling study included 309 participants diagnosed with IBS . The treatment interventions lasted for 10 weeks and included online therapist contact . ICBT-WE comprised mindfulness , work with life values , acceptance , and encouraged reduced avoidance behaviors , while ICBT also included systematic exposure to IBS symptoms and related situations . Severity of IBS symptoms was measured with the Gastrointestinal Symptom Rating Scale - IBS version ( GSRS-IBS ) . The between-group Cohen 's d on GSRS-IBS was 0.47 ( 95 % CI : 0.23 - 0.70 ) at post-treatment and 0.48 ( 95 % CI : 0.20 - 0.76 ) at 6-month follow-up , favoring ICBT . We conclude that the systematic exposure included in the ICBT protocol has incremental effects over the other components in the protocol . This study provides evidence for the utility of exposure exercises in psychological treatments for IBS Purpose This study evaluated the efficacy of a self-guided Web-based cognitive behaviour therapy ( CBT ) intervention compared to an attention control in improving cancer-related distress , health-related quality of life ( HRQOL ) , and maladaptive coping , among people recently diagnosed with cancer . Methods Sixty individuals with cancer diagnosed in the previous 6 months and receiving treatment with curative intent were r and omised to receive either the 6-week intervention Cancer Coping Online ( CCO : n = 30 ) or the 6-week Web-based attention control ( n = 30 ) . Outcome measures , including cancer distress ( the Posttraumatic Stress Scale — Self-Report ) , general distress ( Depression Anxiety Stress Scale ) , quality of life ( EORTC QLQ-C30 ) , and coping ( mini-MAC ) , were administered at baseline , immediately post-intervention , and at 3 and 6 months post-intervention . Results Significant main effects for time were found for cancer distress , global QOL , physical function , role function , social function , and anxious preoccupation . Post hoc between-group comparisons showed CCO participants had statistically significantly higher physical functioning compared to controls at 3 months of follow-up ( d = −0.52 , p = 0.02 ) . Furthermore , compared to controls , post hoc comparisons found moderate between-group effect sizes favouring CCO post-intervention for cancer distress ( d = 0.43 ) and anxious preoccupation ( d = 0.38 ) , and at 6 months of follow-up for global QOL ( d = −0.43 ) . Conclusions These results provide preliminary support for the potential efficacy of a self-guided Web-based CBT programme in improving aspects of HRQOL , cancer-related distress , and anxious preoccupation after cancer diagnosis . This paper provides justification for , and will help inform the development of , subsequent larger multi-site studies 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 The aim of the present study was to investigate two interventions based on Acceptance and Commitment Therapy ( ACT ) for depressive symptoms : A face-to-face treatment ( ACT group ) was compared to a guided self-help treatment delivered via the Internet consisting of two assessment sessions ( pre and post ) and an ACT-based Internet program ( iACT ) . Out patients experiencing at least mild depressive symptoms were r and omized to either approach . The iACT treatment group received access to an ACT-based Internet program and supportive web-based contact over a period of 6 weeks . The face-to-face group received ACT-based treatment once a week over the same period of time . In both groups , the results showed a significant effect on depression symptomatology , and general wellbeing after treatment and at the 18-month follow-up . However , the data indicated that the iACT group changed differently regarding depressive symptoms and wellbeing as compared to the face-to face ACT group . Results showed large pre-treatment to 18-month follow-up within-group effect sizes for all symptom measures in the iACT treatment group ( 1.59 - 2.08 ) , and for most outcome measures in the face-to-face ACT group ( 1.12 - 1.37 ) . This non-inferiority study provides evidence that guided Internet-delivered ACT intervention can be as effective as ACT-based face-to-face treatment for out patients reporting depressive symptoms , and it may offer some advantages over a face-to-face intervention Acceptance-based psychological interventions can potentially minimize the burden of chronic pain . This r and omized controlled trial evaluated an internet-delivered , guided self-help intervention based on Acceptance and Commitment Therapy ( ACT ) . A total of 238 chronic pain sufferers from the general population were r and omly allocated to either ACT ( n = 82 ) , an internet-based control condition Expressive Writing ( n = 79 ) or a waiting list condition ( n = 77 ) . Participants completed measures at baseline , posttreatment ( 3 months ) and at a 3-month follow-up . At follow-up , ACT participants had improved in pain interference in daily life ( primary outcome ) compared to participants in Expressive Writing ( Cohen ’s d = .47 ) , but not compared to waiting list participants ( p value = .11 ) . Those who adhered to the ACT-intervention ( 48 % ) did improve significantly compared to waiting list participants ( d = .49 ) . ACT- participants also showed superior improvement on depression , pain intensity , psychological inflexibility and pain catastrophizing ( d : .28–.60 ) . Significant clinical improvement was present . Especially , 28 % of ACT- participants showed general clinical ly relevant improvement in pain interference , as well as in pain intensity and depression ( vs. Expressive Writing and waiting list 5 % ) . Given these findings , internet-based ACT programs may be a promising treatment modality for chronic pain UNLABELLED The Self-care Pain Management Project assessed the feasibility and efficacy of delivering online mind-body self-care techniques to 78 adults aged 55 and older with chronic pain . To assess feasibility , the study monitored use of the intervention and documented participant satisfaction . A r and omized trial with intervention ( n = 41 ) and waiting list comparison groups ( n = 37 ) was used to assess changes in pain intensity , limitations due to pain , pain self-efficacy , depression , anxiety , and awareness of responses to pain from baseline to follow-up at 6 weeks . There were statistically significant results for between-group difference in awareness of responses to pain , improvements in pain intensity and pain interference for both groups , and increases in confidence with using nonmedical self-care techniques to manage pain for the intervention group . Reductions in mean pain scores reported by the intervention group at log on and log off also suggest that the intervention may have an immediate impact on reducing pain . Findings document the feasibility of a relatively short-term , online mind-body pain management intervention that can have benefits for participants . The characteristics of those who volunteered for an online self-care pain management intervention also have implication s for identifying target population s for such interventions . PERSPECTIVE This article documents the outcomes of an Internet-based self-care pain management intervention that focused on mind-body exercises . The study suggests that the Internet can be an efficient mode for delivering self-care education to older adults with chronic pain and has potential benefits that complement clinical care Background : Acceptance and commitment therapy ( ACT ) is a promising treatment option for fibromyalgia ( FM ) . Studies have shown that many cognitive behavioral protocol s can be transferred to the Internet with sustained efficacy . However , no study has investigated the effect on an Internet-delivered ACT-based protocol for FM . This study evaluated the efficacy , acceptability , and the health economic effects of an Internet-delivered acceptance and values-based exposure treatment for FM . Methods : This open pilot trial included 41 self-referred women with a FM diagnosis . The 10-week Internet-delivered treatment included acceptance , mindfulness , work with life-values , and systematic exposure to FM symptoms and FM-related situations . Participants also had regular contact with an assigned online therapist . Assessment s were made at pretreatment , post-treatment , and 6-month follow-up . Results : The treatment was completed by 70 % of the participants . Attrition rates were low , with 98 % completing the post-treatment assessment and 90 % completing the 6-month follow-up assessment . Multiple imputations were used to replace missing values . Pre- to post-treatment within-group effect sizes were in the moderate to large range ( Cohen 's d = 0.62–1.56 ) on measures of FM symptoms and impact , disability , quality of life , depression , anxiety , fatigue , and psychological flexibility . All improvements were maintained at follow-up . Economical analyses revealed significant societal cost reductions that offset the treatment costs within 2 months of treatment completion . Conclusions : An Internet-delivered psychological treatment based on acceptance and exposure principles seems to be an efficacious , acceptable , and cost-effective treatment for FM . R and omized controlled trials are needed to confirm these results The Internet can reach a large number of people at a low cost and offers the opportunity for 2-way communication . The present study was design ed to evaluate the effects of applied relaxation and problem solving in the treatment of recurrent headache when implemented via the Internet and E-mail . A group of 102 headache sufferers were r and omized to 2 conditions : a 6-week treatment condition or a waiting-list control . The dropout was proportionately large ( 56 % ) , and at the end of the study there were 20 participants in the treatment condition and 25 participants in the control condition . Results showed statistically significant reductions in headache for the treated participants . In 50 % of these , the reduction was clinical ly significant . The Internet has the potential to serve as a complement in the treatment of recurrent headache and deserves further study Chronic headache is a significant public health problem in Western nations . Although controlled trials demonstrate the efficacy and cost-effectiveness of face-to-face behavioral therapy , most headache sufferers have limited access to these treatments . Delivery of behavioral interventions using Internet technology has the potential to reach a larger number of headache sufferers and reduce the burden of disease . This r and omized controlled study evaluated an Internet-delivered behavioral regimen composed of progressive relaxation , limited biofeedback with autogenic training , and stress management versus a symptom monitoring waitlist control . Treatment led to a significantly greater decrease in headache activity than symptom monitoring alone . Thirty-nine percent of treated individuals showed clinical ly significant improvement on self-report measures of headache symptoms at post-treatment . At two-month follow-up , 47 % of participants maintained improvement . Treatment had a significant impact on general headache symptoms and headache-related disability . There was a 35 % within-group reduction of medication usage among the treated subjects . The Internet program was more time-efficient than traditional clinical treatment . Treatment and follow-up dropout rates , 38.1 % and 64.8 % , respectively , were typical of behavioral self-help studies . This approach to self-management of headache is promising ; however , several method ological and ethical challenges need to be addressed Background : This study tested the effectiveness of a computerized mindfulness-based cognitive therapy intervention compared with computerized pain management psychoeducation in a r and omized study . Methods : Using an intention-to-treat approach , 124 adult participants who reported experiencing pain that was unrelated to cancer and of at least 6 months duration were r and omly assigned to computerized mindfulness-based cognitive therapy ( “ Mindfulness in Action ” [ MIA ] ) or pain management psychoeducation programs . Data were collected before and after the intervention and at 6-month follow-up . Results : Participants in both groups showed equivalent change and significant improvements on measures of pain interference , pain acceptance , and catastrophizing from pretreatment to posttreatment and the improvements were maintained at follow-up . Average pain intensity also reduced from baseline to posttreatment for both groups , but was not maintained at follow-up . Participants in both groups reported increases in subjective well-being , these were more pronounced in the MIA than the pain management psychoeducation group . Participants in the MIA group also reported a greater reduction in pain “ right now , ” and increases in their ability to manage emotions , manage stress , and enjoy pleasant events on completion of the intervention . The changes in ability to manage emotions and stressful events were maintained at follow-up . Conclusions : The results of the study provide evidence that although there were equivalent changes across outcomes of interest for participants in both conditions over time , the MIA program showed a number of unique benefits . However , the level of participant attrition in the study highlighted a need for further attention to participant engagement with online chronic pain programs Cognitive behavioral stress management groups have been shown to be decrease psychological symptoms and increase adaptive coping in breast cancer patients , but dissemination of this effective intervention has been challenging . The goal of the present project was to develop an online cognitive behavioral stress management intervention for early stage breast cancer survivors and evaluate its effectiveness using a 2 group × 3 time r and omized , waitlist-controlled design . Intervention and waitlist control group participants were assessed at three time points : at baseline ; at 10 weeks , after which only intervention participants had used the workbook ; and at 20 weeks , after which both groups had used the workbook . Results indicate that at 10 weeks intervention participants showed improved self-efficacy for coping with their cancer and for regulating negative mood and lower levels of cancer-related post-traumatic symptoms as compared to the control group , suggesting that an internet stress management intervention could be effective for helping breast cancer patients increase their confidence in their ability to cope with stress The effectiveness of biofeedback-assisted behavioral treatment with Internet-based client-therapist contact for hypertension was tested in outpatient setting s. A pilot study with a r and omized controlled design was adopted with two conditions ( treatment versus passive controls ) , lasting for 8 weeks . There were two assessment time points ( pre-treatment and post-treatment ) measuring clinic systolic and diastolic blood pressure ( SBP and DBP ) and administration of a question naire collecting demographic and subjective data . Participants included 19 Swedish adults diagnosed with hypertension . The treatment group lowered their SBP 5.9 mm Hg and their DBP 7.6 mm Hg while the control group lowered their SBP 0.8 mm Hg and DBP 3.0 mm Hg . The effect of treatment was significant for DBP but not for SBP . There were no other significant effects of treatment . This pilot study shows encouraging results regarding Internet-based biofeedback treatment for hypertensive adults . However , further research using a larger sample is needed OBJECTIVES There is growing evidence that mindfulness has positive consequences for both psychological and physical health in both clinical and non- clinical population s. The potential benefits of mindfulness underpin a range of therapeutic intervention approaches design ed to increase mindfulness in both clinical and community context s. Self-guided mindfulness-based interventions may be a way to increase access to the benefits of mindfulness . This study explored whether a brief , online , mindfulness-based intervention can increase mindfulness and reduce perceived stress and anxiety/depression symptoms within a student population . METHOD One hundred and four students were r and omly allocated to either immediately start a two-week , self-guided , online , mindfulness-based intervention or a wait-list control . Measures of mindfulness , perceived stress and anxiety/depression were administered before and after the intervention period . RESULTS Intention to treat analysis identified significant group by time interactions for mindfulness skills , perceived stress and anxiety/depression symptoms . Participation in the intervention was associated with significant improvements in all measured domains , where no significant changes on these measures were found for the control group . CONCLUSIONS This provides evidence in support of the feasibility and effectiveness of shorter self-guided mindfulness-based interventions . The limitations and implication s of this study for clinical practice are discussed Background Patients with fibromyalgia ( FM ) experience pain as well as deficits in positive affect and social relations that are not explicitly addressed in most behavioral treatments . Purpose The purpose of this study is to compare the effects of a 12-module online intervention targeting socioemotional regulation via mindful awareness/acceptance ( MSER ) with those of an attention-control treatment , healthy lifestyle tips ( HT ) . Methods Seventy-nine FM patients were r and omly assigned to MSER or HT , with outcomes assessed via online diary reports of pain , coping efficacy , affect , and social relations . Multilevel analyses revealed greater improvements in social functioning , positive affect , and coping efficacy for pain and stress ( all ps < .05 ) in MSER versus HT across the 6-week trial . Conclusions FM patients experience increases in self-efficacy for coping with pain and positive engagement in relationships , marginal increases in positive affect , and decreases in relationship stress from an automated online intervention that targets socioemotional regulation skills . Findings highlight the potential utility of widely accessible , low-cost intervention methods for fibromyalgia ( Clinical trials.gov number NCT01748786 ) OBJECTIVE Our aim in this r and omized controlled trial was to investigate the effects on global tinnitus severity of 2 Internet-delivered psychological treatments , acceptance and commitment therapy ( ACT ) and cognitive behavior therapy ( CBT ) , in guided self-help format . METHOD Ninety-nine participants ( mean age = 48.5 years ; 43 % female ) who were significantly distressed by tinnitus were recruited from the community . Participants were r and omly assigned to CBT ( n = 32 ) , ACT ( n = 35 ) , or a control condition ( monitored Internet discussion forum ; n = 32 ) , and they were assessed with st and ardized self-report measures ( Tinnitus H and icap Inventory ; Hospital Anxiety and Depression Scale ; Quality of Life Inventory ; Perceived Stress Scale ; Tinnitus Acceptance Question naire ) at pre- , posttreatment ( 8 weeks ) , and 1-year follow-up . RESULTS Mixed-effects linear regression analysis of all r and omized participants showed significant effects on the primary outcome ( Tinnitus H and icap Inventory ) for CBT and for ACT compared with control at posttreatment ( 95 % CI [ -17.03 , -2.94 ] , d = 0.70 , and 95 % CI [ -16.29 , -2.53 ] , d = 0.68 , respectively ) . Within-group effects were substantial from pretreatment through 1-year-follow-up for both treatments ( 95 % CI [ -44.65 , -20.45 ] , d = 1.34 ) , with no significant difference between treatments ( 95 % CI [ -14.87 , 11.21 ] , d = 0.16 ) . CONCLUSIONS Acceptance-based procedures may be a viable alternative to traditional CBT techniques in the management of tinnitus . The Internet can improve access to psychological interventions for tinnitus |
11,313 | 30,350,760 | However , the beneficial effects of POM supplementation appeared to be less likely when ( i ) unilateral eccentric exercise was employed , ( ii ) the POM administered was not rich in polyphenols ( < 1·69 g/l ) and ( iii ) insufficient time was provided between POM-ingestion and the assessment of physiological responses/performance ( ≤1 h ) .
The review indicates that POM has the potential to enhance exercise performance and to expedite recovery from intensive exercise .
The findings and recommendations from this review may help to optimise POM-supplementation practice in athletes and coaches to potentially improve exercise-performance and post-exercise recovery | The functional significance of pomegranate ( POM ) supplementation on physiological responses during and following exercise is currently unclear .
This systematic review aim ed ( i ) to evaluate the existing literature assessing the effects of POM supplementation on exercise performance and recovery ; exercise-induced muscle damage , oxidative stress , inflammation ; and cardiovascular function in healthy adults and ( ii ) to outline the experimental conditions in which POM supplementation is more or less likely to benefit exercise performance and /or recovery .
The existing evidence suggests that POM supplementation has the potential to confer antioxidant and anti-inflammatory effects during and following exercise , to improve cardiovascular responses during exercise , and to enhance endurance and strength performance and post-exercise recovery . | PURPOSE Dietary supplementation with polyphenols , particularly ellagitannins , may attenuate the muscular damage experienced after eccentric exercise , producing delayed-onset muscle soreness . The purpose of this study was to determine whether ellagitannin supplementation from Wonderful variety pomegranate extract ( POMx ) improved recovery of skeletal muscle strength after eccentric exercise . METHODS Recreationally active males were r and omized into a crossover design with either pomegranate extract ( POMx ) or placebo ( PLA ) , each given during a period of 9 d . To produce delayed-onset muscle soreness , subjects performed two sets of 20 maximal eccentric elbow flexion exercises with one arm . Maximal isometric elbow flexion strength and muscle soreness as well as serum measures of creatine kinase , myoglobin , interleukin 6 , and C-reactive protein were made at baseline and 2 , 24 , 48 , 72 , and 96 h after exercise . RESULTS With both treatments , strength was similarly reduced 2 h after exercise ( i.e. , 72 % of baseline ) , and recovery of strength was incomplete after 96 h ( i.e. , 91 % of baseline).However , strength was significantly higher in POMx compared with that in PLA at 48 h ( 85.4 % + /- 2.5 % and 78.3 % + /- 2.6 % , P = 0.01 ) and 72 h ( 88.9 % + /- 2.0 % and 84.0 % + /- 2.0 % , P = 0.009 ) after exercise . Serum markers of inflammation and muscle damage did not provide insight regarding possible mechanisms . CONCLUSIONS Supplementation with ellagitannins from pomegranate extract significantly improves recovery of isometric strength 2 - 3 d after a damaging eccentric exercise The aims of the present study were to : ( 1 ) investigate the effect of a weightlifting training session and time-of-day ( TOD ) upon biological parameters ( i.e. , oral temperature , hematological , C-reactive protein ( CRP ) , and oxidative stress ) and ( 2 ) assess their possible link with muscle damage responses . Nine weightlifters ( 21 ± 0.5 years ) performed , in a r and omized order , three Olympic-Weightlifting sessions ( i.e. , at 08:00 , 14:00 , and 18:00 ) . Blood sample s were collected at rest , 3 min and 48 h after each training session . Between pre- and post-training session , ANOVA showed significant increases in oxidative stress markers at the three TODs ( p < 0.01 ) and significant increases for creatine kinase ( CK ) and lactate dehydrogenase ( LDH ) only at 08:00 and 18:00 ( p < 0.05 ) . At rest , the results showed a significant diurnal variation for the majority of the selected parameters except for malondialdehyde ( MDA ) , total bilirubin , and CRP with higher values observed at 18:00 ( p < 0.05 ) . After the training session , given the higher rate of increase during the morning session , these diurnal variations persisted for temperature and WBC ( p < 0.01 ) and were suppressed for CK , LDH , uric acid ( UA ) , catalase , and glutathione peroxidase . The main significant correlations ( p < 0.001 ) were observed between : ( 1 ) CK and MDA ( r = 0.6 ) and CK and UA ( r = 0.66 and r = 0.82 ) during the morning and evening training sessions ; ( 2 ) CK and CRP only during the morning session ( r = 0.5 ) ; and ( 3 ) CRP and WBC during the three training sessions ( r = 0.8 ) . In conclusion , the present findings : ( 1 ) confirm that the muscle damage responses could be induced by a high level of oxidative stress and ( 2 ) suggest to avoid scheduling training sessions in the morning given the higher muscle damage , inflammatory , and oxidative responses at this TOD Recent research has shown that dietary nitrate has favorable effects on blood flow and exercise performance . The purpose of this r and omized , double-blind , placebo-controlled crossover study was to investigate the acute effects of pomegranate extract on blood flow , vessel diameter , and exercise performance in active individuals . Nineteen men and women ( mean ± SD : age , 22.2 ± 2.2 years ; height , 174.8 ± 10.7 cm ; body mass , 71.9 ± 13.5 kg ) were r and omly assigned to a placebo ( PL ) or pomegranate extract ( PE ) group . Participants performed a maximal oxygen consumption treadmill test to determine peak velocity ( PV ) . Participants returned after 24 - 48 h and ingested either PL or PE . Brachial artery blood flow was assessed using ultrasound at baseline and 30 min post-ingestion ( 30minPI ) . Three treadmill runs to exhaustion were performed at 90 % , 100 % , and 110 % PV . Blood flow was assessed immediately after each exercise bout and 30 min postexercise ( 30minPEx ) . After a 7 - 10 day washout , participants repeated the same procedures , ingesting the opposite supplement . Separate repeated measures ANOVAs were performed for blood flow , vessel diameter , and time to exhaustion ( TTE ) . Blood flow was significantly augmented ( p = 0.033 ) 30minPI with PE in comparison with PL . Vessel diameter was significantly larger ( p = 0.036 ) 30minPEx with PE . Ingestion of PE was found to significantly augment TTE at 90 % ( p = 0.009 ) and 100 % PV ( p = 0.027 ) . Acute ingestion of PE 30 min before exercise may enhance vessel diameter and blood flow and delay fatigue during exercise . Results of the current study indicate that PE is ergogenic for intermittent running , eliciting beneficial effects on blood flow Ageing is thought to be associated with decreased vascular function partly due to oxidative stress . Resveratrol is a polyphenol , which in animal studies has been shown to decrease atherosclerosis , and improve cardiovascular health and physical capacity , in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity . We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men . Twenty-seven healthy physically inactive aged men ( age : 65 ± 1 years ; body mass index : 25.4 ± 0.7 kg m(-2 ) ; mean arterial pressure ( MAP ) : 95.8 ± 2.2 mmHg ; maximal oxygen uptake : 2488 ± 72 ml O2 min(-1 ) ) were r and omized into 8 weeks of either daily intake of either 250 mg trans-resveratrol ( n = 14 ) or of placebo ( n = 13 ) concomitant with high-intensity exercise training . Exercise training led to a 45 % greater ( P < 0.05 ) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only ( -4.8 ± 1.7 mmHg ; P < 0.05 ) . The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training ( 980 ± 90 vs. 1174 ± 121 pg ml(-1 ) ; P < 0.02 ) and muscle thromboxane synthase was higher in the resveratrol group after training ( P < 0.05 ) . Resveratrol administration also abolished the positive effects of exercise on low-density lipoprotein , total cholesterol/high-density lipoprotein ratio and triglyceride concentrations in blood ( P < 0.05 ) . Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 ( VCAM-1 ) . Sirtuin 1 protein levels were not affected by resveratrol supplementation . These findings indicate that , whereas exercise training effectively improves several cardiovascular health parameters in aged men , concomitant resveratrol supplementation can blunt these effects Eccentrically biased exercise results in skeletal muscle damage and stimulates adaptations in muscle , whereby indexes of damage are attenuated when the exercise is repeated . We hypothesized that changes in ultrastructural damage , inflammatory cell infiltration , and markers of proteolysis in skeletal muscle would come about as a result of repeated eccentric exercise and that gender may affect this adaptive response . Untrained male ( n = 8) and female ( n = 8) subjects performed two bouts ( bout 1 and bout 2 ) , separated by 5.5 wk , of 36 repetitions of unilateral , eccentric leg press and 100 repetitions of unilateral , eccentric knee extension exercises ( at 120 % of their concentric single repetition maximum ) , the subjects ' contralateral nonexercised leg served as a control ( rest ) . Biopsies were taken from the vastus lateralis from each leg 24 h postexercise . After bout 2 , the postexercise force deficit and the rise in serum creatine kinase ( CK ) activity were attenuated . Women had lower serum CK activity compared with men at all times ( P < 0.05 ) , but there were no gender differences in the relative magnitude of the force deficit . Muscle Z-disk streaming , quantified by using light microscopy , was elevated vs. rest only after bout 1 ( P < 0.05 ) , with no gender difference . Muscle neutrophil counts were significantly greater in women 24 h after bout 2 vs. rest and bout 1 ( P < 0.05 ) but were unchanged in men . Muscle macrophages were elevated in men and women after bout 1 and bout 2 ( P < 0.05 ) . Muscle protein content of the regulatory calpain subunit remained unchanged whereas ubiquitin-conjugated protein content was increased after both bouts ( P < 0.05 ) , with a greater increase after bout 2 . We conclude that adaptations to eccentric exercise are associated with attenuated serum CK activity and , potentially , an increase in the activity of the ubiquitin proteosome proteolytic pathway PURPOSE Vitamin E supplementation may confer a protective effect against eccentrically biased exercise-induced muscle damage through stabilization of the cell membrane and possibly via inhibition of free radical formation . Evidence supporting a protective role of vitamin E after contraction-induced muscle injury in humans is , however , inconsistent . The present study sought to determine the effect of vitamin E supplementation on indices of exercise-induced muscle damage and the postexercise inflammatory response after performance of repeated eccentric muscle contractions . METHODS Young healthy men performed a bout of 240 maximal isokinetic eccentric muscle contractions ( 0.52 rad.s-1 ) after being supplemented for 30 d with either vitamin E ( N = 9 ; 1200 IU.d-1 ) or placebo ( N = 7 ; safflower oil ) . RESULTS Measurements of torque ( isometric and concentric ) decreased ( P < 0.05 ) below preexercise values immediately post- and at 48 h post-exercise . Biopsies taken 24 h postexercise showed a significant increase in the amount of extensive Z-b and disruption ( P < 0.01 ) ; however , neither the torque deficit nor the extent of Z-b and disruption were affected by vitamin E. Exercise result ed in increased macrophage cell infiltration ( P = 0.05 ) into muscle , which was also unaffected by vitamin E. Serum CK also increased as a result of the exercise ( P < 0.05 ) with no effect of vitamin E. CONCLUSION We conclude that vitamin E supplementation ( 30 d at 1200 IU.d-1 ) , which result ed in a 2.8-fold higher serum vitamin E concentration ( P < 0.01 ) , had no affect on indices of contraction-induced muscle damage nor inflammation ( macrophage infiltration ) as a result of eccentrically biased muscle contractions PURPOSE This study investigated the effects of a dietary supplement on exercise-induced markers of cell damage and the inflammatory mediators C-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) . METHODS The supplement contained mixed tocopherols , flavonoids , and docosahexaenoate . Forty healthy , nonsmoking , untrained males ( aged 18 - 35 yr ) were r and omly assigned to receive either the supplement ( N = 20 ) or placebo ( N = 20 ) during the 14-d experimental protocol . Blood sample s were collected on day 0 ( baseline ) , day 7 ( eccentric exercise-induced injury ) , day 10 , and day 14 . OBJECTIVE Markers of cell damage ( creatine kinase ( CK ) and lactate dehydrogenase ( LDH ) ) and inflammation IL-6 and CRP were assessed at these time points in conjunction with subjective range of motion ( ROM ) and perceived pain measurements . Statistical analyses were conducted using nonparametric methods ( P < 0.05 ) . RESULTS Eccentric arm curl exercise was used to induce an acute phase injury response as evidence d by significant ( P < 0.0001 ) increases in CK , LDH , and pain , as well as a decreased range of motion 3 d after the exercise . There were no significant differences between groups in CK and LDH responses . In contrast , there were significant group differences for IL-6 ( P = 0.008 ) and CRP ( P = 0.003 ) . At day 10 , by Mann-Whitney U test of changes , the placebo group had significantly greater increases in IL-6 and CRP than the treatment group ( P = 0.05 and P < 0.01 ) , respectively . CONCLUSION This study suggested that exercise-induced inflammation , evaluated by changes in IL-6 and CRP , was significantly reduced by the dietary supplement The aim of this study was to test the hypothesis that pomegranate juice supplementation would blunt acute and delayed oxidative stress responses after a weightlifting training session . Nine elite weightlifters ( 21.0 ± 1 years ) performed two Olympic-Weightlifting sessions after ingesting either the placebo or pomegranate juice supplements . Venous blood sample s were collected at rest and 3 min and 48 h after each session . Compared to the placebo condition , pomegranate juice supplementation attenuated the increase in malondialdehyde ( −12.5 % ; p < 0.01 ) and enhanced the enzymatic ( + 8.6 % for catalase and + 6.8 % for glutathione peroxidase ; p < 0.05 ) and non-enzymatic ( + 12.6 % for uric acid and + 5.7 % for total bilirubin ; p < 0.01 ) antioxidant responses shortly ( 3 min ) after completion of the training session . Additionally , during the 48 h recovery period , pomegranate juice supplementation accelerated ( p < 0.05 ) the recovery kinetics of the malondialdehyde ( 5.6 % ) and the enzymatic antioxidant defenses compared to the placebo condition ( 9 to 10 % ) . In conclusion , supplementation with pomegranate juice has the potential to attenuate oxidative stress by enhancing antioxidant responses assessed acutely and up to 48 h following an intensive weightlifting training session . Therefore , elite weightlifters might benefit from blunted oxidative stress responses following intensive weightlifting sessions , which could have implication s for recovery between training sessions PURPOSE This study was design ed to ascertain the effects of a combination antioxidant therapy on plasma protein carbonyls ( PC ) , malondialdehyde ( MDA ) , and whole blood total ( TGSH ) , oxidized ( GSSG ) , and reduced ( GSH ) glutathione in non-resistance trained females after eccentric resistance exercise . METHODS Eighteen women ( aged 19 - 31 yr ) were r and omized in a double-blind manner to either an antioxidant supplement ( N = 9 ; 400 IU vitamin E , 1 g vitamin C , and 90 mug selenium per day ) or a lactose placebo ( N = 9 ) for 14 d before and for 2 d after eccentric elbow flexor exercise . Blood sample s taken before and immediately , 2 , 6 , 24 , and 48 h postexercise were analyzed for PC , MDA , TGSH , and GSSG . RESULTS No treatment by time interaction was noted for any variable , with all blood markers experiencing a change after the exercise in both conditions . Time main effects were observed for PC , MDA , and GSSG , with values elevated above preexercise after the eccentric exercise , whereas GSH concentration decreased after the eccentric exercise . Antioxidant supplementation result ed in a condition main effect for PC and MDA , with lower values compared with placebo . The antioxidant treatment attenuated the rise in both PC ( 75 % ) and MDA ( 100 % ) . CONCLUSION These data suggest that eccentric resistance exercise can increase blood biomarkers of oxidative stress in non-resistance trained females , and this vitamin E , C , and selenium supplementation can attenuate the rise in PC and MDA Background Xp and ® 2X is a proprietary blend comprised of branched chain amino acids , creatine monohydrate , beta-alanine ( CarnoSyn ® ) , quercetin , coenzymated B-vitamins , alanyl-glutamine ( Sustamine ® ) , and natural nitrate sources from pomegranate and beet root extracts purported to enhance the neuromuscular adaptations of resistance training . However to date , no long-term studies have been conducted with this supplement . The purpose of this study was to investigate the effects of a multi-ingredient performance supplement ( MIPS ) on skeletal muscle hypertrophy , lean body mass and lower body strength in resistance-trained males . Methods Twenty resistance-trained males ( 21.3 ± 1.9 years ) were r and omly assigned to consume a MIPS or a placebo of equal weight and volume ( food- grade orange flavors and sweeteners ) in a double-blind manner , 30 minutes prior to exercise . All subjects participated in an 8-week , 3-day per week , periodized , resistance-training program that was split-focused on multi-joint movements such as leg press , bench press , and bent-over rows . Ultrasonography measured muscle thickness of the quadriceps , dual-energy X-ray absorptiometry ( DEXA ) determined lean body mass , and strength of the bench press and leg press were determined at weeks 0 , 4 , and 8 of the study . Data were analyzed with a 2 × 3 repeated measures ANOVA with LSD post hoc tests utilized to locate differences . Results There was a significant group-by-time interaction in which the MIPS supplementation result ed in a significant ( p < 0.01 ) increase in strength of the bench press ( 18.4 % vs. 9.6 % ) compared with placebo after 4 and 8 weeks of training . There were no significant group by time interactions between MIPS supplementation nor the placebo in leg press strength ( p = .08 ) . MIPS supplementation also result ed in a significant increase in lean body mass ( 7.8 % vs. 3.6 % ) and quadriceps muscle thickness ( 11.8 % vs. 4.5 % ) compared with placebo ( group*time , p < 0.01 ) . Conclusions These results suggest that this MIPS can positively augment adaptations in strength , and skeletal muscle hypertrophy in resistance-trained men Purpose The aim of this study was to investigate the effect of natural Pomegranate juice supplementation on performance and acute and delayed responses of muscle soreness and biomarkers of muscle damage after a weightlifting training session . Methods Nine elite weightlifters ( 21±0.5 years ) performed two Olympic-Weightlifting-sessions after either placebo ( PLA ) or natural pomegranate juice ( POMj ) supplementations . Heart rate , blood pressure and blood sample s ( hematological parameters , muscle damage and C-reactive protein ( CRP ) ) were collected at rest , 3min and 48h after each session . Weightlifting performance , RPE , and DOMS were also assessed after each training session . Results T-test showed higher performance ( + 8.30 % ) and lower RPE values ( -4.37 % ) using POMj supplementation ( p<0.05 ) in comparison with PLA . For the DOMS values , a significant improvement ( 13.4 % ) was shown only for the knee extensors ( p<0.01 ) using the POMj . Compared to PLA condition , POMj attenuated the acute ( i.e. , 3min ) increase of systolic blood pressure ( SBP ) , HR , CK and LDH ( p<0.05 ; -4.46 % , -1.81 % , -8.75 % , -1.64 % , respectively ) and blunted the significant increase of ASAT , PAL and CRP ( p>0.05 ) . Additionally , during the 48h following the training session , POMj improved the recovery kinetic of SBP ( p<0.01 , 7.97 % ) , CK ( p<0.001 , 11.34 % ) , LDH ( p<0.05 , 7.30 % ) and ASAT ( p<0.05 , 6.77 % ) . Indeed , the present study showed that 48h of recovery associated to natural POMj supplementation was sufficient to reach the resting values of the selected muscle damage markers after intensive training session . Conclusion Natural POMj seems to ameliorate the capacity to adhere to an intensive training program . Therefore , elite weightlifters are advised to use natural POMj during intensive training program and competition to accelerate muscle recovery . Trial Registration Clinical Trials.gov 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 BACKGROUND The present study aim ed to investigate the effect of time-of-days ( TOD ) on some biochemical and hormonal responses after resistance training sessions . METHODS Ten trained subjects ( 22±2 years ) performed , in r and omized order , three resistance-training-sessions at 7 a.m. , 1 p.m. and 5 p.m. Each training-session included six upper and lower body resistance exercises with 3 × 10 repetitions . Blood lactate ( Lac ) , creatine kinase ( CK ) , lactate dehydrogenase ( LDH ) , cortisol ( C ) and testosterone ( T ) were collected at rest , 3 min and 48 h after each-session . RESULTS At rest , steroidal hormones were higher in the morning compared to the evening ( P<0.01 ) , whereas , no significant TOD effect on Lac , CK or LDH was observed . 3min after training , whatever the TOD , Lac , CK and T increased significantly ( P<0.001 ) . However , a significant decrease in C and a significant increase of T/C ratio were registered only after morning training . 3 min and even 48 h after training , the diurnal variations ( i.e. , morning to evening ) of CK and C have been altered with higher early evening values of CK and lower one of C ; whereas , T , Lac and LDH conserved their resting diurnal variation . Additionally , 48 h after the morning session , CK and T/C ratio remained elevated compared to the baseline levels . CONCLUSIONS In conclusion , resistance exercises soliciting both lower and upper limbs seems to alter the diurnal variation of CK and C , to enhance the morning anabolism/catabolism status and to produce more favorable environment for muscular adaptation up to 48 h post-training Background : Numerous antioxidant and anti-inflammatory agents have been identified in tart cherries . Objective : To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage . Methods : This was a r and omised , placebo controlled , crossover design . Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days . A bout of eccentric elbow flexion contractions ( 2 × 20 maximum contractions ) was performed on the fourth day of supplementation . Isometric elbow flexion strength , pain , muscle tenderness , and relaxed elbow angle were recorded before and for four days after the eccentric exercise . The protocol was repeated two weeks later with subjects who took the placebo initially , now taking the cherry juice ( and vice versa ) . The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect . Results : Strength loss and pain were significantly less in the cherry juice trial versus placebo ( time by treatment : strength p<0.0001 , pain p = 0.017 ) . Relaxed elbow angle ( time by treatment p = 0.85 ) and muscle tenderness ( time by treatment p = 0.81 ) were not different between trials . Conclusions : These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage . Most notably , strength loss averaged over the four days after eccentric exercise was 22 % with the placebo but only 4 % with the cherry juice BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Abstract The aim of this study was to investigate the performance of an Olympic-Weightlifting session training at three times of the day on the performance related to biochemical responses . Nine weightlifters ( 21 ± 0.5 years ) performed , in r and omised order , on three Olympic-Weightlifting training ( snatch , clean and jerk ) sessions ( 08:00 a.m. , 02:00 p. m. , 06:00 p. m. ) . Blood sample s were collected : before , 3 min and 48 h after each training session . Haematological parameters and markers of muscle injury were assessed . Resting oral temperature and rating of perceived exertion ( RPE ) were also assessed during each session . ANOVA showed that the performance was better ( P < 0.001 ) at 02:00 p. m. with a less RPE ( P < 0.01 ) compared to the morning and the evening sessions while there was higher ( P < 0.05 ) oral temperature at 06:00 p. m. versus 08:00 a.m. and 02:00 p. m. Muscle damage changed immediately ( without significant effect after 48 h ) after the training sessions with lower values in the evening compared to the morning . In conclusion , the afternoon training is more effective than morning or evening sessions for weightlifters . Therefore , coaches and weightlifters should be advised to schedule their training session in the afternoon hour Trombold , JR , Reinfeld , AS , Casler , JR , and Coyle , EF . The effect of pomegranate juice supplementation on strength and soreness after eccentric exercise . J Strength Cond Res 25(7 ) : 1782 - 1788 , 2011—The purpose of this study was to determine if pomegranate juice supplementation improved the recovery of skeletal muscle strength after eccentric exercise in subjects who routinely performed resistance training . Resistance trained men ( n = 17 ) were r and omized into a crossover design with either pomegranate juice or placebo . To produce delayed onset muscle soreness , the subjects performed 3 sets of 20 unilateral eccentric elbow flexion and 6 sets of 10 unilateral eccentric knee extension exercises . Maximal isometric elbow flexion and knee extension strength and muscle soreness measurements were made at baseline and 2 , 24 , 48 , 72 , 96 , and 168 hours postexercise . Elbow flexion strength was significantly higher during the 2- to 168-hour period postexercise with pomegranate juice compared with that of placebo ( main treatment effect ; p = 0.031 ) . Elbow flexor muscle soreness was also significantly reduced with pomegranate juice compared with that of placebo ( main treatment effect ; p = 0.006 ) and at 48 and 72 hours postexercise ( p = 0.003 and p = 0.038 , respectively ) . Isometric strength and muscle soreness in the knee extensors were not significantly different with pomegranate juice compared with those using placebo . Supplementation with pomegranate juice attenuates weakness and reduces soreness of the elbow flexor but not of knee extensor muscles . These results indicate a mild , acute ergogenic effect of pomegranate juice in the elbow flexor muscles of resistance trained individuals after eccentric exercise Abstract The effects of pomegranate extract ( PE ) supplementation were evaluated on high-intensity exercise performance , blood flow , vessel diameter , oxygen saturation ( SPO2 ) , heart rate ( HR ) , and blood pressure ( BP ) . In a r and omized , crossover design , nineteen recreationally resistance-trained participants were r and omly assigned to PE ( 1000 mg ) or placebo ( PL ) , which were consumed 30 min prior to a repeated sprint ability ( RSA ) test and repetitions to fatigue ( RTF ) on bench and leg press . The RSA consisted of ten six-second sprints on a friction-loaded cycle ergometer with 30 s recovery . Brachial artery blood flow and vessel diameter were assessed by ultrasound . Blood flow , vessel diameter , SPO2 , HR , and BP were assessed at baseline , 30 min post ingestion , immediately post exercise ( IPost ) , and 30 min post exercise ( 30minPost ) . With PE , blood flow significantly increased IPost RSA ( mean difference = 18.49 mL min−1 ; P < .05 ) , and IPost and 30minPost RTF ( P < .05 ) according to confidence intervals ( CI ) . Vessel diameter increased significantly 30minPost RSA according to CI and result ed in a significant interaction IPost and 30minPost RTF ( P < .05 ) . With PE , according to CI , average and peak power output increased significantly in sprint 5 of the RSA ( P < .05 ) . There was no significant difference between PE and PL for bench ( P = .25 ) or leg press ( P = .15 ) repetitions . Acute PE supplementation enhanced vessel diameter and blood flow , suggesting possible exercise performance enhancement from increased delivery of substrates and oxygen . The acute timing and capsule form of PE may be advantageous to athletic population s due to ergogenic effects , taste , and convenience The aim of this study was to investigate the effect of an Olympic-Weightlifting-session followed by 48-h recovery period on the oxidative and antioxidant parameters ’ diurnal variation . Nine weightlifters ( 21 ± 0.5 years ) performed , in r and omized order , three Olympic-Weightlifting-sessions at 08 h:00 , 14 h:00 and 18 h:00 . Blood sample s were collected : at rest and 3 min and 48 h after each session . C-reactive protein ( CRP ) , rate of lipid peroxidation and antioxidant activities were assessed . At rest , analysis of variance showed a significant time of day ( TOD ) effect ( p < 0.05 ) for uric acid , catalase and glutathione peroxidase with higher values at 14 h:00 and 18 h:00 compared with 08 h:00 . However , no significant TOD effect for malondialdehyde , total bilirubin and CRP was observed . Given the profound changes ( p < 0.001 ) in the post-training session values , these diurnal variations have been altered immediately and even 48 h after the training sessions . Despite the significant decreases in the post-training values after the 48-h recovery period ( p < 0.05 ) , levels of lipid peroxidation and enzymatic defense remained elevated ( p < 0.05 ) 48 h after the morning training session . However , after the afternoon and evening sessions , the same period was sufficient to return values to the baseline levels . In conclusion , the morning session seems to generate the most important acute and delayed lipid peroxidation responses . Therefore , weightlifting coaches should avoid scheduling their training sessions in the morning-hours Pomegranate juice contains antioxidants such as soluble polyphenols , tannins , and anthocyanins and may have antiatherosclerotic properties . However , no study has investigated the effects of pomegranate juice on patients who have ischemic coronary heart disease ( CHD ) . We investigated whether daily consumption of pomegranate juice for 3 months would affect myocardial perfusion in 45 patients who had CHD and myocardial ischemia in a r and omized , placebo-controlled , double-blind study . Patients were r and omly assigned into 1 of 2 groups : a pomegranate juice group ( 240 ml/day ) or a placebo group that drank a beverage of similar caloric content , amount , flavor , and color . Participants underwent electrocardiographic-gated myocardial perfusion single-photon emission computed tomographic technetium-99 m tetrofosmin scintigraphy at rest and during stress at baseline and 3 months . Visual scoring of images using st and ardized segmentation and nomenclature ( 17 segments , scale 0 to 4 ) was performed by a blinded independent nuclear cardiologist . To assess the amount of inducible ischemia , the summed difference score ( SDS ) was calculated by subtracting the summed score at rest from the summed stress score . The experimental and control groups showed similar levels of stress-induced ischemia ( SDS ) at baseline ( p > 0.05 ) . After 3 months , the extent of stress-induced ischemia decreased in the pomegranate group ( SDS -0.8 + /- 2.7 ) but increased in the control group ( SDS 1.2 + /- 3.1 , p < 0.05 ) . This benefit was observed without changes in cardiac medications , blood sugar , hemoglobin A1c , weight , or blood pressure in either group . In conclusion , daily consumption of pomegranate juice may improve stress-induced myocardial ischemia in patients who have CHD Muscle ultrastructure and contractile properties were examined before and after a single bout of resistance exercise ( 8 sets of 8 repetitions at 80 % of 1 repetition maximum ) . Eight untrained males performed the concentric ( Con ) phase of arm-curl exercise with one arm and the eccentric ( Ecc ) phase with the other arm . Needle biopsies were obtained from biceps brachii before exercise ( Base ) , immediately postexercise from each arm ( post-Con and post-Ecc ) , and 48 h postexercise from each arm ( 48 h-Con and 48 h-Ecc ) . Electron microscopy was used to quantify the presence of disrupted fibers in each sample . Analysis of variance revealed a greater ( P < or = 0.05 ) proportion of disrupted fibers in post-Con , post-Ecc , 48 h-Con , and 48 h-Ecc sample s compared with Base . Significantly more fibers were disrupted in post-Ecc ( 82 % ) and 48 h-Ecc ( 80 % ) sample s compared with post-Con ( 33 % ) and 48 h-Con ( 37 % ) , respectively . Voluntary and evoked strength measurements recovered to Base values within 24 h in the Con arm but remained depressed ( P < or = 0.05 ) for 72 - 96 h in the Ecc arm . These data indicate that both the raising and lowering phases of weightlifting produced myofibrillar disruption , with the greatest disruption occurring during the lowering phase In the present study , 26 elderly subjects were recruited and r and omly divided into 2 groups , that is , apple ( low in antioxidant capacity ) and pomegranate ( high in antioxidant capacity ) groups , and 250 mL of juice was consumed daily for 4 weeks . Changes in plasma antioxidant capacity , activity of antioxidant enzymes , contents of ascorbic acid , vitamin E , reduced glutathione , malondialdehyde , oxidized low-density lipoprotein and carbonyls , and the degree of DNA damage in mononuclear blood cells were measured . Urine sample s were collected for determination of 8-hydroxy-2'-deoxyguanosine content . Increased plasma antioxidant capacity and decreased plasma carbonyl content were demonstrated after daily consumption of pomegranate juice . In comparison , apple juice consumption presented a less significant effect on antioxidant function in elderly subjects . It is concluded that daily consumption of pomegranate juices is potentially better than apple juice in improving antioxidant function in the elderly . Because the plasma ascorbic acid , vitamin E , and reduced glutathione contents did not differ significantly between the 2 groups in this study , the phenolics may be the functional components contained in pomegranate juice that accounted for the observations |
11,314 | 31,096,667 | Following the PRISMA 2009 guidelines , six electronic data bases ( Food Science and Technology Abstract s ( EBSCO ) , Medline , Scopus , CINAHL , Web of Science and Cochrane ) were search ed for articles investigating the effect of Opuntia spp .
The findings of this review indicate variations in effects between cacti components and products .
Cladode and select Opuntia spp .
products predominately demonstrated significant reductions in serum glucose and insulin , indicating potential as a functional food c and i date .
Prickly Pear fruit was predominately reported to have no significant effects on glucose or insulin .
The quality of evidence appeared to vary based on the type of Opuntia spp .
Studies that used specifically the fruit or cladode had high risk of bias , whereas studies which used combined Opuntia spp .
products had a lower risk of bias .
Conclusion : Currently , there is a lack of evidence to support the recommendation of using Opuntia spp .
fruit products as an alternative or complementary therapy in the reduction of risk or management of Type 2 Diabetes Mellitus . | Background and Objectives : There is confusion as to which component of the Opuntia spp .
cacti has demonstrated anti-hyperglycemic effects or anti-diabetic properties .
It is important to clarify these health benefits due to the increasing need for prevention and treatment of chronic diseases .
The aim of this review is to identify the effects of Opuntia spp .
cacti consumption on biomedical measures ; glucose and insulin with consideration of its ’ components ; fruit , leaf and combined or unidentified Opuntia spp .
products . | Nopal is a plant used in traditional Mexican medicine to treat diabetes . However , there is insufficient scientific evidence to demonstrate whether nopal can regulate postpr and ial glucose . The purpose for conducting this study was to evaluate the glycemic index , insulinemic index , glucose-dependent insulinotropic peptide ( GIP ) index , and the glucagon-like peptide 1 ( GLP-1 ) index , and the effect of nopal on patients with type 2 diabetes after consumption of a high-carbohydrate breakfast ( HCB ) or high-soy-protein breakfast ( HSPB ) on the postpr and ial response of glucose , insulin , GIP , GLP-1 , and antioxidant activity . In study 1 , the glycemic index , insulinemic index , GIP index , and GLP-1 index were calculated for seven healthy participants who consumed 50 g of available carbohydrates from glucose or dehydrated nopal . In study 2 , 14 patients with type 2 diabetes consumed nopal in HCB or HSPB with or without 300 g steamed nopal . The glycemic index of nopal was 32.5±4 , insulinemic index was 36.1±6 , GIP index was 6.5±3.0 , and GLP-1 index was 25.9±18 . For those patients with type 2 diabetes who consumed the HCB+nopal , there was significantly lower area under the curve for glucose ( 287±30 ) than for those who consumed the HCB only ( 443±49 ) , and lower incremental area under the curve for insulin ( 5,952±833 vs 7,313±1,090 ) , and those patients with type 2 diabetes who consumed the HSPB avoided postpr and ial blood glucose peaks . Consumption of the HSPB+nopal significantly reduced the postpr and ial peaks of GIP concentration at 30 and 45 minutes and increased the antioxidant activity after 2 hours measured by the 2,2-diphenyl-1-picrilhidracyl method . These findings suggest that nopal could reduce postpr and ial blood glucose , serum insulin , and plasma GIP peaks , as well as increase antioxidant activity in healthy people and patients with type 2 diabetes AIM OF THE STUDY The aim of this study was to evaluate the acute and chronic effects of OpunDia ( Opuntia ficus-indica ) in obese pre-diabetic men and women . MATERIAL S AND METHODS This double-blind placebo controlled study included participants ( age range of 20 - 50 years ) r and omly assigned to one of the two groups and given a 16-week supply of either the 200 mg OpunDia ( n=15 ) , or placebo ( n=14 ) . The acute phase of the study consisted of an oral glucose tolerance test ( OGTT ) with a 400 mg bolus of OpunDia given 30 min before orally ingesting a 75 g glucose drink . Baseline and post 16-week concentrations of glucose , insulin , hsCRP , adiponectin , proinsulin , Hb1Ac , cholesterol , and a comprehensive metabolic panel were collected along with body composition measured via densitometry ( BOD POD ) . A repeated measures ANOVA was conducted to determine any significant interactions between group and time . Follow-up analysis was performed to determine differences among groups at each time point . Paired t-tests were performed on all variables to determine if any within group differences existed across time . RESULTS There was a statistically significant decrease ( P<0.05 ) in the blood glucose concentrations at the 60 ( 205.92+/-36.90 and 188.84+/-38.43 mg/dL , respectively ) , 90 ( 184.55+/-33.67 and 169.74+/-35.16 mg/dL , respectively ) and 120 min ( 159.24+/-17.85 and 148.89+/-24.86 mg/dL , respectively ) time points with the pre-OGTT compared to the OpunDia bolus trial . There were no between-group differences found with the OGTT time points , area under the curve , blood chemistry variables ( insulin , hsCRP , adiponectin , proinsulin , Hb1Ac ) , diet analysis variables ( carbohydrates , fat , protein and total kcals ) , body composition variables ( fat mass , fat free mass , percent body fat and total body weight ) , or blood chemistry safety parameters ( comprehensive metabolic panel ) pre-to-post 16-week intervention . CONCLUSIONS This study shows the acute blood glucose lowering effects and the long-term safety of the proprietary product OpunDia , thus supporting the traditional use of Opuntia ficus-indica for blood glucose management BACKGROUND The severity of the alcohol hangover may be related to inflammation induced by impurities in the alcohol beverage and byproducts of alcohol metabolism . An extract of the Opuntia ficus indica ( OFI ) plant diminishes the inflammatory response to stressful stimuli . METHODS In this double-blind , placebo-controlled , crossover trial , 64 healthy , young adult volunteers were r and omly assigned to receive OFI ( 1600 IU ) and identical placebo , given 5 hours before alcohol consumption . During 4 hours , subjects consumed up to 1.75 g of alcohol per kilogram of body weight . Hangover severity ( 9 symptoms ) and overall well-being were assessed on a scale ( 0 - 6 ) , and blood and urine sample s were obtained the following morning . Two weeks later , the study protocol was repeated with OFI and placebo reversed . RESULTS Fifty-five subjects completed both the OFI and placebo arms of the study . Three of the 9 symptoms-nausea , dry mouth , and anorexia-were significantly reduced by OFI ( all P<.05 ) . Overall , the symptom index was reduced by 2.7 points on average ( 95 % confidence interval , -0.2 to 5.5 ; P = .07 ) , and the risk of a severe hangover ( > /=18 points ) was reduced by half ( odds ratio , 0.38 ; 95 % confidence interval , 0.16 - 0.88 ; P = .02 ) . C-reactive protein levels were strongly associated with hangover severity ; the mean symptom index was 4.1 ( 95 % confidence interval , 1.2 - 7.1 ; P = .007 ) higher in subjects with morning C-reactive protein levels greater than 1.0 mg/L. In addition , C-reactive protein levels were 40 % higher after subjects consumed placebo compared with OFI . CONCLUSIONS The symptoms of the alcohol hangover are largely due to the activation of inflammation . An extract of the OFI plant has a moderate effect on reducing hangover symptoms , apparently by inhibiting the production of inflammatory mediators Background Oral intake of a specific extract of Opuntia ficus-indica cladode and fruit skin ( OpunDia ™ ) ( OFI ) has been shown to increase serum insulin concentration while reducing blood glucose level for a given amount of glucose ingestion after an endurance exercise bout in healthy young volunteers . However , it is unknown whether OFI-induced insulin stimulation after exercise is of the same magnitude than the stimulation by other insulinogenic agents like leucine as well as whether OFI can interact with those agents . Therefore , the aims of the present study were : 1 ) to compare the degree of insulin stimulation by OFI with the effect of leucine administration ; 2 ) to determine whether OFI and leucine have an additive action on insulin stimulation post-exercise . Methods Eleven subjects participated in a r and omized double-blind cross-over study involving four experimental sessions . In each session the subjects successively underwent a 2-h oral glucose tolerance test ( OGTT ) after a 30-min cycling bout at ~70 % VO2max . At t0 and t60 during the OGTT , subjects ingested 75 g glucose and capsules containing either 1 ) a placebo ; 2 ) 1000 mg OFI ; 3 ) 3 g leucine ; 4 ) 1000 mg OFI + 3 g leucine . Blood sample s were collected before and at 30-min intervals during the OGTT for determination of blood glucose and serum insulin . Results Whereas no effect of leucine was measured , OFI reduced blood glucose at t90 by ~7 % and the area under the glucose curve by ~15 % and increased serum insulin concentration at t90 by ~35 % compared to placebo ( P<0.05 ) . From t60 to the end of the OGTT , serum insulin concentration was higher in OFI+leucine than in placebo which result ed in a higher area under the insulin curve ( + 40 % , P<0.05 ) . Conclusion Carbohydrate-induced insulin stimulation post-exercise can be further increased by the combination of OFI with leucine . OFI and leucine could be interesting ingredients to include together in recovery drinks to resynthesize muscle glycogen faster post-exercise . Still , it needs to be confirmed that such nutritional strategy effectively stimulates post-exercise muscle glycogen re synthesis The effect of a high insoluble-fiber ( IF ) diet containing 15 % cellulose in dry matter , high soluble-fiber ( SF ) diet containing 15 % pectin in dry matter , and low-fiber ( LF ) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated . Each diet contained greater than 50 % digestible carbohydrate in dry matter . A crossover study was used with each dog r and omly assigned to a predetermined diet sequence . Each dog was fed each diet for 56 days . Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus . All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals . Mean ( + /- SEM ) daily caloric intake was significantly ( P less than 0.05 ) less when dogs consumed the IF diet vs the SF and LF diets ( 66 + /- 3 kcal/kg , 81 + /- 5 kcal/kg , and 79 + /- 4 kcal/kg , respectively ) . Serum alkaline phosphatase activity was significantly ( P less than 0.05 ) higher when dogs consumed the LF diet vs the IF and SF diets ( 182 + /- 37 IU/L , 131 + /- 24 IU/L , and 143 + /- 24 IU/L , respectively ) . Mean postpr and ial plasma glucose concentration measured every 2 hours for 24 hours , beginning at the time of the morning insulin injection , was significantly ( P less than 0.05 ) lower at most blood sampling times in dogs fed IF and SF diets , compared with dogs fed the LF diet . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The effect of increasing the intake of dietary fiber on glycemic control in patients with type 2 diabetes mellitus is controversial . METHODS In a r and omized , crossover study , we assigned 13 patients with type 2 diabetes mellitus to follow two diets , each for six weeks : a diet containing moderate amounts of fiber ( total , 24 g ; 8 g of soluble fiber and 16 g of insoluble fiber ) , as recommended by the American Diabetes Association ( ADA ) , and a high-fiber diet ( total , 50 g ; 25 g of soluble fiber and 25 g of insoluble fiber ) , containing foods not fortified with fiber ( unfortified foods ) . Both diets , prepared in a research kitchen , had the same macronutrient and energy content . We compared the effects of the two diets on glycemic control and plasma lipid concentrations . RESULTS Compliance with the diets was excellent . During the sixth week , the high-fiber diet , as compared with the the sixth week of the ADA diet , mean daily prepr and ial plasma glucose concentrations were 13 mg per deciliter [ 0.7 mmol per liter ] lower ( 95 percent confidence interval , 1 to 24 mg per deciliter [ 0.1 to 1.3 mmol per liter ] ; P=0.04 ) and mean median difference , daily urinary glucose excretion 1.3 g ( 0.23 ; 95 percent confidence interval , 0.03 to 1.83 g ; P= 0.008 ) . The high-fiber diet also lowered the area under the curve for 24-hour plasma glucose and insulin concentrations , which were measured every two hours , by 10 percent ( P=0.02 ) and 12 percent ( P=0.05 ) , respectively . The high-fiber diet reduced plasma total cholesterol concentrations by 6.7 percent ( P=0.02 ) , triglyceride concentrations by 10.2 percent ( P=0.02 ) , and very-low-density lipoprotein cholesterol concentrations by 12.5 percent ( P=0.01 ) . CONCLUSIONS A high intake of dietary fiber , particularly of the soluble type , above the level recommended by the ADA , improves glycemic control , decreases hyperinsulinemia , and lowers plasma lipid concentrations in patients with type 2 diabetes |
11,315 | 20,091,626 | Limited evidence suggests that women generally seem satisfied with their care .
The available evidence suggests that medical treatment , with misoprostol , and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service re sources to support all three approaches . | BACKGROUND Miscarriage occurs in 10 % to 15 % of pregnancies .
The traditional treatment , after miscarriage , has been to perform surgery to remove any remaining pregnancy tissues in the uterus .
However , it has been suggested that drug-based medical treatments , or expectant care ( no treatment ) , may also be effective , safe and acceptable .
OBJECTIVES To assess the effectiveness , safety and acceptability of any medical treatment for early incomplete miscarriage ( before 24 weeks ) . | OBJECTIVE Our purpose was to determine whether intracervical placement of laminaria stalks would improve the effectiveness of inducing termination of pregnancies in the second trimester by intra-amniotic injection of prostagl and in F(2)alpha . STUDY DESIGN This is a prospect i ve r and omized clinical trial conducted at Gynecology Department , Lis Maternity Hospital . Fifty women admitted for indicated second trimester pregnancy termination were r and omly assigned to receive either intracervical placement of laminaria ( n = 25 ) or not ( n = 25 ) , with concurrent use of intra-amniotic injection of prostagl and in F(2)alpha and concentrated oxytocin . The outcome measures were : time from induction to delivery and the side effects and complications of treatment . RESULTS There was no significant difference in the mean interval from induction to delivery in the laminaria and no laminaria groups , being 20 + /- 1.3 ( 8 - 30 ) h versus 19 + /- 1.0 ( 8 - 26 ) h , respectively . In addition , this interval was not different in subgroups of primiparas or multiparas . Other outcome measures such as retained placenta ( 4 % in both groups ) , post-partum hemorrhage ( 4 % in both groups ) gastro-intestinal side effects , fever , and use of analgesia were not significantly different between both groups . CONCLUSION We found no additional value in placing laminaria stalks when using intra-amniotic injection of prostagl and in F(2)alpha followed by concentrated oxytocin infusion for second trimester termination of pregnancy OBJECTIVE To compare the efficacy of surgical evacuation of the uterus with medical evacuation using misoprostol in cases of spontaneous abortion . DESIGN A prospect i ve , r and omized , controlled trial . SETTING A university teaching hospital . PATIENT(S ) Six hundred thirty-five women who aborted spontaneously and who consented to pretreatment r and omization . INTERVENTION(S ) Routine surgical evacuation or medical evacuation of the uterus using misoprostol . MAIN OUTCOME MEASURE(S ) Immediate , short-term ( 2 - 3 weeks ) , and medium-term ( 6 months ) medical complications . RESULT ( S ) There was a significantly lower incidence of immediate and short-term complications in the group treated with misoprostol compared with the surgically treated group . There were also fewer major complications in the 6 months after treatment in the medically treated group . Approximately 50 % of the medically treated group subsequently required surgical evacuation , and these subjects required significantly more analgesia . CONCLUSION ( S ) Treatment with misoprostol can reduce the dem and for surgical evacuation in cases of spontaneous abortion , and its use is associated with fewer medical complications Objective The aim of this r and omized prospect i ve study was to compare efficacy and side effects of saline moistened misoprostol with dry misoprostol , administered 800 μg intravaginally every 6 h up to a maximum of 3 doses in 24 h for second trimester pregnancy termination . Material s and methods A total of 81 women seeking termination of second trimester pregnancy ( 55 fetal death , 17 fetal structural anomaly , 5 chromosomal abnormality , 4 other reasons ) were r and omly assigned to one of two treatment groups : ( 1 ) intravaginal non-moistened ( dry ) misoprostol in group A ( n = 40 ) or ( 2 ) misoprostol moistened with 3 ml of saline in group B ( n = 41 ) . Results All of the patients in either group aborted within 48 h ( 100 % success rate ) . Delivery was achieved in a median ( interquartile range ) of 13 ( 40 ) h with the group A protocol and 12 ( 36 ) h with the group B protocol ( P = 0.652 ) . Delivery with first dose , delivery within 12 h and delivery within 24 h were similar ( P > 0.05 ) in group B ( 34.1 , 87.5 and 60 % , respectively ) and group A ( 25 , 82.9 , 46.3 , respectively ) . Both treatment regimens were tolerable and with similar side effects . Conclusion Misoprostol moistened with saline was not more effective than dry misoprostol for second trimester pregnancy termination BACKGROUND When compared with the conventional surgical evacuation for the treatment of miscarriage , medical evacuation has been largely accepted as an effective and safe management . However , there is a lack of data on the long-term reproductive outcome of these two treatment modalities , which is crucial in patient counselling . The current study evaluates and compares the long-term fertility and pregnancy outcome following these two treatments . METHODS A cohort of 604 women enrolled in a previous r and omized controlled trial comparing medical and surgical evacuation for miscarriage were followed up prospect ively by telephone interview at a median of 6 ( range 4 - 9 ) years using a structured question naire . RESULTS A total of 423 women were contacted and four declined to participate ( response rate 69.4 % ) . Of these , 261 women ( 131 medical and 130 surgical evacuations ) had attempted to become pregnant since the miscarriage . There were no differences in their baseline characteristics including age , reproductive and contraceptive history . The natural conception rates were the same ( 97.7 % , P = 0.99 ) and the cumulative pregnancy rates were similar between groups , being 60 and 80 % at 12 and 24 months respectively . The median time-to-pregnancy was 8 months in both groups ( P = 0.97 ) and the subsequent live birth rates ( 85.2 versus 88.2 % , P = 0.72 ) result ing from the immediate pregnancy following previous treatment were similar . CONCLUSIONS The long-term conception rate and pregnancy outcome are not different following medical or surgical evacuation for miscarriage . Women should be reassured that their long-term fertility potential will not be compromised after medical treatment OBJECTIVE The purpose of this study was to estimate whether the efficacy of treatment with intravaginal misoprostol for first-trimester pregnancy failure is enhanced by the addition of saline solution . STUDY DESIGN Eighty women with embryonic/fetal death or anembryonic pregnancy were assigned r and omly to receive either 800 microg of misoprostol with saline solution ( group I , 41 women ) or without ( group II , 39 women ) . Treatment was repeated on day 3 if the gestational sac remained . Curettage was performed if the gestational sac remained on day 8 or as necessary during at least 30 days of follow-up . Data were analyzed with the Student t test and the chi(2 ) or Fisher exact test . RESULTS By the first follow-up visit , 73 % ( group I ) and 64 % ( group II ) of women passed the gestational sac ( P=.38 ) . By the second follow-up visit , expulsion rates were 83 % and 87 % , respectively ( P=.59 ) . Five subjects in each group underwent curettage . CONCLUSION Misoprostol is effective for the treatment of failed first-trimester pregnancy . The expulsion rate is not improved by adding saline solution BACKGROUND We aim ed to compare patients ' health-related quality of life after a misoprostol strategy to a curettage in women with early pregnancy failure after failed expectant management . METHODS A multicentre r and omized clinical trial was performed in The Netherl and s. In all , 154 women with early pregnancy failure confirmed at ultrasonography who had been managed expectantly unsuccessfully for > or = 1 week were r and omly assigned to undergo either treatment with misoprostol ( n=79 ) or curettage ( n=75 ) . The main outcome measures were health-related quality of life and satisfaction with treatment . RESULTS In the misoprostol strategy 47 % of the women needed additional curettage , as compared to 4 % after curettage . In both groups , health-related quality of life was impaired most severely 2 days after treatment . In the misoprostol group , health-related quality of life was more severely impaired ; after 2 days this was due to more pain and after 2 and 6 weeks this was due to a worse general health perception . Health-related quality of life was temporarily significantly more impaired in women in whom misoprostol failed as compared to women in whom misoprostol treatment was successful . In both treatment groups , an equal percentage of women ( 58 % ) would choose the same treatment in the future . In women treated with misoprostol , however , this choice depended on the initial success of misoprostol : in cases where misoprostol had caused complete evacuation , 76 % of the women would opt for the same treatment , whereas only 38 % of women who needed curettage after unsuccessful misoprostol would do so ( P<0.01 ) . CONCLUSION Our study shows that , although both the misoprostol strategy and the curettage strategy result ed in complete evacuation in the end , women are willing to accept some disadvantages of misoprostol to avoid curettage . A treatment inconvenience using misoprostol is accepted as long as initial evacuation rate is high . This finding should be an integral part of counselling women when deciding upon management of early pregnancy failure A total of 85 women with antepartum fetal death between 14 and 42 weeks gestation was r and omly assigned to one of two regimens of intravenous infusion of the prostagl and in analogue 16‐phenoxy‐17 , 18 , 19 , 20‐tetranor‐PGE2‐methylsulphonamide ( sulprostone ) for inducing labour . Women received either 1 μg/min until delivery or the commonly recommended treatment of 1500 μg in 8 h followed by another , identical course of treatment if delivery did not occur within 24 h. The 1 μg/min dose schedule used half the amount of prostagl and in and result ed in statistically significantly fewer gastrointestinal side‐effects compared with the conventional treatment . All women were delivered vaginally and there were no differences in induction‐to‐delivery intervals between the two treatments . Sulprostone infused at a rate of 1 μg/min result ed in a 50 % chance of being delivered within 12 h and a 90 % chance of being delivered within 24 h , with an overall frequency of side‐effects of 20 % OBJECTIVE To compare the efficacy of intramuscular methotrexate plus vaginal misoprostol to vaginal misoprostol alone in completing abortion in women with non-viable early first trimester pregnancy . METHOD Twenty-one women with non-viable pregnancy up to 49 days gestation were r and omized to receive intramuscular methotrexate , followed 2 days later by vaginal misoprostol or misoprostol alone . We also collected patient satisfaction information . RESULT Complete abortion occurred in all 12 ( 100 % ) women in the combined group and eight of nine ( 89 % , RR = 1.13 , CI 0.89 - 1.42 ) women in the misoprostol only group . Of the women , 75 % rated their experience as good and would choose medical management again . CONCLUSION Either methotrexate plus misoprostol or misoprostol alone effectively completed abortion in women with non-viable early pregnancy and represent acceptable medical alternatives to surgery or expectant management BACKGROUND Responses to miscarriage range from relief to devastation , yet there have been no r and omized controlled studies that demonstrate significant effects of counseling with women who miscarry . OBJECTIVE To test the effects of caring-based counseling , measurement , and time on the integration of loss ( miscarriage impact ) and women 's emotional well-being ( moods and self-esteem ) in the first year after miscarrying . METHOD ANCOVA was used in this r and omized , longitudinal Solomon four-group experimental investigation . Enrolled were 242 ; 185 completed . Outcomes included : self-esteem , overall emotional disturbance , anger , depression , anxiety , confusion , overall miscarriage impact , personal significance , devastating event , lost baby , and isolated . RESULTS During the first year after loss ( a ) caring was effective in reducing overall emotional disturbance , anger , and depression ; and ( b ) time passing led to increased self-esteem and decreased anxiety , depression , anger , confusion , and personal significance of loss . CONCLUSION Caring , measurement , and time had some positive and significant effects on the integration of loss and enhancement of well-being in the first year subsequent to miscarrying AIM To evaluate and compare effectiveness , side effects and patient acceptability between oral and sublingual 600 µg misoprostol for the treatment of incomplete abortion . METHODS A r and omized controlled trial was conducted . Pregnant women of less than 14 weeks gestation , diagnosed with incomplete abortion , were r and omly assigned to receive 600 µg misoprostol orally or sublingually . The patients were evaluated at 48 h after drug administration for complete abortion . RESULTS A total of 64 women were recruited to the study ( 32 in the oral group and 32 in the sublingual group ) . The complete abortion rate was not statistically different between oral and sublingual groups ( 87.5 % versus 84.4 % , P > 0.05 ) . There was no statistical difference in side effects and satisfaction rate . Fever/chills were the most common side effects . CONCLUSION Both sublingual and oral 600 µg misoprostol are useful for the management of incomplete abortion . Side effects and satisfaction rates are not different . Thus , these methods may be used as alternative treatments of incomplete abortion BACKGROUND Dilatation and curettage ( D&C ) has been the usual treatment for early pregnancy failure ( EPF ) . Medical management with misoprostol may be an effective alternative . Bleeding patterns during and after medical management of EPF are unknown . METHODS A prospect i ve cohort study was conducted at University-based clinics and physician offices . Eighty women < 11 weeks estimated gestational age with a diagnosis of missed abortion or fetal demise were enrolled . Treatment consisted of either 800 micro g of moistened ( 2 ml of saline ) or dry vaginal misoprostol . Self-reported bleeding and sanitary product usage were recorded in a daily 2 week diary . Haemoglobin was assessed at enrollment and 2 weeks later . RESULTS After misoprostol treatment , patients reported bleeding or spotting every day for the 14 days observed . Self-assessed heavy bleeding days were few ( median 3 ) and usually occurred immediately after treatment . Sanitary pad use was highly variable ( mean 30.5 , range 2 - 125 pads over the 2 week period ) and not related to changes in haemoglobin . The mean decrease in haemoglobin was 0.5 g/dl ( SD 1.2 ) . Complete expulsion without D&C occurred in 85 % of subjects . CONCLUSIONS Bleeding for at least 2 weeks after vaginal misoprostol for EPF is common . Heavy bleeding is usually limited to a few days after treatment . Clinical ly important changes in haemoglobin are rare OBJECTIVE The purpose of this study was to compare the psychologic impact and client satisfaction of routine surgical evacuation of the uterus with medical evacuation in cases of spontaneous abortion . STUDY DESIGN This was a prospect i ve , r and omized controlled trial . Two hundred eighteen women who were admitted to a university teaching hospital after spontaneous abortion and who consented to the study were r and omized to routine surgical evacuation or medical evacuation of the uterus with the use of misoprostol . General psychologic well-being , level of depression , fatigue symptoms , psychiatric morbidity , social functioning , client satisfaction , and acceptance were measured in the 2 groups . RESULTS The 2 groups did not differ in any of the measured psychological outcomes . Significantly more participants who experienced successful evacuation of the uterus with the misoprostol protocol would choose the same mode of treatment if they were able to choose again . However , participants for whom the medical treatment failed to evacuate the uterus and subsequent surgical evacuation was required are significantly less satisfied with the treatment . CONCLUSION Medical treatment of spontaneous abortion with misoprostol is psychologically safe and more compatible with the ethnomedical beliefs of our Chinese participants . Client satisfaction and acceptance should be taken into consideration in the evaluation of treatment outcomes Objectives To compare complete abortion rate , duration of abortion , and side effects between 600 μg powdery sublingual misoprostol and 600 μg sublingual misoprostol tablet for management of embryonic death or anembryonic pregnancy . Material s and methods Fifty-four pregnant women up to 13 weeks of gestation diagnosed with embryonic death or anembryonic pregnancy were r and omized to receive 600 μg powdery sublingual misoprostol or 600 μg sublingual misoprostol tablet . Complete abortion was evaluated by transvaginal ultrasound at 48 h. Results Twenty-six patients received 600 μg powdery sublingual misoprostol and 28 patients received 600 μg sublingual misoprostol tablet . Complete abortion rate was 34.6 % in powdery sublingual misoprostol group and 32.1 % in sublingual misoprostol tablet group ( P = 0.847 ) . Duration of abortion in powdery sublingual misoprostol group and sublingual misoprostol tablet group was similar ( 34.7 ± 18.8 vs. 36.9 ± 17.8 h , respectively , P = 0.656 ) . There was no significant difference in the side effects between both groups . Conclusions Single dose of 600 μg of powdery sublingual misoprostol does not improve its efficacy for management of embryonic death or anembryonic pregnancy when compared to sublingual misoprostol tablet OBJECTIVE The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination . STUDY DESIGN We performed a r and omized clinical trial in patients who were at 14 to 23 weeks of gestation and who were admitted for medical termination of pregnancy . All patients received 800 microg of vaginal misoprostol and were assigned r and omly to 400 microg of oral misoprostol or 400 microg of vaginal misoprostol every 8 hours . Efficacy and side effects were compared . The mean induction time of the study group was compared with that of an historic control group that had received 400 microg vaginally every 12 hours . RESULTS Forty-three women were assigned r and omly , 22 women to vaginal misoprostol and 21 women to oral misoprostol . Induction time and hospital stay were slightly shorter for the oral group ; however , the differences were not significant . Side effects were similar for both groups . CONCLUSION After an initial 800 microg dose of vaginal misoprostol , a regimen of 400 microg of oral misoprostol every 8 hours is as effective as the same dose of vaginal misoprostol with no additional side effects , which provides a convenient alternative for midtrimester pregnancy termination Background : It has been established that sublingual ( SL ) route of misoprostol has a great potential to be developed for medical abortion , but there is dearth of evidence to reveal satisfaction rate and safety profile among patients of oral and SL routes . Thus , this study was conducted to provide an insight into the acceptability and safety profile of the same . Material s and Methods : A r and omized controlled trial was carried out by giving 200 mg mifepristone orally , followed by administration of 600 μg misoprostol orally to 50 women and sublingually to 50 women . The primary endpoints of study were measurements of acceptability and safety profile parameters ( average blood loss , nausea , vomiting , diarrhea , hot flushes , fever ) of both the groups . The secondary endpoints of the study were number of doses required for complete abortion , success rate and the induction to evacuation interval in both the groups . Results : SL route of administration was more acceptable than the oral route ( P = 0.009 ) . Average blood loss was higher in the oral group than in the SL group ( P = 0.001 ) . Amongst the side effects , 34 % in the SL group and 52 % in the oral group had nausea ( P = 0.264 ) , 22 % in the SL group and 44 % in the oral group had vomiting ( P = 0.031 ) , 48 % in the SL group and 86 % in the oral group had diarrhea ( P < 0.05 ) , hot flushes were presented by 24 % in the SL group and 50 % in the oral group ( P < 0.05 ) , fever was presented by 20 % in the SL group and 44 % in the oral group ( P < 0.05 ) , and the number of cases aborted with only one dose was higher ( 86 % ) in the SL group as compared to 63 % in the oral group ( P = 0.004 ) . The evacuation ( success ) rates were 92 % in the SL group and 84 % in the oral group ( P = 0.218 ) and the mean ± SD induction to evacuation intervals in the SL and oral groups were 5.6 ± 4.54 hours and 9.44 ± 5.61 hours , respectively ( P = 0.0002 ) . Conclusion : The SL route had fewer undesirable effects , was more satisfactory , required less number of doses and was more acceptable to the patient compared to the oral route OBJECTIVE To compare the safety , efficacy , and acceptability of 400-μg sublingual misoprostol with that of manual vacuum aspiration ( MVA ) in 2 Egyptian hospitals . METHODS Participating women were r and omized to either MVA or misoprostol treatment for incomplete abortion . The primary outcome , complete uterine evacuation , was determined 1 week later , as were adverse effects , change in hemoglobin , acceptability , and satisfaction . RESULTS Complete uterine evacuation was achieved in 98.3 % of women who received misoprostol and 99.7 % who underwent MVA ( relative risk [ RR ] 0.99 ; 95 % confidence interval [ CI ] , 0.97 - 1.00 ) . A decrease in hemoglobin of 2g/dL or more was comparably rare in the 2 groups ( 0.3 % misoprostol vs 0.9 % MVA ; RR 0.34 [ 95 % CI , 0.04 - 3.21 ] ) . Mean change in hemoglobin was also clinical ly similar ( -0.5 g/dL misoprostol vs -0.4 g/dL MVA ; P<0.01 ) . Heavy bleeding was rare ( 2.4 % misoprostol vs 1.6 % MVA ; RR 1.55 [ 95 % CI , 0.51 - 4.68 ] ) following treatment . Nearly all women ( 96.8 % misoprostol vs 98.3 % MVA ) were satisfied with their treatment but those who received misoprostol were significantly more likely to prefer that method in the future ( 81.9 % vs 62.8 % ; RR 1.30 [ 95 % CI , 1.19 - 1.43 ] ) . CONCLUSION The high efficacy , safety , and acceptability of 400-μg sublingual misoprostol indicate that it is analogous to surgery as a first-line treatment for incomplete abortion . Misoprostol might improve post-abortion care when re sources are limited and surgical treatment is unavailable BACKGROUND Vaginal misoprostol has been shown to be an effective single agent for medical abortion . This r and omized , double-blinded , placebo-controlled trial compared a regimen of mifepristone and misoprostol with misoprostol alone for termination of early pregnancy . METHODS 250 women with gestations < or = 56 days were r and omized by a r and om number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 microg vaginal misoprostol . Administration of misoprostol was repeated every 24 h up to three doses if abortion failed to occur . Abortion success was defined as complete abortion without the use of surgical aspiration . RESULTS Successful medical abortions occurred in 114 out of 119 subjects ( 95.7 % ) after mifepristone followed by vaginal misoprostol . In all , 110 out of 125 subjects ( 88.0 % ) successfully aborted after placebo and vaginal misoprostol . The higher success rate of complete abortion with the mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen ( P < 0.05 ) . CONCLUSIONS A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies < or = 56 days than misoprostol alone . The 88 % efficacy obtained with vaginal misoprostol alone may be clinical ly acceptable when mifepristone is not available OBJECTIVE The purpose of this study was to compare the clinical efficacy and side effects of 3 doses of intravaginal misoprostol for second-trimester pregnancy termination . STUDY DESIGN This was a prospect i ve r and omized , double-blind controlled clinical trial of 150 women who underwent pregnancy termination between 14 and 30 weeks of gestation . Three intravaginal misoprostol regimens were compared : 200 microg misoprostol at 6-hour intervals ( group 1 ) , 400 microg misoprostol at 6-hour intervals ( group 2 ) , and a loading dose of 600 microg misoprostol followed by 200 microg at 6-hour intervals ( group 3 ) . RESULTS There was a significant difference in the median time to achieve delivery among the 3 groups : group 1 ( 18.2 hours [ IQ , 13.3 - 32.5 hours ] ) vs group 2 ( 15.1 hours [ IQ , 10.9 - 23.7 hours ] ) vs group 3 ( 13.2 hours [ IQ , 11.2 - 21.7 hours ] ; P = .035 ) . Fifty-nine percent of the women in group 1 , 76 % of the women in group 2 , and 80 % of the women in group 3 delivered within 24 hours ( P = .013 ) . There were 7.8 % of the women in group 1 , 0 % of the women in group 2 , and 2 % of the women in group 3 who were undelivered at 48 hours ( P = .02 ) . There was an increase in the incidence of fever in the first 12 hours ( P = .038 ) and in the incidence of vomiting within 3 hours of the initial dose ( P = .048 ) in group 3 compared with the other groups . CONCLUSION Intravaginal misoprostol 400 microg at 6-hour intervals appears to be the preferred regimen for second-trimester pregnancy termination , with a shorter commencement to delivery interval than the 200 microg regimen and fewer maternal side-effects than the 600 microg loading dose regimen OBJECTIVE To determine whether management of incomplete first-trimester abortion with vaginal misoprostol in an under-re source d setting is a viable treatment option . METHODS A total of 94 women were r and omized to 600 microg of misoprostol intravaginally or to surgical curettage . The women receiving misoprostol were administered a second dose if the abortion was incomplete ; and if still not complete after a week , evacuation of retained products of conception was performed . All women had a follow-up visit 2 weeks following complete abortion . RESULTS The overall success rate of medical management was 91.5 % , with 15 of 47 successful cases after 1 dose of misoprostol ; 8.5 % of the 47 women required evacuation of retained products of conception after 1 week because of treatment failure . The success rate in the surgical arm was 100 % . Patients in the medical arm had a longer duration of bleeding and a greater need for analgesia . There were no differences in hemoglobin levels , white blood cell count , adverse effects , pain score , and satisfaction with treatment at the follow-up visit . However , more women who received the medical treatment would recommend it or choose it in the future . CONCLUSION Medical management using 600 microg of misoprostol in 2 doses is effective to treat incomplete first-trimester abortions in an under-re source d setting when there is no evidence of uterine sepsis BACKGROUND The study was conducted to compare the efficacy and acceptability of second-trimester induction termination using vaginal misoprostol to hypertonic saline and d-cloprostenol , a prostagl and in F(2alpha ) ( PGF ) analogue , in Tashkent , Uzbekistan . STUDY DESIGN Eleven clinics providing second-trimester induction terminations were r and omized to provide one of two regimens for second-trimester induction termination : vaginal misoprostol 400 mcg every 3 h or hypertonic 10 % saline intrauterine instillation plus an intravenous PGF analogue , d-cloprostenol , 2.5 mg/h . Demographic information , and obstetric and medical history data were collected , and interviewers administered question naires to measure procedural pain and satisfaction . Differences in procedure time and complication rate , the primary outcomes , were analyzed with survival analysis and chi(2 ) tests . RESULTS Of 228 participants , 120 received misoprostol and 108 received hypertonic saline and d-cloprostenol ; the groups did not significantly differ by age , parity or gestational age . Both misoprostol and saline procedures were effective , with 99.2 % and 100 % successful abortion rates , respectively . Median procedure time ( 13.1 vs. 29.2 h , p<.001 ) , and number of women with retained placenta ( 2 vs. 70 , p<.001 ) or hemorrhage ( 3 vs. 19 , p=.001 ) were lower for the misoprostol group . Both provider ( p<.001 ) and patient ( p<.001 ) procedural satisfaction scores were higher for the misoprostol group . CONCLUSION While equally effective , vaginal misoprostol had a shorter time to abortion , was more acceptable to providers and patients and had fewer complications than saline instillation plus intravenous administration of a PGF analogue in Tashkent . This evidence supports change of the existing st and ard of care for second-trimester induction termination in Uzbekistan This study was design ed to investigate the use of oral mifepristone ( RU 486 ) for the induction of natural expulsion of concepti in women with spontaneously interrupted pregnancy in the first trimester . It consisted of a double-blind placebo-controlled study of mifepristone ( 600 mg ) against placebo . A total of 46 women consulting for interrupted pregnancy were diagnosed at ultrasound with no clinical sign of miscarriage . Measurements were made of the occurrence of natural expulsion , the frequency of complete expulsion , the need for subsequent surgical evacuation , analgesia and the need for transfusion . Natural expulsion occurred within 5 days in 82 % of patients receiving mifepristone treatment versus 8 % of placebo-treated patients ( P < 0.001 ) . All patients experienced bleeding after RU 486 and two needed emergency aspiration for haemorrhagic expulsion . The treatment failed in four patients , who underwent evacuation under local anaesthesia . In the control group , 19 patients underwent evacuation under local ( n = 10 ) or general ( n = 9 ) anaesthesia . It was concluded that a st and ard oral pilot dose of 600 mg of mifepristone induces natural expulsion in 82 % of women with non-developing first trimester intrauterine pregnancies OBJECTIVE To evaluate serial hormone concentrations in subjects treated with vaginally administered misoprostol for early pregnancy failure . DESIGN As part of a r and omized clinical trial , serum was collected on treatment days 1 , 3 , 8 , and 15 . SETTING Multicenter clinical trial . PATIENT(S ) Women with a nonviable first-trimester pregnancy . INTERVENTION(S ) Serum concentrations of human chorionic gonadotropin ( hCG ) , progesterone , and sex hormone binding globulin ( SHBG ) were evaluated . MAIN OUTCOME MEASURE(S ) A logistic regression model was constructed to assess the associations of percent and complete expulsion of the gestational sac and /or successful management . RESULT ( S ) The percent change from the day of treatment until the first follow-up visit was predictive for complete expulsion for progesterone ( P ) ( P<.005 ) and hCG ( P<.005 ) , but not for SHBG . The actual value was not significantly associated with complete expulsion or successful management . A decrease ( day 1 - 3 ) of 79 % for both hCG and P was associated with a 90 % probability of complete passage of the gestational sac . A 90 % probability of successful management was noted if P decreased by 78 % on day 3 or 59 % on day 7 , or hCG decreased by 74 % on day 3 or 78 % on day 7 compared with pretreatment values . CONCLUSION ( S ) Percent change , but not absolute change , in serial hormone values are strongly associated with both the complete expulsion of the gestational sac with one dose of misoprostol and ultimate success BACKGROUND The increased pressure on health care expenses implies that physicians should consider economic aspects as part of the clinical decision-making process . Direct and indirect costs of a strategy starting with misoprostol in treatment of early pregnancy failure as compared to curettage is therefore performed . METHODS We performed a cost-minimization analysis alongside a multicentre r and omized trial . Clinical data and data on the use of medical re sources were obtained from a r and omized trial comparing misoprostol and curettage , which had shown that misoprostol reduced the need for curettage in 53 % . In a sensitivity analysis the percentage of women who needed curettage after misoprostol varied between 25 and 90 % . RESULTS Direct costs per case were significantly lower in the misoprostol group ( mean 433 ) than in the curettage group ( mean 683 ) ( mean difference 250 , 95 % CI 184 to 316 , P < 0.001 ) . These significant differences existed under a wide range of alternative assumptions about unit costs . The differences in direct cost in favour of misoprostol were large for women who had complete evacuation after initial misoprostol treatment as compared to those who needed additional curettage after failed misoprostol . Mean indirect costs were equal for both groups ( misoprostol mean 486 ; curettage mean 428 ; mean difference 60 , 95 % CI -61 to 179 , P = 0.51 ) . The mean total costs for a strategy starting with misoprostol was 915 versus 1107 for curettage , with a mean difference between both groups of 192 ( 95 % CI 33 to 351 , P = 0.04 ) . An increase of the complete evacuation rates for initial misoprostol therapy to 90 % in the sensitivity analysis increased the cost difference between misoprostol and curettage to 550 . CONCLUSION The use of misoprostol for early pregnancy failure after failed expectant management is less costly than curettage OBJECTIVE : We sought to compare endometrial thickness after misoprostol or dilation and curettage ( D&C ) for early pregnancy failure and to assess the predictive value of endometrial thickness for subsequent D&C after misoprostol treatment . METHODS : In a r and omized trial of early pregnancy failure management , 491 women were treated with misoprostol vaginally , and 161 were treated with D&C. Transvaginal ultrasonography was planned for 2 and 14 days after misoprostol treatment , and 14 days after D&C. RESULTS : The mean endometrial thickness 14 days after treatment was 9.0 mm for the misoprostol group and 6.9 mm for the D&C group , ( difference 2.1 mm , 95 % confidence interval [ CI ] 1.0–3.2 ) . After the ultrasonograms 2 and 14 days after misoprostol , 13 ( 3.8 % ) and 12 ( 3.2 % ) women , respectively , subsequently underwent D&C. Women requiring D&C after successful expulsion had significantly greater endometrial thickness than those who did not at 2 days ( mean difference 5.2 mm , 95 % CI 1.6–8.8 ) and 14 days ( mean difference 5.5 mm , 95 % CI 2.3–8.8 ) after misoprostol . However , endometrial thickness was a poor predictor of subsequent D&C. The areas under the receiver operating characteristic curves for endometrial thickness at 2 and 14 days were 0.71 and 0.73 , respectively . Regardless of cutoff values used for predicting subsequent D&C , endometrial thickness had a positive predictive value of 40 % or less . CONCLUSION : The difference in endometrial thickness between misoprostol treatment and D&C for early pregnancy failure is not clinical ly significant . Endometrial thickness is not a useful predictor of subsequent surgical intervention after successful expulsion of the gestational sac after misoprostol for early pregnancy failure . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00177333 LEVEL OF EVIDENCE : Objectives To compare fertility rates after the three methods of managing early miscarriage in women recruited to the MIST ( miscarriage treatment ) r and omised controlled trial . Setting Early pregnancy clinics of acute hospitals in the south west region of Engl and . Participants 1199 women who had had an early miscarriage ( < 13 weeks ) confirmed by scan . Intervention Expectant , medical , or surgical management . Main outcome measures Self reported pregnancy rates and live birth rates . Results Of 1199 women recruited to the trial , 1128 consented to follow-up . Of these , 762 women replied giving pregnancy details ( 68 % response rate ) . Respondents were representative of the trial participants . The live birth rate five years after the index miscarriage was similar in the three management groups : 177/224 ( 79 % , 95 % confidence interval 73 % to 84 % ) in the expectant management group , 181/230 ( 79 % , 73 % to 84 % ) in the medical group , and 192/235 ( 82 % , 76 % to 86 % ) in the surgical group . There was also no significant difference according to previous birth history . Older women and those with previous miscarriages were significantly less likely to subsequently give birth . Conclusion Method of miscarriage management does not affect subsequent pregnancy rates with around four in five women giving birth within five years of the index miscarriage . Women can be reassured that long term fertility concerns need not affect their choice of miscarriage management . Trial registration National Research Register N0467011677/N0467073587 BACKGROUND This study was conducted to evaluate the efficacy and side effects of a new regimen of 800 microg misoprostol administered intravaginally every 6 h up to a maximum of three doses in 24 h for second trimester pregnancy termination . METHODS A total of 66 women seeking termination of second trimester pregnancy ( 30 fetal structural anomaly , six chromosomal abnormality and 30 fetal death ) were r and omly assigned to one of two treatment groups : ( i ) intravaginal misoprostol moistened with 3 ml of 5 % acetic acid in group A ( n = 33 ) ; or ( ii ) intravaginal misoprostol moistened with 3 ml of saline in group B ( n = 33 ) . RESULTS The overall median ( range ) induction-abortion interval was 10 h ( 2 - 46 ) [ 10 h ( 4 - 35 ) in 36 live fetuses and 9 h ( 2 - 46 ) in 30 dead fetuses , P = 0.515 ] . All of the patients in both groups aborted within 48 h ( 100 % success rate ) . The median ( range ) induction-abortion interval revealed a significantly faster delivery time ( P < 0.001 ) in group A [ 8 h ( 2 - 24 ) ] than in group B [ 14 h ( 3 - 46 ) ] . CONCLUSIONS This new regimen of 800 microg of vaginal misoprostol every 6 h for a maximum of three doses in 24 h was an effective alternative method for second trimester abortion . In addition , misoprostol moistened with acetic acid was significantly more effective than misoprostol moistened with saline BACKGROUND Misoprostol is effective for cervical priming prior to suction evacuation in first trimester pregnancy termination . This is the first r and omized study to compare vaginal misoprostol versus expectant treatment in women presenting with spontaneous miscarriage . METHODS Sixty women presenting with spontaneous miscarriage were recruited to the study at the Queen Mary Hospital between 1998 and 1999 . They were r and omized to group 1 : misoprostol ; and group 2 : expectant management . Women in the misoprostol group received vaginal misoprostol 400 microg on days 1 , 3 and 5 . The expectant group was followed up according to the same schedule . Suction evacuation was performed if there was excessive bleeding or abdominal pain ; or if a gestational sac was detected by transvaginal scan on day 15 . RESULTS Fifty-nine women completed the trial . Those who did not require suction evacuation up to the time of return of normal menstruation were considered to be successful . The incidence of side-effects was comparable between the two groups . Three women in the expectant group and one in the misoprostol group underwent emergency suction evacuation because of excessive bleeding . The mean duration of vaginal bleeding was similar for both groups ( 14.6 days in the misoprostol group versus 15.0 days in the expectant group ) . The successful rate in the misoprostol group was significantly higher than that of the expectant group ( 83.3 versus 48.3 % , P < 0.05 ) . CONCLUSION We recommend repeated vaginal misoprostol 400 microg given on days 1 , 3 and 5 as a treatment option for women with first trimester spontaneous miscarriage Summary Gemeprost ( Cervagem ) has been used widely compared with Misoprostol ( Cytotec ) alone in second trimester pregnancy termination . This prospect i ve r and omised trial was to evaluate the efficacy of intravaginal Misoprostol ( alone ) and Gemeprost in second trimester termination of pregnancy . A total of 54 women with 27 on each arm were involved . A total of 25 patients ( 92.6 % ) in the Misoprostol group and 22 patients ( 81.5 % ) in the Gemeprost group delivered within 48 h. The Misoprostol group delivered earlier , although average number of tablets required were similar . The side-effects were not significant between the two groups in fact , but there was more pyrexia in the Gemeprost group ( p = 0.004 ) . Misoprostol in second trimester termination of pregnancy is clinical ly as effective and less costly than the st and ard regimen of Gemeprost The object of this study was to compare intravaginal misoprostol and dinoprostone ( prostagl and in E2 ) for second-trimester pregnancy termination , and to examine the role of the nitric oxide donor , glyceryl trinitrate , as a possible alternative to prostagl and ins to induce cervical ripening in second-trimester pregnancy termination . This was a r and omised clinical trial . The trial involved pregnant women between 13 and 28 weeks ' gestation admitted with clear medical or obstetric indications for pregnancy termination , and was carried out in the department of obstetrics and gynecology , Assiut University Hospital , Egypt . Patients were classified into Group A , where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms ; Group B , where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg ; and Group C , where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg . Twenty-four hours after the start of induction , the rate of complete abortion in the three groups was 100 % , 66.67 % and 0 % , respectively . The rate of complete abortion was 100 % in the nitric oxide ( glyceryl trinitrate)-induced group after introducing a complementary procedure . The induction – abortion interval was significantly shorter , the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone . A higher rate of side effects occurred with the misoprostol-induced group ( 74 % ) compared with the other two groups ( 46.6 % and 0 % ) . Misoprostol is a cheap , effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects . Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered . Glyceryl trinitrate is an effective drug for cervical ripening ( softening ) but it has no role in the stimulation of uterine contractions OBJECTIVE This study was undertaken to compare the efficacy and side effects of a high-dose vaginal misoprostol regimen to concentrated intravenous oxytocin plus low-dose vaginal misoprostol for midtrimester labor induction . STUDY DESIGN Women at 14 to 24 weeks , with obstetric or fetal indications for delivery and no prior cesarean , were r and omly assigned to receive either vaginal misoprostol 600 microg x 1 , then 400 microg every 4 hours x 5 ( group 1 ) or escalating dose-concentrated oxytocin infusions ( 277 - 1667 mU/min ) plus vaginal misoprostol 400 microg x 1 , then 200 microg every 6 hours x 2 , then 100 microg x 1 ( group 2 ) . Analysis was by intent to treat . Primary outcomes were live birth rate and induction-to-delivery interval . RESULTS The intended sample size was 70 women per group ; however , the trial was terminated at the initial interim analysis because of a highly significant difference in 1 of the primary study outcomes . Twenty women were assigned to group 1 and 18 were assigned to group 2 . Median induction-to-delivery interval was significantly shorter in group 1 ( 12 hours , range 4 - 44 hours ) versus group 2 ( 18 hours , range 7 - 36 hours ; P = .01 ) . Induction success rate at 12 hours was significantly higher in group 1 ( 60 % ) compared with group 2 ( 22 % , P = .02 ) . No significant difference was noted in the live birth rate between groups 1 and 2 ( 13 % , 0 % , P = .16 ) . The incidence of retained placenta requiring curettage , chorioamnionitis , intrapartum fever , nausea , emesis , and diarrhea were similar between both groups . CONCLUSION Compared with concentrated oxytocin plus low-dose vaginal misoprostol , high-dose vaginal misoprostol significantly shortens midtrimester labor inductions In 87 patients with a missed abortion prior to 13 weeks , the application of a prostagl and in ( PG ) E1 derivative ( 1 mg gemeprost , Cergem ® ) was compared to conventional surgical termination of pregnancy by cervical dilatation and curettage . In 33 patients with PGE1 application , complete expulsion of the abnormal pregnancy occurred after an average of 2.8 ± 1.5 vaginal suppositories . PGE1 treatment was effective in 76.7 % , and surgical management was effective in 90.9 % of patients . Sixty percent of the patients in the PGE1 group required analgesia because of uterine pain in comparison to 4.5 % in the surgical group . The possibility of medical termination with synthetic PG derivatives should be further investigated Objective To compare the effectiveness of vaginal misoprostol administered 6 or 12 hourly for second trimester pregnancy termination Objective : To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination . Methods : This is a prospect i ve study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks . Two regimens of misoprostol were used . Group 1 : 400 µg of oral plus 400 µg vaginal misoprostol every 8 h ( combined regimen ) and group 2 : 400 µg of vaginal misoprostol every 3 h up to a maximum of five doses ( vaginal regimen ) . Results : The induction-to-abortion interval was significantly longer in group 1 ( 25.5 ± 24.45 h ) than in group 2 ( 15 ± 7.14 h ) ( p = 0.016 ) . The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7 % in group 2 ( p = 0.006 ) . The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders . Conclusions : Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination Background : Medical management and expectant care have been considered possible alternatives to surgical evacuation of the uterus for first trimester spontaneous miscarriage in recent years Objective To estimate and compare the costs of surgical and medical treatment of miscarriage to the National Health Service Objective : The objective of this study was to compare NO-donor isosorbide mononitrate to misoprostol , both applied as vaginal tablets for cervical ripening prior to first trimester curettage in patients with missed abortion . Material s and methods : Thirty women with missed abortion were assigned after a r and om list to be treated either with 200 μg gemeprost ( Cytotec , Pfizer , Germany ) or with 40 mg isosorbide mononitrate for cervical priming at least 3 h before curettage . Vaginal bleeding or the intracervical presence of products of conception was documented . The largest number of Hegar ’s dilator , which could be introduced without difficulty and the largest number of Hegar ’s dilator at which cervical dilation was performed and the ease of mechanical dilation was assessed . Results : There were no significant differences in cervical ripeness before procedure nor in ease of dilation . In the misoprostol group , the cervical canal was more dilated before any procedure ( median of Hegar ’s dilator 6 vs. 5 ) and after dilation ( median of Hegar ’s dilator 11 vs. 10 ) , although this difference was not significant . Vaginal bleeding occurred in two patients in each group . Products of conception were only found in the cervix of one patient of the misoprostol group . Synopsis : Vaginal application of isosorbidemononitrate in cervical priming prior to curettage abortion is as effective as vaginal application of misoprostol AIM To evaluate the efficacy of two routes of misoprostol administration ( sublingual and vaginal ) for the treatment of missed abortion . METHODS Two hundred and twenty women with confirmed missed abortion who received 400 microg/6 h misoprostol either sublingually or vaginally , were included in this r and omized control trial . All women were admitted to hospital for follow-up care for 2 days . If the pregnancy was not completely evacuated during this time , the patient underwent immediate surgical completion . Efficacy was defined as the percentage of women discharged from the study without the need for surgical intervention . RESULTS The effectiveness was high in the sublingual group and statistically different ( sublingual 84.5 % , vaginal 46.4 % P = 0.000 RR = 0.54 95%CI = 0.442 - 0.681 ) . The groups differed in terms of complications like bleeding ( 88.2 % vs 65.5 % ) , pain ( 85.5 % vs 56.4 % ) , diarrhea ( 69.1 % vs 36.4 % ) and fever ( 23.6 % vs 13.3 % ) in the sublingual group versus the vaginal group , but the mean time to expulsion was shorter ( 9.68 h SD = 5.51 95%CI = 8.61 - 10.57 ) in the sublingual group than the vaginal group ( 16.64 h SD = 14.01 95%CI = 13.8 - 19.48 ) , P = 0.000 . Women in the sublingual group were highly satisfied with the method . CONCLUSION Sublingual misoprostol for the medical management of missed abortion is more effective and more acceptable than the vaginal route . However , it showed more adverse effects OBJECTIVE To investigate whether 600-μg oral misoprostol is an effective alternative to manual vacuum aspiration ( MVA ) for the treatment of incomplete abortion . METHODS From June 16 , 2004 , to July 20 , 2005 , 230 women of reproductive age presenting with incomplete abortion were r and omized in an open-label trial to either 600-μg oral misoprostol or MVA for the treatment of incomplete abortion . RESULTS Regardless of the assigned method , more than 98 % of participants experienced complete uterine evacuation following initial treatment . Efficacy , acceptability , and satisfaction ratings were similar and high for both methods . CONCLUSION 600-μg oral misoprostol is a safe , effective , and acceptable alternative to MVA for the treatment of incomplete abortion Misoprostol a synthetic prostagl and in E/1 analog widely prescribed for the prevention and treatment of peptic ulcer has become an important drug in obstetrics and gynecology . We have recently reported its ability to bring about cervical changes uterine contractions and successful induction of labor at term . Misoprostol has also been found to be effective in inducing abortion and therefore offers an effective alternative to the available medical and surgical options in second-trimester abortion . Because of the different pharmacokinetics when given orally or vaginally the optimum dosage and route of administration have not been definitively determined w4x . We performed a prospect i ve r and omized-controlled clinical trial at Wad Medeni Teaching Hospital to compare the efficacy of oral misoprostol with that of vaginal misoprostol for pregnancy termination in cases of intrauterine fetal demise in the second trimester . ( excerpt OBJECTIVE To compare the efficacy of the medical treatment to surgical uterine evacuation and patient satisfaction in each group . DESIGN A r and omized , controlled study . SETTING An outpatient clinic in the Department of Gynecology and Obstetrics in Oulu University Hospital , Oulu , Finl and . PATIENT(S ) Ninety-eight eligible women who had had miscarriages . INTERVENTION(S ) Medical treatment of miscarriage ( n = 49 ) with 200 mg of mifepristone and 0.8 mg of misoprostol 1 - 3 days after the event or surgical uterine evacuation ( n = 49 ) . Question naires to collect data of experienced pain and patient satisfaction . MAIN OUTCOME MEASURE(S ) The complete abortion rate with the primary treatment ( primary outcome ) and the patient satisfaction ( secondary outcome ) . RESULT ( S ) The success rate was equal ( 100 % in surgical and 90 % in medical group ) . More infections were diagnosed in the surgical group . Surgically treated patients were more satisfied with the treatment ( 100 % vs. 88 % ) . Medical treatment was considered more painful and fewer patients ( 70 % vs. 91 % ) would choose the medical method in the future . CONCLUSION ( S ) Medical treatment is an effective alternative to surgical treatment and increases the choice available to women . Surgical treatment is associated with more infections . More medically treated patients experienced pain and dissatisfaction Abstract Objective To ascertain whether a clinical ly important difference exists in the incidence of gynaecological infection between surgical management and expectant or medical management of miscarriage . Design R and omised controlled trial comparing medical and expectant management with surgical management of first trimester miscarriage . Setting Early pregnancy assessment units of seven hospitals in the United Kingdom . Participants Women of less than 13 weeks ' gestation , with a diagnosis of early fetal demise or incomplete miscarriage . Interventions Expectant management ( no specific intervention ) ; medical management ( vaginal dose of misoprostol preceded , for women with early fetal demise , by oral mifepristone 24 - 48 hours earlier ) ; surgical management ( surgical evacuation ) . Main outcome measures Confirmed gynaecological infection at 14 days and eight weeks ; need for unplanned admission or surgical intervention . Results 1200 women were recruited : 399 to expectant management , 398 to medical management , and 403 to surgical management . No differences were found in the incidence of confirmed infection within 14 days between the expectant group ( 3 % ) and the surgical group ( 3 % ) ( risk difference 0.2 % , 95 % confidence interval − 2.2 % to 2.7 % ) or between the medical group ( 2 % ) and the surgical group ( 0.7 % , − 1.6 % to 3.1 % ) . Compared with the surgical group , the number of unplanned hospital admissions was significantly higher in both the expectant group ( risk difference − 41 % , − 47 % to − 36 % ) and the medical group ( − 10 % , − 15 % to − 6 % ) . Similarly , when compared with the surgical group , the number of women who had an unplanned surgical curettage was significantly higher in the expectant group ( risk difference − 39 % , − 44 % to − 34 % ) and the medical group ( − 30 % , − 35 % to − 25 % ) . Conclusions The incidence of gynaecological infection after surgical , expectant , and medical management of first trimester miscarriage is low ( 2 - 3 % ) , and no evidence exists of a difference by the method of management . However , significantly more unplanned admissions and unplanned surgical curettage occurred after expectant management and medical management than after surgical management . Trial registration National Research Register : N0467011677/N0467073587 OBJECTIVES To assess if there was any potential relationship between endometrial thickness and final treatment outcome in women successfully treated with misoprostol for a first trimester anembryonic gestation , embryonic demise or fetal demise . METHODS Eighty women were treated with up to two doses of misoprostol 800 microg vaginally for early pregnancy failure . Subjects were scheduled to return 2 ( range 1 - 4 ) , 7 ( range 5 - 9 ) and 14 ( range 12 - 17 ) days after treatment . Transvaginal ultrasonography was performed at each follow-up visit . RESULTS The median endometrial thickness at each of the follow-up visits for women who had expelled the gestational sac was 14 mm , 10 mm , and 7 mm , respectively . The endometrial thickness at the first follow-up visit exceeded 15 mm in 20 subjects ( 36 % ) and 30 mm in four subjects ( 7 % ) . Only three women had a suction aspiration for bleeding after documented expulsion . The endometrial thickness for these women was 11 , 13 , and 14 mm at the first follow-up visit . CONCLUSIONS There is no obvious relationship between increasing endometrial thickness and the need for surgical intervention in women treated with misoprostol for early pregnancy failure A combination of the antiprogestagen mifepristone and an exogenous prostagl and in given by intramuscular injection or intravaginal pessary is a highly effective means of inducing abortion in early pregnancy . However , the search for a stable oral prostagl and in preparation has been largely unsuccessful . The effect of misoprostol , an orally active prostagl and in used to treat peptic ulcer , on uterine contractility was investigated in 33 women in early pregnancy ( under 56 days ' amenorrhoea ) . After administration of misoprostol in doses ranging from 200 micrograms to 600 micrograms , there was a significant increase in uterine pressure . In a second group of women who were given 200 - 1000 micrograms misoprostol 48 h after the administration of 200 mg mifepristone , there was a significant increase in the amplitude and frequency of uterine contractions . Complete abortion took place in 18 of the 21 women who received misoprostol after mifepristone , but in only 2 of 40 women given misoprostol alone . Our findings show that misoprostol increases uterine activity in early pregnancy and suggest that , in combination with mifepristone , it may be a highly effective method of inducing therapeutic abortion BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) inhibit the bio synthesis of prostagl and ins and concerns have been expressed that they might attenuate the effects of exogenous prostagl and ins . This r and omized study was conducted to evaluate whether NSAID given during medical abortion with mifepristone/misoprostol in the second trimester has a negative effect on the efficacy of the abortifacient by prolonging the induction-to-abortion interval . METHODS Seventy-four women were treated with the anti-progesterone mifepristone , followed by repeated doses of misoprostol 36 - 48 h later . They were r and omized to receive a prophylactic pain treatment of either paracetamol and codeine or diclofenac with the first dose of misoprostol . RESULTS Co-treatment of NSAID with misoprostol did not attenuate the efficacy of mifepristone and misoprostol . There was no significant difference between the NSAID and the non-NSAID group in the induction-to-abortion interval ( 5.4 versus 6.5 h ) or the total doses of misoprostol needed ( 2 versus 3 ) . The frequency of surgical intervention was similar ( 55.6 versus 52.6 % ) . Women in the group treated with NSAID required significantly less opiates ( P = 0.042 ) . CONCLUSION Co-treatment with NSAID and misoprostol does not interfere with the action of mifepristone and /or misoprostol to induce uterine contractions and pregnancy expulsion in medical abortion . Prophylactic NSAID administration reduces the need for opiate injections Objective To test the feasibility of mounting a r and omised controlled trial comparing mifepristone – misoprostol versus dilation and evacuation ( D&E ) for midtrimester abortion Summary : This prospect i ve , r and omized study compared the efficacy of intravaginal misoprostol ( Cytotec ) and gemeprost ( Cervagem ) as an abortifaeient for intrauterine deaths in second trimester pregnancy . Side‐effects , complications and the cost‐effectiveness associated with each drug were assessed . 21 out of 25 patients ( 84 % ) in the misoprostol group aborted whereas only 17 out of 25 patients ( 68 % ) in die gemeprost group aborted within 24 hours after the initiation of therapy . In the misoprostol group , the abortion rate was influenced by the gestational age with 100 % abortion rate for those > 17 weeks ' gestation compared to 67 % for those with a gestational age of 13–16 weeks . Side‐effects were rare in either group and no major complications were reported in either group . Misoprostol was definitely more cost‐effective compared to gemeprost as the mean cost of inducing an abortion using misoprostol was RM 1.08 whereas that of gemeprost was RM 105 . We thus concluded that misoprostol was at least as effective as gemeprost as an abortifacient for intrauterine death in second trimester pregnancy . Moreover , it was less costly , with very few side‐effects Objectives To compare the efficacy of repeated doses of 100 μg vs. 200 μg misoprostol given sublingually for induction of second trimester abortion . Methods One hundred and sixty-two women at 15–22 weeks ' gestation were r and omized to receive every 2 h either 100 μg ( group 1 ; n = 81 ) or 200 μg ( group 2 ; n = 81 ) misoprostol sublingually . The primary outcome measure was the abortion rate within 24 h. The secondary outcome measures were the induction-abortion interval , the total misoprostol dose required , and side effects of the regimen . Results There was no significant difference between the two groups with regard to the abortion rates within 12 h ( 43.2 % in group 1 vs. 48.1 % in group 2 ; p = 0.52 ; relative risk [ RR ] : 0.81 ; 95 % confidence interval [ CI ] : 0.4–1.5 ) and 24 h ( 92.6 % in group 1 vs. 91.4 % in group 2 ; p = 0.77 ; RR : 1.11 ; 95 % CI : 0.37–3.6 ) . The induction-abortion intervals in the two groups were of similar length ( 885 minutes in group 1 vs. 912 minutes in group 2 ; p = 0.72 ) . When the total dose of misoprostol was compared between the two groups , women belonging to group 2 on average had received significantly more misoprostol than those in group 1 ( 1274 ± 592 μg [ 7 ± 3 doses ] vs. 614 ± 432 μg [ 6 ± 4 doses ] , respectively ; p = 0.000 ) . Conclusions Sublingual administration of repeated doses of 100 μg misoprostol for abortion induction appears to be equally effective to that of repeated doses of 200 μg OBJECTIVE Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy . STUDY DESIGN Women seen for midtrimester pregnancy termination were r and omly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours . The protocol was followed for 24 hours , after which time further management was at the discretion of the attending physician . The primary outcome measure was the induction-to-delivery interval . Sample size was calculated a priori . Statistical analysis was performed with the t test for continuous variables and the chi(2 ) test for categorical variables . P < .05 was considered significant . RESULTS One hundred fourteen women were r and omized , with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol . The two groups were comparable with respect to maternal age , parity , indication for pregnancy termination , gestational age , and maternal weight . The mean induction-to-delivery interval was significantly shorter for the vaginal group ( 19.6 + /- 17.5 hours vs 34.5 + /- 28.2 hours , P < .01 ) . Length of stay was also shorter in the vaginal group ( 32.3 + /- 17.3 hours vs 50.9 + /- 27.9 hours , P < .01 ) . Significantly more patients in the vaginal group were delivered within 24 hours ( 85.1 % vs 39.5 % , P < .01 ) , and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours ( 38.2 % vs 7 % , P < .01 ) . The only complication was an increase in febrile morbidity in the vaginal group ( 25 % vs 6.7 % , P = .046 ) . This did not result in an increased use of antibiotics , and all the fevers resolved post partum without further complications . CONCLUSIONS Vaginal administration of misoprostol result ed in a shorter induction-to-delivery interval . The shorter length of stay should result in improved patient care OBJECTIVES To evaluate the use of a double balloon catheter in the termination of pregnancy with fetal death in the second and third trimesters , in comparison with the administration of extra-amniotic PGF2-alpha . METHODS Twenty cases with IUFD at > 20 weeks of gestation were divided into two groups . Group I was subjected to the double balloon alone , while in Group II extra-amniotic instillation of PGF2-alpha via a Foley 's catheter was used . RESULTS There were no significant differences between the two groups with regard to induction-expulsion time , induction-delivery time and failure rate . CONCLUSIONS The double balloon catheter proved to be an effective non-pharmacological method . The technique was simple and well tolerated by the patients . The side-effects of the prostagl and in and the cost of the medication were avoided Objective : This study was design ed to determine whether use of prostagl and in E1 ( PGE1 ) is justified to improve the known clinical outcome of prostagl and in E2 ( PGE2 ) gel , because PGE2 gel preparations are more costly than PGE1 tablets in most countries , and data to support the use of the gel in clinical practice is not conclusive . The aim was to compare the safety and efficacy of PGE1 gel when applied in both an in-hospital or ambulatory setting to oxytocin infusion in those women with unfavorable cervical conditions prior to surgical abortion for either medical or obstetrical indications with intrauterine fetal demise . Surgical dilatation of the unripe cervix may result in cervical injury of uterine perforation which could prolong the hospital stay . Methods : We used PGE1 gel prepared from tablets and administered in the ambulatory form ( group 1 ) , the same PGE1 gel administered in the labor room ( group 2 ) and intravenously administered oxytocin in the labor room ( group 3 ) for the induction of abortus in women complicated with intrauterine fetus death and missed abortion . Patients requesting abortion were eligible for inclusion , with > 8 and < 13 weeks of gestation . Eighty-nine women with unfavorable cervices ( Bishop score ≤4 ) were included in this study . Comparisons between the three groups for such variables were done by ANOVA . Results : The statistical test did reveal significant differences in the cervical changes , doses of PGE1 used and maternal labor stay between the three groups . The difference in effect on cervical ripening was seen following PGE1 application in both of these groups , but no difference was seen with the oxytocin use . Cervical score changed in 100 % of both groups with the PGE1 gel and 89.6 % of the group with oxytocin use , within 6 days in the latter group . The mean number of days of maternal labor stay were 1.5 , 4.6 and 6.2 respectively . There was no difference regarding the effect on clinical characteristics of the women on the final Bishop score . The number , initial and final Bishop score , vaginal bleeding and other complications were not different . Conclusions : Duration of hospital stay may be decreased by applying PGE1 gel in an ambulatory setting when compared to in-hospital PGE1 gel applications or intravenous oxytocin infusion for cervical ripening . Further research is necessary to determine the safety of PGE1 gel application for preabortion cervical ripening prior to surgical abortion OBJECTIVE : To compare the effectiveness and side effects of oral and vaginal misoprostol for the termination of second and third trimester pregnancy with intrauterine fetal death . METHODS : Eighty pregnant women at 16‐41 weeks ' gestation with intrauterine fetal death were r and omized in two groups to receive either 400 & mgr;g of misoprostol orally every 4 hours ( n = 40 ) or 200 & mgr;g of misoprostol vaginally every 12 hours ( n = 40 ) until the termination of pregnancy was completed . The adverse effects , progress , and outcomes of delivery were assessed . RESULTS : The groups were similar in age , weight , height , gestational age , parity , and modified Bishop scores before intervention . The mean induction‐to‐delivery time in the oral group ( 13.95 [ st and ard deviation ( SD ) = 5.63 ] hours ) was significantly shorter than the time in the vaginal group ( 18.87 [ SD = 10.38 ] hours , P = .001 ) . The number of deliveries within 24 hours after the initial drug administration in the oral group ( 92.5 % ) was significantly higher than the number in the vaginal group ( 67.5 % , P < .001 ) , and all delivered within 48 hours after the initial drug administration . However , the gastrointestinal side effects in the oral group was significantly higher than in the vaginal group ( P = .005 ) . CONCLUSION : Misoprostol ( 400 & mgr;g given orally every 4 hours ) was more effective than misoprostol ( 200 & mgr;g given vaginally every 12 hours ) for the termination of second and third trimester pregnancy with intrauterine fetal death , but with more gastrointestinal side effects . ( Obstet Gynecol 2003;101:70‐73 . © 2003 by The American College of Obstetricians and Gynecologists . OBJECTIVE To compare the effect of vaginal misoprostol with that of placebo when used prior to dilation and aspiration in women with a missed abortion . METHOD Eighty-four pregnant women with a missed abortion were r and omized to receive either vaginal misoprostol ( 200 micrograms ) or placebo the day before the planned dilatation and aspiration under inhalation anesthesia . RESULT Thirty-five women ( 83.33 % ) in the misoprostol group and 6 women ( 17.14 % ) in the placebo group aborted spontaneously prior to the scheduled dilatation and aspiration , P < 0.0001 . The mean insertion to spontaneous expulsion time was 11.63 + /- 6.14 h in the misoprostol group compared to 11.95 + /- 5.43 h in placebo . In the misoprostol group two women required intramuscular pethidine for analgesia . In the placebo group there were two cases of blood loss in excess of 500 ml and one woman with a uterine perforation . CONCLUSION Vaginal administration of misoprostol to women with a missed abortion produced spontaneous expulsion of the pregnancy and reduced the need for surgical treatment STUDY OBJECTIVE To determine the frequency of intrauterine adhesions ( IUA ) after conservative management , medical evacuation , and surgical evacuation for spontaneous abortion . DESIGN Prospect i ve follow-up study ( Canadian Task Force classification II-2 ) . SETTING Gynecology unit in a teaching hospital . PATIENTS Eighty-two women who had been treated with conservative management , medical evacuation , or surgical evacuation of retained products of conception after spontaneous abortions in a r and omized , controlled trial . MEASUREMENTS AND MAIN RESULTS Hysteroscopic diagnosis of IUA 6 months after initial treatment was the primary outcome measure . No cases of IUA were found in patients managed conservatively or by medical evacuation , whereas two cases ( 7.7 % ) of filmy IUA were detected in those managed by surgical evacuation . There was no statistical significant difference in the rate of self-reported reduced menstrual flow 6 months after initial treatment by any method . CONCLUSION The prevalence of IUA was low after each modality of treatment for spontaneous abortion . Conservative management and medical evacuation are both acceptable alternatives to st and ard surgical evacuation OBJECTIVE To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination . METHODS A r and omized clinical trial of medical pregnancy termination between 14 and 26 weeks ' gestation was conducted . Three misoprostol regimens were compared : 400 μg vaginally at 6-hour intervals ( group 1 ) , 400 μg orally at 3-hour intervals ( group 2 ) , and a loading dose of 600 μg vaginally followed by 200 μg orally at 3-hour intervals ( group 3 ) . A sample size of 225 women was required for equivalence of the three regimens , with an interim safety analysis planned at 80 women . RESULTS A significant difference between the groups was evident at the interim safety analysis and the study ceased . The subset of 84 women recruited before the study closure is described . There was a significant difference in the median time to achieve delivery among the three groups : group 1 , 14.5 hours ( 95 % confidence interval 12.0 , 16.9 ) , versus group 2 , 25.5 hours ( 13.5 , 23.8 ) , versus group 3 , 16.4 hours ( interquartile range 14.2–37.3 ) ( P = .042 ) . Within 24 hours of commencement 85.7 % of women in group 1 , 44.8 % in group 2 , and 74.1 % in group 3 delivered ( P = .003 ) . At 48 hours 0 % in group 1 , 20.7 % in group 2 , and 3.7 % in group 3 were undelivered ( P = .011 ) . There was no difference in women 's perceptions of the termination process . CONCLUSION In second-trimester pregnancy termination , a vaginal misoprostol regimen of 400 μg every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 μg every 3 hours Objective To compare the pharmacokinetics of vaginal and oral administration of the prostagl and in E1 analogue , misoprostol . Methods Twenty women received 400-μg doses of misoprostol either orally or as tablets placed in the vagina . Serum levels of the principal metabolite , misoprostol acid , were measured at 7.5 , 15 , 30 , 45 , 60 , 90 , 120 , and 240 minutes . The first ten women were pregnant and undergoing firsttrimester abortions , and the last ten were not pregnant and had additional blood sampling at 360 minutes . We compared the pharmacokinetics of misoprostol acid after oral and vaginal administration . Results All 20 subjects completed the study . The maximum mean ( ± st and ard deviation [ SD ] ) of misoprostol acid differed significantly between the oral and vaginal groups ( 277 ± 124 compared with 165 ± 86 pg/mL , respectively ; P = .03 , analysis of variance ) , as did the mean ± SD time to peak levels ( 34 ± 17 compared with 80 ± 27 minutes , respectively ; P < .001 ) and areas under the misoprostol concentration versus time curve ( mean ± SD ) up to 4 hours ( n = 20 , 273.3 ± 110.0 compared with 503.3 ± 296.7 pg . hour/mL , respectively ; P = .033 ) and up to 6 hours ( n = 10 , 300.0 ± 103.3 compared with 956.7 ± 541.7 pg . hour/mL , respectively ; P = .029 ) . The extent of absorption was highly variable among subjects in each group . Conclusion There are significant differences in the pharmacokinetics of misoprostol administered by vaginal and oral routes that may explain the difference observed in clinical efficacy . Assuming that the pharmacologic effect of misoprostol is related to its concentration in the plasma , our observation of the prolonged serum concentrations in the vaginal group suggests that vaginal administration could be dosed at longer intervals than oral OBJECTIVE To compare the efficacy of two routes of misoprostol administration ( oral and vaginal ) for treatment of missed abortion . METHODS Two hundred women with confirmed missed abortion received 800 mcg misoprostol either orally or vaginally . All women returned for follow-up care 2 days later . If the pregnancy was not completely evacuated at this time , women could wait an additional 5 days or undergo immediate surgical completion . Efficacy was defined as the percent of women discharged from the study without need for surgical intervention . RESULTS Efficacy was high in both groups and not statistically different ( oral=89.0 % , vaginal=92.9 % ) . While the groups did not differ in terms of the completion rate by day 2 ( oral=41.6 % , vaginal=52.7 % ) , the mean time to expulsion was longer ( 21.04 h ) in the oral group than the vaginal group ( 13.47 h ) , p=0.041 . Women in both groups were highly satisfied with the method . CONCLUSIONS Medical management of missed abortion with either oral or vaginal misoprostol is highly effective and highly acceptable BACKGROUND This r and omized controlled trial compared the use of sublingual misoprostol with or without an additional 1 week course of sublingual misoprostol for the medical management of silent miscarriage . METHODS A total of 180 women who had silent miscarriage ( < 13 weeks ) was given 600 microg of misoprostol every 3 h for a maximum of three doses . These women were r and omized into two groups : ( i ) no extended course of misoprostol or ( ii ) an extended course of sublingual misoprostol 400 microg daily for 1 week . The primary outcome measure was complete miscarriage rate . RESULTS The success rates for complete miscarriage were similar in both groups ( group 1 : 92.2 % ; 95 % CI : 86.1 - 97.5 % and group 2 : 93.2 % ; 95 % CI : 84.6 - 96.8 % ) . There were no serious complications . The incidence of diarrhoea was higher ( P < 0.01 ) in the group with an extended course of sublingual misoprostol . Other side-effects were similar . CONCLUSION Sublingual misoprostol is useful for the management of silent miscarriage . An additional 1 week course of sublingual misoprostol did not improve the success rate or shorten the duration of vaginal bleeding . Instead , it increased the incidence of diarrhoea OBJECTIVE To compare the efficacy of misoprostol administered sublingually or orally for uterine evacuation after early pregnancy failure . METHOD Forty-eight hours after receiving 200 mg of mifepristone orally , 100 women were r and omized to receive misoprostol sublingually or orally . RESULTS The evacuation rates were 92 % in the sublingual and 84 % in the oral administration group ; the mean+/-SD induction-to-evacuation intervals were 5.6+/-4.54 hours and 9.44+/-5.61 hours , this difference being significant ; and the adverse effects were similar in the 2 groups . CONCLUSION The sublingual route was found to be as effective but faster than the oral route for uterine evacuation after early pregnancy failure OBJECTIVES Although a number of studies have shown misoprostol 's promise as a nonsurgical treatment for incomplete abortion , few have systematic ally examined treatment protocol s. This study documents the effectiveness of 600 versus 1,200 microg oral misoprostol for this indication . METHODS From May 2002 to January 2003 , 300 women with incomplete abortion were recruited at a large tertiary facility in Vietnam and r and omized to either a single-dose ( 600 microg ) or a repeated-dose ( 600 microg x 2 ) regimen of oral misoprostol for the treatment of their condition . RESULTS Misoprostol effectively evacuated the uterus for nearly all women ( 94.6 % ; n=279 ) , with most reporting bleeding for 4 days ( + /-2.3 ) and pain/cramps lasting 1 day ( + /-1.0 ) . Women indicated that the side effects were tolerable ( 96 % ) and that their experience was satisfactory ( 95 % ) . CONCLUSIONS Oral misoprostol ( 600 or 1,200 microg ) offers a safe , effective and acceptable treatment for incomplete abortion . Larger studies to assess the advantages and disadvantages of misoprostol as compared with st and ard surgical care are needed to assess its role in postabortion care programs worldwide Oxytocin is extensively used to induce or augment uterine contractions , especially to facilitate the third stage of labor in humans . Administration of oxytocin to parturient sows reduces duration of labor whereas mortality of the offspring may remain unchanged . This study aim ed to evaluate whether time of administration of oxytocin during parturition may alter the uterine response and fetal outcomes . Two hundred parturient sows were r and omly assigned to intramuscularly receive either saline solution ( control group ) or oxytocin 0.083 IU/kg immediately after the delivery of the 1st , 4th or 8th piglet ( groups O-1 , 0 - 4 and 0 - 8 , respectively ) . Uterine effects and fetal outcomes were registered in all groups . The duration of labor was 20 - 40 min shorter ( P < 0.0001 ) and time interval between babies was reduced by 3 - 5 min ( P < 0.0001 ) in the three groups receiving oxytocin . The duration and intensity of contractions , meconium-stained piglets and intrapartum deaths decreased as time at which oxytocin administered during labor was increased . In group 0 - 8 , we observed approximately 70 % less meconium-stained piglets and intrapartum deaths than in the control group . In conclusion , oxytocin administered at early phases of parturition to sows may increase duration and intensity of uterine contractions as well as adverse fetal outcomes Objective To determine whether misoprostol ( a prostagl and in El analogue ) 400 μg orally ( group 1 ) or 800 μg vaginally ( group 2 ) will cause complete uterine evacuation in women with early pregnancy failure . Methods Twenty subjects were recruited for a prospect i ve , non-blinded , r and omized clinical trial . Early pregnancy failure was diagnosed by transvaginal ultrasound examination ; only women with a closed cervical os and minimal vaginal bleeding were enrolled . Subjects returned 24 hours after misoprostol administration for a transvaginal ultrasound examination . If the gestational sac was still present , the misoprostol dose was repeated and the subject returned again 24 hours later . Subjects who failed to expel the pregnancy were offered a suction curettage . Results Twelve and eight women were r and omized to groups 1 and 2 , respectively . Complete uterine evacuation occurred in three of 12 [ 25 % , 95 % confidence interval ( CI ) 1 % , 50 % ] and seven of eight ( 88 % , 95 % CI 65 % , 100 % , P = .010 ) subjects in groups 1 and 2 , respectively . Vomiting occurred in 30 % and 13 % , respectively , and diarrhea in 50 % and 38 % , respectively . Conclusion Vaginal misoprostol 800 μg is more effective than oral misoprostol 400 μg for uterine evacuation of early pregnancy failure and may be an effective alternative to dilation and curettage Misoprostol is one of the most popular products used for pregnancy termination because of its high efficacy , low cost and stability at room temperature . It was found that a dosage of 400 mcg of intravaginal misoprostol is optimal for secondtrimester termination [ 1–3 ] ; however , the optimal time interval between doses has not been established . We conducted this study to compare the efficacy of intravaginal misoprostol , 400 mcg , administered every 3 and 6 h. Pregnant women with live fetus and unfavorable cervix at accurate gestational age of 14–28 weeks with indications for pregnancy termination were allocated into either group of 3-h interval or 6-h interval by block r and omization . A Bishop score was obtained for cervical assessment just before initiating misoprostol . Exclusion BACKGROUND A prospect i ve r and omized controlled trial was conducted to compare the efficacy and side-effects of vaginal versus oral misoprostol in the medical management of incomplete miscarriage . METHODS Two hundred and one patients who miscarried consented to r and omization using computer-generated r and omization model prior to treatment . A total of 800 microg of misoprostol was given either vaginally or orally to the r and omized subjects . A second dose was repeated 4 h later if the product of conception had not been passed . RESULTS The incidence of complete uterine evacuation following vaginal and oral misoprostol was similar [ ( 58/95 ) 61.1 % versus ( 67/103 ) 64.4 % ] . There was a significantly decreased incidence of diarrhoea [ ( 12/95 ) 13.6 % versus ( 62/103 ) 65.3 % , P < 0.01 ] with the use of vaginal misoprostol . CONCLUSIONS Vaginal misoprostol was as effective as oral misoprostol in medical uterine evacuation in patients with incomplete miscarriage . There was also a reduction in the incidence of diarrhoea with the use of vaginal misoprostol Objective To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy . Methods Eighty-one women between 12 and 24 weeks ' gestation requesting abortion were r and omized to receive intravaginally either 100 μg of misoprostol at 6-hour intervals ( n = 27 ) , 200 μg of misoprostol at 12-hour intervals ( n = 26 ) , or 1.0 mg of gemeprost at 3-hour intervals ( n = 28 ) . The regimen was continued until abortion , or for 36 hours , with assessment of the rate of complete and incomplete abortions as well as side effects within 48 hours from the start of the treatment . Results The final rates of terminations were 74 % in the 100 μg misoprostol group , 92 % in the 200-μg misoprostol group , and 89 % in the gemeprost group . Abortion was complete in 37 % , 61 % and 32 % in each group , respectively ( P = .03 , when the 200-μg misoprostol group was compared with the two other groups ) . The inductions- to-abortion interval was longer ( P = .001 ) in he misoprostol groups ( mean 23.1 hours for the 100-μg and 27.8 hours for the 200-μg dose ) than in the gemeprost group ( 14.5 hours ) . There was less pain ( P = .01 ) , and vomiting ( P = .01 ) in the misoprostol groups that in the gemeprost group . The mean blood loss in the misoprostol groups was lower than in the gemeprost group ( P = .001 ) . Conclusion Intravaginal application of 200 μg of misoprostol at 12-hour intervals in induction of second-trimester abortion is equally effective to a st and ard gemeprost regimen . Misoprostol causes fewer side effects and is cheaper and more practical to use Objective : To compare the safety , efficacy , and acceptability of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion in a hospital setting in Kampala , Ug and a. Methods : Three hundred seventeen women with clinical ly diagnosed incomplete first-trimester abortions were r and omized to treatment with either manual vacuum aspiration or 600 & mgr;g misoprostol orally to complete their abortions . All women received antibiotics posttreatment and were followed up 1–2 weeks later . Results : Regardless of treatment allocation , nearly all women in this study successfully completed their abortions with either oral misoprostol or manual vacuum aspiration ( 96.3 % versus 91.5 % , relative risk 1.05 , 95 % confidence interval 0.98–1.14 ) . Complications were less frequent in those receiving misoprostol than those having manual vacuum aspiration ( 0.9 % versus 9.8 % , relative risk 0.1 , 95 % confidence interval 0.01–0.78 ) . In the 6 hours after treatment , women using misoprostol reported heavier bleeding but lower levels of pain than those treated with manual vacuum aspiration . Rates of acceptability were similarly high among women in the 2 treatment groups , with 94.2 % and 94.7 % of women reporting that their treatment was satisfactory or very satisfactory in the misoprostol and manual vacuum aspiration groups , respectively . Conclusion : For treatment of first-trimester uncomplicated incomplete abortion , both manual vacuum aspiration and 600 & mgr;g oral misoprostol are safe , effective , and acceptable treatments . Based on availability of each method and the wishes of individual women , either option may be presented to women for the treatment of incomplete abortion . Level of Evidence : OBJECTIVE : To compare the efficacy , side effects , and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostagl and in ( PGE2 ) for second-trimester labor induction . METHODS : One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were r and omly assigned to receive either vaginal misoprostol 600 μg 1 × , 400 μg every 4 hours 5 × ( misoprostol group , n = 60 ) or escalating-dose concentrated oxytocin infusions ( 277–1,667 mU/min ) plus vaginal PGE2 10 mg every 6 hours 4 × ( oxytocin group , n = 66 ) . Both groups received concurrent extra-amniotic saline infusion for cervical ripening . Women who failed their assigned regimen received 20 mg of PGE2 suppositories every 4 hours until delivery . Analysis was by intent to treat . RESULTS : Demographic characteristics were similar between study groups . Median induction-to-delivery interval was significantly shorter in the misoprostol group ( 12 hours ) than in the oxytocin group ( 17 hours ; P < .001 ) . There was a higher induction success rate at 24 hours in the misoprostol group ( 95 % ) than in the oxytocin group ( 85 % ; P = .06 ) , although this difference did not reach statistical significance . The incidence of live birth ( 25 % versus 17 % ) , chorioamnionitis ( 5 % versus 2 % ) , and postpartum hemorrhage greater than 500 mL ( 3 % versus 3 % ) were similar between the misoprostol and oxytocin groups , respectively . Diarrhea ( 2 % versus 11 % ; P = .04 ) , nausea/emesis ( 25 % versus 42 % ; P = .04 ) , and retained placenta requiring curettage ( 2 % versus 15 % ; P = .008 ) were significantly less common in the misoprostol group when compared with the oxytocin group , respectively . Isolated intrapartum fever , however , was more frequent in the misoprostol group ( 67 % ) than in the oxytocin group ( 21 % ; P < .001 ) . CONCLUSION : Compared with concentrated oxytocin plus low-dose vaginal PGE2 , high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals , fewer side effects , a lower incidence of retained placenta , and comparable incidence of live birth . LEVEL OF EVIDENCE : OBJECTIVE Our purpose was to compare the efficacy , safety , and adverse effects of intra-amniotically administered (15S)-15-methyl-prostagl and in F(2alpha ) and intravaginally administered misoprostol for second-trimester uterine evacuation . STUDY DESIGN Fifty-one patients were r and omly assigned to receive either a single 2.5-mg intra-amniotic injection of (15S)-15-methyl-prostagl and in F(2)(alpha ) ( n = 26 ) or two 200-microg intravaginal doses of misoprostol ( n = 25 ) at 12-hour intervals . The primary outcome measured was evacuation of the uterus within 24 hours . RESULTS The mean time from initiation of termination to uterine evacuation was less in the prostagl and in group than in the misoprostol group ( 17.5 + /- 8.6 hours vs 22.3 + /- 12.5 hours ) , but this was not statistically significant ( P > .05 ) . The rate of successful fetal evacuation at 24 hours was significantly higher in the prostagl and in group than in the misoprostol group ( 88 % vs 60 % , P = .02 ) . The complete-abortion rate and the incidence of adverse effects were similar in both groups . CONCLUSION The use of an intra-amniotic injection of (15S)-15-methyl-prostagl and in F(2alpha ) for midtrimester pregnancy termination is safe and is associated with a greater number of successful uterine evacuations within 24 hours , without an increase in adverse effects , than intravaginal administration of misoprostol OBJECTIVE To evaluate and compare the effectiveness and side effects of two regimens of oral misoprostol , single dose ( 600 microg ) and repeated dose ( 1200 microg ) , in the treatment of incomplete abortion . METHODS A prospect i ve r and omized controlled trial was conducted . One-hundred women who had incomplete abortion ( gestational age < 20 weeks ) and consented to r and omization by computer-generated r and omization model prior to treatment . A single oral 600-microg dose or repeated oral dose after 4 h ( total 1200 microg ) was given to the r and omized women . RESULTS The overall incidence of complete abortion was 86.9 % . This incidence was not statistically different between the single-dose and repeated-dose groups ( 81.6 % vs. 92 % , p > 0.05 ) . However , there was a significantly decreased incidence of diarrhea ( 18.4 % vs. 40 % , p < 0.05 ) with the use of single-dose treatment . Overall rate of acceptability and tolerable side effects were 88.9 % and 97.9 % , respectively . These rates were similar in both groups ( 87.8 % vs. 90 % and 98 % vs. 98 % , p > 0.05 ) . CONCLUSIONS Oral misoprostol may be a practical alternative in the management of incomplete abortion . Oral misoprostol is acceptable and tolerable to women . Single-dose regimen is as effective as repeated-dose regimen , with a reduction in the incidence of diarrhea OBJECTIVE To study the effectiveness of single application of intravaginal misoprostol versus intracervical prostagl and in E2 gel for ripening the unfavorable cervix and labor induction . METHOD One hundred and ten patients with indications for induction of labor with unfavorable cervices were r and omized to receive either 100 microgram tablets of misoprostol placed in the posterior vaginal fornix or prostagl and in E2 1.5 mg in gel placed into the endocervix . Those , who were not in active labor after 24 hours , had labor induced with amniotomy and oxytocin . RESULTS Among 110 patients recruited , 60 received misoprostol and 50 received prostagl and in E2 gel . The average interval from start of induction to vaginal delivery was 19.14 + /- 10.64 hours in misoprostol group and 21.37 + /- 13.09 hours in the prostagl and in E2 group ( p = 0.33 ) . Five patients ( 8 % ) in the misoprostol group had induction of labor after 24 hours of the treatment compared with 13 patients ( 26 % ) in the PGE2 group . The difference was significant ( p = 0.03 ) . Oxytocin augmentation was 35 % in the misoprostol group and 34 % in the prostagl and in E2 group ( p = 0.86 ) . There were no significant differences between routes of delivery . Nineteen patients ( 31 % ) in misoprostol group and 16 patients ( 32 % ) in the PGE2 gel group had cesarean deliveries . There was one case ( 1.7 % ) of uterine hyperstimulation in the misoprostol group and none in the PGE2 gel group . There were no significant difference in Apgar scores < 7 at 1 and 5 minutes , or admission to the neonatal intensive care unit between the 2 groups . CONCLUSION Vaginal misoprostol is an effective agent for cervical ripening and induction of labor . Complications associated with prostagl and in administration were not statistically different between the 2 groups , but hyperstimulation occurred more in misoprostol group Miscarriage treated surgically and medically were compared in a r and omised controlled trial evaluating pain and bleeding . Surgery is associated with less pain ( P < 0.03 ) and vaginal bleeding ( duration and severity , P = 0.001 ) than medical treatment , fewer daily hospital attendances ( 2.5 compared with three , P = 0.04 ) but a greater drop in haemoglobin concentration ( difference , 1 g/dl ; CI95 % = 0.3 - 1.6 ) BACKGROUND A r and omized controlled trial comparing sublingual with vaginal administration of misoprostol for medical management of silent miscarriages . METHODS Eighty women who had silent miscarriages ( < 13 weeks ) were r and omized to receive 600 micro g of misoprostol every 3 h for a maximum of three doses either sublingually or vaginally . RESULTS The success rates of medical management were the same in both groups ( 87.5 % ; 95 % CI : 74 - 95 % ) . There were no serious complications . The incidence of diarrhoea was higher in the sublingual ( 70 % ) than the vaginal route ( 27.5 % ) ( P < 0.005 ) . Other side effects were similar in each group , although fatigue was experienced by more women in the sublingual group than in the vaginal group ( 65 versus 40 % : P = 0.043 ) . The overall acceptability of medical management was good . Most women would choose the medical method if they were allowed to choose again and would recommend the method to others . CONCLUSION The current regimen of misoprostol is useful for the management of silent miscarriage in terms of complete miscarriage rate and patient acceptability . Sublingual misoprostol may offer an alternative for women who do not like repeated vaginal administration of the drug OBJECTIVE To assess the feasibility of introducing misoprostol for the treatment of incomplete abortion in Quito , Ecuador . METHODS In a r and omized prospect i ve study conducted at a large tertiary-level maternity hospital and a private secondary -level clinic between November 2006 and November 2007 , women with incomplete abortion were treated with either 600 μg of oral misoprostol ( n=122 ) or manual vacuum aspiration ( MVA ) ( n=120 ) . All participants were requested to return for follow-up care on day 7 to determine the success of the treatment and to document their satisfaction with the method and the adverse effects experienced . RESULTS Sixteen percent of women ( 39/242 ) did not return for their follow-up visit and their outcomes are unknown . Among those who did return , 94 % ( 100/106 ) of women showed successful completion of abortion after treatment with misoprostol , as compared with 100 % ( 97/97 ) of women treated with MVA . Most women described their adverse effects after treatment as tolerable ( misoprostol , 95 % ; MVA , 91 % ) . Nearly all women reported being satisfied with their treatment ( 196/203 ) ; there were no differences among the women 's reports of satisfaction according to treatment received . CONCLUSION An oral dose of 600 μg of misoprostol was found to be an acceptable and effective non-surgical option for treating incomplete abortion . Clinical trials.gov NCT00674232 OBJECTIVE To determine whether misoprostol medical management of early pregnancy failures is more effective than expectant management . STUDY DESIGN Patients diagnosed with early pregnancy failures , closed cervix , and minimal vaginal bleeding were r and omized to 800 microg of misoprostol or placebo placed vaginally . Patients were evaluated by ultrasound imaging 24 hours and 48 hours after study drug administration , with repeat administration if 24-hour imaging showed a persistent gestational sac . Treatment success was defined as expulsion of uterine contents within 48 hours . Patient follow-up occurred 2 weeks after expulsion of uterine contents . RESULTS Treatment success occurred in 15 of 18 ( 83 % ) misoprostol patients and 2 of 16 ( 13 % ) placebo patients ( P < .0001 ) . Side effects were similar between groups except for vaginal bleeding , which was more common in the misoprostol group ( P = .001 ) . Patient satisfaction and pain perception were similar between groups . CONCLUSION Misoprostol appears to be highly effective for treating early pregnancy failures , with few side effects and high patient satisfaction Objective To compare the efficacy of antiprogesterone ( mifepristone ) in combination with a synthetic prostagl and in E , analogue ( misoprostol ) for outpatient treatment of miscarriages BACKGROUND Little is known about the effectiveness of misoprostol treatment in women with early pregnancy failure who have been managed expectantly . We therefore performed a r and omized trial on this subject . METHODS Women with early pregnancy failure , who had been managed expectantly for at least 1 week , were assigned r and omly ( using a computer-generated list ) to receive either vaginal misoprostol 800 microg or curettage . If , after 24 h , there had not been complete evacuation , a further 800 microg of misoprostol was administered . In the absence of complete evacuation after > days , curettage was performed . The primary end-point was the complete evacuation of the products of conception , with secondary end-points being the occurrence of side effects , pain intensity , need for analgesics , and intensity and duration of bleeding . RESULTS In the misoprostol group , 47 % ( 37/79 ) required curettage due to incomplete evacuation . After 1 week , evacuation was complete in 85 % ( 67 out of 79 ) of the misoprostol group and 93 % ( 70 out of 75 ) of the curettage group . Severity of pain , bleeding and emergency evacuation was higher in the misoprostol group . The complication rate was 0 % for misoprostol and 4 % for curettage . CONCLUSIONS Curettage is superior to misoprostol in the evacuation of early pregnancy failure after failed expectant management . However , misoprostol could be clinical ly useful since it reduces the need for curettage by half and has a lower complication rate , at the expense of increased pain , vaginal bleeding and emergency evacuation OBJECTIVE To identify ultrasound measurements that are the best predictors of the presence of retained products of conception ( RPOC ) within the uterine cavity in women with clinical diagnosis of incomplete miscarriage . METHODS This was a prospect i ve observational study , set in a dedicated early pregnancy assessment unit in a London teaching hospital . Endometrial thickness and the volume of suspected retained products of conception were measured by transvaginal ultrasound scan preoperatively . Indications for surgical intervention were heavy vaginal bleeding or continuous bleeding lasting > 7 days . The main outcome measure was histological evidence of chorionic villi in surgical specimens . RESULTS Among the patients , 109 ( 85 % ) had evidence of chorionic villi on histology , whilst decidua was only found in the remaining 19 ( 15 % ) . There was no identifiable cut-off for endometrial thickness or volume that could be used to differentiate between retained products of conception and decidua . CONCLUSION Measurements of endometrial thickness or volume on ultrasound scan are not good tests for diagnosing an incomplete miscarriage The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination . Sixty women in second trimester of gestation with indications for pregnancy termination were r and omly assigned in two equal groups to receive either vaginal or oral misoprostol . The dosing regimen was 400 microg as the initial dose followed by 400 microg up to 3 doses ( 1200 microg ) if needed in each group . Efficacy and side effects were compared . The percentage of women who delivered was significantly higher in vaginal group than the oral group ( 86.7 vs. 43.3 p = 0.0006 ) . No significant differences in complication rates and induction to delivery interval were noted between the two groups . Vaginal administration of misoprostol result ed in a higher success rate for second trimester pregnancy termination , whereas , no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups In South Africa surgical curettage under general anaesthesia is considered to be the st and ard management for incomplete miscarriage . It constitutes a substantial proportion of the gynaecological services rendered and therefore places an ever increasing burden on the medical re sources available . Research into the safety and efficacy of outpatient surgical curettage has result ed in a cost effective procedure with minimal illness.1 2 Henshaw et al , however , have shown that medical management of an uncomplicated incomplete first trimester miscarriage with misoprostol , a synthetic prostagl and in analogue , had a 96 % success rate and may be a suitable cost saving alternative.3 We compared medical with surgical management in terms of efficacy and morbidity . We conducted a r and omised clinical trial of 50 consecutive patients fulfilling the following eligibility criteria : history of Objectives To study if misoprostol 400 μg , administered vaginally , increased the successful resolution of early miscarriage compared with placebo Searle , Chicago , IL , USA ) with that of dinoprostone ( Prostin E2 , Pharmacia & Upjohn N.V.y S.A. , Puurs , Belgium ) in the treatment of missed abortion , 60 women with a diagnosis of missed abortion were r and omly allocated to treatment with either vaginal misoprostol or dinoprostone in a prospect i ve r and omized study at Tawam Hospital — a teaching hospital tertiary care unit in the United Arab Emirates . Diagnosis of missed abortion was based on ultrasonographic demonstration of an embryo greater than 7 mm with no cardiac activity or of irregular gestational sac with mean sac diameter greater than 16 mm w1x . A group OBJECTIVE To compare the safety , efficacy , and acceptability of misoprostol versus manual vacuum aspiration ( MVA ) for treatment of incomplete abortion in Maputo , Mozambique . METHODS A total of 270 women with clinical ly diagnosed incomplete abortions of up to 12 weeks of gestation were r and omized to either 600 mug oral misoprostol or MVA . Women were followed-up seven days later to evaluate whether the abortion was complete . RESULTS Success was high for both MVA and misoprostol groups ( 100 % vs 91 % , P=0.002 ) . Women in the MVA arm reported fewer side effects but higher pain scores . Women who received misoprostol were significantly more likely to be " very satisfied " with the treatment and willing to choose the method again . CONCLUSION Although oral misoprostol was less effective than MVA in this study , it was more acceptable to women . Misoprostol is well-suited for use in low-re source setting s , and should be promoted as an option for the treatment of incomplete abortion BACKGROUND The most widely used medical method of terminating second-trimester pregnancy is the intravaginal administration of prostagl and in E2 ( dinoprostone [ PGE2 ] ) . This treatment is highly effective but is associated with severe gastrointestinal side effects and hyperpyrexia . METHODS We conducted a prospect i ve , r and omized trial comparing the efficacy and safety of misoprostol , a prostagl and in E1 analogue ( 200 micrograms intravaginally every 12 hours ) , with the efficacy and safety of PGE2 ( 20 mg intravaginally every 3 hours ) . The study population included 55 pregnant women between 12 and 22 weeks ' gestation who were undergoing termination of pregnancy for either intrauterine fetal death ( 37 women ) or medical or genetic reasons ( 18 women ) . RESULTS The rate of successful abortions within 24 hours was 81 percent ( 22 of 27 women ) with PGE2 and 89 percent ( 25 of 28 women ) with misoprostol ( P = 0.47 ) . All the women who received misoprostol had successful abortions within 38 hours . Among those who had an abortion within 24 hours , the mean interval from treatment to abortion was similar in both groups ( 10.6 hours with PGE2 and 12.0 hours with misoprostol , P = 0.33 ) . The rate of complete abortion , defined as the passage of the fetus and the placenta simultaneously , was 32 percent for PGE2 and 43 percent for misoprostol ( P = 0.56 ) . Certain side effects were more frequent in the women receiving PGE2 than in those receiving misoprostol : pyrexia ( 63 percent vs. 11 percent ; P < 0.001 ) , uterine pain ( 67 percent vs. 57 percent , P = 0.58 ) , vomiting ( 33 percent vs. 4 percent , P = 0.005 ) , and diarrhea ( 30 percent vs. 4 percent , P = 0.012 ) . The average cost per treatment was $ 315.30 for PGE2 , as compared with $ 0.97 for misoprostol . CONCLUSIONS Misoprostol is at least as effective as PGE2 for the termination of second-trimester pregnancy involving either a dead or a living fetus , but it is less costly , is easier to administer , and is associated with fewer adverse effects OBJECTIVE To estimate the efficacy of vaginal misoprostol for medical management of missed abortion . METHODS Fifty women with missed abortion were r and omized to treatment with up to two 800‐mg doses of misoprostol vaginally or a placebo . Participants were review ed daily for 2 days , then again at 1 week . A blood sample for hemoglobin and serum β‐human chorionic gonadotropin ( βhCG ) was obtained on day 1 and the hemoglobin level checked again on day 7 . Complete abortion was defined as expulsion of the products of conception without dilation and curettage ( D&C ) and a negative follow‐up urine βhCG test after 4 weeks , or as no products of conception obtained at D&C in cases of suspected incomplete abortion . RESULTS The rate of complete abortion was 80 % ( 20 of 25 ) in the misoprostol group and 16 % ( four of 25 ) in the placebo group , relative risk 0.20 ( 0.08 , 0.50 ) , P < .001 . The rate of D&C was 28 % ( seven of 25 ) in the misoprostol group and 84 % ( 21 of 25 ) in the placebo group , relative risk 0.33 ( 0.17 , 0.64 ) , P < .001 . One participant in the misoprostol group had an emergency D&C for heavy bleeding . No participants required blood transfusion . The mean reduction in hemoglobin from day 1 to day 7 was 3.2 g/L in the misoprostol group versus 4.3 g/L in the placebo group , P = .72 . Patient satisfaction with misoprostol treatment was high with 19 of 21 participants reporting they would try medical management again if they experienced another missed abortion . CONCLUSION Medical management of missed abortion is effective , reduces the need for D&C , and is associated with high levels of patient satisfaction OBJECTIVES : Misoprostol shows promise for treatment of incomplete abortion . We evaluated 2 simple misoprostol regimens to estimate whether they were effective in treating incomplete abortion . METHODS : A total of 169 women was r and omly assigned to either a single or double dose of 600 & mgr;g misoprostol . The women , who would have received a surgical evacuation of the uterus for incomplete abortion , were patients at 2 hospitals in Bangkok , Thail and . The 2 groups of women were compared for success of treatment ( no need for surgical evacuation ) , side effects , and acceptability . RESULTS : Sixty-six percent of women in the single-dose group and 70 % of women in the double-dose group had complete abortions with misoprostol . More than 90 % of women in the single- and double-dose groups reported that the side effects were tolerable ; frequency of side effects was similar between the 2 groups . Women found the treatment acceptable . Approximately 90 % of women in both groups would recommend the treatment to a friend . Acceptability and efficacy were different at the 2 participating clinics . CONCLUSION : Misoprostol is an effective treatment for incomplete abortion . Simple regimens may be as effective as more complicated ones and a single dose of 600 & mgr;g should be further evaluated in larger trials . LEVEL OF EVIDENCE : OBJECTIVE We aim ed to determine whether second-trimester abortion using isosorbide mononitrate ( IMN ) in addition to gemeprost is more effective and reduces side effects compared with gemeprost alone . STUDY DESIGN Eighty women who were age 13 to 23 weeks ' gestation were r and omly assigned to receive per vaginam either IMN 40 mg ( group 1 , 40 women ) or placebo ( group 2 , 40 women ) in addition to gemeprost 1 mg up to 3 times daily 3 hours apart for 2 days . Analysis of variance , a chi 2 test , and a multivariate analysis were performed . RESULTS Of the 72 women analyzed , 68 % ( group 1 ) and 38 % ( group 2 ) underwent abortion within day 1 ( P < .05 ) . However , group 1 was associated with more headache ( 18 % of women ) 3 hours after induction compared to group 2 ( 0 % of women , P = .038 ) . CONCLUSION IMN in addition to gemeprost is effective for second-trimester abortion , but is associated with more headache compared with gemeprost alone OBJECTIVE The purpose of this study was to determine whether medical treatment of early pregnancy failure represents a reasonable alternative to surgical therapy . STUDY DESIGN Patients who were diagnosed with pregnancy failure before 12 weeks of gestation were r and omly assigned to receive either medical ( intravaginal misoprostol ) or surgical therapy ( dilatation and curettage ) . In the medical arm of the study , 800 microg of misoprostol was placed within the posterior vaginal fornix . Patients subsequently were seen 24 and 48 hours after the initial dosing ; intravaginal misoprostol was readministered only if ultrasound images revealed evidence of persistent pregnancy tissue . By 72 hours after initial study entry , if either a gestational sac or placental tissue was present , the medical treatment was considered a failure , and uterine curettage was performed . Statistical analysis was performed with the two-tailed unpaired t test , chi(2 ) analysis , Fisher exact test , and Mann-Whitney U test ; a probability value of < .05 was considered statistically significant . RESULTS A total of 50 women were enrolled , with 2 patients in the surgical arm experiencing spontaneous pregnancy loss before their scheduled procedures . Twenty-five women received medical therapy ; 25 women were r and omized to surgical procedure . Fifteen patients in the medical group ( 60 % ; 95 % CI , 0.41 - 0.79 ) had successful pregnancy termination and did not require curettage . There were no significant differences between the medical and surgical groups with respect to either posttreatment hematocrit level or the time needed to achieve negative human chorionic gonadotropin test results . CONCLUSION Intravaginal misoprostol is an effective agent for the treatment of early pregnancy failure . Medical treatment of early pregnancy failure represents a reasonable alternative to immediate surgical therapy In a double-blind controlled multicentric study involving 94 patients with an intrauterine fetal death , we investigated the efficacy and tolerance of mifepristone ( RU 486 ) , a steroid compound that antagonizes progesterone action at the receptor level . Success of treatment was defined as the occurrence of fetal expulsion within 72 hours after the first drug intake . Mifepristone treatment ( 600 mg per day for 2 days ) was considered to be effective in 29 of 46 patients ( 63 % ) . There were only eight successes in 48 patients ( 17.4 % ) in the placebo group ( p = 0.001 , chi 2 test ) . Tolerance was good in the mifepristone group . In the placebo group , disseminated intravascular coagulation occurred in one woman for whom the investigator waited several weeks for spontaneous expulsion . This large double-blind controlled study provides evidence that mifepristone is of interest in the management of intrauterine fetal death . It could provide a pharmacologic alternative to the use of prostagl and ins in this indication We evaluated the efficacy of initiating a second trimester medical abortion outside of a health care facility using patient self-administered serial intravaginal misoprostol . Patients scheduled for second trimester medical termination of pregnancy were r and omized to an inpatient or outpatient group . Both groups received a single 200-microg vaginal misoprostol tablet every 6 h. No other abortifacients were used . The home group self-administered the misoprostol and returned to the hospital for clinical reasons or after 24 h and again at 48 h. Forty-two women were assigned to the inpatient and 45 to the outpatient groups . There was no difference between the groups in demographics or indications for terminations . The median hours from first misoprostol to delivery of the fetus was 12 and 14 ( inpatient versus outpatient , respectively ; p = 0.28 ) . The total median hours in hospital were 24 versus 11 ( inpatient versus outpatient , respectively ; p < 0.05 ) . Two patients ( 4 % ) in the outpatient group delivered the fetus outside of the hospital . There were no cases of hemorrhage in either group . Outpatient initiation of second trimester medical termination with self-administered misoprostol is effective and decreases time of hospitalization BACKGROUND We aim ed to determine whether outpatient treatment of miscarriage with vaginal misoprostol is more effective than expectant management in reducing the need for surgical evacuation of retained products of conception ( ERPC ) . METHODS Of 131 eligible women with first trimester miscarriage , 104 agreed to r and omization to either 600 microg misoprostol or placebo intravaginally . They were assessed the following day and administered a second dose of their allocated treatment if miscarriage was not complete . Those not successful after two doses were seen on day 7 , and , if miscarriage was not complete , an ERPC was performed . RESULTS The success rate of medical management was 88.5 % ( 46/52 ) compared with 44.2 % ( 23/52 ) for expectant management . There was no significant difference in success rate ( 100 versus 85.7 % ) in women treated with an incomplete miscarriage . Women with early pregnancy failure had a success rate of 87 % with misoprostol compared with 29 % with expectant management [ odds ratio ( OR ) 15.96 ; 95 % confidence interval ( CI ) 5.26 , 48.37 ] . The complete miscarriage rate was achieved quicker in the medical group than the expectant group by day 1 ( 32.7 versus 5.8 % ) and by day 2 ( 73.1 versus 13.5 % ) of treatment . There were no differences in side-effects , bleeding duration , analgesia use , pain score and satisfaction with treatment . Women in the expectant group made more outpatient visits ( 5.06 versus 4.44 % ; OR = -0.62 , 95 % CI -1.04 , -0.19 ) . More women in the medical group ( 90.4 versus 73.1 % ; OR 1.26 , 95 % CI 1.05 , 1.50 ) would elect the same treatment in the future . CONCLUSIONS Medical management using 600 microg misoprostol vaginally is more effective than expectant management of early pregnancy failure . Misoprostol did not increase the side-effect profile and patient acceptability was superior to expectant management Results of this study indicate that pretreatment with indomethacin significantly increases the abortifacient effect of an intravenous infusion of PGE2 in patients admitted for abortion as a result of fetal death in utero . Indomethacin pretreatment shortened the duration of PGE2-induced abortion in primigravid and multigravid groups of patients by about 4 and 2 hours respectively . When primigravid and multigravid groups were combined , the dose of PGE2 needed for complete delivery decreases in the indomethacin-treated group by 39.9 % OBJECTIVE To compare the effectiveness of misoprostol administered intravaginally every 6 versus every 12 hours for termination of second-trimester pregnancies . METHODS One hundred pregnant women at 12 - 22 weeks ' gestation were r and omized to receive 200 microg of misoprostol intravaginally either every 6 or every 12 hours for up to 48 hours . RESULTS The incidences of abortion within 48 hours after initial drug administration were 87.2 and 89.2 % , the complete abortion rates 43.9 and 33.3 % , and the mean abortion intervals 13.8 and 14.0 hours in the 6- and 12-hour groups , respectively . Side effects were similar between groups . CONCLUSION Misoprostol administered vaginally is effective for terminating second-trimester pregnancies . Shortening the dosing interval from 12 to 6 hours produced no significant benefit OBJECTIVE Our purpose was to determine whether intracervical placement of laminaria tents would improve the effectiveness of the prostagl and in analog misoprostol for the elective termination of pregnancies in the second trimester . STUDY DESIGN Sixty-eight women between 12 and 22 weeks of gestation with either an intrauterine fetal death ( n = 40 ) or medical or genetic indications for pregnancy termination ( n = 30 ) were r and omized to receive 200 micrograms of misoprostol administered vaginally every 12 hours with or without intracervical placement of laminaria concurrently with the first dose of misoprostol . RESULTS The rate of abortion 24 hours after initiation of treatment was 69.7 % in the 33 women receiving misoprostol alone and 68.6 % in the 35 women treated with misoprostol and laminaria . The abortion rates 48 hours after initiation of treatment were 84.8 % and 91.4 % , respectively , an insignificant difference . The complete abortion rate was also similar between women receiving misoprostol alone ( 39.3 % ) and the group receiving misoprostol and laminaria ( 37.5 % ) . There were no significant differences in the incidence of fever , vomiting , diarrhea , or pain . The mean interval from initiation of treatment to abortion was also similar , 15.7 hours in those receiving misoprostol alone and 17.4 hours in those treated with misoprostol and laminaria . In both groups women who had live fetuses at the start of the procedure had a higher failure rate of abortion and a longer time interval to abortion than women whose fetus was dead . CONCLUSIONS Laminaria tents inserted concurrently with the first dose of misoprostol do not significantly improve the abortifacient effect of vaginal misoprostol in the second trimester of pregnancy OBJECTIVE The purpose of this study was to compare the efficacy and adverse effects of vaginal misoprostol and intra-amniotic PGF2alpha for midtrimester abortion . STUDY DESIGN One hundred thirty-two women between 12 and 24 weeks ' gestation , seeking abortion in a tertiary hospital , were r and omized to receive vaginal misoprostol ( 400 microg every 3 hours ) or intra-amniotic PGF2alpha ( carboprost 1.5 mg ) . Main outcome measures were induction-to-abortion interval , success rates at 24 and 48 hours , and adverse effects . RESULTS Successful abortion rates at 24 and 48 hours between intra-amniotic PGF2alpha and vaginal misoprostol were not statistically different . However , vaginal misoprostol results in a significantly shorter mean induction-to-abortion interval , compared with intra-amniotic PGF2alpha ( misoprostol : 16.2 hours ; intra-amniotic PGF2alpha : 20.8 hours ; P = .006 ) , particularly among multiparous women ( misoprostol : 13.1 hours ; intra-amniotic PGF2alpha 18.3 hours ; P = .011 ) and for gestation below 130 days ( misoprostol : 14.6 hours ; intra-amniotic PGF2alpha : 20.2 hours ; P = .015 ) . Fever and shivering were commoner with vaginal misoprostol . CONCLUSION Vaginal misoprostol should be the regimen of choice for midtrimester abortion , particularly for multiparous women and women in the early second trimester OBJECTIVE To compare the effectiveness and safety of misoprostol and mifepristone , followed when needed by misoprostol , for the treatment of women with early pregnancy failure . DESIGN Prospect i ve r and omized nonblinded controlled trial . SETTING University-affiliated tertiary medical center . PATIENT(S ) One hundred fifteen consecutive women diagnosed as having a blighted ovum or missed abortion of < 9 weeks of gestation enrolled . INTERVENTION(S ) The patients received orally 600 mg mifepristone ( group I ) or orally 800 microg misoprostol ( group II ) . Most patients in both groups subsequently received 48 hours later orally 800 microg misoprostol . MAIN OUTCOME MEASURE(S ) Failure was defined as surgical intervention due to retained gestational sac 48 hours after completion of the drug protocol , severe symptoms , or suspected retained products of conception after the menstrual period . RESULT ( S ) The success rate was similar in groups I and II : 38 of 58 patients ( 65.5 % ) versus 42 of 57 patients ( 73.6 % ) , respectively . No cases of severe infection or bleeding necessitating blood transfusion occurred . CONCLUSION ( S ) Misoprostol is an effective and safe treatment for early pregnancy failure and could replace surgical curettage in over two-thirds of the patients . Mifepristone offers no advantage compared with misoprostol as initial treatment OBJECTIVE To compare the efficacy of methods for second trimester pregnancy termination . METHODS A prospect i ve r and omized study of women undergoing pregnancy termination between 14 and 28 weeks gestation . Three hundred and forty patients with poor cervical condition ( Bishop score < or = 4 ) in whom one of five termination methods were used were assessed : ( i ) extraamniotic administration of ethacridine lactate ( 82 patients ) ; ( ii ) intracervical prostagl and in ( PG ) E2 gel ( 100 patients ) ; ( iii ) intravenous infusion of concentrated oxytocin ( 36 patients ) ; ( iv ) vaginal misoprostol ( 49 patients ) ; and ( v ) balloon insertion ( 73 patients ) . Oxytocin infusion was used in all but concentrated oxytocin group to augment labor , when necessary . Patients in whom effective uterine contractions and cervical dilatation was not obtained within 48 h with the primary termination method were registered as failures . RESULTS The efficacy of each method were evaluated in terms of abortion within time . Abortion within 48 h were achieved in 98.8 % ( 81/82 ) of the patients in ethacridine group ; 97.3 % ( 35/36 ) of the patients in concentrated oxytocin group ; 90.0 % ( 90/100 ) of the patients in PGE2 group ; 97.2 % ( 71/73 ) of the patients in balloon group ; 77.5 % ( 38/49 ) of the patients in misoprostol group ( P = 0.000 , P < 0.01 , Wilcoxon ( Gehan ) statistic ) . The overall median induction-abortion interval + /- S.D. ( in h ) in each group were as follows : ethacridine lactate : 15.7 + /- 9.6 , PGE2 gel : 20.0 + /- 14.5 , concentrated oxytocin : 12.2 + /- 14.4 , misoprostol : 24.0 + /- 22.2 , balloon : 16.0 + /- 15.4 ( one way ANOVA , P = 0.003 , P < 0.01 ) . CONCLUSION In comparison with the five methods , the use of extraamniotic ethacridine , intravenous concentrated oxytocin , and balloon was found to provide more effective treatment than intracervical PGE2 and misoprostol in terms of achievement of abortion within 24 and 48 OBJECTIVE To assess the effectiveness and tolerability of misoprostol to reduce the amount and duration of vaginal bleeding following surgical evacuation for first trimester spontaneous abortion . METHODS A total of 160 patients who underwent surgical evacuation for first trimester spontaneous abortion between 8 and 12 weeks of pregnancy were r and omized into 2 groups to receive either 200 microg of oral misoprostol immediately after evacuation followed every 6 hours for 48 hours or no misoprostol . Pain scores , duration and amount of bleeding , and endometrial thickness were assessed over 10 days . RESULTS Women who received misoprostol had significantly fewer bleeding days after evacuation ( 4.11+/-2.69 vs 5.89+/-3.06 ; P<0.001 ) , fewer patients reported vaginal bleeding lasting 10 days or more ( 3.8 % vs 15.0 % ; P=0.014 ) , and endometrial thickness 10 days after evacuation was less ( 6.25+/-2.38 vs 7.23+/-1.94 ; P=0.05 ) . Pain scores were comparable in both groups ( 1.54+/-0.65 vs 1.63+/-0.83 ; P=0.40 ) after 10 days . CONCLUSION Oral misoprostol is effective in reducing the prevalence and amount of vaginal bleeding after surgical evacuation for first trimester spontaneous abortion BACKGROUND This study was conducted to compare the safety , effectiveness and acceptability of 400 mcg sublingual misoprostol and 600 mcg oral misoprostol for treatment of incomplete abortion . STUDY DESIGN We used an open-label r and omized controlled trial conducted from July 2005 to August 2006 in a large tertiary level maternity hospital in Antananarivo , Madagascar , and a large tertiary level hospital in Chisinau , Moldova . Three hundred consenting women seeking treatment for clinical ly diagnosed incomplete abortion with uterine size < or=12 weeks since last menstrual period were r and omized to misoprostol either 600 mcg orally or 400 mcg sublingually . The primary outcome measure was the complete resolution of clinical signs and symptoms of incomplete abortion without need for surgical intervention . Women were seen for follow-up on Day 7 and , if necessary , on Day 14 to assess abortion status . The study was powered to detect a 7 % difference in efficacy with a total of 142 women required in each arm . RESULTS Efficacy rates were 94.6 % and 94.5 % , for the oral and sublingual routes , respectively ( RR : 1.00 , 95 % CI=0.95 - 1.06 , p=.98 ) . At 1 week follow-up , more than 80 % of women had completed abortions ( 77.8 % oral and 84.8 % sublingual , p=.12 ) . Mean pain scores were 2.95 and 3.04 , respectively , for the oral and sublingual groups . Side effects included abdominal pain , bleeding , headaches and dizziness/weakness with no differences reported between the two groups . Acceptability and satisfaction were high for both routes and women indicated a preference for medical versus surgical treatment if ever needed in the future . CONCLUSIONS Both treatment regimens were very effective . Four hundred micrograms of sublingual misoprostol and 600 mcg oral misoprostol appear to have similar safety and effectiveness profiles when used for the treatment of incomplete abortion . A lower 400-mcg misoprostol dose may provide an alternative treatment option as well as have potential benefits in terms of cost OBJECTIVE To assess the efficacy of sublingual misoprostol after surgical management of early termination of pregnancy ( ETP ) regarding duration and amount of bleeding , presence of retained products of conception ( RPOC ) , and endometrial thickness . DESIGN Prospect i ve , r and omized clinical trial . SETTING University hospital . PATIENT(S ) One hundred five patients admitted for possible management of early pregnancy failure and unwanted pregnancy . INTERVENTION(S ) Manual vacuum aspiration ( control and study groups ) plus 400 microg sublingual misoprostol ( study group ) at pregnancy termination , and transvaginal ultrasonography ( both groups ) 10 days after the procedure . MAIN OUTCOME MEASURE(S ) Duration and amount of bleeding and presence of RPOC and endometrial thickness 10 days after the procedure . RESULT ( S ) Bleeding lasted 3.2 and 5.1 days in the study and control groups . Severe vaginal bleeding occurred in two patients in the study group and in six patients in the control group . Mean endometrial thickness was 5.5 mm in the study group and 6.9 mm in the control group . These differences were statistically significant . No cases of RPOC occurred in the study group ; two cases occurred in the control group . CONCLUSION ( S ) In countries in which surgical management of ETP is still done , using sublingual misoprostol postoperatively may reduce the duration and amount of bleeding |
11,316 | 27,271,314 | AUTHORS ' CONCLUSIONS Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue .
The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics .
However , it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation , disease activity or some other mechanism | BACKGROUND Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis ( RA ) , with no accepted evidence -based management guidelines .
Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage .
OBJECTIVES To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis . | BACKGROUND Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate , a st and ard treatment for this disease . There is evidence that antitumour necrosis factor alpha ( TNFalpha ) is efficacious in relief of signs and symptoms . We therefore investigated whether infliximab , a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate . METHODS In an international double-blind placebo-controlled phase III clinical trial , 428 patients who had active rheumatoid arthritis , who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks , were r and omised to placebo ( n=88 ) or one of four regimens of infliximab at weeks 0 , 2 , and 6 . Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate ( median 15 mg/week for > or = 6 months , range 10 - 35 mg/wk ) . Patients were assessed every 4 weeks for 30 weeks . FINDINGS At 30 weeks , the American College of Rheumatology ( 20 ) response criteria , representing a 20 % improvement from baseline , were achieved in 53 , 50 , 58 , and 52 % of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks , respectively , compared with 20 % of patients receiving placebo plus methotrexate ( p<0.001 for each of the four infliximab regimens vs placebo ) . A 50 % improvement was achieved in 29 , 27 , 26 , and 31 % of infliximab plus methotrexate in the same treatment groups , compared with 5 % of patients on placebo plus methotrexate ( p<0.001 ) . Infliximab was well-tolerated ; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group . INTERPRETATION During 30 weeks , treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate OBJECTIVE To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis ( RA ) . METHODS MTX-naive patients with RA ( n = 637 ) were r and omized to receive placebo plus MTX ( group 1 ) , golimumab 100 mg plus placebo ( group 2 ) , golimumab 50 mg plus MTX ( group 3 ) , or golimumab 100 mg plus MTX ( group 4 ) . Subcutaneous injections of golimumab or placebo were administered every 4 weeks . The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week . The primary end point , the proportion of patients meeting the American College of Rheumatology 50 % improvement criteria ( achieving an ACR50 response ) at week 24 , required significant differences between groups 3 and 4 combined ( combined group ) versus group 1 and significant differences in a pairwise comparison ( group 3 or group 4 versus group 1 ) . RESULTS An intent-to-treat ( ITT ) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 ( 38.4 % and 29.4 % , respectively ; P=0.053 ) , while a post hoc modified ITT analysis ( excluding 3 untreated patients ) of the ACR50 response showed statistically significant differences between the combined group and group 1 ( 38.5 % versus 29.4 % ; P=0.049 ) and between group 3 ( 40.5 % ; P=0.038 ) but not group 4 ( 36.5 % ; P=0.177 ) and group 1 . Group 2 was noninferior to group 1 for the ACR50 response at week 24 ( 33.1 % ; 95 % confidence interval lower bound -5.2 % ; predefined delta value for noninferiority -10 % ) . The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters , including response/remission according to the Disease Activity Score in 28 joints . Serious adverse events occurred in 7 % , 3 % , 6 % , and 6 % of patients in groups 1 , 2 , 3 , and 4 , respectively . CONCLUSION Although the primary end point was not met , the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than , and the efficacy of golimumab alone is similar to , the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients , with no unexpected safety concerns Background : Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor . Objective : To evaluate the efficacy and safety of certolizumab pegol versus placebo , plus methotrexate ( MTX ) , in patients with active rheumatoid arthritis ( RA ) . Methods : An international , multicentre , phase 3 , r and omised , double-blind , placebo-controlled study in active adult-onset RA . Patients ( n = 619 ) were r and omised 2:2:1 to subcutaneous certolizumab pegol ( liquid formulation ) 400 mg at weeks 0 , 2 and 4 followed by 200 mg or 400 mg plus MTX , or placebo plus MTX , every 2 weeks for 24 weeks . The primary end point was ACR20 response at week 24 . Secondary end points included ACR50 and ACR70 responses , change from baseline in modified Total Sharp Score , ACR core set variables and physical function . Results : Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo ( p⩽0.001 ) ; rates were 57.3 % , 57.6 % and 8.7 % , respectively . Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression ; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4 , respectively , versus 1.2 for placebo ( rank analysis p⩽0.01 ) . Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo ; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50 , respectively , versus −0.14 for placebo ( p⩽0.001 ) . Most adverse events were mild or moderate , with low incidence of withdrawals due to adverse events . Five patients developed tuberculosis . Conclusion : Certolizumab pegol plus MTX was more efficacious than placebo plus MTX , rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression . Trial registration number : OBJECTIVE To assess the long-term impact of etanercept on fatigue in patients with recent-onset ( mean duration 11 months ) or established ( mean duration 12 years ) rheumatoid arthritis ( RA ) . METHODS Patients participating in either of 2 multicenter , r and omized , double-blind clinical trials were included . In one trial , patients with recent-onset RA received either etanercept 25 mg twice weekly or methotrexate in a double-blind fashion for 12 months , then open label for 12 months . All patients then received open-label etanercept . In the second trial , patients with established RA received etanercept 25 mg or placebo twice weekly for 6 months in a double-blinded fashion , then open-label etanercept . Up to 46 months of followup data were included . Fatigue was measured regularly using the Health Assessment Question naire vitality domain . RESULTS Patients with recent-onset RA who received etanercept had a significantly faster improvement in fatigue than those receiving methotrexate in the first 2 months . Subsequently , patients receiving etanercept and methotrexate had 23 - 29 % and 17 - 24 % reductions in fatigue scores , respectively . In the group with established RA , patients who received etanercept had significantly greater reductions in fatigue than those receiving placebo during the blinded period . Patients initially receiving etanercept sustained a mean fatigue reduction of 25 - 36 % for the entire followup . Patients achieving clinical ly meaningful improvement in fatigue were more likely to meet the American College of Rheumatology improvement criteria . CONCLUSION Etanercept therapy reduces fatigue in patients with recent-onset or established RA . Improvement in fatigue was sustained for up to 46 months , and correlated with other RA-relevant outcomes Background Patient reported outcomes ( PROs ) are especially useful in assessing treatments for rheumatoid arthritis ( RA ) since they measure dimensions of health-related quality of life that can not be captured using strictly objective physiological measures . The aim of this study was to compare the effects of combination etanercept and methotrexate ( ETN + MTX ) versus combination synthetic disease modifying antirheumatic drugs ( DMARDs ) and methotrexate ( DMARD + MTX ) on PRO measures among RA patients from the Asia-Pacific region , a population not widely studied to date . Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied . Methods Patients were r and omized to either ETN + MTX ( N = 197 ) or DMARD + MTX ( N = 103 ) in an open-label , active-comparator , multicenter study , with PRO measures design ed as prospect i ve secondary endpoints . The Health Assessment Question naire ( HAQ ) , Functional Assessment of Chronic Illness Therapy Fatigue Scale ( FACIT-Fatigue ) , Medical Outcomes Short Form-36 Health Survey ( SF-36 ) , Hospital Anxiety and Depression Scale ( HADS ) and the Work Productivity and Activity Impairment Question naire : General Health ( WPAI : GH ) were used . Results Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5 , compared to patients in the DMARD + MTX group . SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group ; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms . Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue , HADS , and WPAI : GH mean scores . Conclusion Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures , compared to combination therapy with usual st and ard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region . Trial registration clintrials.gov # Objective : The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis ( RA ) despite methotrexate therapy . Methods : Patients were r and omly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules ( group 1 , n = 133 ) , golimumab 100 mg injections plus placebo capsules ( group 2 , n = 133 ) , golimumab 50 mg injections plus methotrexate capsules ( group 3 , n = 89 ) , or golimumab 100 mg injections plus methotrexate capsules ( group 4 , n = 89 ) . Injections were administered subcutaneously every 4 weeks . The co- primary endpoints were the proportion of patients with 20 % or greater improvement in the American College of Rheumatology criteria ( ACR20 ) at week 14 and the change from baseline in the health assessment question naire-disability index ( HAQ-DI ) score at week 24 . Results : The proportion of patients who achieved an ACR20 response at week 14 was 33.1 % in the placebo plus methotrexate group , 44.4 % ( p = 0.059 ) in the golimumab 100 mg plus placebo group , 55.1 % ( p = 0.001 ) in the golimumab 50 mg plus methotrexate group and 56.2 % ( p<0.001 ) in the golimumab 100 mg plus methotrexate group . At week 24 , median improvements from baseline in HAQ-DI scores were 0.13 , 0.13 ( p = 0.240 ) , 0.38 ( p<0.001 ) and 0.50 ( p<0.001 ) , respectively . During the placebo-controlled portion of the study ( to week 16 ) , serious adverse events occurred in 2.3 % , 3.8 % , 5.6 % and 9.0 % of patients and serious infections occurred in 0.8 % , 0.8 % , 2.2 % and 5.6 % , respectively . Conclusion : The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function Introduction The objective of this study was to assess the impact of certolizumab pegol ( CZP ) treatment on health-related quality of life ( HRQoL ) , fatigue and other patient-reported outcomes ( PROs ) in patients with rheumatoid arthritis ( RA ) . Methods Patients with active RA ( N = 982 ) were r and omized 2:2:1 to subcutaneous CZP ( 400 mg at weeks 0 , 2 and 4 ; followed by CZP 200 mg or 400 mg ) plus methotrexate ( MTX ) every other week , or placebo ( PBO ) plus MTX . PRO assessment s included HRQoL , fatigue , physical function , arthritis pain and disease activity . Adjusted mean changes from baseline in all PROs were obtained using analysis of covariance ( ANCOVA ) applying last observation carried forward ( LOCF ) imputation . The proportion of patients achieving clinical ly meaningful improvements in each PRO was obtained using logistic regression and by applying non-responder imputation to missing values after rescue medication or withdrawal . The correlations between PRO responses and clinical responses were also assessed by tetrachoric correlation using non-responder imputation . Results Patients treated with CZP plus MTX reported significant ( P < 0.001 ) , clinical ly meaningful improvements in HRQoL at the first assessment ( week 12 ) ; reductions in fatigue , disease activity and pain and improvements in physical function were reported at week 1 . In particular , CZP-treated patients reported improvements in mental health . Mean changes from baseline in the SF-36 Mental Component Summary ( MCS ) at week 52 for CZP 200 mg and 400 mg plus MTX , and PBO plus MTX were 6.4 , 6.4 and 2.1 , respectively ( P < 0.001 ) . In addition , mental health and vitality scores in CZP-treated patients approached age- and gender-adjusted US population norms . Improvements in all PROs were sustained . Similar benefits were reported with both CZP doses . Changes in SF-36 MCS scores had the lowest correlation with disease activity scores ( DAS28 ) and American College of Rheumatology 20 % improvement ( ACR20 ) response rates , while improvements in pain showed the highest correlation . Conclusions Treatment with CZP plus MTX result ed in rapid and sustained improvements in all PROs , indicating that the benefits of CZP extend beyond clinical efficacy endpoints into areas that are more relevant and meaningful for patients on a daily basis . Trial Registration Clinical Trials.gov NCT00152386 BACKGROUND Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses . Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis . METHODS In this double-blind , r and omised , placebo-controlled , parallel group phase III study , 623 patients with moderate to severe active rheumatoid arthritis were r and omly assigned with an interactive voice response system , stratified by site with a r and omisation list provided by the study sponsor , to receive tocilizumab 8 mg/kg ( n=205 ) , tocilizumab 4 mg/kg ( 214 ) , or placebo ( 204 ) intravenously every 4 weeks , with methotrexate at stable pre- study doses ( 10 - 25 mg/week ) . Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20 % improvement in both swollen and tender joint counts . The primary endpoint was the proportion of patients with 20 % improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria ( ACR20 response ) at week 24 . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00106548 . FINDINGS The intention-to-treat analysis population consisted of 622 patients : one patient in the 4 mg/kg group did not receive study treatment and was thus excluded . At 24 weeks , ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo ( 120 [ 59 % ] patients in the 8 mg/kg group , 102 [ 48 % ] in the 4 mg/kg group , 54 [ 26 % ] in the placebo group ; odds ratio 4.0 [ 95 % CI 2.6 - 6.1 ] , p<0.0001 for 8 mg/kg vs placebo ; and 2.6 [ 1.7 - 3.9 ] , p<0.0001 for 4 mg/kg vs placebo ) . More people receiving tocilizumab than those receiving placebo had at least one adverse event ( 143 [ 69 % ] in the 8 mg/kg group ; 151 [ 71 % ] in the 4 mg/kg group ; 129 [ 63 % ] in the placebo group ) . The most common serious adverse events were serious infections or infestations , reported by six patients in the 8 mg/kg group , three in the 4 mg/kg group , and two in the placebo group . INTERPRETATION Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis . FUNDING F Hoffmann-La Roche , Chugai Pharmaceutical BACKGROUND SKI306X , which consists of biologically active ingredients from Clematis m and sburica , Tricbosantbes kirilowii , and Prunella vulgaris , was developed and tested in pre clinical trials in Korea . Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect , and that it can delay the destruction of cartilage in rheumatoid arthritis ( RA ) . OBJECTIVE The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA . METHODS This study was a 6-week , multicenter , r and omized , double-blind , double-dummy , Phase III , noninferiority clinical trial . Eligible patients were aged 18 to 80 years , had a history of RA with a disease duration of > or =3 months , and were functional American College of Rheumatology ( ACR ) class I , II , or III before entry . After a washout period of 2 weeks , patients were r and omized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks . The primary end point was a change in patient assessment of pain intensity using a visual analog scale ( VAS ) . The secondary end points were a 20 % improvement in response rate as defined by the ACR ( ACR20 ) and the frequency of rescue medication use . Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups , and all patients were assessed for adverse events ( AEs ) , clinical laboratory data , and vital signs . AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator . RESULTS Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and r and omized to 1 of 2 treatment groups . Ninety-one patients ( 10 male , 81 female ; mean [ SD ] age , 52.13 [ 12.64 ] years ; mean [ SD ] duration of RA , 9.08 [ 10.23 ] years ; no. [ % ] of ACR class I , II , and III , 13 [ 14.29 ] , 44 [ 48.35 ] and 34 [ 37.36 ] patients , respectively ) received SKI306X 200 mg TID and 92 patients ( 10 male , 82 female ; mean [ SD ] age , 51.78 [ 10.94 ] years ; mean [ SD ] duration of RA , 8.78 [ 7.78 ] years ; no. [ % ] of ACR class I , II , and III , 14 [ 15.22 ] , 44 [ 47.83 ] , and 34 [ 36.96 ] patients , respectively ) received celecoxib 200 mg BID . An analysis of the change in reported pain intensity as determined by VAS ( mm ) score between baseline and week 3 ( mean [ SD ] , 13.64 [ 16.62 ] vs 14.45 [ 15.89 ] ) , and between baseline and week 6 ( 18.4 [ 20.8 ] vs 17.9 [ 19.1 ] , respectively ) suggested that SKI306X was not inferior to celecoxib . The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 ( 16/87 [ 18.4 % ] vs 24/87 [ 27.6 % ] , respectively ) and at week 6 ( 29/87 [ 33.3 % ] vs 29/87 [ 33.3 % ] ) . The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 ( 54/87 [ 62.1 % ] vs 47/87 [ 54.0 % ] , respectively ) or week 6 ( 57/87 [ 65.5 % ] vs 49/87 [ 56.3 % ] ) . Drug-related AEs were reported by 27 ( 29.7 % ) patients in the SKI306X group and 22 ( 23.9 % ) patients in the celecoxib group . The most frequent drug-related AEs were epigastric pain ( 9/91 [ 9.9 % ] ) in the SKI306X group and glutamyltranferase elevation ( 4/92 [ 4.3 % ] ) in the celecoxib group . No significant between-group differences were observed in the prevalence of drug-related clinical - or laboratory-determined AEs . CONCLUSION The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA Objective . To investigate the effect of tocilizumab on patient-reported outcomes ( PROs ) in RA patients with inadequate responses to TNF inhibitors ( TNFis ) . Methods . In a Phase III r and omized controlled trial , 489 patients received 4 or 8 mg/kg tocilizumab or placebo every 4 weeks plus MTX for 24 weeks . Mean changes from baseline over time and proportions of patients reporting improvements greater than or equal to minimum clinical ly important differences ( MCIDs ) in PROs were analyzed . Results . At week 24 , 8 mg/kg result ed in significantly greater improvements vs placebo in pain , global assessment of disease activity ( P = 0.001 ) , Health Assessment Question naire-Disability Index ( HAQ-DI ; P < 0.0001 ) , Functional Assessment of Chronic Illness Therapy-Fatigue ( P = 0.0150 ) and Medical Outcomes Survey Short Form 36 ( SF-36 v2 ) Physical Component Summary ( PCS ; P = 0.0003 ) scores , all greater than MCID ; 4 mg/kg result ed in greater improvements in pain ( P = 0.0100 ) , HAQ-DI ( P = 0.0030 ) and SF-36 PCS ( P = 0.0020 ) scores . Tocilizumab-associated improvements were evident as early as week 2 . At week 24 , more tocilizumab-treated than control patients reported improvements greater than or equal to MCID in SF-36 domain scores and related PROs ( 50.9–84.9 % vs 35.0–51.7 % ) and achieved ACR50 responses and /or Disease Activity Score 28 ( DAS28 ) remission with PRO improvements greater than or equal to MCID ( 36.2–51.2 % vs 10–20.7 % and 10.7–37.5 % vs 0.0–3.4 % , respectively ) . Conclusion . Tocilizumab treatment in patients with inadequate responses to TNFis result ed in rapid and sustained improvements in multiple PROs that were statistically significant and clinical ly meaningful , consistent with previous efficacy reports . Trial Registration . Clinical Trials.gov , http:// clinical trials.gov/ , NCT00106522 OBJECTIVE This study vali date d a brief measure of fatigue in rheumatoid arthritis ( RA ) , the Functional Assessment of Chronic Illness Therapy ( FACIT ) Fatigue Scale . METHODS The FACIT Fatigue was tested along with measures previously vali date d in RA : the Multidimensional Assessment of Fatigue ( MAF ) and Medical Outcomes Study Short-Form 36 ( SF-36 ) Vitality . The sample included 636 patients with RA enrolled in a 24 week double blind , r and omized clinical trial ( RCT ) of adalimumab versus placebo . RESULTS The FACIT Fatigue showed good internal consistency ( alpha = 0.86 to 0.87 ) , strong association with SF-36 Vitality ( r = 0.73 to 0.84 ) and MAF ( r = -0.84 to -0.88 ) , and the ability to differentiate patients according to clinical change using the American College of Rheumatology ( ACR ) response criteria ( ACR 20/50/70 ) . Psychometric performance of the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures . A minimally important difference in FACIT Fatigue change score of 3 - 4 points was confirmed in a separate sample of 271 patients with RA enrolled in a second double blind RCT of adalimumab versus placebo . CONCLUSION The FACIT Fatigue is a brief , valid measure for monitoring this important symptom and its effects on patients with RA OBJECTIVE Fatigue is commonly reported by patients with rheumatoid arthritis ( RA ) but is rarely a treatment target . The aim of this study was to explore the concept of fatigue as experienced by patients with RA . METHODS Fifteen patients with RA and fatigue ( > or = 7 on a 10-cm visual analog scale ) were individually interviewed and asked about the description , cause , consequence , and management of fatigue . Transcripts were systematic ally analyzed by 2 research ers independently , relevant phrases were coded , and earlier transcripts were checked for the emerging codes . A r and om sample of analyses were independently review ed . A total of 191 codes arising from the data were grouped into 46 categories and overarching themes . RESULTS Vivid descriptions reflect 2 types of fatigue : severe weariness and dramatic overwhelming fatigue . RA fatigue is different from normal tiredness because it is extreme , often not earned , and unresolving . Participants described physical , cognitive , and emotional components and attributed fatigue to inflammation , working the joints harder , and unrefreshing sleep . Participants described far-reaching effects on physical activities , emotions , relationships , and social and family roles . Participants used self-management strategies but with limited success . Most did not discuss fatigue with clinicians but when they did , they felt it was dismissed . Participants held negative views on the management of fatigue . CONCLUSION The data show that RA fatigue is important , intrusive , and overwhelming , and patients struggle to manage it alone . These data on the complexity of fatigue experiences will help clinicians design measures , interventions , and self-managment guidance OBJECTIVE To evaluate the safety , immunogenicity , pharmacokinetics , and efficacy of intravenous administration of tumor necrosis factor binding protein ( TNFbp ) dimer in patients with rheumatoid arthritis ( RA ) . METHODS This phase I/II study was a multicenter , r and omized , double blind , placebo controlled , ascending dose study evaluating TNFbp dimer administered by i.v . infusion . Thirty-three patients with RA divided into 3 cohorts received TNFbp dimer ( 30 , 100 , 300 microg/kg ) or placebo during a 5 min infusion at baseline and at 3 and 6 weeks ; patients were followed at routine intervals after each infusion through 77 days postinfusion . Pharmacokinetics were analyzed using a log-linear regimen and comparisons were made between half-life after first , 2nd , and 3rd doses . Plasma TNFbp dimer concentrations and serum antibody levels were used in the measurement of pharmacokinetics . RESULTS Administration of 30 microg/kg of TNFbp dimer was generally well tolerated ; the maximum tolerated dose was 100 microg/kg . No serious adverse events were reported . A significant antibody response affected the half-life and clearance of TNFbp dimer at each dose group . Anti-TNFbp antibodies were noncytotoxic and nonagonistic . Clinical evaluations provided evidence of in vivo activity of TNFbp dimer in these patients . CONCLUSION TNFbp dimer administered to patients with long st and ing RA result ed in significant antibody production to the study drug . This effect reduced the half-life and clearance of the TNFbp . This TNFbp will not be a viable option for treating patients with RA secondary to immunogenicity OBJECTIVE To investigate the effectiveness of 4 different treatment strategies for recent-onset rheumatoid arthritis ( RA ) on 2-year patient-reported outcomes , including functioning and quality of life . METHODS A total of 508 patients with recent-onset RA were r and omly assigned to 1 ) sequential monotherapy , 2 ) step-up combination therapy , both starting with methotrexate , 3 ) initial combination therapy , including a tapered high-dose prednisone , or 4 ) initial combination therapy with methotrexate and infliximab . Treatment was adjusted every 3 months if the Disease Activity Score ( DAS ) remained > 2.4 . The McMaster Toronto Arthritis Patient Preference Disability Question naire , the Short Form 36 ( SF-36 ) , and scores for pain , global health , and disease activity measured on a 100-mm visual analog scale ( VAS ) were compared between groups at baseline and every 3 months thereafter for 2 years . RESULTS After 2 years , all patient-reported outcomes had improved significantly from baseline , irrespective of the treatment strategy . SF-36 subscale scores approached population norms for 3 physical components , and achieved population norms ( P > 0.05 ) for bodily pain and 4 mental components . Improvement in functioning , VAS scores , and physical items of the SF-36 occurred significantly earlier in patients treated with initial combination therapies ( all comparisons after 3 months : overall P < 0.001 ; P < 0.05 for groups 1 and 2 versus groups 3 and 4 ) . CONCLUSION All 4 DAS-driven treatment strategies result ed in substantial improvements in functional ability , quality of life , and self-assessed VAS scores after 2 years . Initial combination therapy led to significantly faster improvement in all patient-reported measures OBJECTIVE Human cartilage glycoprotein 39 ( HC gp-39 ) appears to be a relevant autoantigen in patients with rheumatoid arthritis ( RA ) . Administration of major histocompatibility complex ( MHC ) Class II complexed antigens without requisite costimulatory signals can induce immunologic tolerance . We evaluated the safety , pharmacokinetics , and preliminary efficacy of AG4263 in patients with RA . AG4263 is a soluble complex of native HLA-DR4 ( beta*0401 ) complexed to Org 36601 , a 13-mer peptide derived from HC gp-39 ( also referred to as CDP263 ) . METHODS Thirty-one HLA-DRB1 * 0401 positive patients with persistent RA disease activity despite concurrent methotrexate were r and omized to 7 infusions of AG4263 ( n = 24 ) or placebo ( n = 7 ) over 6 weeks . The initial dose of 0.5 micro g/kg was escalated in subsequent cohorts to a maximum of 150 micro g/kg . Safety analyses included recording of adverse events and measurement of CD4/CD8 counts , reactivity to recall antigens , and development of antibodies to HLA-DR4 . Efficacy was assessed using the Paulus 20 criteria . RESULTS Treatment was well tolerated , with injection site reaction the most common adverse event . There was no loss of reactivity to recall antigens , change in cell counts , or antibodies to HLA-DR . The mean half-life of AG4263 was 12.5 h. Some evidence of clinical response was seen ; responses were more common among patients receiving the highest doses of AG4263 and among those with baseline T cell reactivity to CDP263 . CONCLUSION AG4263 was safe , well tolerated , and without evidence of generalized immune suppression . Along with the observed trend toward clinical efficacy , the results suggest that this therapeutic approach warrants further investigation in patients with RA Objectives : This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo . The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score ( based on erythrocyte sedimentation rates ; DAS28 ( ESR ) ) for the abatacept vs placebo groups at day 197 . Methods : Patients with rheumatoid arthritis ( RA ) and an inadequate response to methotrexate ( MTX ) were r and omised 3:3:2 to abatacept ( ∼10 mg/kg every 4 weeks , n = 156 ) , infliximab ( 3 mg/kg every 8 weeks , n = 165 ) , or placebo ( every 4 weeks , n = 110 ) and background MTX . Safety and efficacy were assessed throughout the study . Results : Similar patient demographics and clinical characteristics were present at baseline between groups , with mean scores of ∼1.7 for HAQ-DI and 6.8 for DAS28 ( ESR ) . At 6 months , mean changes in DAS28 ( ESR ) were significantly greater for abatacept vs placebo ( –2.53 vs –1.48 , p<0.001 ) and infliximab vs placebo ( –2.25 vs –1.48 , p<0.001 ) . For abatacept vs infliximab treatment at day 365 , reductions in the DAS28 ( ESR ) were –2.88 vs –2.25 . At day 365 , the following response rates were observed for abatacept and infliximab , respectively : American College of Rheumatology ( ACR ) 20 , 72.4 and 55.8 % ; ACR 50 , 45.5 and 36.4 % ; ACR 70 , 26.3 and 20.6 % ; low disease activity score ( LDAS ) , 35.3 and 22.4 % ; DAS28-defined remission , 18.7 and 12.2 % ; good European League Against Rheumatism ( EULAR ) responses , 32.0 and 18.5 % ; and Health Assessment Question naire Disability Index ( HAQ-DI ) , 57.7 and 52.7 % . Mean changes in physical component summary ( PCS ) were 9.5 and 7.6 , and mental component summary ( MCS ) were 6.0 and 4.0 , for abatacept and infliximab , respectively . Over 1 year , adverse events ( AEs ) ( 89.1 vs 93.3 % ) , serious AEs ( SAEs ) ( 9.6 vs 18.2 % ) , serious infections ( 1.9 vs 8.5 % ) and discontinuations due to AEs ( 3.2 vs 7.3 % ) and SAEs ( 2.6 vs 3.6 % ) were lower with abatacept than infliximab . Conclusions : In this study , abatacept and infliximab ( 3 mg/kg every 8 weeks ) demonstrated similar efficacy . Overall , abatacept had a relatively more acceptable safety and tolerability profile , with fewer SAEs , serious infections , acute infusional events and discontinuations due to AEs than the infliximab group . Trial registration number : NCT00095147 OBJECTIVE To assess the effects of treatment with rituximab plus methotrexate on patient-reported outcomes in patients with active rheumatoid arthritis ( RA ) who experienced inadequate response to anti-tumor necrosis factor therapy . METHODS Patients with active RA were r and omly assigned to rituximab ( 1,000 mg on days 1 and 15 ) or placebo . The primary end point was the proportion of patients with an American College of Rheumatology 20 % response at week 24 . Additional goals were to assess treatment effects on pain , fatigue , functional disability , health-related quality of life , and disease activity by comparing mean changes between groups . The analysis was conducted in the intent-to-treat population . The proportion of patients who achieved the minimum clinical ly important difference on the Health Assessment Question naire ( HAQ ) disability index ( DI ) , Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) , and Short Form 36 ( SF-36 ) was determined . RESULTS Rituximab patients had statistically significantly greater pain relief . The FACIT-F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24 . Mean improvement from baseline in functional disability ( measured by the HAQ DI ) was significantly greater in rituximab patients from weeks 8 to 24 . The mean + /- SD change from baseline for the SF-36 Physical Component Score was 6.64 + /- 8.74 for rituximab patients and 1.48 + /- 7.32 for placebo patients ( P < 0.0001 ) . The mean change from baseline for the SF-36 Mental Component Score was 5.32 + /- 12.41 for rituximab patients and 2.25 + /- 12.23 for placebo patients ( P = 0.0269 ) . CONCLUSION Rituximab produced rapid , clinical ly meaningful , and statistically significant improvements in patient-reported pain , fatigue , functional disability , health-related quality of life , and disease activity . These effects were sustained throughout the study BACKGROUND Effective new therapies are needed for rheumatoid arthritis . Current therapies target the products of activated macrophages ; however , T cells also have an important role in rheumatoid arthritis . A fusion protein -- cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis . CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells , blocking the engagement of CD28 on T cells and preventing T-cell activation . A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis . METHODS We r and omly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight ( 105 patients ) , 10 mg of CTLA4Ig per kilogram ( 115 patients ) , or placebo ( 119 patients ) for six months . All patients also received methotrexate therapy during the study . The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology ( ACR ) , which define the response according to its extent : 20 percent ( ACR 20 ) , 50 percent ( ACR 50 ) , or 70 percent ( ACR 70 ) . Additional end points included measures of the health-related quality of life . RESULTS Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo ( 60 percent vs. 35 percent , P<0.001 ) . Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group . The group given 10 mg of CTLA4Ig per kilogram had clinical ly meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey . CTLA4Ig was well tolerated , with an overall safety profile similar to that of placebo . CONCLUSIONS In patients with active rheumatoid arthritis who were receiving methotrexate , treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life . CTLA4Ig is a promising new therapy for rheumatoid arthritis Objective . To evaluate the effect of golimumab on physical function , general health , and fatigue in patients with active rheumatoid arthritis ( RA ) despite methotrexate ( MTX ) therapy . Methods . In the multicenter , r and omized , placebo-controlled GO-FORWARD study , 444 adults with active RA despite MTX received subcutaneous placebo + MTX ( crossover to golimumab 50 mg at Week 24 ) , golimumab 100 mg + placebo , golimumab 50 mg + MTX , or golimumab 100 mg + MTX every 4 weeks . Physical function and general health were assessed using the Health Assessment Question naire-Disability Index ( HAQ-DI ) and Physical and Mental Component Summary ( PCS , MCS ) scores of the Medical Outcomes Study Short Form-36 question naire ( SF-36 ) , respectively , through Week 52 . Fatigue was measured through Week 24 using the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-Fatigue ) question naire . Results . Mean improvements from baseline in HAQ-DI , SF-36 PCS , and FACIT-Fatigue scores ( Weeks 14 and 24 ) were significantly greater for golimumab 50 mg + MTX and 100 mg + MTX versus placebo + MTX . Significantly greater proportions of patients treated with golimumab + MTX achieved clinical ly meaningful improvements from baseline to Weeks 14 and 24 in HAQ-DI , PCS , and FACIT-Fatigue scores . Mean improvements in SF-36 PCS ( Week 14 ) , MCS ( Week 24 ) , and FACIT-Fatigue ( Weeks 14 and 24 ) scores were significantly greater for golimumab 100 mg + placebo versus placebo + MTX . Mean improvements from baseline in HAQ-DI , SF-36 PCS , and MCS scores through Week 24 were sustained through Week 52 . Conclusion . Patients with active RA despite MTX had significant improvement in physical function , general health , and fatigue following golimumab + MTX therapy ; improvements in physical function and general health were maintained through Week 52 . ( Clinical Trials Registration NCT00264550 OBJECTIVE To evaluate the efficacy and safety of adalimumab ( D2E7 ) , a fully human monoclonal tumor necrosis factor alpha antibody , in combination with methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) despite treatment with MTX . METHODS In a 24-week , r and omized , double-blind , placebo-controlled study , 271 patients with active RA were r and omly assigned to receive injections of adalimumab ( 20 mg , 40 mg , or 80 mg subcutaneously ) or placebo every other week while continuing to take their long-term stable dosage of MTX . The primary efficacy end point was the American College of Rheumatology criteria for 20 % improvement ( ACR20 ) at 24 weeks . RESULTS An ACR20 response at week 24 was achieved by a significantly greater proportion of patients in the 20-mg , 40-mg , and 80-mg adalimumab plus MTX groups ( 47.8 % , 67.2 % , and 65.8 % , respectively ) than in the placebo plus MTX group ( 14.5 % ) ( P < 0.001 ) . ACR50 response rates with the 20-mg , 40-mg , and 80-mg adalimumab dosages ( 31.9 % , 55.2 % , and 42.5 % , respectively ) were significantly greater than that with placebo ( 8.1 % ) ( P = 0.003 , P < 0.001 , and P < 0.001 , respectively ) . The 40-mg and 80-mg doses of adalimumab were associated with an ACR70 response ( 26.9 % and 19.2 % , respectively ) that was statistically significantly greater than that with placebo ( 4.8 % ) ( P < 0.001 and P = 0.020 ) . Responses were rapid , with the greatest proportion of adalimumab-treated patients achieving an ACR20 response at the first scheduled visit ( week 1 ) . Adalimumab was safe and well tolerated ; comparable numbers of adalimumab-treated patients and placebo-treated patients reported adverse events . CONCLUSION The addition of adalimumab at a dosage of 20 mg , 40 mg , or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant , rapid , and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo OBJECTIVE Rheumatoid arthritis ( RA ) patients who have inadequate response to anti-tumour necrosis factor ( TNF ) therapy currently have treatment options that are limited and less than optimal in their risk-to-benefit ratio . Abatacept provides a new generation of RA medications that has previously been demonstrated to have positive clinical outcomes with this population . The current study sought to demonstrate the efficacy of abatacept on quality of life ( QoL ) for RA patients with inadequate response to anti-TNF therapy . METHODS Patients were entered into a double-blind , placebo-controlled , multicentre r and omized clinical trial , with 258 patients r and omized to abatacept + disease-modifying anti-rheumatic drugs ( DMARDs ) and 133 patients r and omized to placebo + DMARDS . The QoL was measured with the Short Form Health Survey ( SF-36 ) , Health Assessment Question naire ( HAQ ) and fatigue visual analogue scale , and was analysed with basic ( ANOVA , chi-square ) and multigroup growth curve techniques to assess differential change over time . RESULTS Treatment group QoL improved significantly more than placebo on the HAQ and fatigue indices , as well as seven of the eight SF-36 scales and SF-36 physical and mental summary scores . Improvement rate was faster for abatacept than for placebo on the QoL measures , and the improvements from abatacept related to normal levels of QoL on many domains . CONCLUSION Clinical ly relevant benefits of abatacept over placebo are discussed regarding improving QoL. Importantly , the larger rate of change for abatacept over placebo provides clinicians with a medication that can lead to meaningful changes in a patient 's life within a few weeks , even when the patient previously failed anti-TNF therapy Background Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody , being investigated for the treatment of rheumatoid arthritis ( RA ) . This multicenter , phase II , r and omized , double-blind , placebo-controlled , parallel-group , dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate . Methods Patients were r and omized to receive one of four regimens , in addition to methotrexate , for 12 weeks : canakinumab 150 mg subcutaneously ( SC ) every 4 weeks ( q4wk ) , canakinumab 300 mg SC ( 2 injections of 150 mg SC ) every 2 weeks , a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks ' , or placebo SC every 2 weeks . Results Among 274 patients with evaluable efficacy data , the percentage of responders according to American College of Rheumatology 50 criteria ( the primary endpoint , based on a 28-joint count ) was significantly higher with canakinumab 150 mg SC q4wk than with placebo ( 26.5 % vs. 11.4 % , respectively ; p = 0.028 ) . Compared to placebo , this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28 , scores on the Health Assessment Question naire and Functional Assessment of Chronic Illness Therapy-Fatigue , swollen 28-joint count , and patient 's and physician 's global assessment s of disease activity . No safety concerns were raised with canakinumab therapy , particularly with regard to infections . Few injection-site reactions occurred . Conclusion The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate . Trial Registration ( Clinical Trials.gov identifier : NCT00784628 Background : Tumour necrosis factor α ( TNFα ) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis ( RA ) . Treatment with TNFα inhibitors reduces disease activity and improves outcomes for patients with RA . This study evaluated the efficacy and safety of certolizumab pegol 400 mg , a novel , poly-(ethylene glycol ) (PEG)ylated , Fc-free TNFα inhibitor , as monotherapy in patients with active RA . Methods : In this 24-week , multicentre , r and omised , double-blind , placebo-controlled study , 220 patients previously failing ⩾1 disease-modifying antirheumatic drug ( DMARD ) were r and omised 1:1 to receive subcutaneous certolizumab pegol 400 mg ( n = 111 ) or placebo ( n = 109 ) every 4 weeks . The primary endpoint was 20 % improvement according to the American College of Rheumatology criteria ( ACR20 ) at week 24 . Secondary endpoints included ACR50/70 response , ACR component scores , 28-joint Disease Activity Score Erythrocyte Sedimentation Rate 3 ( DAS28(ESR)3 ) , patient-reported outcomes ( including physical function , health-related quality of life ( HRQoL ) , pain and fatigue ) and safety . Results : At week 24 , the ACR20 response rates were 45.5 % for certolizumab pegol 400 mg every 4 weeks vs 9.3 % for placebo ( p<0.001 ) . Differences for certolizumab pegol vs placebo in the ACR20 response were statistically significant as early as week 1 through to week 24 ( p<0.001 ) . Significant improvements in ACR50 , ACR components , DAS28(ESR)3 and all patient-reported outcomes were also observed early with certolizumab pegol and were sustained throughout the study . Most adverse events were mild or moderate and no deaths or cases of tuberculosis were reported . Conclusions : Treatment with certolizumab pegol 400 mg monotherapy every 4 weeks effectively reduced the signs and symptoms of active RA in patients previously failing ⩾1 DMARD compared with placebo , and demonstrated an acceptable safety profile . Trial registration number : NCT00548834 A controlled study has been carried out to assess the efficacy of rituximab , a chimeric antibody that binds to the B-cell surface antigen CD20 , in 20 patients with mixed cryoglobulinemia ( MC ) and hepatitis C virus (HCV)-positive chronic active liver disease , resistant to interferon alpha ( IFN-alpha ) therapy . They received an intravenous infusion of 375 mg/m(2 ) rituximab once a week for 4 consecutive weeks . Infusion of rituximab had a good safety profile and no severe side effects were reported . Sixteen patients ( 80 % ) showed a complete response ( CR ) , characterized by rapid improvement of clinical signs ( disappearance of purpura and weakness arthralgia and improvement of peripheral neuropathy ) , and decline of cryocrit . CR was associated with a significant reduction of rheumatoid factor ( RF ) activity and anti-HCV antibody titers . Decline of IgG anti-HCV titers in the cryoprecipitates was usually associated with a favorable response ( r = 0.81 ; P < .005 ) . No differences in the dynamics of B-cell depletion and recovery were found between responders and nonresponders . Molecular monitoring of the B-cell response revealed disappearance/deletion of peripheral clones in the responders and great stability in the nonresponders . Rituximab had a deep impact on hepatitis C viremia ; HCV RNA increased approximately twice the baseline levels in the responders , whereas it remained much the same in the nonresponders . Twelve ( 75 % ) of 16 responders remained in remission throughout the follow-up . The results indicate that rituximab has clinical and biologic activity in patients with HCV(+ ) MC . However , in view of the increased viremia in the responders , additional modes of application and combination of rituximab with other agents need to be investigated OBJECTIVES In early and active RA despite MTX , continuous treatment with TNF blockers in combination with MTX is recommended . To compare this strategy with an initial combination of MTX and adalimumab ( ADA ) given for 3 months and then adjusted based on the disease activity status . METHODS Prospect i ve unblinded r and omized multicentre controlled 1-year trial in which 65 patients with early ( < 6 months ) and active [ disease activity score ( DAS28(ESR ) ) > 5.1 ] RA were assigned to Group 1 ( 32 patients ): MTX ( 0.3 mg/kg/week , maximum of 20 mg/week , without escalating dose regimen ) or to Group 2 ( 33 patients ): initial combination therapy with MTX ( as in Group 1 ) and ADA ( 40 mg eow ) . In both groups , treatment was adjusted every 3 months . The aim was to achieve a low DAS ( DAS28(ESR ) < 3.2 ) . RESULTS From Week 12 until Week 52 , seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy ( P = 0.28 ) . The 1-year area under the curve ( AUC ) of DAS28 was lower in Group 2 owing to an initial better response . The total intake of anti-TNF-alpha and the mean increase in total modified Sharp score was similar in the two groups . CONCLUSIONS Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-alpha treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX OBJECTIVE T cells are involved in the pathogenesis of rheumatoid arthritis ( RA ) . In animal models of autoimmune diseases , blockade of costimulatory molecules on antigen-presenting cells has been demonstrated to be effective in preventing or treating this disease by preventing T cell activation . To date , the effect of costimulatory blockade in patients with RA is unknown . The goal of this multicenter , multinational study was to determine the safety and preliminary efficacy of costimulatory blockade using CTLA-4Ig and LEA29Y in RA patients who have been treated unsuccessfully with at least 1 disease-modifying agent . METHODS CTLA-4Ig , LEA29Y ( 0.5 , 2 , or 10 mg/kg ) , or placebo was administered intravenously to 214 patients with RA . Patients received 4 infusions of study medication , on days 1 , 15 , 29 , and 57 , and were evaluated on day 85 . The primary end point was the proportion of patients meeting the American College of Rheumatology 20 % improvement criteria ( ACR20 ) . All patients were monitored for treatment safety and tolerability . RESULTS CTLA-4Ig and LEA29Y infusions were well tolerated at all dose levels . Peri-infusional adverse events were carefully monitored , and showed similar incidence across all dose groups with the exception of headaches , which were slightly more frequent in the 2 treatment groups . The incidence of discontinuations due to worsening of RA was 19 % , 12 % , and 9 % at 0.5 , 2 , and 10 mg/kg , respectively , in the CTLA-4Ig-treated patients and 3 % , 3 % , and 6 % at 0.5 , 2 , and 10 mg/kg , respectively , in the LEA29Y-treated patients ( versus 31 % in the placebo group ) . ACR20 responses on day 85 had increased in a dose-dependent manner ( 23 % , 44 % , and 53 % of CTLA-4Ig-treated patients and 34 % , 45 % , and 61 % of LEA29Y-treated patients at 0.5 , 2.0 , and 10 mg/kg , respectively , versus 31 % of placebo-treated patients ) . CONCLUSION Both of the costimulatory blocking molecules studied were generally safe and well tolerated . As compared with placebo , both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA BACKGROUND Tumour necrosis factor alpha ( TNFalpha ) inhibitors are frequently used to treat rheumatoid arthritis , but whether use of a different TNFalpha inhibitor can improve patient response is unknown . We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid arthritis who had previously received one or more TNFalpha inhibitors . METHODS 461 patients with active rheumatoid arthritis from 82 sites in 10 countries were r and omly allocated by interactive voice response system , stratified by study site and methotrexate use , to receive subcutaneous injections of placebo ( n=155 ) , 50 mg golimumab ( n=153 ) , or 100 mg golimumab ( n=153 ) every 4 weeks between Feb 21 , 2006 , and Sept 26 , 2007 . Allocation was double-blind . Eligible patients had been treated with at least one dose of a TNFalpha inhibitor previously . Patients continued stable doses of methotrexate , sulfasalazine , hydroxychloroquine , oral corticosteroids , and non-steroidal anti-inflammatory drugs . The primary endpoint was achievement at week 14 of 20 % or higher improvement in American College of Rheumatology criteria for assessment of rheumatoid arthritis ( ACR20 ) . At week 16 , patients who had less than 20 % improvement in tender and swollen joint counts were given rescue therapy and changed treatment from placebo to 50 mg golimumab , or from 50 mg to 100 mg golimumab . Drug efficacy was assessed by intention to treat and safety was assessed according to the study drug given . This study is registered with Clinical Trials.gov , number NCT00299546 . FINDINGS Patients had discontinued previous TNFalpha inhibitors because of lack of effectiveness ( 269 [ 58 % ] patients ) or reasons unrelated to effectiveness ( 246 [ 53 % ] patients ) , such as intolerance and accessibility issues . Patients had active disease , which was indicated by a median of 14.0 ( IQR 9.0 - 22.0 ) swollen and 26.0 ( 16.0 - 41.0 ) tender joints for the whole group . 28 ( 18 % ) patients on placebo , 54 ( 35 % ) patients on 50 mg golimumab ( odds ratio 2.5 [ 95 % CI 1.5 - 4.2 ] , p=0.0006 ) , and 58 ( 38 % ) patients on 100 mg golimumab ( 2.8 [ 1.6 - 4.7 ] , p=0.0001 ) achieved ACR20 at week 14 . Two patients were never treated , and 57 patients did not complete the study because of adverse events , unsatisfactory treatment effect , loss to follow-up , death , or other reasons . 155 patients on placebo , 153 on 50 mg golimumab , and 153 on 100 mg golimumab were assessed for drug efficacy . For weeks 1 - 16 , serious adverse events were recorded in 11 ( 7 % ) patients on placebo , 8 ( 5 % ) on 50 mg golimumab , and 4 ( 3 % ) on 100 mg golimumab . For weeks 1 - 24 , after some patients were given rescue therapy , serious adverse events were recorded in 15 ( 10 % ) patients on placebo , 14 ( 5 % ) on 50 mg golimumab , and 8 ( 4 % ) on 100 mg golimumab . INTERPRETATION Golimumab reduced the signs and symptoms of rheumatoid arthritis in patients with active disease who had previously received one or more TNFalpha inhibitors . FUNDING Centocor Research and Development and Schering-Plough Research Institute OBJECTIVE To define clinical ly meaningful changes in 2 widely used health-related quality of life ( HQL ) instruments in studies of patients with rheumatoid arthritis ( RA ) . METHODS Patients with RA ( n = 693 ) who were enrolled in 2 double-blind , placebo-controlled clinical trials completed the Short Form 36 ( SF-36 ) modified health survey and the Health Assessment Question naire ( HAQ ) disability index at baseline and 6-week followup assessment s. Data on 5 RA severity measures were also collected at baseline and at 6 weeks ( patient and physician global assessment s , joint swelling and tenderness counts , and global pain assessment ) . Comparison of changes in the SF-36 scales and HAQ scores was made between groups of patients known to differ in the level of change on each RA severity measure . RESULTS With few exceptions , changes in the SF-36 and HAQ scores were different between patients who differed in the level of change on each RA severity measure . Changes in the SF-36 and HAQ scores were more strongly related to changes in the patient and physician global assessment s and patient pain assessment than to changes in the joint swelling and tenderness counts . CONCLUSION Based on these results , minimally important changes in the SF-36 scales and HAQ disability scores were determined , which will be useful in interpreting HQL results in clinical trials Objective : To evaluate the responsiveness of patient reported outcomes ( PROs ) , including fatigue , sleep , activity limitation , and quality of life , in patients with rheumatoid arthritis ( RA ) . Methods : Data were considered from a r and omised controlled trial comparing abatacept ( n = 258 ) with placebo ( n = 133 ) on a background of DMARD treatment in RA patients who were inadequate responders to anti-TNF therapy ( ATTAIN study ) . PROs assessed included SF-36 , activity limitation , fatigue , and sleep . For each outcome the treatment difference , relative per cent improvement , st and ardised response mean ( SRM ) , and relative efficiency for assessing an outcome ’s ability to detect a treatment effect relative to tender joint count ( TJC ) were calculated . A relative efficiency > 1 suggests a measure that is more efficient than TJC in detecting treatment effect . Results : Moderate to large SRMs ( ⩾0.6 ) were observed for the PRO measures . In particular , SRMs ( 95 % confidence interval ) were : physician global , 0.72 ( 0.51 to 0.94 ) ; HAQ , 0.63 ( 0.42 to 0.85 ) ; SF-36 physical component score , 0.62 ( 0.40 to 0.83 ) ; SF-36 bodily pain , 0.68 ( 0.46 to 0.90 ) ; and fatigue , 0.59 ( 0.38 to 0.81 ) . Relative efficiencies for physician global ( 1.6 ) , SF-36 bodily pain domain ( 1.4 ) , pain intensity ( 1.4 ) , HAQ ( 1.2 ) , SF-36 physical component score ( 1.2 ) , fatigue ( 1.1 ) , and patient global assessment ( 1.04 ) were all more responsive than TJC . The SF-36 mental component score ( 0.3 ) , swollen joint count ( 0.6 ) , activity limitation ( 0.8 ) , sleep ( 0.7 ) , and C reactive protein ( 0.9 ) were less responsive . Conclusions : Using PROs for evaluating treatments for RA can detect improvements and will identify changes that are important to patients . In general , physical assessment s are more responsive to an effective treatment than mental assessment OBJECTIVE To evaluate the efficacy and safety of 2 dosage regimens of lyophilized certolizumab pegol ( a novel PEGylated anti-tumor necrosis factor agent ) as adjunctive therapy to methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) with an inadequate response to MTX therapy alone . METHODS In this 52-week , phase III , multicenter , r and omized , double-blind , placebo-controlled , parallel-group trial , 982 patients were r and omized 2:2:1 to receive treatment with subcutaneous certolizumab pegol at an initial dosage of 400 mg given at weeks 0 , 2 , and 4 , with a subsequent dosage of 200 mg or 400 mg given every 2 weeks , plus MTX , or placebo plus MTX . Co- primary end points were the response rate at week 24 according to the American College of Rheumatology 20 % criteria for improvement ( ACR20 ) and the mean change from baseline in the modified total Sharp score at week 52 . RESULTS At week 24 , ACR20 response rates using nonresponder imputation for the certolizumab pegol 200-mg and 400-mg groups were 58.8 % and 60.8 % , respectively , as compared with 13.6 % for the placebo group . Differences in ACR20 response rates versus placebo were significant at week 1 and were sustained to week 52 ( P < 0.001 ) . At week 52 , mean radiographic progression from baseline was reduced in patients treated with certolizumab pegol 200 mg ( 0.4 Sharp units ) or 400 mg ( 0.2 Sharp units ) as compared with that in placebo-treated patients ( 2.8 Sharp units ) ( P < 0.001 by rank analysis ) . Improvements in all ACR core set of disease activity measures , including physical function , were observed by week 1 with both certolizumab pegol dosage regimens . Most adverse events were mild or moderate . CONCLUSION Treatment with certolizumab pegol 200 or 400 mg plus MTX result ed in a rapid and sustained reduction in RA signs and symptoms , inhibited the progression of structural joint damage , and improved physical function as compared with placebo plus MTX treatment in RA patients with an incomplete response to MTX OBJECTIVE To examine the efficacy and safety of different rituximab doses plus methotrexate ( MTX ) , with or without glucocorticoids , in patients with active rheumatoid arthritis ( RA ) resistant to disease-modifying antirheumatic drugs ( DMARDs ) , including biologic agents . METHODS A total of 465 patients were r and omized into 9 treatment groups : 3 rituximab groups ( placebo [ n = 149 ] , 500 mg [ n = 124 ] , or 1,000 mg [ n = 192 ] on days 1 and 15 ) each also taking either placebo glucocorticoids , intravenous methylprednisolone premedication , or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks . All patients received MTX ( 10 - 25 mg/week ) ; no other DMARDs were permitted . RESULTS Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20 % improvement criteria ( achieved an ACR20 response ) at week 24 ( 55 % and 54 % , respectively ) compared with placebo ( 28 % ; P < 0.0001 ) . ACR50 responses were achieved by 33 % , 34 % , and 13 % of patients , respectively ( P < 0.001 ) , and ACR70 responses were achieved by 13 % , 20 % , and 5 % of patients ( P < 0.05 ) . Changes in the Disease Activity Score in 28 joints ( -1.79 , -2.05 , -0.67 ; P < 0.0001 ) and moderate to good responses on the European League Against Rheumatism criteria ( P < 0.0001 ) reflected the ACR criteria responses . Glucocorticoids did not contribute significantly to the primary efficacy end point , ACR20 response at 24 weeks . Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events ; oral glucocorticoids conferred no additional safety benefit . Rituximab was well tolerated ; the type and severity of infections was similar to those for placebo . CONCLUSION Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA . The primary end point ( ACR20 response ) was independent of glucocorticoids , although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion OBJECTIVE To compare the benefits of initiating treatment with methotrexate ( MTX ) and infliximab ( anti-tumor necrosis factor alpha [ anti-TNFalpha ] monoclonal antibody ) with those of MTX treatment alone in patients with rheumatoid arthritis ( RA ) of < or =3 years ' duration . METHODS RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor . One thous and forty-nine patients were r and omly assigned in a 4:5:5 ratio to 3 treatment groups : MTX-placebo , MTX-3 mg/kg infliximab , and MTX-6 mg/kg infliximab . MTX dosages were rapidly escalated to 20 mg/week , and infliximab or placebo infusions were given at weeks 0 , 2 , and 6 , and every 8 weeks thereafter through week 46 . RESULTS At week 54 , the median percentage of American College of Rheumatology improvement ( ACR-N ) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group ( 38.9 % and 46.7 % versus 26.4 % , respectively ; P < 0.001 for both comparisons ) . Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone ( mean + /- SD changes in van der Heijde modification of the total Sharp score at week 54 : 0.4 + /- 5.8 and 0.5 + /- 5.6 versus 3.7 + /- 9.6 , respectively ; P < 0.001 for each comparison ) . In addition , physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group . Infliximab therapy was associated with a significantly higher incidence of serious infections , especially pneumonia . CONCLUSION For patients with active RA in its early stages , combination therapy with MTX and infliximab provides greater clinical , radiographic , and functional benefits than treatment with MTX alone OBJECTIVES The aims of this study were to examine the relationship between external home help ( EHH ) use ( ie , help provided by someone other than family or friends ) and clinical response and patient-reported outcomes in patients with rheumatoid arthritis ( RA ) , and to determine whether abatacept treatment in addition to methotrexate reduces the need for EHH . METHODS EHH use was recorded monthly in the Abatacept in Inadequate responders to Methotrexate ( AIM ) trial , a 12-month , r and omized , double-blind , placebo-controlled trial of abatacept in patients with active RA also receiving methotrexate . Clinical response was defined using American College of Rheumatology ( ACR ) criteria , European League Against Rheumatism ( EULAR ) criteria , and Disease Activity Scale (DAS)-28 score . Patient-reported outcomes included the Health Assessment Question naire ( HAQ ) , 100-mm visual analog scales ( VASs ) for pain and fatigue , and the Medical Outcomes Study 36-item Short Form Health Survey ( SF-36 ) for health-related quality of life . Analysis of covariance and regression analysis were performed to investigate the relationship between change in EHH use and both clinical response and patient-reported outcomes . RESULTS Of 590 patients enrolled in the study , 232 ( 39.3 % ) were receiving EHH at baseline ( mean age , 50.2 years ; 88 % female ; 85 % white ; mean duration of RA , 8.8 years ; mean [ SD ] EHH use , 15.6 [ 11.3 ] days ) . The level of EHH use was consistently higher with poorer scores on the HAQ , pain and fatigue VASs , DAS28 , and SF-36 . At 12 months , the mean reduction from baseline in EHH use was significantly greater in patients with ACR-50 or ACR-70 clinical response , EULAR good or moderate response , DAS28 remission , and clinical ly meaningful improvements in patient-reported outcomes . On multiple regression analysis , change in SF-36 Physical Functioning subscale score was the most important contributor to change in EHH after adjustment for other variables . The mean reduction from baseline in EHH use was significantly greater with abatacept compared with placebo over the study period ( all , P<0.001 ) . CONCLUSIONS In this exploratory analysis of data from patients with active RA from the AIM trial , EHH use was decreased significantly with improvements in clinical response , disease activity , and patient-reported outcomes . Treatment with abatacept in addition to methotrexate was associated with significantly decreased EHH use , suggesting that abatacept may have been associated with improved function and increased physical independence in these patients with RA Tumour necrosis factor alpha ( TNF alpha ) is a critical inflammatory mediator in rheumatoid arthritis , and may therefore be a useful target for specific immunotherapy . In support of this hypothesis , we previously observed beneficial responses in patients with active rheumatoid arthritis after open-label administration of a chimeric monoclonal antibody to TNF alpha ( cA2 ) . We now report the results of a four-centre , r and omised double-blind trial of a single infusion of 1 or 10 mg/kg cA2 compared with placebo in 73 patients with active rheumatoid arthritis . The primary endpoint of the study was the achievement at week 4 of a Paulus 20 % response , an amalgam of six clinical , observational , and laboratory variables . Intention-to-treat analysis of data from individual patients showed only 2 of 24 placebo recipients responding at this time , compared with 11 of 25 patients treated with low-dose cA2 ( p = 0.0083 ) and 19 of 24 patients treated with high-dose cA2 ( p < 0.0001 ) . Over half of the high-dose cA2 patients responded by the more stringent 50 % Paulus criteria at this time ( p = 0.0005 ) . The magnitude of these responses was impressive , with maximum mean improvements in individual disease-activity assessment s , such as tender or swollen-joint counts and in serum C-reactive protein , exceeding 60 % for patients on high-dose treatment . There were two severe adverse events . 1 patient on 1 mg/kg cA2 developed pneumonia ( " possibly " treatment-related ) and 1 on 10 mg/kg had a fracture ( " probably not " treatment-related ) . The results provide the first good evidence that specific cytokine blockade can be effective in human inflammatory disease and define a new direction for the treatment of rheumatoid arthritis OBJECTIVE Certolizumab pegol ( CZP ) is known to be effective as monotherapy at a dosage of 400 mg every 4 weeks in patients with active RA who have failed DMARDs . The aim of this study was to investigate every 4-week CZP in addition to continued MTX therapy in patients with an inadequate response to MTX alone . METHODS Patients with active RA with inadequate response to MTX , on background MTX , were r and omized to double-blind treatment with CZP 400 mg or placebo every 4 weeks for 24 weeks ( NCT00544154 ) . The primary efficacy end-point was the ACR 20 % improvement criteria ( ACR20 ) response rate at Week 24 . Other end-points included ACR50 and ACR70 response rates , ACR core components , 28-joint DAS ( ESR ) with three variables ( DAS28 - 3 ) and health-related quality -of-life outcomes in addition to safety . RESULTS Of 247 r and omized patients , 126 received CZP and 121 received placebo , in addition to MTX . ACR20 response rates were 45.9 vs 22.9 % , respectively [ P < 0.001 analysed by the Cochran-Mantel-Haenszel ( CMH ) method ] , with improvements being apparent from Week 1 . Statistically significant improvements over placebo were seen with CZP for ACR50 , ACR core components , DAS28 - 3 and physical functioning . Rates of treatment-related adverse events were similar between groups ( 25.0 vs 27.7 % ) , and there were no deaths or serious opportunistic infections . CONCLUSION CZP 400 mg every 4 weeks plus MTX demonstrated a favourable risk-benefit profile with rapid onset of action in RA patients with an inadequate response to an earlier MTX therapy OBJECTIVE To determine the minimal clinical ly important differences ( MCID ) in the patient-reported outcomes of activity ( 0 - 30 , number of days of limitation ) , fatigue ( 0 = none , 100 = complete ) , and sleep quality ( 0 = no problems , 100 = worst case ) for patients with rheumatoid arthritis ( RA ) . METHODS Two r and omized controlled trials comparing abatacept to placebo in RA patients were considered : ATTAIN ( n = 391 ) and AIM ( n = 652 ) . An internal anchor-based approach was used to derive the MCID using the Health Assessment Question naire , patient global assessment , and pain as anchors . Minimal important change in activity , fatigue , and sleep were determined by estimating mean changes in these outcomes in patients showing change in a narrow range about the MCID of the internal anchor . Correlation analysis was used to determine the consistency of the changes in the outcomes and anchors , and a Delphi process was used to determine the final MCID values . RESULTS For the 2 trials , consistent patterns of change for activity , fatigue , and sleep and the internal anchors were found with correlations in the range of 0.5 , 0.7 , and 0.4 , respectively . The mean changes for activity , fatigue , and sleep in a narrow range about the MCID of the 3 internal anchors corresponding to the 2 trials were : 3.4 to 4.3 for activity ; 6.7 to 17.0 for fatigue ; and 4.1 to 7.3 for sleep . Following the Delphi process the MCID determined were 4 for activity , 10 for fatigue , and 6 for sleep . CONCLUSION These MCID for activity limitation , fatigue , and sleep problems can be used in design ing clinical trials and providing benchmarks in assessing patient improvement BACKGROUND Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis . The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis ( COMET ) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept . METHODS 542 out patients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3 - 24 months were r and omly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate ( same titration ) plus etanercept 50 mg a week . Co primary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints ( DAS28 ) and radiographic non-progression measured with modified total Sharp score . Treatment was allocated with a computerised r and omisation and enrolment system , which masked both participants and carers . Analysis was done by modified intention to treat with last observation carried forward for missing data . This study is registered with Clinical Trials.gov , number NCT00195494 ) . FINDINGS 274 participants were r and omly assigned to receive combined treatment and 268 methotrexate alone . 132 of 265 ( 50 % , 95 % CI 44 - 56 % ) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 ( 28 % , 23 - 33 % ) taking methotrexate alone ( effect difference 22.05 % , 95%CI 13.96 - 30.15 % , p<0.0001 ) . 487 evaluable patients had severe disease ( DAS28>5.1 ) . 196 of 246 ( 80 % , 75 - 85 % ) and 135 of 230 ( 59 % , 53 - 65 % ) , respectively , achieved radiographic non-progression ( 20.98 % , 12.97 - 29.09 % , p<0.0001 ) . Serious adverse events were similar between groups . INTERPRETATION Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate . FUNDING Wyeth Research Objectives : To compare the effects of etanercept ( ETN ) 50 mg once weekly plus methotrexate ( MTX ) versus MTX alone on patient-reported outcomes ( PROs ) and the relationship between remission and PRO improvement . Methods : In this double-blind , r and omised clinical trial ( COMET ) , PROs included : the Health Assessment Question naire ( HAQ ) , EuroQoL health status , fatigue and pain visual analogue scales , Hospital Anxiety and Depression Scale , and Medical Outcomes Short-Form-36 . Mean changes from baseline were analysed by analysis of covariance using the last observation carried forward method . Results from week 52 are presented . Results : Most PROs demonstrated significantly greater improvements with ETN+MTX than MTX alone , including physical functioning , pain , fatigue and overall health status . A significantly greater improvement in HAQ score was observed in the ETN+MTX than the MTX group ( −1.02 vs −0.72 ; p<0.001 ) and a greater proportion reached the minimal clinical ly important difference of 0.22 ( 88 % vs 78 % ; p<0.006 ) . The relationship between PRO score and clinical status indicated that improvement was greatest among patients achieving remission . Conclusions : Early treatment with ETN+MTX leads to significantly greater improvements in multiple dimensions of PROs than MTX alone . The close relationship between disease activity and PRO improvement suggests that early treatment , with remission as a goal , should maximise the chance of restoring normal functioning and AIM Investigation of efficacy of antibodies ot interferons in rheumatoid arthritis ( RA ) versus relevant efficacy of the tumor necrosis factor ( TNF ) , comparison of the above cytokines in monotherapy and combined treatment . MATERIAL S AND METHODS An open controlled r and omized trial of clinical benefit and tolerance of anticytokine antibodies was performed in a group of RA patients at stage II , III and IV ( 1 , 20 and 4 patients , respectively ) . The activity degree II and III was in 10 and 15 patients , respectively . All the patients had articular functional insufficiency of the second degree . 21 patients failed previous therapy with basic drugs including immunodepressants . RESULTS The anticytokine antibodies proved to be highly effective in RA . Positive changes in teh disease activity were achieved early after the end of the 5-day course in 88 % of patients . The most definite immediate therapeutic effect was noted in usage of TNF antibodies both in monotherapy and in combination with other anticytokines . Long-term effect was the best in patients given antibodies to interferon gamma . Interferon-alpha antibodies produced weaker effect . The combined treatment had no advantages over the monotherapy . CONCLUSION A significant therapeutic effect of antibodies to interferon-gamma is indicative of an important role of this cytokine in RA pathogenesis . Anticytokine antibodies are promising as a component of combined therapy of patients with resistant RA OBJECTIVE To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate ( MTX ) over a 2-year period in patients with rheumatoid arthritis ( RA ) who previously experienced an incomplete response to MTX . METHODS Four hundred twenty-eight patients were r and omly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks , with an additional year of followup . The protocol was later amended to allow for continued treatment during the second year . Of 259 patients who entered the second year of treatment , 216 continued to receive infliximab plus MTX for 102 weeks . Ninety-four of these 259 patients experienced a gap in therapy of > 8 weeks before continuing therapy . Infusions were administered at weeks 0 , 2 , and 6 , followed by treatment every 4 weeks or every 8 weeks ( alternating with placebo infusions in the interim 4-week visits ) at a dose of 3 or 10 mg/kg for a total of 102 weeks ( including the gap in therapy ) . For safety and efficacy assessment s , data on the patients who were r and omized to receive treatment , irrespective of whether treatment was administered for 102 weeks , were evaluated using all actual observations available . The efficacy measures included the Health Assessment Question naire ( HAQ ) ( physical function ) , Short Form 36 health survey ( SF-36 ) ( health-related quality of life ) , total radiographic scores ( structural damage ) , and the American College of Rheumatology 20 % improvement criteria ( ACR20 ) ( signs and symptoms ) . RESULTS The infliximab plus MTX regimens result ed in significantly greater improvement in HAQ scores ( P < or = 0.006 ) and SF-36 physical component summary scores ( P < or = 0.011 ) compared with the MTX-only group . There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens . Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen . The proportion of patients achieving an ACR20 response at week 102 varied from 40 % to 48 % for the infliximab plus MTX groups compared with 16 % for the MTX-only group . CONCLUSION Throughout 102 weeks of therapy , infliximab plus MTX provided significant , clinical ly relevant improvement in physical function and quality of life , accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone Background The primary aim of rheumatoid arthritis ( RA ) treatment is to induce remission , the absence of disease activity . The objective of this study was to explore the association between clinical endpoints used to gauge RA treatment efficacy and patient-reported outcomes of health-related quality of life , fatigue , and physical function in RA patients treated with secukinumab in a phase 2 r and omized controlled trial ( RCT ) . Method Adult RA patients ( n = 237 ) with incomplete responses to methotrexate were r and omized equally to receive monthly s.c . injections of secukinumab 25 mg , 75 mg , 150 mg , 300 mg or placebo . Clinical endpoints used in this study included the ACR response criteria and its components and simplified disease activity score . Patient-reported outcomes ( PRO ) included Health Assessment Question naire-Disability Index ( HAQ-DI ) , Medical Outcomes Study Short Form-36 [ SF-36 ] Survey , and Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-Fatigue ) . Patients were categorized into mutually exclusive groups according to the magnitude and direction of change from baseline to week 16 in each clinical endpoint . Definitions of minimal important differences [ MID ] in each clinical endpoint were used to categorize patients , as well as thresholds beyond MID . Mean changes from baseline to week 16 were computed for each PRO and analyses of variance to test the differences in PRO changes observed across groups of patients that differed in each clinical endpoint . Analyses were limited to patients r and omized to secukinumab treatment . All dose groups were combined ( n = 187 ) . Results Mean changes from baseline in each PRO differed significantly across groups of patients in the expected direction . With few exceptions , there was considerable agreement between clinical endpoints and PROs concerning the magnitude of change defined as clinical ly meaningful . More importantly , results demonstrated that greater improvements in clinical endpoints were associated with incrementally better improvements in HRQoL , fatigue , and physical function . Conclusion Results of this study show considerable agreement between minimal thresholds of improvement established for PROs and clinical outcome measures used in RA treatment studies and provide thresholds to be considered in gauging the importance of a treatment effect that goes beyond what is considered as minimally important for PRO measures OBJECTIVE Atacicept is a recombinant fusion protein that binds and neutralizes B lymphocyte stimulator and a proliferation-inducing lig and . The purpose of this study was to investigate the tolerability , pharmacokinetics , and pharmacodynamics of atacicept treatment in patients with rheumatoid arthritis ( RA ) and to collect exploratory data on clinical outcomes . METHODS In this multicenter , phase Ib , r and omized , placebo-controlled , dose-escalating trial , 73 patients were enrolled into 6 escalating-dose cohorts . Patients received atacicept or placebo as single doses ( 70 , 210 , or 630 mg ) or as repeated doses given at 2-week intervals ( 3 doses of 70 mg , 3 doses of 210 mg , or 7 doses of 420 mg ) , followed by 10 weeks of trial assessment s , with a followup assessment at 3 months after the final dose . RESULTS Atacicept was well tolerated , with few differences between treatment groups and no obvious safety concerns . The pharmacokinetics profile was nonlinear , but was consistent and predictable across all doses and regimens . Treatment-related decreases in immunoglobulin ( particularly IgM ) and rheumatoid factor levels were evident , and a clear decrease in anti-citrullinated protein antibodies was observed in the cohort that received 7 doses of 420 mg . The B cell response was biphasic , with an initial transient increase ( dominated by memory B cells ) followed by a dose-related decrease ( dominated by mature B cells ) . Clinical assessment s showed trends toward improvement with the 3-month treatment . Little effect on the erythrocyte sedimentation rate or C-reactive protein levels was seen . CONCLUSION Atacicept was well tolerated both systemically and locally . The results demonstrated that the biologic activity of atacicept was consistent with its mechanism of action OBJECTIVE In patients with longst and ing severe rheumatoid arthritis ( RA ) receiving chronic treatment with adalimumab , health related quality of life ( HRQOL ) was assessed using new instruments [ Functional Assessment of Chronic Illness Therapy-Fatigue scale ( FACIT-Fatigue ) and Health Utilities Index Mark 3 ( HUI3 ) ] and a more conventional instrument [ Medical Outcomes Study Short Form-36 Health Survey ( SF-36 ) ] . METHODS Different measures for collecting patient-reported outcomes were applied simultaneously during the 3-year study period . Sociodemographic and medical history data were assessed at the baseline visit . Clinical examinations ( e.g. , joint examination and morning stiffness ) , disease assessment s , and HRQOL data were recorded every 8 weeks . For dichotomous and categorical variables , absolute and relative frequencies were calculated . Metric measures were described using mean and st and ard deviation and /or st and ard error of the mean . HRQOL data were analyzed using observed cases . RESULTS All assessed measures ( FACIT-Fatigue , HUI3 , SF-36 ) showed a rapid and statistically significant improvement from baseline following initiation of adalimumab therapy . This effect was maintained over the study period for a mean of 1.6 years in all applied measures . HRQOL data from all tested instruments were significantly correlated with each other . CONCLUSION Chronic therapy with adalimumab improved measures of fatigue and HRQOL in patients with longst and ing RA BACKGROUND A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor alpha ( TNF-alpha ) inhibitors . We conducted a r and omized , double-blind , phase 3 trial to evaluate the efficacy and safety of abatacept , a selective costimulation modulator , in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti-TNF-alpha therapy . METHODS Patients with active rheumatoid arthritis and an inadequate response to anti-TNF-alpha therapy were r and omly assigned in a 2:1 ratio to receive abatacept or placebo on days 1 , 15 , and 29 and every 28 days thereafter for 6 months , in addition to at least one disease-modifying antirheumatic drug . Patients discontinued anti-TNF-alpha therapy before r and omization . The rates of American College of Rheumatology ( ACR ) 20 responses ( indicating a clinical improvement of 20 percent or greater ) and improvement in functional disability , as reflected by scores for the Health Assessment Question naire ( HAQ ) disability index , were assessed . RESULTS After six months , the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group ( P<0.001 ) ; the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group ( 20.3 percent vs. 3.8 percent , P<0.001 ; and 10.2 percent vs. 1.5 percent , P=0.003 ) . At six months , significantly more patients in the abatacept group than in the placebo group had a clinical ly meaningful improvement in physical function , as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index ( 47.3 percent vs. 23.3 percent , P<0.001 ) . The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent , respectively , in the abatacept group and 71.4 percent and 3.0 percent , respectively , in the placebo group . The incidence of serious infections was 2.3 percent in each group . CONCLUSIONS Abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti-TNF-alpha therapy OBJECTIVE This study examined the effect of abatacept , a costimulation modulator , on the health-related quality of life ( HRQOL ) of patients with rheumatoid arthritis ( RA ) . METHODS Three hundred thirty-nine patients with RA on a background of methotrexate ( MTX ) , who participated in a multicenter , double-blind , placebo-controlled trial , were r and omized to abatacept 2 mg/kg , abatacept 10 mg/kg , or placebo . HRQOL was assessed at pretreatment , and at 3 , 6 , and 12 months posttreatment using the SF-36 Health Survey ( SF-36 ) . Changes in SF-36 scores from baseline to 12 months were compared across treatment and placebo groups to examine HRQOL benefits of abatacept . A link between American College of Rheumatology improvement and changes in SF-36 scores was established to demonstrate the association between HRQOL outcomes and clinical response . RESULTS After 12 months of treatment , patients r and omized to abatacept 10 mg/kg showed significantly better HRQOL outcomes overall versus patients r and omized to placebo ( MANOVA F = 4.71 , p < 0.001 ) or to abatacept 2 mg/kg ( MANOVA F = 1.97 , p = 0.05 ) . Differences in SF-36 change scores between abatacept 10 mg/kg and placebo groups reached statistical significance on all 8 domain scales , the 2 summary measures , and the SF-36 utility index ( SF-6D ) . Differences in SF-36 change scores between abatacept 10 mg/kg and abatacept 2 mg/kg reached statistical significance on 5 of the 8 domain scales , the physical summary measure , and the SF-6D . Improvement in HRQOL was highly related to clinical response . CONCLUSION Abatacept 10 mg/kg plus MTX demonstrated a stronger HRQOL response than placebo plus MTX . The abatacept 2 mg/kg arm showed a very weak and transient response OBJECTIVE To determine the efficacy and safety of treatment with rituximab plus methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) who had an inadequate response to anti-tumor necrosis factor ( anti-TNF ) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population . METHODS We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the R and omized Evaluation of Long-Term Efficacy of Rituximab in RA ( REFLEX ) Trial , a 2-year , multicenter , r and omized , double-blind , placebo-controlled , phase III study of rituximab therapy . Patients with active RA and an inadequate response to 1 or more anti-TNF agents were r and omized to receive intravenous rituximab ( 1 course , consisting of 2 infusions of 1,000 mg each ) or placebo , both with background MTX . The primary efficacy end point was a response on the American College of Rheumatology 20 % improvement criteria ( ACR20 ) at 24 weeks . Secondary end points were responses on the ACR50 and ACR70 improvement criteria , the Disease Activity Score in 28 joints , and the European League against Rheumatism ( EULAR ) response criteria at 24 weeks . Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) , Health Assessment Question naire ( HAQ ) Disability Index ( DI ) , and Short Form 36 ( SF-36 ) instruments , as well as Genant-modified Sharp radiographic scores at 24 weeks . RESULTS Patients assigned to placebo ( n = 209 ) and rituximab ( n = 311 ) had active , longst and ing RA . At week 24 , significantly more ( P < 0.0001 ) rituximab-treated patients than placebo-treated patients demonstrated ACR20 ( 51 % versus 18 % ) , ACR50 ( 27 % versus 5 % ) , and ACR70 ( 12 % versus 1 % ) responses and moderate-to-good EULAR responses ( 65 % versus 22 % ) . All ACR response parameters were significantly improved in rituximab-treated patients , who also had clinical ly meaningful improvements in fatigue , disability , and health-related quality of life ( demonstrated by FACIT-F , HAQ DI , and SF-36 scores , respectively ) and showed a trend toward less progression in radiographic end points . Rituximab depleted peripheral CD20 + B cells , but the mean immunoglobulin levels ( IgG , IgM , and IgA ) remained within normal ranges . Most adverse events occurred with the first rituximab infusion and were of mild-to-moderate severity . The rate of serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7 per 100 patient-years in the placebo group . CONCLUSION At 24 weeks , a single course of rituximab with concomitant MTX therapy provided significant and clinical ly meaningful improvements in disease activity in patients with active , longst and ing RA who had an inadequate response to 1 or more anti-TNF therapies Objective : To examine the impact of added abatacept treatment on health related quality of life ( HRQoL ) in patients with rheumatoid arthritis ( RA ) who have inadequate response to methotrexate ( MTX ) . Methods : The impact of abatacept treatment on HRQoL was examined in a longitudinal , r and omised double blind , placebo controlled clinical trial . Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups . The relationship between American College of Rheumatology ( ACR ) clinical markers and disease duration with changes in HRQoL indicators was also examined . Finally , a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population . Results : Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures , including physical function , fatigue , all eight domains of the SF-36 , and the physical and mental component summaries ( PCS and MCS ) . Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains . By day 169 , all HRQoL measures were significantly better with abatacept than with placebo . HRQoL gains were associated with greater ACR clinical improvement , and the effects were consistent for patients with different disease duration . A significantly greater percentage of patients treated with abatacept reached normative levels of PCS , MCS , physical functioning , and fatigue compared with patients treated with MTX alone . Conclusion : Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA OBJECTIVE To evaluate the efficacy , radiographic changes , and safety of abatacept and methotrexate therapy through 2 years in a long-term extension of a previously published 1-year study . METHODS Patients who received placebo during year 1 were switched to abatacept . Patients taking abatacept continued to take it . Efficacy and safety were assessed through 2 years . RESULTS Of 539 patients enrolled in the initial 1-year study , 488 completed 1 year of the long-term extension ( 2 % discontinued for lack of efficacy ) . At 2 years , patients taking abatacept had maintained their responses on the American College of Rheumatology ( ACR ) improvement criteria and the Disease Activity Score in 28 joints ( DAS28 ; using the C-reactive protein [ CRP ] level ) , as well as their physical function ( according to the Health Assessment Question naire [ HAQ ] disability index [ DI ] ) and health-related quality of life ( HRQOL ; assessed with the Short Form 36 [ SF-36 ] health survey ) , that were observed at the end of the double-blind period ( year 1 versus year 2 values were 81.9 % versus 80.3 % for ACR 20 % improvement , 25.4 % versus 30.9 % for a DAS28 [ CRP ] of < 2.6 , 71.8 % versus 66.8 % for the HAQ DI , and 9.7 versus 10.6 and 7.3 versus 7.2 , respectively , for the mean change in the physical and mental components summary scores of the SF-36 ) . In the abatacept group , post hoc analysis demonstrated further inhibition of radiographic progression during year 2 ( 57 % reduction in mean change of total score in year 2 versus year 1 ; P<0.0001 ) , and minimal radiographic progression was observed ( mean change in total score from baseline was 1.1 and 1.6 at year 1 and 2 , respectively ) . Rates of adverse events ( AEs ) and severe AEs were consistent throughout the cumulative period . CONCLUSION The improvements in signs and symptoms , physical function , and HRQOL observed after 1 year of abatacept treatment were maintained through 2 years of treatment . This durability was accompanied by a safety profile consistent with that in the double-blind portion of the study . Radiographic progression was further inhibited in year 2 compared with year 1 , suggesting an increasing effect of abatacept on the inhibition of structural damage in year 2 BACKGROUND Etanercept , which blocks the action of tumor necrosis factor , reduces disease activity in patients with long-st and ing rheumatoid arthritis . Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown . METHODS We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept ( 10 or 25 mg ) or weekly oral methotrexate ( mean , 19 mg per week ) for 12 months . Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology . Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale . On this scale , an increase of 1 point represents one new erosion or minimal narrowing . RESULTS As compared with patients who received methotrexate , patients who received the 25-mg dose of etanercept had a more rapid rate of improvement , with significantly more patients having 20 percent , 50 percent , and 70 percent improvement in disease activity during the first six months ( P<0.05 ) . The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group ( P= 0.001 ) , and the respective increases during the first 12 months were 0.47 and 1.03 ( P=0.002 ) . Among patients who received the 25-mg dose of etanercept , 72 percent had no increase in the erosion score , as compared with 60 percent of patients in the methotrexate group ( P=0.007 ) . This group of patients also had fewer adverse events ( P=0.02 ) and fewer infections ( P= 0.006 ) than the group that was treated with methotrexate . CONCLUSIONS As compared with oral methotrexate , subcutaneous [ corrected ] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis OBJECTIVES Fatigue is an important systemic symptom of rheumatoid arthritis ( RA ) but has rarely been evaluated consistently after initiation of treatment in RA patients . This study examined the effects of adalimumab ( HUMIRA , Abbott Laboratories , Abbott Park , IL , USA ) , a fully human , anti-tumor necrosis factor ( anti-TNF ) monoclonal antibody , on reducing fatigue in patients with RA . METHODS A total of 1526 patients with RA were enrolled in 3 r and omized , placebo-controlled clinical trials of adalimumab versus placebo plus methotrexate ( MTX ) or placebo plus st and ard antirheumatic therapies . Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy ( FACIT ) fatigue scale question naire ( which has been vali date d in RA ) at baseline , mid- study , and at the end of the study . Logistic regression models were constructed using baseline demographic variables to test for treatment effect . In addition , sensitivity analyses were performed to determine the robustness of the data . RESULTS At baseline in the 3 trials , patients ' fatigue ranged from 27.9 - 29.7 , representing considerable fatigue on the FACIT fatigue scale . Fatigue was significantly and consistently reduced in adalimumab-treated patients in the 3 clinical trials . Relative to placebo plus MTX , the adalimumab 40-mg-every-other-week dosage group reported statistically significantly less fatigue at all time points post-baseline . Improvements between adalimumab and placebo ranged from 3 - 7 points across all 3 trials , with a 3 - 4-point change representing a minimum clinical ly important difference . CONCLUSION Adalimumab treatment was shown to significantly reduce fatigue in patients with moderate to severe RA . Changes in fatigue in all 3 trials were found to be clinical ly important OBJECTIVES To identify factors associated with poor physical function in rheumatoid arthritis and to assess whether baseline joint damage has an impact on improvement in physical function during infliximab treatment . METHODS 428 patients with active rheumatoid arthritis despite methotrexate treatment received methotrexate alone or with infliximab ( 3 mg/kg or 10 mg/kg every four or eight weeks ) for 54 weeks ( the ATTRACT trial ) . Data on clinical outcomes and physical function ( assessed by the health assessment question naire ( HAQ ) ) were collected . Structural damage was assessed using the van der Heijde modification of the Sharp score . Odds ratios ( OR ) for factors associated with severe functional disability ( HAQ > or = 2.0 ) at baseline were estimated using multiple logistic regression analyses , and baseline factors related to the change in physical function after treatment at week 54 were determined . RESULTS Baseline radiographic scores were correlated with baseline HAQ scores . After adjustment for demographic characteristics in the logistic regression model , baseline disease activity scores , radiological joint damage , fatigue , and morning stiffness were found to be associated with severe functional disability ( HAQ > 2.0 ) , with OR values of 2.00 ( 1.53 to 2.63 ) , 1.82 ( 1.15 to 2.87 ) , 1.19 ( 1.05 to 1.34 ) , and 1.07 ( 1.01 to 1.13 ) , respectively . In multiple linear regression analysis , physical disability , joint damage , and fatigue at baseline were correlated with less improvement in physical function after treatment . Infliximab treatment was associated with greater improvement in physical function . CONCLUSIONS Greater joint damage at baseline was associated with poorer physical function at baseline and less improvement in physical function after treatment , underlining the importance of early intervention to slow the progression of joint destruction OBJECTIVE Tumor necrosis factor ( TNF ) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis ( RA ) . We investigated the ability of adalimumab , a human anti-TNF monoclonal antibody , to inhibit the progression of structural joint damage , reduce the signs and symptoms , and improve physical function in patients with active RA receiving concomitant treatment with methotrexate ( MTX ) . METHODS In this multicenter , 52-week , double-blind , placebo-controlled study , 619 patients with active RA who had an inadequate response to MTX were r and omized to receive adalimumab 40 mg subcutaneously every other week ( n = 207 ) , adalimumab 20 mg subcutaneously every week ( n = 212 ) , or placebo ( n = 200 ) plus concomitant MTX . The primary efficacy end points were radiographic progression at week 52 ( total Sharp score by a modified method [ TSS ] ) , clinical response at week 24 ( improvements of at least 20 % in the American College of Rheumatology core criteria [ ACR20 ] ) , and physical function at week 52 ( disability index of the Health Assessment Question naire [ HAQ ] ) . RESULTS At week 52 , there was statistically significantly less radiographic progression , as measured by the change in TSS , in the patients receiving adalimumab either 40 mg every other week ( mean + /- SD change 0.1 + /- 4.8 ) or 20 mg weekly ( 0.8 + /- 4.9 ) as compared with that in the placebo group ( 2.7 + /- 6.8 ) ( P < or = 0.001 for each comparison ) . In addition , there were statistically significant changes in the components of the TSS . At week 24 , ACR20 responses were achieved by 63 % and 61 % of patients in the adalimumab 40 mg every other week and 20 mg weekly groups , respectively , versus 30 % of patients in the placebo group ( P < or = 0.001 for each comparison ) . At week 52 , ACR20 responses were achieved by 59 % and 55 % of patients taking adalimumab 40 mg every other week and 20 mg weekly , respectively , versus 24 % of patients taking placebo ( P < or = 0.001 for each comparison ) . At week 52 , physical function as measured by the HAQ demonstrated statistically significant improvement with adalimumab 40 mg every other week and 20 mg weekly compared with placebo ( mean change in HAQ score -0.59 and -0.61 , respectively , versus -0.25 ; P < or = 0.001 for each comparison ) . A total of 467 patients ( 75.4 % ) completed 52 weeks of treatment . Adalimumab was generally well tolerated . Discontinuations occurred in 22.0 % of adalimumab-treated patients and in 30.0 % of placebo-treated patients . The rate of adverse events ( both serious and nonserious ) was comparable in the adalimumab and placebo groups , although the proportion of patients reporting serious infections was higher in patients receiving adalimumab ( 3.8 % ) than in those receiving placebo ( 0.5 % ) ( P < or = 0.02 ) , and was highest in the patients receiving 40 mg every other week . CONCLUSION In this 52-week trial , adalimumab was more effective than placebo at inhibiting the progression of structural joint damage , reducing the signs and symptoms , and improving physical function in patients with active RA who had demonstrated an incomplete response to MTX Objective . Rheumatoid arthritis ( RA ) is associated with significant impairments in health-related quality of life ( HRQOL ) . We evaluated patient-reported outcomes including HRQOL outcomes following adalimumab plus methotrexate ( MTX ) therapy in patients with early RA . Methods . PREMIER was a phase III , multicenter , r and omized , double-blind , active-comparator clinical trial in early RA . Patients aged ≥ 18 years were r and omly assigned to receive adalimumab 40 mg every other week ( eow ) plus weekly MTX , weekly MTX , or adalimumab 40 mg eow for 104 weeks . American College of Rheumatology ( ACR ) criteria were used to evaluate clinical efficacy and response . Outcomes were assessed using the Health Assessment Question naire Disability Index ( HAQ-DI ) , Short-Form 36 Health Survey ( SF-36 ) , Short-Form 6 Dimension ( SF-6D ) , visual analog scale ( VAS ) assessment s of global disease activity ( patient ’s global assessment ; PtGA ) and pain , Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) , and Health Utility Index Mark 3 ( HUI-3 ) . Results . Of 799 patients enrolled , 268 received adalimumab plus MTX , 257 received MTX monotherapy , and 274 received adalimumab monotherapy . Patients treated with adalimumab plus MTX demonstrated significant baseline to Week 104 improvements in HAQ-DI ( p < 0.0001 ) , SF-36 Physical Component Summary ( p < 0.0001 ) , 4 SF-36 domains [ physical function ( p < 0.0001 ) , bodily pain ( p < 0.0001 ) , vitality ( p = 0.0139 ) , role limitations -physical ( p = 0.0005 ) ] , SF-6D ( p = 0.0152 ) , VAS-PtGA ( p < 0.0001 ) , VAS-pain ( p < 0.0001 ) , FACIT-F ( p < 0.0001 ) , and HUI-3 ( p = 0.0034 ) scores versus patients treated with MTX monotherapy . Both SF-6D and HUI-3 were found to be sensitive preference-based measures for assessing the effects of treatment on multidimensional function . No clinical ly meaningful differences between adalimumab and MTX monotherapy groups were observed for most measures . For each measure , there was significant association between HRQOL improvement and ACR clinical response . Conclusion . Adalimumab plus MTX significantly improved physical functioning and HRQOL in patients with early RA over 2 years of treatment . ( Clinical Trials.gov identifier NCT00195663 ) OBJECTIVE We undertook this study to evaluate safety , tolerability , pharmacokinetics , pharmacodynamics , and efficacy of LY2439821 , a humanized anti-interleukin-17 ( anti-IL-17 ) monoclonal antibody , in a first in-human trial in rheumatoid arthritis ( RA ) patients taking oral disease-modifying antirheumatic drugs ( DMARDs ) . METHODS This r and omized , double-blind , placebo-controlled study consisted of 2 parts . In part A , 20 patients received 1 intravenous ( IV ) dose of LY2439821 ( 0.06 , 0.2 , 0.6 , or 2.0 mg/kg , escalating ) or placebo followed by 8 weeks of evaluation . End points included safety , tolerability , and pharmacokinetics . In part B , 77 patients received 1 IV dose of LY2439821 ( 0.2 , 0.6 , or 2.0 mg/kg ) or placebo every 2 weeks for a total of 5 doses , with a total evaluation period of 16 weeks . End points included safety , tolerability , pharmacokinetics/pharmacodynamics , and efficacy ( Disease Activity Score in 28 joints [ DAS28 ] and percentages of patients meeting American College of Rheumatology 20 % , 50 % , or 70 % improvement criteria [ achieving an ACR20 , ACR50 , or ACR70 response ] ) . The primary efficacy end point was the DAS28 at week 10 . RESULTS Baseline characteristics were similar across all groups . Changes in the DAS28 were significantly greater in the 0.2 mg/kg , 2.0 mg/kg , and all-LY2439821-combined groups ( -2.3 , -2.4 , and -2.3 , respectively ) than in the placebo group ( -1.7 ) at week 10 ( P < or = 0.05 ) , and these differences were significant as early as week 1 . Percentages of ACR20 , ACR50 , and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points . There was no apparent dose-response relationship in treatment-emergent adverse events . CONCLUSION LY2439821 added to oral DMARDs improved signs and symptoms of RA , with no strong adverse safety signal noted . This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA Context Abatacept , an agent that selectively modulates the co-stimulatory signal required for T-cell activation , may benefit some patients with rheumatoid arthritis . Contribution This 1-year , r and omized , double-blind trial compared once-monthly infusions of abatacept with placebo in 652 patients with symptomatic rheumatoid arthritis despite ongoing methotrexate treatment . Compared with placebo recipients , patients who received abatacept more often had improved physical function , more frequently met st and ard response criteria , and less often had radiographic progression of joint damage . They also had serious infections ( 2.5 % vs. 0.9 % ) and infusion reactions more often . Implication s Adding abatacept can reduce disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate . The Editors Rheumatoid arthritis is characterized by synovial membrane hyperplasia and inflammatory cell infiltrate , including activated T cells ( 1 ) . T cells contribute to the initiation and perpetuation of rheumatoid arthritis immunopathology , leading to inflammation and , ultimately , joint destruction . Activated T cells proliferate and induce monocytes , macrophages , and synovial fibroblasts to produce proinflammatory cytokines , such as tumor necrosis factor- , interleukin-1 , and interleukin-6 ( 1 ) , and stimulate osteoclastogenesis and matrix metalloproteinase secretion ( 2 ) , as well as immunoglobulin production by B cells ( 3 ) . The central role of activated T cells in rheumatoid arthritis immunopathology makes T-cell activation a rational therapeutic target . T cells require 2 signals for full activation : an antigen-specific signal ( signal 1 ) and a co-stimulatory signal ( signal 2 ) ( 4 ) . One of the best-characterized co-stimulatory pathways is the engagement of CD80 or CD86 on antigen-presenting cells with CD28 on T cells ( 5 ) . In the normal immune response , endogenous cytotoxic T-lymphocyte antigen-4 ( CTLA-4 ) downregulates CD28-mediated T-cell activation by binding to CD80 or CD86 with higher avidity than CD28 ( 6 ) . Abatacept is a soluble , recombinant , fully human fusion protein , comprising the extracellular domain of CTLA-4 and the Fc portion of IgG1 , modified to prevent complement fixation . Abatacept is the first in a new class of agents for treating rheumatoid arthritis that selectively modulate the co-stimulatory signal required for full T-cell activation . A phase IIa study of patients with rheumatoid arthritis and an inadequate response to disease-modifying antirheumatic drugs showed the efficacy of abatacept as monotherapy ( 7 ) . In a phase IIb study of abatacept plus methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate , signs and symptoms of rheumatoid arthritis , physical function , and health-related quality of life statistically significantly improved over 1 year ( 8 , 9 ) . We present findings from the phase III , 1-year Abatacept in Inadequate Responders to Methotrexate ( AIM ) trial , which was design ed to further evaluate the safety and clinical efficacy of abatacept plus methotrexate and to assess the effects of abatacept on the radiographic progression of structural damage . Methods The institutional review boards or independent ethics committees approved a common clinical protocol for each site , and we performed the study in accordance with the ethical principles of the Declaration of Helsinki . All patients provided written informed consent to the study protocol before r and omization . Patients Eligible patients were at least 18 years of age , had had rheumatoid arthritis for at least 1 year , and met the American Rheumatism Association criteria for rheumatoid arthritis ( 10 ) . Rheumatoid arthritis was persistent and active despite methotrexate treatment . All patients must have been treated with methotrexate ( 15 mg/wk ) for 3 months or longer , with a stable dose for 28 days before enrollment . We required patients to undergo a washout of all other disease-modifying antirheumatic drugs at least 28 days before r and omization . We allowed corticosteroid use , with dosages equal to 10 mg of prednisone or less per day , stabilized for 25 days before r and omization . At r and omization , we required patients to have 10 or more swollen joints , 12 or more tender joints , and C-reactive protein levels of 10.0 mg/L or greater ( normal range , 1.0 mg/L to 4.0 mg/L ) while receiving methotrexate . We required tuberculin skin testing before r and omization . We excluded patients with a positive tuberculin skin test result unless they had completed treatment for latent tuberculosis before enrollment . Study Design Our 1-year , multicenter , multinational , r and omized , double-blind , placebo-controlled study aim ed to compare the efficacy and safety of abatacept versus placebo in combination with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate treatment . We used a central r and omization system , and the Drug Management Group within Bristol-Myers Squibb , Princeton , New Jersey , generated the r and omization schedule . Stratification per site was not performed . Patients were r and omly assigned in a 2:1 ratio to receive either a fixed dose of abatacept , approximately 10 mg/kg of body weight , or placebo . Patients weighing less than 60 kg , 60 to 100 kg , or more than 100 kg received 500 mg , 750 mg , or 1000 mg of abatacept , respectively . We administered study medication by 30-minute intravenous infusion on days 1 , 15 , and 29 and then every 28 days up to and including day 337 . No premedication was required . The protocol specified that all patients were to receive methotrexate , 15 mg or more per week , although methotrexate at 10 mg per week was acceptable if the patient had a history of toxicity . During the first 6 months , we did not allow adjustments in methotrexate dose , except in cases of toxicity . We permitted use of stable dosages of nonsteroidal anti-inflammatory drugs and corticosteroid dosages equal to 10 mg of prednisone or less per day . Between 6 and 12 months , we allowed the following adjustments , as the investigator deemed necessary : 1 ) adjustment in methotrexate dose , 2 ) addition of 1 other disease-modifying antirheumatic drug ( hydroxychloroquine , sulfasalazine , gold , or azathioprine ) , or 3 ) adjustment in corticosteroid dose equal to 10 mg of prednisone or less per day . However , investigators were blinded to treatment group assignment throughout the 1-year study . Clinical Efficacy Measures Our 3 primary objectives were to evaluate the proportion of patients in each group with a 20 % improvement in American College of Rheumatology ( ACR ) response criteria ( ACR 20 ) at 6 months , the proportion of patients in each group with clinical ly significant improvement ( 0.3 unit ) in the Health Assessment Question naire Disability Index ( HAQ-DI ) score ( 11 ) at 1 year , and the radiographic progression of joint erosions ( assessed by comparing changes from baseline in the Genant-modified Sharp score ) ( 12 , 13 ) at 1 year . Table 1 summarizes the outcome measures used to assess the response to treatment . Table 1 . Outcome Measures for Assessing Response to Treatment of Rheumatoid Arthritis * Secondary objectives included assessing ACR 50 and ACR 70 responses at 6 months and all ACR responses at 1 year . In addition , we determined the proportions of patients achieving a major clinical response and a protocol -defined extended major clinical response at 1 year . We also assessed changes in disease activity by using the Disease Activity Score 28 ( DAS28 ) ( 20 , 21 ) . We assessed improvements in physical function over 1 year by using the HAQ-DI , which measures physical function during daily activities ( 22 ) . We evaluated changes in health-related quality of life by using the Medical Outcomes Study Short Form-36 Health Survey ( SF-36 ) ( 17 ) , which evaluates physical and mental health status ( Table 1 ) ( 18 , 19 ) . Physicians blinded to treatment group assignment performed assessment s at enrollment and at every visit before treatment administration on days 1 , 15 , and 29 ; every 28 days up to and including day 169 ( 6 months ) ; and on days 225 , 281 , and 365 ( 1 year ) . Radiographic Evaluation We performed st and ardized radiography of the h and s or wrists and feet at baseline and at 1 year or upon early termination ( if applicable ) . Two independent expert readers who were blinded to treatment group assignment , chronological order of radiography , and patients ' clinical response assessed all radiographic images for changes in erosion and joint-space narrowing by using the Genant-modified Sharp scoring system . Safety and Immunogenicity We monitored all patients who received at least 1 dose of the study medication for adverse events , serious adverse events , infusion reactions , clinical laboratory test abnormalities , and clinical ly significant changes in vital signs . Adverse events were self-reported by the patient and elicited by general question ing and examination at each visit . We attributed an adverse event to the study treatment on the basis of the investigator 's opinion , and we deemed an event as serious by st and ard regulatory definition . An external safety advisory panel , consisting of 5 physicians ( 3 rheumatologists , 1 oncologist , and 1 infectious disease expert ) , assessed overall safety in a blinded fashion by using reports of adverse events and laboratory results on a quarterly basis . We obtained serum sample s before infusions on days 1 , 29 , 85 , 169 , 281 , and 365 or 28 days after the last dose of the study medication in patients who discontinued before 1 year . We assessed immunogenicity by immunoassay to measure the antibody response to the entire abatacept molecule and also specifically to the CTLA-4 portion of the molecule ( 7 ) . Statistical Analysis The protocol estimated that 680 patients would need to be enrolled to r and omly assign 540 patients . We based sample sizes on a 5 % level of significance ( 2-tailed ) . The study had 99 % power to detect a difference of 20 % in ACR 20 between the 2 groups . On the basis of the OBJECTIVE To evaluate the effect of rituximab treatment on health-related quality of life ( HRQOL ) in patients with active rheumatoid arthritis ( RA ) , who have had an inadequate response to disease-modifying antirheumatic drugs , including biologic agents . METHODS A r and omized , multicenter , double-blind , placebo-controlled clinical trial involving 367 rheumatoid factor-positive patients was conducted . Patients received 2 infusions 2 weeks apart of placebo ( n = 122 ) , rituximab 500 mg ( n = 123 ) , or rituximab 1000 mg ( n = 122 ) , with or without glucocorticoids . All patients received stable doses of methotrexate ( 10 25 mg/wk ) . Measures included SF-36 , assessed at baseline and at 24 weeks , as well as the HAQ and FACIT-Fatigue scale assessed at baseline and monthly for 24 weeks . Patients exceeding prespecified minimal clinical ly important differences ( MCID ) were examined . Clinical efficacy measurements ( ACR20/50/70 and EULAR responses ) were compared with HRQOL outcomes . RESULTS At 24 weeks , the rituximab 500 mg and 1000 mg groups both reported statistically significantly greater improvements on the SF-36 physical component summary ( 4.37 and 4.89 points higher , respectively , vs placebo ; p < 0.001 ) . SF-36 physical function , bodily pain , vitality , social function , and role-physical subscale scores also statistically significantly improved vs placebo . At 24 weeks , 62.6 % and 67.2 % of the rituximab 500 mg and 1000 mg groups , respectively , exceeded the MCID of 0.22 in HAQ ( p < 0.001 ) . For FACIT-Fatigue , 55.3 % and 65.6 % of patients exceeded the MCID of 3.5 points compared with 35.2 % of placebo over 24 weeks ( p < 0.001 ) . ACR20/50/70 and EULAR responders demonstrated greater improvements in mean baseline to 24 week changes in SF-36 and FACIT-Fatigue scores compared with nonresponders ( p < 0.05 ) . CONCLUSION Both rituximab doses in combination with methotrexate were effective in improving all HRQOL outcomes in patients with active RA consistent with clinical efficacy To assess the effect of rituximab plus methotrexate ( MTX ) compared with MTX alone on patient‐reported outcomes ( PROs ) and health‐related quality of life ( HRQOL ) in patients with active early rheumatoid arthritis ( RA ) previously untreated with MTX OBJECTIVE To examine the efficacy and safety of the humanized anti-interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs ( DMARDs ) in patients with active rheumatoid arthritis ( RA ) . METHODS A total of 1,220 patients were r and omized ( 2:1 ratio ) in the phase III , double-blind , placebo-controlled , multicenter TOWARD ( Tocilizumab in Combination With Traditional DMARD Therapy ) study . Patients remained on stable doses of DMARDs and received tocilizumab 8 mg/kg or placebo ( control group ) every 4 weeks for 24 weeks . RESULTS At week 24 , the proportion of patients achieving a response according to the American College of Rheumatology criteria for 20 % improvement ( ACR20 ) was significantly greater in the tocilizumab plus DMARD group than in the control group ( 61 % versus 25 % ; P<0.0001 ) . Secondary end points including 50 % or 70 % improvement ( ACR50/70 ) , the Disease Activity Score in 28 joints ( DAS28 ) , DAS28 remission responses ( DAS28<2.6 ) , European League Against Rheumatism responses , and systemic markers such as the C-reactive protein and hemoglobin levels showed superiority of tocilizumab plus DMARDs over DMARDs alone . Seventy-three percent of patients in the tocilizumab group had > or=1 adverse event ( AE ) , compared with 61 % of patients in the control group . AEs leading to withdrawal from the study were infrequent ( 4 % of patients in the tocilizumab group and 2 % of those in the control group ) . Serious AEs occurred in 6.7 % and 4.3 % of patients in the tocilizumab and control groups , respectively , and serious infections occurred in 2.7 % and 1.9 % , respectively . Elevations in the alanine aminotransferase level , from normal at baseline to > 3-fold the upper limit of normal , occurred in 4 % of patients in the tocilizumab group and 1 % of those in the control group , and elevated total cholesterol levels were observed in 23 % and 6 % of patients , respectively . Sixteen patients started lipid-lowering therapy during the study . Grade 3 neutropenia occurred in 3.7 % of patients receiving tocilizumab and none of the patients in the control group , and no grade 4 neutropenia was reported . CONCLUSION Tocilizumab combined with any of the DMARDs evaluated was safe and effective in reducing articular and systemic symptoms in patients with an inadequate response to these agents OBJECTIVE This study , known as STAR ( Safety Trial of Adalimumab in Rheumatoid Arthritis ) , evaluated the safety and efficacy of adalimumab ( Humira ) , a fully human monoclonal tumor necrosis factor-alpha ( TNF-a ) antibody , when given with st and ard antirheumatic therapy in patients with active rheumatoid arthritis ( RA ) not adequately responding to such therapies . St and ard antirheumatic therapy included traditional disease modifying antirheumatic drugs ( DMARD ) , low dose corticosteroids , nonsteroidal antiinflammatory drugs ( NSAID ) , and /or analgesics . METHODS In this 24-week , double-blind , placebo-controlled study , 636 patients with RA were r and omly assigned to receive adalimumab 40 mg subcutaneously ( sc ) every other week ( n = 318 ) or placebo ( n = 318 ) while continuing st and ard antirheumatic therapy . The frequencies of adverse events , serious adverse events , severe or life-threatening adverse events , adverse events leading to withdrawal , infection , or serious infection were the primary endpoints . Secondary endpoints were determined by American College of Rheumatology ( ACR ) response criteria . RESULTS During the study , the majority of patients received concomitant traditional DMARD ( 83.5 % ) and /or corticosteroids , NSAID , and /or analgesics ( 97.3 % ) . Overall , 56.0 % of patients continued treatment with one , 23.6 % with 2 , and 3.9 % with > or = 3 traditional DMARD . At 24 weeks , there were no statistically significant differences between the adalimumab and placebo groups in their respective rates of adverse events ( 86.5 % vs 82.7 % ) , serious adverse events ( 5.3 % vs 6.9 % ) , severe or life-threatening adverse events ( 11.9 % vs 15.4 % ) , or those leading to withdrawal ( 2.8 % vs 2.2 % ) . There were also no statistically significant differences in the rates of infections ( 52.2 % vs 49.4 % ) or serious infections ( 1.3 % vs 1.9 % ) between the groups . The incidence and types of adverse events did not vary between adalimumab- and placebo-treated patients by the number of concomitant traditional DMARD ( 0 , 1 , or 2 ) . Adalimumab-treated patients compared with placebo-treated patients achieved statistically superior ACR20 ( 52.8 % vs 34.9 % ) , ACR50 ( 28.9 % vs 11.3 % ) , and ACR70 ( 14.8 % vs 3.5 % ) response rates at Week 24 ( p < or = 0.001 ) . CONCLUSION This study demonstrated that addition of adalimumab 40 mg given sc every other week to concomitant st and ard antirheumatic therapy is well tolerated and provides significant improvements in signs and symptoms of RA . The data indicate that adalimumab is a safe and effective therapeutic option in patients with active RA who have an inadequate response to st and ard antirheumatic therapy , including one or more traditional DMARD , corticosteroids , NSAID , and analgesics BACKGROUND Present treatment strategies for rheumatoid arthritis include use of disease-modifying antirheumatic drugs , but a minority of patients achieve a good response . We aim ed to test the hypothesis that an improved outcome can be achieved by employing a strategy of intensive outpatient management of patients with rheumatoid arthritis -- for sustained , tight control of disease activity -- compared with routine outpatient care . METHODS We design ed a single-blind , r and omised controlled trial in two teaching hospitals . We screened 183 patients for inclusion . 111 were r and omly allocated either intensive management or routine care . Primary outcome measures were mean fall in disease activity score and proportion of patients with a good response ( defined as a disease activity score < 2.4 and a fall in this score from baseline by > 1.2 ) . Analysis was by intention-to-treat . FINDINGS One patient withdrew after r and omisation and seven dropped out during the study . Mean fall in disease activity score was greater in the intensive group than in the routine group ( -3.5 vs -1.9 , difference 1.6 [ 95 % CI 1.1 - 2.1 ] , p<0.0001 ) . Compared with routine care , patients treated intensively were more likely to have a good response ( definition , 45/55 [ 82 % ] vs 24/55 [ 44 % ] , odds ratio 5.8 [ 95 % CI 2.4 - 13.9 ] , p<0.0001 ) or be in remission ( disease activity score < 1.6 ; 36/55 [ 65 % ] vs 9/55 [ 16 % ] , 9.7 [ 3.9 - 23.9 ] , p<0.0001 ) . Three patients assigned routine care and one allocated intensive management died during the study ; none was judged attributable to treatment . INTERPRETATION A strategy of intensive outpatient management of rheumatoid arthritis substantially improves disease activity , radiographic disease progression , physical function , and quality of life at no additional cost Objectives Evaluate the efficacy of intravenous golimumab 2 mg/kg+methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) receiving MTX . Methods Patients ( n=592 ) with active disease ( ≥6/66 swollen , ≥6/68 tender joints , C-reactive protein ≥1.0 mg/dl , rheumatoid factor positive and /or anticyclic citrullinated protein antibody positive at screening ) despite MTX ( 15–25 mg/week ) participated in this double-blind , placebo-controlled , phase 3 study . Patients were r and omised ( 2:1 ) to receive intravenous golimumab 2 mg/kg , or placebo infusions at weeks 0 and 4 and every ( q ) 8 weeks ; patients continued MTX . Placebo patients with < 10 % improvement in combined swollen/tender joint counts at week 16 could early escape to intravenous golimumab 2 mg/kg . The primary endpoint was week 14 American College of Rheumatology 20 % ( ACR20 ) response . Analyses employed non-responder imputation and last-observation-carried-forward . Results At week 14 , significantly ( p<0.001 ) larger proportions of golimumab+MTX than placebo+MTX patients achieved ACR20 response ( 59 % vs 25 % , respectively ) , a disease activity score of good/moderate ( EULAR ) response ( 81 % vs 40 % ) , and greater median improvement in health assessment question naire scores ( 0.500 vs 0.125 ) . Improvements versus placebo+MTX were observed by week 2 . Similar proportions of patients receiving golimumab+MTX and placebo+MTX , respectively , reported adverse events through week 16 ( 47 % and 44 % ) and week 24 ( 53 % and 49 % ) . Serious adverse events were reported by more golimumab+MTX ( 4.1 % ) than placebo+MTX ( 2 % ) patients at week 24 . Conclusion The addition of intravenous golimumab rapidly and significantly improved signs and symptoms in patients with active RA despite ongoing MTX , in some patients by week 2 Objective : To examine the effect of infliximab plus methotrexate ( MTX ) compared with placebo plus MTX on bone loss in patients with early rheumatoid arthritis ( RA ) in a double-blind r and omised study design . Further , to explore the associations between bone loss and markers of RA disease . Methods : All 20 patients with RA ( 10 patients in each treatment group ) had active , early RA . Bone mineral density ( BMD ) was assessed at the h and , lumbar spine ( L2–4 ) and hip by dual energy x-ray absorptiometry at baseline and 12 months ’ follow-up . Clinical data were collected at regular visits . Results : BMD loss was significantly reduced in the infliximab group compared with the placebo group at the femoral neck ( −0.35 % vs −3.43 % , p = 0.01 ) and total hip ( −0.23 % vs −2.62 % , p = 0.03 ) but not at the h and ( −2.09 % vs −2.82 % , p = 0.82 ) and spine ( −0.75 % vs −1.77 % , p = 0.71 ) . Measures of disease process and joint damage were found to be independently associated with bone loss . Conclusions : This study provides strong evidence of a causal link between inflammation and bone loss in RA . The anti-inflammatory effect of infliximab was potent enough to arrest inflammatory bone loss at the hip but not at the spine and h and |
11,317 | 29,803,711 | Compared with traditional therapy , SLIT add-on therapy was associated with significant improvements in lower and upper airway scores , a higher forced expiratory volume in 1 second , and maximal expiratory flow at 25 % of forced vital capacity , and improved bronchial reactivity .
Drug consumptions were significantly decreased as well .
Airway inflammatory parameters , such as nasal eosinophil infiltration , were markedly improved .
The findings of this study suggested that long-term SLIT add-on therapy is a complementary treatment for adults with asthma in addition to conventional medicine .
It not only reduces symptom scores but also improves lung function and airway inflammation | BACKGROUND Sublingual immunotherapy ( SLIT ) reduces symptom scores and the use of rescue medication in children with allergic asthma , but the effect of SLIT therapy in adult patients has not been reported .
OBJECTIVE To examine the efficacy and adverse effects of SLIT add-on vs conventional medication in adult patients with mild to moderate asthma . | Sublingual immunotherapy is widely recognized as a viable treatment for allergic rhinitis and asthma , but the optimal dosage is still under debate , expecially with modified allergens . We assessed the clinical effects of a monomeric allergoid across 3 different maintenance doses in mite-monosensitized patients with rhinitis and intermittent asthma . Eighty-nine patients allergic to HDM were r and omized to 3 maintenance doses of monomeric allergoid ( Lais ® , Lofarma ) or medications only . All the patients recorded their symptoms and rescue drug consumption in a diary card from November to February . Additionally , nasal eosinophil count , spirometry and methacholine bronchial challenge were performed at the beginning of the study and after 3 years . The symptom scores showed a clear improvement in all the three active arms versus baseline and versus the controls , irrespective of the dose . Likewise , a similar improvement versus baseline was seen for nasal inflammation and bronchial hyperreactivity . The SLIT with monomeric allergoids produces clinical ly significant results across a wide range of doses . The absence of significant side effects , even at high doses , is probably due to their low level of allergenicity IMPORTANCE The house dust mite ( HDM ) sublingual allergen immunotherapy ( SLIT ) tablet is a potential novel treatment option for HDM allergy-related asthma . OBJECTIVES To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid ( ICS ) reduction period . DESIGN , SETTING S , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites . The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products , and with HDM allergy-related rhinitis . Key exclusion criteria were FEV1 less than 70 % of predicted value or hospitalization due to asthma within 3 months before r and omization . Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50 % for 3 months and then completely withdrawn for 3 months . INTERVENTIONS 1:1:1 r and omization to once-daily treatment with placebo ( n = 277 ) or HDM SLIT tablet ( dosage groups : 6 SQ-HDM [ n = 275 ] or 12 SQ-HDM [ n = 282 ] ) in addition to ICS and the short-acting β2-agonist salbutamol . MAIN OUTCOMES AND MEASURES Primary outcome was time to first moderate or severe asthma exacerbation during the ICS reduction period . Secondary outcomes were deterioration in asthma symptoms , change in allergen-specific immunoglobulin G4 ( IgG4 ) , change in asthma control or asthma quality -of-life question naires , and adverse events . RESULTS Among 834 r and omized patients ( mean age , 33 years [ range , 17 - 83 ] ; women , 48 % ) , 693 completed the study . The 6 SQ-HDM and 12 SQ-HDM doses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo ( hazard ratio [ HR ] : 0.72 [ 95 % CI , 0.52 - 0.99 ] for the 6 SQ-HDM group , P = .045 , and 0.69 [ 95 % CI , 0.50 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) . The absolute risk differences based on the observed data ( full analysis set ) in the active groups vs the placebo group were 0.09 ( 95 % CI , 0.01 - 0.15 ) for the 6 SQ-HDM group and 0.10 ( 95 % CI , 0.02 - 0.16 ) for the 12 SQ-HDM group . There was no significant difference between the 2 active groups . Compared with placebo , there was a reduced risk of an exacerbation with deterioration in asthma symptoms ( HR , 0.72 [ 95 % CI , 0.49 - 1.02 ] for the 6 SQ-HDM group , P = .11 , and 0.64 [ 95 % CI , 0.42 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) and a significant increase in allergen-specific IgG4 . However , there was no significant difference for change in asthma control question naire or asthma quality -of-life question naire for either dose . There were no reports of severe systemic allergic reactions . The most frequent adverse events were mild to moderate oral pruritus ( 13 % for the 6 SQ-HDM group , 20 % for the 12 SQ-HDM group , and 3 % for the placebo group ) , mouth edema , and throat irritation . CONCLUSIONS AND RELEVANCE Among adults with HDM allergy-related asthma not well controlled by ICS , the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction , with an estimated absolute reduction at 6 months of 9 to 10 percentage points ; the reduction was primarily due to an effect on moderate exacerbations . Treatment-related adverse events were common at both active doses . Further studies are needed to assess long-term efficacy and safety . TRIAL REGISTRATION clinical trialsregister.eu Identifier : 2010 - 018621 - 19 Sublingual immunotherapy ( SLIT ) with monomeric carbamylated allergoid administered in accordance with the st and ard regimen has proven to be effective and safe . Achieving clinical benefit , however , requires a lengthy period of time so it is not very suitable for short-lasting allergies . We thus performed this study to compare an administration protocol starting in the coseasonal period ( with a 4-day build-up phase ) with a precoseasonal scheme to verify if the former regimen provides the same benefit in a shorter period of time . The prospect i ve , r and omized , drug therapy-controlled study was conducted in 33 rhinitic patients monosensitized to Olea with or without asthma . Ten patients were assigned to the coseasonal therapy with 5000 allergic units (AU)/week for 6 weeks , 11 to the precoseasonal therapy with 3000 AU/week for 10 weeks , and 12 to drug therapy . They were treated from April or May to June 2008 . A visual analog scale ( VAS ) was performed at baseline and after treatment to assess the well being of the patients . Drug consumption was evaluated by means of a monthly diary . There was greater VAS improvement in both the SLIT groups versus the controls , but it was statistically significant only in the coseasonal group ( p < 0.01 ) . Furthermore , there was a reduction in the rescue medication only in the coseasonal SLIT ( p < 0.05 versus drug therapy ) . One mild adverse event was observed . The allergoid SLIT was shown to be effective and safe in Olea allergy in particular when a coseasonal regimen was used Sublingual immunotherapy with monomeric allergoid ( allergoid SLIT ) , given according to the st and ard scheme , has proved effective and safe in many clinical trials . However , its build-up phase requires a long time ranging from 16 days to 14 weeks . This study therefore investigated whether , with a four-day up-dosing , the same benefit could be achieved in a shorter time . Thirty rhinitic and /or asthmatic patients ( 16 M and 14 F , mean age 36±8.2 years ) allergic to house dust mites ( HDM ) with or without other sensitizations were r and omized to allergoid SLIT or st and ard drug therapy . The build-up phase lasted four days . The first day the patients took a 300 AU tablet , the second day two 300 AU tablets , the third day three 300 AU tablets and the fourth day four 300 AU tablets . The total amount taken during the up-dosing was 3000 AU . Patients were then treated for 12 months at the dosage of 2000 AU/week ( total amount of allergen : 104,000 AU/year ) . The symptom score and drug consumption were recorded from November to February on monthly diary cards . At baseline and after 12 months a Visual Analogue Scale ( VAS ) was used to rate the patients ' well-being . Skin prick test reactivity was evaluated before and after the 12-month treatment in both groups using 10 mg/mL histamine as reference . VAS scores rose significantly ( about 45 % ) in both groups in comparison to baseline ( p=0.001 ) . In addition , there was a significantly greater reduction of the global symptoms score ( about 52 % ) - but not in drug consumption - in the SLIT group in comparison to controls ( p=0.0004 ) . The SLIT group showed a highly significant reduction ( about 39 % ) in skin prick test reactivity ( p=0.000003 ) while the control group remained unchanged ( p=0.5226 ) . No severe adverse events were observed . Even with this short four-day up-dosing , the allergoid SLIT proves to be safe . In addition , it is already effective in patients allergic to HDM after 12 months , and significantly reduces allergen-specific skin reactivity BACKGROUND Few studies have compared the effects of immunotherapy and inhaled steroids . The main limitation of such studies is the long duration required to fully appreciate the effects of immunotherapy . OBJECTIVE To compare the effects of inhaled budesonide and sublingual immunotherapy ( SLIT ) in mild persistent asthma for up to 5 years . METHODS Patients with mild persistent asthma and rhinitis due to grass pollen were enrolled in an open r and omized controlled trial . After a run-in season , they were r and omized to either budesonide , 800 microg/d , in the pollen season or continuous grass SLIT for 5 years . All patients received rescue medications . Symptoms were evaluated by diary cards filled out from May to July at baseline and after 3 and 5 years . In-season nasal eosinophils and bronchial hyperresponsiveness were also assessed . RESULTS Fifty-one patients were enrolled and 46 completed the study . The bronchial symptom scores and the use of bronchodilators decreased significantly in both groups , but the improvement was greater in the SLIT patients at 3 and 5 years . The nasal symptom score and the intake of nasal steroids decreased only in the SLIT group , and the difference vs the budesonide group was always significant . In the SLIT group vs the budesonide group , a statistically significant decrease of nasal eosinophils was found at 3 and 5 years ( P < .01 ) . The bronchial hyperresponsiveness improved significantly only in the SLIT group . CONCLUSION In patients with grass pollen-induced asthma , in the long term SLIT was equally effective as inhaled budesonide in treating bronchial symptoms and provided an additional benefit in treating rhinitis symptoms and bronchial hyperresponsiveness RATIONALE Heterogeneity in asthma expression is multidimensional , including variability in clinical , physiologic , and pathologic parameters . Classification requires consideration of these disparate domains in a unified model . OBJECTIVES To explore the application of a multivariate mathematical technique , k-means cluster analysis , for identifying distinct phenotypic groups . METHODS We performed k-means cluster analysis in three independent asthma population s. Clusters of a population managed in primary care ( n = 184 ) with predominantly mild to moderate disease , were compared with a refractory asthma population managed in secondary care ( n = 187 ) . We then compared differences in asthma outcomes ( exacerbation frequency and change in corticosteroid dose at 12 mo ) between clusters in a third population of 68 subjects with predominantly refractory asthma , clustered at entry into a r and omized trial comparing a strategy of minimizing eosinophilic inflammation ( inflammation-guided strategy ) with st and ard care . MEASUREMENTS AND MAIN RESULTS Two clusters ( early-onset atopic and obese , noneosinophilic ) were common to both asthma population s. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation ( early-onset symptom predominant and late-onset inflammation predominant ) were specific to refractory asthma . Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster ( 3.53 [ SD , 1.18 ] vs. 0.38 [ SD , 0.13 ] exacerbation/patient/yr , P = 0.002 ) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster ( mean difference , 1,829 mug beclomethasone equivalent/d [ 95 % confidence interval , 307 - 3,349 mug ] ; P = 0.02 ) . CONCLUSIONS Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms BACKGROUND No studies have directly compared the effects of immunotherapy and antileukotrienes due to the long time required to appreciate the clinical effects of immunotherapy . We compared the effect of montelukast ( MK ) and SLIT added to st and ard therapy in moderate asthma over 5 years . METHODS Open r and omized controlled trial . Patients with moderate asthma ( and rhinitis ) solely due to birch pollen were r and omized to receive either MK ( 10 mg/d ) or birch sublingual immunotherapy ( SLIT ) in the pollen seasons , in addition to formoterol/fluticasone . All the patients also received salbutamol and cetirizine as rescue medications . Asthma and rhinitis symptoms were recorded on diary cards from February to May at baseline and after 3 and 5 years of study . In-season nasal eosinophils and bronchial hyperresponsiveness were also evaluated . RESULTS Thirty-three adult patients were enrolled and 29 completed the study . The groups were homogeneous at baseline . Bronchial and nasal symptom scores were lower at 3 and 5 years compared to baseline in the SLIT group . Bronchial hyperresponsiveness and bronchodilator use decreased significantly in both groups at 5 years , but only in the SLIT group at 3 years . In the SLIT group there was a significant decrease in nasal eosinophils compared to baseline and to the MK group . CONCLUSION In patients with birch pollen-induced moderate asthma and rhinitis , the addition of SLIT provides a greater clinical benefit than that of MK BACKGROUND Sublingual immunotherapy ( SLIT ) has been proved effective in allergic rhinitis , but there are few studies assessing its effects on inflammation and on the lower airways . OBJECTIVE We sought to evaluate at the same time the effects of SLIT on rhinitis symptoms , nasal inflammation , and lower airways function in patients with birch pollinosis . METHODS Adult patients with rhinitis and asthma monosensitized to birch were evaluated during a run-in pollen season and then r and omized to receive openly either drugs alone or drugs plus SLIT and reevaluated in the subsequent 4 pollen seasons . Rhinitis symptoms and consumption of bronchodilators were assessed by means of diary card . A nasal smear for eosinophil count was carried out in and out of pollen seasons , and pulmonary function tests with methacholine challenge were performed at each season . RESULTS Of 79 enrolled patients , 27 dropped out , with a significantly higher rate of dropouts in the control group . There was a decrease in symptoms and bronchodilator use in the SLIT group versus the control group , becoming significant at the second and third pollen seasons , respectively ( P < .01 at all times ) . Nasal eosinophils decreased significantly in the active group , starting from the third pollen season ( P < .01 ) . In the SLIT group a significant increase in FEV 1 , specific airways conductance , and maximal expiratory flow at 25 % of forced vital capacity was seen starting from the second year and was associated with an increase in the methacholine threshold dose ( P < .01 ) . The differences were significant also at the intragroup comparison over time . CONCLUSION SLIT achieved a significant clinical benefit in birch pollinosis , reduced the eosinophil infiltration in nasal mucosa , and significantly improved pulmonary function during the pollen seasons Background Sublingual immunotherapy ( SLIT ) is recommended for allergic diseases . However , clinical studies containing evidence -based data of this treatment in young children , which is rarely reported in the literature , are needed . This study was design ed to assess the efficacy and safety of SLIT in children , including very young children . Methods Two hundred sixty-four children aged 3–13 years old ( 133 children , 3–5 years old ) with Dermatophagoides farinae – induced allergic rhinitis with or without asthma treated by st and ard pharmacotherapy had r and omly received either SLIT ( SLIT group ) or no SLIT ( control group ) for 12 months . Symptoms , medications , visual analog scale ( VAS ) and presence of adverse events ( AEs ) were assessed at monthly visits . Skin-prick test and Dermatophagoides farinae – specific IgE and IgG4 were measured before and after treatment . Results Both treatments were effective in the global clinical scores during the first seven visits when compared with baseline ( all , p < 0.01 ) , and SLIT showed lower symptoms scores and VAS scores throughout this period ( all , p < 0.01 ) . These improvements continued until the later visits only in the SLIT group . Also , the asthma medication consumption was decreased by SLIT treatment only at the end of study ( p < 0.01 ) . The specific IgG4 was significantly increased after SLIT treatment when compared with the control group , but no significant change of specific IgE was observed in either groups . In the SLIT group , there was no significant difference between children less than or more than 5 year old in terms clinical efficacy , onset of action , immunologic parameters , and safety . No severe systemic AEs were reported . Conclusion SLIT is effective and well-tolerated in children with allergic rhinitis 3–13 years old OBJECTIVE To evaluate the efficacy and safety of the sublingual immunotherapy with Dermatophagoides fannie drops on children with allergic rhinitis of different age groups ( 4 - 5 years old group and 11 - 12 years old group ) . METHODS Sixty-two children aged 4 - 5 years , and 71 children aged 11 - 12 years , who suffered from dust mite induced allergic rhinitis , was r and omly divided into the sublingual immunotherapy ( SLIT ) + drug group and drug group . SLIT + drug group was treated with a st and ardized sublingual immunotherapy drops of Dermatophagoides fannie and combined with symptomatic therapy , drug group was treated with mometasone furoate nasal spray and desloratadine tablets as symptomatic treatment . These children were followed up for 2 years with one visit in every 3 months , then visited at the end of the study and 2-years after the treatment ended . Symptom scores and medication scores were recorded at each visit . Comprehensive evaluation of symptoms , medication , and patients ' degree of satisfaction were used . RESULTS Two years after SLIT finished , symptom scores ( SLIT + drug group : 1.13 ± 1.05 ; drug group : 4.68 ± 3.09 ) , medication scores ( SLIT + drug group : 0.07 ± 0.04 ; drug group : 0.36 ± 0.25 ) of SLIT + drug group were significantly lower than those in drug group ( t value were -8.43 , -8.87 , respectively , all P < 0.01 ) . Also , the subjective assessment of patients ' symptoms , medication , and treatment satisfaction in SLIT + drug group was significantly lower than those in drug group . Subjective assessment symptoms , medication , and treatment satisfaction in age group 4 - 5 was the same as in age group 11 - 12 . After SLIT ended for 2 years , subjective assessment and treatment satisfaction in age 11 - 12 group was better than those in age 4 - 5 group in medication score . CONCLUSIONS SLIT demonstrated clinical improvement in children of different ages during 2 years treatment . Two years after withdrawal , the symptom scores , medication score and subjective satisfaction in 11 years old group are better than those in 4 - 5 years old group BACKGROUND Sublingual-specific immunotherapy ( SLIT ) is considered as a valid treatment of respiratory allergies . AIM We performed a case-control study to evaluate the effect of SLIT in children with allergic asthma and rhinitis . PATIENTS AND METHODS The study plan included 140 patients ( age 6 - 14 yr , 43 % girls and 57 % boys ) presenting allergic rhinitis and /or asthma , 70 treated with SLIT actively for three years and 70 controls never treated with specific immunotherapy ( only symptomatic drugs ) . Rhinitis Symptom Score ( RSS ) , Asthma Symptom Score ( ASS ) and Medication Score ( MS ) were evaluated at beginning and during the 3 years of immunotherapy . results : There was a significant improvement of RSS ( mean ± SD ) in the SLIT group : baseline 5.31 ± 2.01 , third year 1.38 ± 1.06 ( p < 0.0001 vs baseline ) . CONTROL GROUP baseline 5.00 ± 1.08 , third year 4.68 ± 1.152 ( P ¼ NS ) . ASS ( mean ± SD ) in the SLIT group : baseline 4.09 ± 2.21 , third year 1.23 ± 1.4 ( p < 0.0001 vs baseline ) . CONTROL GROUP baseline 4.04 ± 2.46 , third year 3.62 ± 2.26 ( p ¼ NS ) . MS ( mean ± SD ) in the SLIT group : baseline 3.30 ± 1.4 , third year 0.88 ± 1.26 ( p < 0.0001 vs baseline ) . CONTROL GROUP baseline 3.19 ± 1.23 , third year 3.39 ± 1.12 ( p ¼ NS ) . There are no statistically significant differences among monosensitized/polysensitized patients and at different age ranges . None of the patients included reported severe systemic reactions or anaphylaxis . CONCLUSIONS During the treatment , the active group showed sustained reductions in mean asthma and rhinitis symptom scores when compared with controls to confirm the efficacy and safety of sublingual immunotherapy BACKGROUND Sublingual immunotherapy ( SLIT ) has proven efficacy in treating respiratory allergy . OBJECTIVE To compare the clinical and functional effects and the effect on nasal eosinophils of SLIT with either single or combination allergens . METHODS We performed an open-labeled , controlled , 4 parallel-group r and omized study with 58 patients sensitized to birch and grasses only who had rhinitis and bronchial hyperreactivity in both pollen seasons . Patients were recruited for the study from January 1 , 1999 , to June 30 , 2001 . The patients received SLIT for birch , SLIT for grass , SLIT for birch and grass , or drugs only . Symptom and medication scores , forced expiratory volume in 1 second , bronchial hyperreactivity , and nasal eosinophil counts were evaluated in both pollen seasons at baseline and after 2 and 4 years . RESULTS Ten patients dropped out and 48 completed the study . No change in all the considered parameters vs baseline was seen in patients treated with drugs only . Those patients receiving SLIT for grass or birch had a significant clinical improvement and nasal eosinophil reduction vs baseline and vs patients who did not receive SLIT in the target season ( P < .01 ) but also in the unrelated pollen season ( P < .05 ) . The patients receiving SLIT for grass and birch improved as well , and their improvement in clinical symptoms and inflammation was significantly greater than in patients treated with SLIT for the single allergens . Minor changes were seen in the forced expiratory volume in 1 second , since it remained within the reference range in the whole population . CONCLUSION In patients sensitized to grass and birch , SLIT with the 2 allergens provided the best clinical results . Nevertheless , SLIT with birch only or grass only also provided a measurable improvement in the grass season and birch season , respectively BACKGROUND Sublingual immunotherapy ( SLIT ) with monomeric allergoid , given according to the st and ard scheme , result ed effective and safe . However , the achievement of a clinical benefit requires a long time . We thus performed this study using an administration protocol starting in the co-seasonal period with a 3-day build-up phase and lasting only 6 months , in order to obtain the above benefit in a shorter time . METHODS AND RESULTS The study , prospect i ve , r and omised and controlled versus drug therapy , was conducted on 65 rhinitic and /or asthmatic patients allergic to Parietaria with or without other sensitisations . Twenty-four were allocated to 1,000 AU/week , 21 to 3,000 AU/week and 21 to drug therapy . They were treated from April to September 2006 . At baseline , 3 and 6 months a Visual Analogue Scale ( VAS ) was performed to assess the patients ' well-being . Drug consumption was evaluated by means of monthly diary cards . Bronchial reactivity was investigated at baseline and 6 months by methacholine challenge test . There was a greater VAS improvement in both the SLIT groups than in the controls after 6 months ( p<0.05 ) . In patients taking 3,000 AU/week this was already evident after 3 months . There was a significant reduction in rescue medication consumption between 3 and 6 months ( p<0.05 ) in all three groups . The bronchial reactivity was reduced only in the SLIT groups ( p<0.001 ) . No adverse events were observed . CONCLUSIONS At 6 months the allergoid SLIT showed itself to be effective and safe . In addition the subjective clinical benefit was obtained in a more rapid period , i.e. 3 instead of 6 months , when a higher maintenance dose was administered BACKGROUND Based on experimental results , the sublingual route for immunotherapy ( IT ) has been accepted as a viable alternative to the injection route , but few data on the effects on asthma are so far available . OBJECTIVE In the present open controlled trial we evaluated whether a preseasonal IT with grass polllen in orosoluble tablets added to pharmacotherapy , can improve non-specific bronchial hyperreactivity . The clinical efficacy was evaluated as well . METHODS Fifty-one patients ( mean age 27.4 years ) suffering from rhinoconjunctivitis and /or mild-intermittent/mild-persistent asthma due to grass pollen were allocated to two groups receiving pharmacotherapy alone ( n = 25 ) or pharmacotherapy plus IT in tablets ( n = 26 ) . A methacholine test was performed in asthmatic subjects out of the pollen seasons at baseline and after 3 years of treatment . Symptom scores and drug intake were evaluated during pollen seasons by a diary card . RESULTS A significant increase p = .01 ) in the PD20 at the methacholine test was observed in the IT group compared to the control group . A significant clinical improvement both for rhinitis ( p = .001 ) and asthma ( p = .001 ) was observed in the IT group , and this improvement was paralleled by a clear-cut reduction of drug intake ( p = .001 ) . An improvement of rhinitis symptoms without modification of drug intake was seen in the control group ( p = .01 ) The treatment was well tolerated and no relevant side effect was reported during the 3 years . CONCLUSION The investigated local IT reduced the nonspecific bronchial hyperreactivity . Furthermore , it was clinical ly effective and safe BACKGROUND Sublingual immunotherapy ( SLIT ) with monomeric carbamylated allergoid proved to be well tolerated , safe and effective in patients with respiratory allergy . St and ard administration regimens are expected to require a long time before clinical benefit can be appreciated . We investigated whether pre-seasonal and perennial regimens differently affect the clinical efficacy of grass pollen SLIT . METHODS Adult patients with allergic rhino-conjunctivitis with/without mild intermittent asthma due to grass pollen were included into this open prospect i ve study and r and omised to receive SLIT with a continuous regimen ( Group 1 : 1,000 AU/week for the entire study period ) or a pre-seasonal regimen ( Group 2 : 5,000 AU/week for 10 weeks/year for 2 years ) , or on dem and drug therapy alone ( Group 3 ) for two years . At entry ( November 2005 ) , at the end of the first and second pollen season , a Visual Analogue Scale ( VAS ) was used to assess patients ' well-being . Symptom score and drug consumption were evaluated during the seasons . Methacholine challenge was performed at study entry and conclusion . Adverse events were recorded along the whole study duration . RESULTS Thirty-two patients were divided into Group 1 ( n = 10 ) , Group 2 ( n = 11 ) and Group 3 ( n = 11 ) . A significant VAS improvement was observed in both SLIT groups , after the first and second pollen season , compared to baseline and to Group 3 ( p < 0.05 ) . Less symptoms and need for medications result ed during the second season ( p < 0.05 ) . No relevant variations in bronchial hyper-reactivity have been observed between the three groups . Only 2 patients experienced local or mild reactions in SLIT groups . CONCLUSION Both pre-seasonal and continuous regimen of SLIT with monomeric allergoid turned out effective and safe , suggesting that a pre-seasonal course with 5,000 AU/week for 10 weeks may represent a convenient option in patients with grass pollen allergic rhinitis with/without mild intermittent asthma . Further research is urgently needed to consoli date these preliminary evidence BACKGROUND The efficacy and safety of sublingual immunotherapy with carbamylated allergoid ( allergoid SLIT ) is well recognised . Yet , few data concerning its antiinflammatory effects on the respiratory airways are so far available . Thus we decided to evaluate whether it can reduce the allergic inflammation and improve the clinical symptoms in comparison to pharmacotherapy . METHODS The study was perspective , controlled and r and omised . It was conducted on 56 patients allergic to House Dust Mite with ( n=36 ) or without Parietaria . Thirty-three of them were allocated to SLIT ( 22 M , 11 F mean age 15 years ) and 22 ( 13 M , 10 F , mean age 21 years ) to pharmacotherapy They were followed-up for 1 year . Symptoms and drugs consumption were assessed by monthly diary cards . Bronchial reactivity was investigated at baseline and after a 12-month treatment , through a methacholine ( MCh ) test . An evaluation of the nasal eosinophils was also performed at the same times . RESULTS There was a greater reduction of the mean symptom score ( p < 0.01 ) and drug consumption ( p < 0.001 ) in the SLIT than in the control group . MCh PD20 increased only in the SLIT group ( p < 0.0005 ) The reduction of nasal eosinophils was statistically greater ( p < 0.05 ) only in the SLIT group . CONCLUSIONS A 1-year SLIT reduces the allergic symptoms and the respiratory airways inflammation more than pharmacotherapy Background : Some aspects of sublingual immunotherapy ( SLIT ) still need to be addressed : magnitude of the clinical efficacy , effect on the bronchial hyperreactivity adherence to treatment , preventive effect . We attempted to clarify these points in a r and omized open , controlled , two parallel group study in a real‐life setting The aim of this study was to assess the efficacy and safety of sublingual immunotherapy ( SLIT ) in a Clinical Practice Improvement ( CPI ) program carried out in allergology . The study was conducted between 1992 and 2001 using an observational type methodology in line with st and ard clinical practice . The program consisted of 4 basic steps : setting up of a decision-making tree ; st and ardization of main diagnostic and therapeutic aspects ; data collection ; definition and evaluation of main clinical endpoints . Study patients were screened among 1508 patients with pollen and /or dust mite respiratory allergy , 350 of which , one year after having experienced a pharmacological treatment failure , were administered immunotherapy by injection ( n = 111 ) or alternative route ( n = 239 ) . For each one of the three immunotherapy treatment groups ( nasal , SLIT or injective ) there was a control group of patients who , despite their poor response to pharmacological treatment , continued with pharmacological therapy alone ( n = 314 in total ; 68 , 192 and 54 respectively ) . The observation of 130 SLIT patients , 106 of which were treated for at least 36 months , towards the control group evidence d that such therapy , apart from result ing efficient and particularly safe , has an unfailing protective effect against the development of asthma and new allergic sensitizations BACKGROUND Investigations meeting current st and ards are limited for the effect of house dust mite ( HDM ) allergy immunotherapy in asthmatic patients . OBJECTIVE This trial investigated the efficacy and safety of a st and ardized quality ( SQ ; allergen st and ardization method proprietary to the trial sponsor ) HDM SLIT-tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease . This publication reports the results of the endpoints related to asthma . METHODS Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were r and omized 1:1:1:1 to double-blind daily treatment with one of 3 active doses ( 1 , 3 , or 6 SQ-HDM ) or placebo . Their use of inhaled corticosteroid ( ICS ) was st and ardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control . The primary end point was a reduction in ICS dose from the individual subject 's baseline dose after 1 year of treatment . RESULTS The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg ( P = .004 ) . Relative mean and median reductions were 42 % and 50 % for 6 SQ-HDM and 15 % and 25 % for placebo , respectively . No statistically significant differences were observed for the other assessed asthma parameters , reflecting the intended controlled status of the trial subjects . The most common adverse events were local reactions in the mouth . The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo . CONCLUSION Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control . All active doses were well tolerated The efficacy and safety of sublingual immunotherapy in house dust mite – induced asthma have yet to be firmly established . We report the results of a double‐blind , placebo‐controlled , r and omized clinical trial performed in mainl and China |
11,318 | 28,614,246 | Conclusion : The low expression of nm23-H1 is associated with poorer prognosis in patients with NPC , suggesting that it is a prognostic factor and potential biomarker for survival in NPC | Background : Developing a new reliable prognostic marker to predict the prognosis and supply better and more suitable therapy for patients with nasopharyngeal carcinoma ( NPC ) is urgent .
Therefore , we performed this systematic review of the literature with meta- analysis to clarify and explore the associate expression of nm23-H1 with prognosis of NPC patients . | Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items OBJECTIVE To investigate the relationship between the expressions of KAI1 , nm23 , ETS-1 , vascular endothelial growth factor ( VEGF ) and microvascular density ( MVD ) and lymph node metastasis and prognosis in nasopharyngeal carcinoma ( NPC ) . METHODS The Envision immunohistochemical method was used to detect the expressions of KAI1 , nm23 , ETS-1 and VEGF in 50 cases of non-keratinizing carcinoma ( NKC ) with cervical lymph node metastasis , 30 cases of NKC without cervical lymph node metastasis at the primary diagnoses and 30 cases of non-tumor nasopharyngeal tissues ( NP ) . The microvascular density was counted by immunostaining with CD34 . RESULTS ( 1 ) The expression rates of KAI1 and nm23 protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively , the difference being significant ( P < 0.05 ) ; The expression rates of ETS-1 and VEGF protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively , the difference being significant ( P < 0.05 ) . ( 2 ) In 80 NKC cases , the MVD was respectively lower in KAI1 and nm23 protein positive groups than those in the negative groups ( P < 0.05 ) ; the MVD was respectively higher in ETS-1 and VEGF protein positive groups than those in the negative groups ( P < 0.05 ) . ( 3 ) There was significant difference between the MVD , the number of NKC without cervical lymph node metastasis cases in the single expression of KAI1 or nm23 protein and in common expression of KAI1 and nm23 protein ( P < 0.05 ) , in the same as between the single expression of ETS-1 or VEGF protein and in common expressions of ETS-1 and VEGF protein ( P < 0.05 ) . ( 4 ) There was positive correlation between the expressions of KAI1 and nm23 protein ( P < 0.01 ) , as well as between the expressions of ETS-1 and VEGF protein ( P < 0.01 ) . ( 5 ) the 5-year survival rates of the patients correlated with cervical lymph node metastasis and the expressions of KAI1 , nm23 , ETS-1 and VEGF proteins in NKC ( P < 0.05 ) . CONCLUSIONS The expressions of KAI1 , nm23 , ETS-1 and VEGF proteins were highly related to MVD in NPC , cervical lymph node metastasis and prognosis . They might be considered to be reference indicator for evaluating the cervical lymph node metastasis and prognosis of NPC BACKGROUND Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy ( CRT ) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998 . However , the outcome for the radiotherapy-alone ( RT ) group in that trial was substantially poorer than those in other trials , and there were no data on late toxicities . Verification of the long-term therapeutic index of this regimen is needed . METHODS Patients with nonkeratinizing nasopharyngeal carcinoma staged T1 - 4N2 - 3M0 were r and omly assigned to RT ( 176 patients ) or to CRT ( 172 patients ) using cisplatin ( 100 mg/m(2 ) ) every 3 weeks for three cycles in concurrence with radiotherapy , followed by cisplatin ( 80 mg/m(2 ) ) plus fluorouracil ( 1000 mg per m(2 ) per day for 4 days ) every 4 weeks for three cycles . Primary endpoints included overall failure-free rate ( FFR ) ( the time to first failure at any site ) and progression-free survival . Secondary endpoints included overall survival , locoregional FFR , distant FFR , and acute and late toxicity rates . All statistical tests were two-sided . RESULTS The two treatment groups were well balanced in all patient characteristics , tumor factors , and radiotherapy parameters . Adding chemotherapy statistically significantly improved the 5-year FFR ( CRT vs RT : 67 % vs 55 % ; P = .014 ) and 5-year progression-free survival ( CRT vs RT : 62 % vs 53 % ; P = .035 ) . Cumulative incidence of acute toxicity increased with chemotherapy by 30 % ( CRT vs RT : 83 % vs 53 % ; P < .001 ) , but the 5-year late toxicity rate did not increase statistically significantly ( CRT vs RT : 30 % vs 24 % ; P = .30 ) . Deaths because of disease progression were reduced statistically significantly by 14 % ( CRT vs RT : 38 % vs 24 % ; P = .008 ) , but 5-year overall survival was similar ( CRT vs RT : 68 % vs 64 % ; P = .22 ; hazard ratio of CRT = 0.81 , 95 % confidence interval = 0.58 to 1.13 ) because deaths due to toxicity or incidental causes increased by 7 % ( CRT vs RT : 1.7 % vs 0 , and 8.1 % vs 3.4 % , respectively ; P = .015 ) . CONCLUSIONS Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone . Although there was no statistically significant increase in major late toxicity , increase in noncancer deaths narrowed the result ant gain in overall survival OBJECTIVE To investigate the expressions of E-cadherin , CD44H , matrix metalloproteinase-3 ( MMP-3 ) , nm23H1 and vascular endothelial growth factor ( VEGF ) in nasopharyngeal carcinoma and its relationship to the effect of radiotherapy . Furthermore , to analyze the predict value of radiotherapy effect . METHODS The expressions of E-cadherin , CD44H , MMP-3 , nm23H1 and VEGF in 62 patients with nasopharyngeal carcinoma were determined by immunohistochemical SP method . There were 62 patients ( 17 to 70 years old ) with nasopharyngeal carcinoma which were treated by radiotherapy from March 1995 to October 1995 and the period of follow-up had full 10 years . RESULTS The expressions of CD44H ( chi2 = 18.739 , P = 0.028 ) and VEGF ( chi2 = 18.523 , P = 0.030 ) were closely related with short-term effect after radiotherapy in nasopharyngeal carcinoma . The short-term effect was descent along with enhancement of their expressions . In the group of low expressions in CD44H and nm23H1 , 3-year overall survival rate were 65.5 % and 45.5 % , and 5-year overall survival rate were 47.3 % and 22.7 % . In the group of high expressions in CD44H and nm23H1 , 3-year overall survival rate were 54.6 % and 75.9 % , and 5-year overall survival rate were 27.8 % and 53.2 % . There were respectively significant difference between two group of expressions in CD44H ( chi2 = 7.31 , P = 0.0069 ) and nm23H1 ( chi2 = 15.64 , P = 0.0001 ) . CONCLUSIONS These findings indicated that to detect the expressions of CD44H and VEGF gene may predict short-term effect of radiotherapy . Furthermore , to detect the expressions of CD44H and nm23H1 gene may predict long-term effect of radiotherapy in nasopharyngeal carcinoma Due to its anatomical location and high radiosensitivity , the mainstay treatment for primary nasopharyngeal carcinoma ( NPC ) is radiotherapy ( RT ) . For patients presenting with early UICC stages I and IIA disease , RT alone achieves overall survival figures of 90 % and 84 % respectively [ 1 ] . With the use of intensitymodulated radiotherapy ( IMRT ) the local control rates have further improved and rates of xerostomia reduced through sparing of the parotid gl and s [ 2,3 ] . Over 60 % of patients with NPC present with locoregionally intermediate to advanced UICC stages IIB−IV disease . With local control increasingly achievable using IMRT , the predominant site of failure is distant metastases . Since NPC is also highly chemosensitive , combining chemotherapy with primary RT has been extensively studied in the past two decades . While the number of stage IIB patients included in prospect i ve clinical trials have been limited [ 4,5 ] , this group of patients are at increased risk of developing distant metastases and are therefore recommended to be treated with concurrent chemotherapy radiotherapy ( CRT ) , which is the st and ard treatment for stages III and IV NPC [ 6 ] . Meta- analysis of prospect i ve r and omised trials demonstrated that concurrent CRT improved both progression-free survival ( HR 0.63 ) and overall survival ( HR 0.60 ) [ 7 ] . In North America , the st and ard CRT regimen is cisplatin 100mg/m2 on days 1 , 22 , and 43 , concurrent with RT followed by adjuvant cisplatin 80mg/m2 D1 and 5-fluorouracil 1000mg/m2 D1−4 for three cycles [ 8 ] . In Asia , weekly cisplatin 40mg/m2 for 6−8 weeks concurrent with RT has been reported to improve five-year overall survival with good tolerability [ 9 ] . R and omised studies of adjuvant chemotherapy after RT alone have all been negative and tolerance of adjuvant chemotherapy after CRT is difficult , especially in patients whose nutritional status is not optimal [ 10 ] . R and omised trials of neoadjuvant chemotherapy followed by RT alone have demonstrated improvement in disease-free survival but not overall survival [ 11,12 ] . Single-arm phase 2 studies have demonstrated encouraging results using sequential neoadjuvant and CRT [ 13,14 ] and a r and omised phase 2 trial of neoadjuvant docetaxel/cisplatin followed by cisplatin/RT versus cisplatin/RT reported good tolerability and survival improvement [ 15 ] . At least five ongoing international and national studies are study ing this strategy and the role of neoadjuvant chemotherapy will be better defined in the near future . In distant metastatic disease , the best outcome has been achieved with an aggressive multi-disciplinary approach in patients with lung metastases only [ 16 ] . Doublet platinum-based chemotherapy is the st and ard first-line systemic treatment achieving high response rates of 60−80 % ; however , the median survival remains around 12−20 months . Clinical benefit has been demonstrated using cetuximab , the monoclonal antibody against epidermal growth factor receptor in combination with carboplatin in platinum-refractory metastatic NPC [ 17 ] . Trials are ongoing combining cetuximab with CRT in locoregionally advanced NPC . Other targeted therapies being investigated include bevacizumab , multitargeted anti-angiogenic agents , AKT inhibitors as well as epigenetic therapies [ 18 ] . Epstein – Barr virus ( EBV ) is universally associated with endemic undifferentiated NPC . Quantitative plasma EBV DNA using real-time polymerase chain reaction technique has a sensitivity and specificity of 96 % and 93 % respectively [ 19 ] . Pre and posttreatment EBV DNA are highly prognostic and may be useful for guiding therapy [ 20–22 ] . Immunotherapeutic approaches targeting EBV antigens in NPC cells are under investigation . Adoptive transfer of cytotoxic lymphocytes , pulsing dendritic cells with LMP-2 peptides and recombinant Modified Vaccinia Ankara vaccine encoding EBV antigens have been reported with promising results [ 23 ] . In conclusion , IMRT has been established as the st and ard technique for NPC , and concurrent cisplatin RT with or without adjuvant chemotherapy is the current st and ard of care for locoregionally |
11,319 | 23,406,070 | Qualitative comparisons of different simulation curricula are limited , although feedback , mastery learning , and higher fidelity were associated with improved learning outcomes .
CONCLUSIONS Technology-enhanced simulation for EM learners is associated with moderate or large favorable effects in comparison with no intervention and generally small and nonsignificant benefits in comparison with other instruction . | OBJECTIVES Technology-enhanced simulation is used frequently in emergency medicine ( EM ) training programs .
Evidence for its effectiveness , however , remains unclear .
The objective of this study was to evaluate the effectiveness of technology-enhanced simulation for training in EM and identify instructional design features associated with improved outcomes by conducting a systematic review . | & NA ; To increase cardiopulmonary arrest survival , the American Heart Association developed basic and advanced cardiac life support ( ACLS ) courses that expose participants to realistic learning situations . This experimental study compared results of two ACLS classes on measures of knowledge ( content exam ) and resuscitation skills ( performance exam ) . Both the control and experimental groups consisted of physicians , nurses , emergency medical technicians , respiratory therapists , and advanced health care providers . The control group used low‐fidelity simulation ( LFS ) ; the experimental group was exposed to enhanced realism via high‐fidelity simulation ( HFS ) . The findings showed a positive correlation between enhanced practice and learning but no significant correlation between posttest and skills test scores for the LFS and HFS groups . The HFS group did score higher on both cognitive and behavioral tests , but the difference was not statistically significant . Participants from both groups indicated satisfaction with their forms of simulation experience and course design . In addition , participants ' self‐confidence to care for a victim of cardiopulmonary arrest was increased after completing their course ; profession and work experience had no effect on responses . The largest difference noted was in verbal responses to course satisfaction . The experimental group stated that learning using HFS was enjoyable and adamantly recommended that ACLS should only be taught using HFS . Further study is required to assess if practicing beyond the course enhances short‐ and long‐term retention of ACLS techniques Objective : To compare the usefulness for training of a porcine model ( larynx , trachea , and pig skin ) and a manikin model using a Portex cricothyrotomy kit ( PCK ) . Methods : In a prospect i ve r and omised crossover trial , participants in the airway workshop performed crico-thyrotomy using a PCK on the porcine and manikin models ( Tracheostomy Trainer and Case ) . The porcine model was made with larynxes and trachea from freshly slaughtered pigs and covered with a piece of thinned pigskin stapled to a wooden board . Participants were asked to assess the following : reality of skin turgor ; difficulty with skin penetration , l and mark recognition and procedure ; reality of the model ; and preference for each model using a visual analogue scale ( VAS ) of 0–10 cm . The VAS scores for each model were compared . Results : 49 participants were included in the study . Mean ( SD ) VAS scores for the reality of skin turgor , degree of difficulty with skin penetration and l and mark recognition were higher with the porcine model than with the manikin model ( 7.0 ( 2.1 ) vs 4.7 ( 2.0 ) , 6.4 ( 2.4 ) vs 3.6 ( 2.2 ) , 5.1 ( 2.2 ) vs 4.2 ( 2.5 ) , respectively ) . There was no difference between the models in the difficulty of the procedure ( 5.0 ( 2.4 ) vs 4.7 ( 3.2 ) ) . The porcine model had a higher VAS score for overall reality and preference of the model ( 7.1 ( 2.0 ) vs 4.8 ( 2.3 ) and 7.1 ( 2.0 ) vs 4.8 ( 2.2 ) , respectively ) . Conclusion : The porcine model is a more useful training tool than the manikin model for cricothyrotomy with PCK because of its reality and similarity to human anatomy Traditional teaching of laryngoscopy is difficult due to the trainer and trainee lacking a shared view . The Karl Storz BERCI DCI ® Video Laryngoscope provides a video image for the trainer and a direct view identical to that of a st and ard laryngoscope for the trainee . Forty‐nine novice subjects were r and omly assigned to a control group ( n = 24 ) taught using a st and ard Macintosh laryngoscope or a study group ( n = 25 ) taught using the Video Laryngoscope . Following training all subjects were assessed using a st and ard laryngoscope . Under simulated difficult airway conditions the study group performed better in terms of number of attempts ( p = 0.02 ) , number of repositioning manoeuvres required ( p = 0.046 ) and teeth trauma ( p = 0.034 ) . The study group were more confident of the success of their tube placement ( p = 0.035 ) , found it easier than the control group ( p = 0.042 ) and had improved knowledge of airway anatomy ( p = 0.011 ) . We conclude that video laryngoscopy confers benefits in the teaching of tracheal intubation OBJECTIVE : Poor communication and teamwork may contribute to errors during neonatal resuscitation . Our objective was to evaluate whether interns who received a 2-hour teamwork training intervention with the Neonatal Resuscitation Program ( NRP ) demonstrated more teamwork and higher quality resuscitations than control subjects . METHODS : Participants were noncertified 2007 and 2008 incoming interns for pediatrics , combined pediatrics and internal medicine , family medicine , emergency medicine , and obstetrics and gynecology ( n = 98 ) . Pediatrics and combined pediatrics/internal medicine interns were eligible for 6-month follow-up ( n = 34 ) . A r and omized trial was conducted in which half of the participants in the team training arm practice d NRP skills by using high-fidelity simulators ; the remaining practice d with low-fidelity simulators , as did control subjects . Blinded , trained observers viewed video recordings of high-fidelity – simulated resuscitations for teamwork and resuscitation quality . RESULTS : High-fidelity training ( HFT ) group had higher teamwork frequency than did control subjects ( 12.8 vs 9.0 behaviors per minute ; P < .001 ) . Intervention groups maintained more workload management ( control subjects : 89.3 % ; low-fidelity training [ LFT ] group : 98.0 % [ P < .001 ] ; HFT group : 98.8 % ; HFT group versus control subjects [ P < .001 ] ) and completed resuscitations faster ( control subjects : 10.6 minutes ; LFT group : 8.6 minutes [ P = .040 ] ; HFT group : 7.4 minutes ; HFT group versus control subjects [ P < .001 ] ) . Overall , intervention teams completed the resuscitation an average of 2.6 minutes faster than did control subjects , a time reduction of 24 % ( 95 % confidence interval : 12%–37 % ) . Intervention groups demonstrated more frequent teamwork during 6-month follow-up resuscitations ( 11.8 vs 10.0 behaviors per minute ; P = .030 ) . CONCLUSIONS : Trained participants exhibited more frequent teamwork behaviors ( especially the HFT group ) and better workload management and completed the resuscitation more quickly than did control subjects . The impact on team behaviors persisted for at least 6 months . Incorporating team training into the NRP curriculum is a feasible and effective way to teach interns teamwork skills . It also improves simulated resuscitation quality by shortening the duration Current Advanced Cardiac Life Support ( ACLS ) course instruction involves a 2-day course with traditional lectures and limited team interaction . We wish to explore the advantages of a scenario-based performance-oriented team instruction ( SPOTI ) method to implement core ACLS skills for non-English-speaking international paramedic students . The objective of this study was to determine if scenario-based , performance-oriented team instruction ( SPOTI ) improves educational outcomes for the ACLS instruction of Korean paramedic students . Thirty Korean paramedic students were r and omly selected into two groups . One group of 15 students was taught the traditional ACLS course . The other 15 students were instructed using a SPOTI method . Each group was tested using ACLS megacode examinations endorsed by the American Heart Association . All 30 students passed the ACLS megacode examination . In the traditional ACLS study group an average of 85 % of the core skills were met . In the SPOTI study group an average of 93 % of the core skills were met . In particular , the SPOTI study group excelled at physical examination skills such as airway opening , assessment of breathing , signs of circulation , and compression rates . In addition , the SPOTI group performed with higher marks on rhythm recognition compared to the traditional group . The traditional group performed with higher marks at providing proper drug dosages compared to the SPOTI students . However , the students enrolled in the SPOTI method result ed in higher megacode core compliance scores compared to students trained in traditional ACLS course instruction . These differences did not achieve statistical significance due to the small sample size BACKGROUND Recent literature describes " cognitive dispositions to respond " ( CDRs ) that may lead physicians to err in their clinical reasoning . OBJECTIVES To assess learner perception of high-fidelity mannequin-based simulation and debriefing to improve underst and ing of CDRs . METHODS Emergency medicine ( EM ) residents were exposed to two simulations design ed to bring out the CDR concept known as " vertical line failure . " Residents were then block-r and omized to a technical/knowledge debriefing covering the medical subject matter or a CDR debriefing covering vertical line failure . They then completed a written survey and were interviewed by an ethnographer . Four investigators blinded to group assignment review ed the interview transcripts and coded the comments . The comments were qualitatively analyzed and those upon which three out of four raters agreed were quantified . A r and om sample of 84 comments was assessed for interrater reliability using a kappa statistic . RESULTS Sixty-two residents from two EM residencies participated . Survey results were compared by technical ( group A , n = 32 ) or cognitive ( group B , n = 30 ) debriefing . There were 255 group A and 176 group B comments quantified . The kappa statistic for coding the interview comments was 0.42 . The CDR debriefing group made more , and qualitatively richer , comments regarding CDR concepts . The technical debriefing group made more comments on the medical subjects of cases . Both groups showed an appreciation for the risk of diagnostic error . CONCLUSIONS Survey data indicate that technical debriefing was better received than cognitive debriefing . The authors theorize that an underst and ing of CDRs can be facilitated through simulation training based on the analysis of interview comments OBJECTIVE To compare the ' 4-stage ' teaching technique ( demonstration , deconstruction , formulation , performance ) with the traditional ' 2-stage ' teaching technique ( deconstruction , performance ) in laryngeal mask airway ( LMA ) insertion . METHODS Using a prospect i ve r and omised study design , participants were taught LMA insertion on a manikin by either the ' 2-stage ' or ' 4-stage ' teaching method . Subjects were eligible if they had never inserted a LMA . Skill acquisition was assessed immediately following training , and skill retention assessed a number of weeks later . The primary outcome was LMA insertion on a manikin , with successful ventilation within 30 s. Other outcomes included overall time to LMA insertion , and number of errors . Assessors were blinded to the teaching method used for each subject . RESULTS A total of 120 participants were r and omised between the two teaching groups ( 60 subjects in each group ) . Mean time to LMA insertion at acquisition was 39.7 s for 2-stage and 34.7 s for 4-stage ( p>0.05 ) , and proportion completing within 30 s was 41.67 % for 2-stage and 48.33 % for the 4-stage teaching group ( p>0.05 ) . With skill retention assessment , mean time to LMA insertion was 44.3 s for 2-stage and 42.5 s for the 4-stage teaching group ( p>0.05 ) . Proportion completing task within 30 s was 34.0 % for 2-stage and 41.67 % for 4-stage group ( p>0.05 ) . Overall , there was no significant difference found in skill acquisition or in skill retention between the 2 or 4-stage teaching method . CONCLUSION The 2-stage teaching technique is not statistically different to the 4-stage teaching method in efficacy of LMA insertion skill acquisition or retention OBJECTIVES The objective of the study was to compare the learning and retention rates of resident physicians trained in posterior epistaxis management with nasal gauze packing on a simulation model following two training methods . METHODS This was a prospect i ve , repeated- measures study . An objective , criterion-referenced performance st and ard , consisting of the number of major steps completed in the proper sequence , and the number of minor steps completed within a specified time , was used by an evaluator to assess performances . Subjects underwent two pretraining assessment s 1 week prior to and the day of training and then were r and omized to one of two training methods : the traditional " observation " method or a " pause- and -perfect " method . After training , both groups repeated the procedure until meeting the performance st and ard . Subjects were retested 1 and 3 months after training . RESULTS Twenty-eight subjects participated . Baseline performance measures were similar between groups and did not change prior to training . During performance testing , experimental subjects completed a greater percentage of major steps ( 84 % ) and minor steps ( 86 % ) in less time ( 25 minutes ) than the controls ( 65 and 68 % , in 35 minutes ) during the first attempt . All subjects met the st and ard within three attempts . There were no differences in major and minor steps completed between the two groups at either 1 week or 3 months after training , but performance times were shorter in the experimental group . After 3 months , 13 % of control and none of experimental subjects met the performance st and ard . CONCLUSIONS The pause- and -perfect training method produced more rapid progress toward a performance st and ard during the initial attempt and better performance times after 3 months than the traditional , observational training method . Without further practice , this skill deteriorated after 3 months with both methods of training Introduction : Major resuscitation councils endorse the use of the laryngeal mask airway ( LMA ) by paramedics for lifesaving airway interventions . Learning and maintaining adequate skill level is important for patient safety . The aim of this project was to develop a training program that provides student paramedics with initial knowledge and experience in LMA insertion skills but equally important to provide ongoing skill retention . Methods : After ethics approval and informed consent , 55 first year Paramedic degree students watched a manufacturer 's LMA instruction video and practice d insertion in three different part task trainers . Six months later , subjects were r and omized to an intervention ( review ing the video and 10 minutes unsupervised practice ) or control group before participating in a high-fidelity simulated clinical scenario . For equity of training , the control group received the intervention after the scenario . Main outcomes measured were time to insertion ; success rate ; and LMA skill retention ( sum of LMA orientation ; cuff inflation ; bite block ; securing ; patient positioning ; and overall subject performance ) . Results : Fifty subjects completed the study . Those in the intervention group displayed significantly shorter insertion times ( P = 0.029 ) , fewer attempts to achieve success ( P = 0.033 ) , and had significantly higher LMA skill performance levels ( P = 0.019 ) at 6 months . Conclusions : We devised a short intervention based on our training program using a video and practice in part task trainers . In an assessment using high-fidelity simulation , we demonstrated significant improvements in maintenance of LMA insertion skills in student paramedics at 6 months . Our model of just-in-time assessment and reinforcement of training prevents skill decay and has implication s for healthcare skills training in general STUDY OBJECTIVES To determine the effect of manikin-only training on field success of endotracheal intubation by paramedics . DESIGN Prospect i ve evaluation of individual field endotracheal intubation success rates for paramedics after they participated in a manikin-only or a manikin-plus-cadaver training program . TYPES OF PARTICIPANTS Paramedics responding to emergency calls involving adult medical or trauma victims . INTERVENTIONS All participants were trained using a controlled manikin training program ; then , half were r and omly selected for additional instruction using fresh human cadavers . MEASUREMENTS AND MAIN RESULTS Individuals trained using only the manikin program had mean + /- SD individual success rates of 82 + /- 32 % , and individuals who received additional cadaver training had mean individual success rates of 83 + /- 31 % . Overall success rates for the two groups were 86 % for the manikin-only group and 85 % for the manikin-plus-cadaver-trained group . The sample size was not adequate to allow rejection of the null hypothesis . CONCLUSION Paramedics trained in endotracheal intubation using a systematic manikin-only teaching program can attain acceptable individual success rates in the actual field setting Objective : To compare the acceptability and preference between manikin models and fresh frozen cadaver ( FFC ) for direct laryngoscopic orotracheal intubation training . Methods : In this prospect i ve crossover trial , participants in the airway workshop performed direct laryngoscopic orotracheal intubation on four airway training manikins : Airway Management Trainer ( Ambu , St Ives , UK ) , Airway Trainer ( Laerdal , Medical , Stavanger , Norway ) , Airsim ( Trucorp , Belfast , Northern Irel and ) and “ Bill 1 ” ( VBM , Sulz , Germany ) , and FFC . Participants were asked to access the following : reality of jaw mobility , difficulty with mouth opening , reality of neck flexibility , difficulty with intubation , overall model reality and model preference for each model using a visual analogue scale ( VAS ) of 0–10 cm . The VAS scores for each model were compared . Results : Fifty-six participants were included in the study . The FFC had a highest VAS score for reality of jaw mobility , overall reality and preference of model . Trucorp manikin and Laerdal manikin followed cadaver . There were no significant statistical differences between Trucorp manikin and Laerdal manikin . In difficulty with mouth opening and difficulty with intubation , Trucorp manikin had the lowest VAS score . Conclusion : The FFC is a more realistic and preferred model for direct laryngoscopic orotracheal intubation training . Trucorp and Laerdal manikin can be used as alternative models Objective : The objective of the study was to compare the effectiveness of repetitive pediatric simulation ( RPS ) training ( scenario-debriefing-scenario ) to st and ard pediatric simulation ( STN ) training ( scenario-debriefing ) . Methods : Pediatric and emergency medicine residents prospect ively participated in simulated pediatric resuscitation training sessions in an in situ simulation room . Residents anonymously reported their knowledge , skills , and confidence after each session . Four learners and 2 faculty preceptors ( 1 pediatric emergency medicine attending physician and 1 pediatric emergency medicine fellow ) participated in each session . Scenarios were performed on a high-fidelity simulator ( SimBaby ; Laerdal Medical , Stavanger , Norway ) , and video debriefing was used for all training sessions . St and ard pediatric simulation was used in the initial 6 months of the study , whereas RPS was used in the second 6 months of the study . Results : One hundred fifteen subjects completed simulation sessions during the study period . The RPS group reported higher overall debriefing quality and were more likely to report that the simulation session was an excellent method of teaching . The RPS group reported greater improvement in knowledge and skills than did the STN group . Similar scores were reported for confidence , overall performance , stress levels , and realism of the simulator in both the STN and RPS groups . Conclusions : Feedback is a key feature of effective medical simulation . Repetitive pediatric simulation provides learners with a discrete opportunity to apply the knowledge and skills discussed during debriefing in an immediate second simulation session and thereby complete Kolb 's experiential learning cycle . In this study , the RPS debriefing format was associated with higher self-reported knowledge and skills . The RPS group reported more positive attitudes toward simulation than the STN group PURPOSE Complex skills , such as ureteroscopy and stone extraction , are increasingly taught to novice urology trainees using bench models in surgical skills laboratories . We determined whether h and s-on training improved the performance of novices more than those taught only by a didactic session and whether there was a difference in the performance of subjects taught on a low versus a high fidelity model . MATERIAL S AND METHODS We r and omized 40 final year medical students to a didactic session or 1 of 2 h and s-on training groups involving low or high fidelity bench model practice . Training sessions were supervised by experienced endourologists . Testing involved removal of a mid ureteral stone using a semirigid ureteroscope and a basket . Blinded examiners tested subjects before and after training . Performance was measured by a global rating scale , checklist , pass rating and time needed to complete the task . RESULTS There was a significant effect of h and s-on training on endourological performance ( p < 0.01 ) . With respect to bench model fidelity the low fidelity group did significantly better than the didactic group ( p < 0.05 ) . However , no significant difference was found between the high and low fidelity groups ( p > 0.05 ) . The low fidelity model cost Canadian $ 20 to produce , while the high fidelity model cost Canadian $ 3,700 to purchase . CONCLUSIONS H and s-on training using bench models can be successful for teaching novices complex endourological skills . A low fidelity bench model is a more cost-effective means of teaching ureteroscopic skills to novices than a high fidelity model OBJECTIVES In this study , an endovaginal ultrasound ( US ) task trainer was combined with a high-fidelity US mannequin to create a hybrid simulation model . In a scenario depicting a patient with ectopic pregnancy and hemorrhagic shock , this model was compared with a st and ard high-fidelity simulation during training sessions with emergency medicine ( EM ) residents . The authors hypothesized that use of the hybrid model would increase both the residents ' self-reported educational experience and the faculty 's self-reported ability to evaluate the residents ' skills . METHODS A total of 45 EM residents at two institutions were r and omized into two groups . Each group was assigned to one of two formats involving an ectopic pregnancy scenario . One format incorporated the new hybrid model , in which residents had to manipulate an endovaginal US probe in a task trainer ; the other used the st and ard high-fidelity simulation mannequin together with static photo images . After finishing the scenario , residents self-rated their overall learning experience and how well the scenario evaluated their ability to interpret endovaginal US images . Faculty members review ed video recordings of the other institution 's residents and rated their own ability to evaluate residents ' skills in interpreting endovaginal US images and diagnosing and managing the case scenario . Visual analog scales ( VAS ) were used for the self-ratings . RESULTS Compared to the residents assigned to the st and ard simulation scenario , residents assigned to the hybrid model reported an increase in their overall educational experience ( Delta VAS = 10 , 95 % confidence interval [ CI ] = 4 to 18 ) and felt the hybrid model was a better measure of their ability to interpret endovaginal US images ( Delta VAS = 17 , 95 % CI = 7 to 28 ) . Faculty members found the hybrid model to be better than the st and ard simulation for evaluating residents ' skills in interpreting endovaginal US images ( Delta VAS = 13 , 95 % CI = 6 to 20 ) and diagnosing and managing the case ( Delta VAS = 10 , 95 % CI = 2 to 18 ) . Time to reach a diagnosis was similar in both groups ( p = 0.053 ) . CONCLUSIONS Use of a hybrid simulation model combining a high-fidelity simulation with an endovaginal US task trainer improved residents ' educational experience and improved faculty 's ability to evaluate residents ' endovaginal US and clinical skills . This novel hybrid tool should be considered for future education and evaluation of EM residents |
11,320 | 29,210,501 | Women found the process of seeking help difficult , with several barriers preventing them from both seeking and accepting professional support .
Despite this , women described the support received as beneficial and particularly valued the therapeutic relationship .
Women reported 1 ) feeling more positive and confident after receiving a psychological and /or psychosocial intervention and 2 ) experiencing better relationships with their infant and other family members .
DISCUSSION Although seeking and accepting professional support for PPD was a difficult process , women highly valued mental health care support and perceived it as beneficial . | INTRODUCTION Postpartum depression ( PPD ) is a serious maternal disorder that can have adverse effects on maternal and infant health .
The importance of offering effective and acceptable treatments is well recognized , particularly given the numerous barriers women in many setting s face in accessing interventions for PPD .
The aim of this systematic review was to synthesize qualitative research exploring women 's experiences of professional psychological and psychosocial support for PPD . | Background Postnatal depression affects 10–15 % of all mothers in Western societies and remains a major public health concern for women from diverse cultures . British Pakistani and Indian women have a higher prevalence of depression in comparison to their white counterparts . Research has shown that culturally adapted interventions using Cognitive Behavioural Therapy ( CBT ) may be acceptable and may help to address the needs of this population . The aim of this study was to assess the acceptability and overall experience of the Positive Health Programme by British South Asian mothers . Methods This was a nested qualitative study , part of an exploratory r and omized controlled trial ( RCT ) conducted to test the feasibility and acceptability of a culturally-adapted intervention ( Positive Health Programme or PHP ) for postnatal depression in British South Asian women . In-depth interviews ( N = 17 ) were conducted to determine the views of the participants on the feasibility and acceptability of the intervention . Results The participants found the intervention acceptable and experienced an overall positive change in their attitudes , behaviour , and increased self-confidence . Conclusions The findings suggest that the culturally adapted Positive Health Programme is acceptable to British South Asian women . These results support that culturally sensitive interventions may lead to better health outcomes and overall satisfaction . Trial registration Protocol registered on Clinical trials.gov OBJECTIVE We examined the course and predictors of postpartum depression in the 18 months following interpersonal psychotherapy ( IPT ) . METHOD We enrolled 120 community women with major depression in a 12-week r and omized trial of individual IPT during the postpartum period ( O'Hara , Stuart , Gorman , & Wenzel , 2000 ) . At 6 , 12 , and 18 months posttreatment , women participated in clinical interviews to establish the course of depression over the previous 6 months . We used survival analyses to characterize recovery and recurrence in the follow-up and growth curve modeling techniques to identify predictors of change in depression during the follow-up period . Potential predictors included severity , chronicity , and personal history of depression . RESULTS Of 35 women who recovered with acute treatment , 20 ( 57 % ) achieved sustained recovery during follow-up ; average time to recurrence was 33.40 weeks ( SD = 18.43 weeks ) . Over 80 % of women who did not recover with acute treatment experienced recovery at some point during follow-up ; average time to recovery was 28.60 weeks ( SD = 17.51 weeks ) . Time depressed each month decreased over the follow-up period . Posttreatment depressive severity and length of the index episode predicted changes in depression over time . Posttreatment depression severity , personal history of depression , and weeks of treatment in the follow-up were significant predictors of time depressed during follow-up . CONCLUSIONS IPT result ed in long-term benefits past the termination of acute treatment , even for women who did not initially recover . Though the vast majority of women who did not recover with acute treatment did recover during the follow-up period , continuation of IPT may accelerate the process BACKGROUND A prospect i ve epidemiology study evaluated the role of specific social and psychological variables in the prediction of depressive symptomatology and disorders following childbirth in a community sample . Measures of social support used previously in clinical ly depressed population s facilitated further comparison . METHODS Nulliparous pregnant women ( N = 507 ) were interviewed during pregnancy with the Interview Measure of Social Relationships ( IMSR ) and a context ual assessment of pregnancy-related support and adversity and 427 were followed up at 3 months postpartum with the 30-item GHQ , including six depression items . To establish the clinical representativeness of the GHQ , high GHQ scorers and a r and om sub sample of low scorers were interviewed using the SCAN . Regression models were developed using the GHQ Depression scale ( GHQ-D ) , the IMSR and other risk factor data . RESULTS GHQ-D after childbirth was predicted by lack of perceived support from members of the woman 's primary group and lack of support in relation to the event becoming pregnant ; this held even after controlling for antenatal depression , neuroticism , family and personal psychiatric history and adversity . Informant-rated deficits in provision of social support also predicted later depression . The size of the primary social network group previously found to be related to depression in women , did not predict depressive symptom development . CONCLUSION Predictors of depressive symptom development differ from predictors of recovery from clinical depression in women . Interventions should be design ed to reduce specific deficits in social support observed in particular study population Few interventions for Postnatal Depression ( PND ) have focused on parenting difficulties ; the aim of this research was to investigate the feasibility and evaluate a parenting intervention ( Baby Triple P ) in women with PND . This was a pilot r and omised controlled trial ( RCT ) to evaluate and determine the feasibility of the newly developed Baby Triple P compared with treatment as usual ( TAU ) in women with PND . In all , 27 female participants aged from 18 to 45 years ( mean age = 28.4 years , st and ard deviation ( SD ) = 6.1 ) , with a primary diagnosis of major depression and an infant under 12 months ( mean age = 6.2 months , SD = 3.2 months ) , were recruited from primary care trusts in Greater Manchester , United Kingdom . Participants were r and omly allocated to receive either eight Baby Triple P sessions in addition to TAU or TAU only . Outcomes were assessed at post-treatment ( Time 2 ) and 3 months post-treatment ( Time 3 ) . Self-report outcomes were as follows : Beck Depression Inventory , Oxford Happiness Inventory , What Being the Parent of a New Baby is Like , Postpartum Bonding Question naire and the Brief Parenting Beliefs Scale – baby version . An assessor-rated observational measure of mother – infant interaction , the CARE Index and measure of intervention acceptability were also completed . Significant improvements from Time 1 to Time 2 and Time 1 to Time 3 were observed across both groups . Although women allocated to Baby Triple P showed more favourable improvements , the between-group differences were not significant . However , the intervention was highly acceptable to women with PND . A large-scale RCT is indicated Post-partum depression affects 10 - 13 % of Japanese women , but many do not receive appropriate treatment or support . This intervention study evaluated the effectiveness of home visits by mental health nurses for Japanese women with post-partum depression . Eighteen post-partum women met the inclusion criteria and were r and omly allocated into the intervention ( n = 9 ) or control ( n = 9 ) group at 1 - 2 months after giving birth . The intervention group received four weekly home visits by a mental health nurse . Control group participants received usual care . Two women in the intervention group did not complete the study . Depressive symptoms and quality of life were measured at 1 and 6 weeks ' postintervention . In addition , participants completed an open-ended question naire on satisfaction and meaning derived from the home visits . Women in the intervention group had significant amelioration of depressive symptoms over time and reported positive benefits from the home visits , but there were no statistically significant differences between groups . Significant differences ( P < 0.05 ) were observed at times 2 and 3 between groups in terms of increased median scores of physical , environmental , and global subscales , and the total average score of the World Health Organization/ quality of life assessment instrument . On the psychological subscale , significant differences ( P = 0.042 ) were observed between groups at time 2 . The qualitative analysis of comments about home visitation revealed four categories related to ' setting their mind at ease ' , ' clarifying thoughts ' , ' improving coping abilities ' , and ' removing feelings of withdrawal from others ' . These results suggest that home visits by mental health nurses can contribute to positive mental health and social changes for women with post-partum depression . A larger trial is warranted to test this approach to care BACKGROUND Postnatal depression is a public health problem requiring intervention . To provide effective care , information is needed on the experiences of those with high levels of depressive symptoms who are offered and accept , or decline , psychological intervention postnatally . AIM To provide the first integrated in-depth exploration of postnatal women 's experiences of the identification and management of symptoms of depression and the offer and acceptance of postnatal care by health visitors taking part in the PoNDER trial . SETTING General practice : primary care within the former Trent regional health authority , Engl and . METHOD Thirty women with 6-week Edinburgh Postnatal Depression Scale ( EPDS ) scores ≥ 18 and probable depression completed semi-structured interviews . All women had taken part in the Post-Natal Depression Economic Evaluation and R and omised controlled ( PoNDER ) trial where intervention group health visitors received training in identification of depressive symptoms and provided psychologically informed sessions based on cognitive-behavioural therapy or person-centred counselling principles . RESULTS When accepted , psychological sessions were experienced as positive , effective , and ' ideal care ' . Women approved of using the EPDS but did not underst and the health visitor 's role in supporting women . Seeking help and accepting sessions depended on women 's perspectives of their health visitor as an individual . CONCLUSION Women 's experience of their health visitors providing psychological sessions to help with postnatal depressive symptoms is highly positive . Women will better accept support from health visitors if they recognise their role in postnatal depression and find them easy to relate to on personal matters . There is a case for specific enhancement of interpersonal skills in health visiting , or alternatively offering a choice of health visitors to women |
11,321 | 12,651,793 | RESULTS AND CONCLUSIONS The epidemiology of non-attendance has been well described , but there is little work on the reasons for non-attendance . | BACKGROUND Non-attendance in general practice has received increasing attention over the past few years .
Its relationship with access to health care has been recognized and is of particular relevance in light of the access targets set out in the NHS Plan . | Objective : To test the effectiveness of different systems of reminding patients about their appointments in order to reduce the rate of failed attendance . The expense in implementing a reminder system for patients was also estimated . Design : A clinical study in a single-h and ed dental practice .Subjects : Patients were reminded about their appointment using either postal , manual telephone or automated telephone reminders ( or all three combined ) . A control group received no reminders . 500 patient attendances were recorded in each group . Results : Patients failed to attend for 130 of the 2500 appointments considered in the study . There was a significant reduction in the failed attendance rate from 9.4 % ( with no reminder ) to a minimum of 3 % when a reminder was given to the patient before the appointment . However , there was no significant difference among the four reminder test groups , indicating that the form of the reminder made no difference to the failure rate . Conclusions : Reminding patients using postal or manual telephone techniques is effective at improving attendance . All of the reminder methods , telephone and postal , provided net cost savings rather than additional The new-patient no-show rate reached 55 percent in an urban , university-based family practice center in mid-1981 . A prospect i ve descriptive study revealed that the no-show rates varied significantly with hour of appointment , patient age , source of referral , delay in appointment date , and chronicity of illness . Study findings led to alterations in the scheduling system , with a subsequent drop in the new-patient no-show rate to 40 percent BACKGROUND The dem and for anticoagulation management is increasing . This has led to care being provided in non-hospital setting s. While clinical studies have similarly demonstrated good clinical care in these setting s , it is still unclear as to which alternative is the most efficient . AIM To determine the costs borne by patients when attending an anticoagulation management clinic in either primary or secondary care and to use this information to consider the cost-effectiveness of anticoagulation management in primary and secondary care , both from the National Health Service and patient perspectives . DESIGN OF STUDY Observational study comparing two cohorts of patients currently attending anticoagulation management clinics . SETTING Four primary care clinics in Birmingham and one in Warwickshire , and the haematology clinics at the University of Birmingham Hospitals Trust and the City Hospital NHS Trust . METHOD The survey of patients attending the clinics was used to ascertain patient costs . This information was then used in conjunction with the findings of a recent r and omised controlled trial to establish cost-effectiveness . RESULTS Patient costs were lower in primary care than in secondary care setting s ; the mean ( st and ard deviation ) costs per visit were Pound Sterling6.78 ( Pound Sterling5.04 ) versus Pound Sterling14.58 ( Pound Sterling9.08 ) . While a previous cost-effectiveness analysis from a health sector perspective alone found a higher cost for primary care , the adoption of the societal perspective lead to a marked change in the result : a similar total cost per patient in both sectors . CONCLUSION There are significantly higher costs borne by patients attending secondary care anticoagulation management clinics than similar patients attending primary care clinics . This study also demonstrates that the perspective adopted in an economic evaluation can influence the final result OBJECTIVE --To ascertain which social and psychological characteristics are associated with patients attending surgeries without appointments . DESIGN -- Prospect i ve study of patients attending an urban centre group practice . SETTING --Urban health centre group practice with five doctors and 12,000 patients in an area of high ( greater than 20 % ) unemployment and social deprivation . PATIENTS --All attenders at the open access surgery and one in four consecutive attenders by appointment , selected sequentially from the first three appointments , during 10 days in January 1989 . Patients participating in the pilot study , reattending during the study period , or attending antenatal clinics were excluded . MAIN OUTCOME MEASURES -- Patients ' attitude to making appointments and reasons for attending , including perception of urgency , with respect to sociodemographic and psychosocial data obtained from a self completed question naire before the consultation . Doctors ' diagnosis and perception of urgency obtained from a separate question naire . RESULTS --86 % ( 141/172 ) Of patients attending without appointments and 96 % ( 139/145 ) with appointments responded to the question naire . The need for consultation was considered to be " very urgent " or " fairly urgent " in significantly more of the open access group than the appointments group ( 89 % , 124/139 v 66 % , 91/138 ; chi 2 = 27.04 , df = 3 ; p less than 0.001 ) , although the doctors did not share the same views . Significantly more patients had self limiting conditions of recent onset in the open access than in the appointments group ( 75 % , 101/135 v 48 % , 59/123 : p less than 0.001 ) . Overall , open access attendance was significantly linked with social support ( 39 % , 48/124 v 26 % , 32/123 ; p less than 0.05 ) and with marital separations or intentions to separate ( 10 % , 9/87 v 0/92 ; 47 % , 32/87 v 22 % , 20/92 respectively ; both p less than 0.001 ) , but the doctors recorded significantly fewer psychological and social problems in these patients ( p less than 0.05 ) . Although almost half those in the appointments group considered that making appointments was inconvenient , more of those in the open access group agreed with this view ( 47 % , 60/129 v 61 % , 80/131 ) . CONCLUSIONS --There was an important link between social support problems and a negative attitude to making appointments . In our previous experience encouraging patients to make appointments has been unsuccessful ; practice s serving areas with a high prevalence of social deprivation providing a mixed open access and appointments system may better serve patients ' needs |
11,322 | 25,621,688 | Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism , except when it is given IM and even the increase with IM administration is minimal | Abstract Testosterone replacement therapy is used for the treatment of age-related male hypogonadism , and prostate-specific antigen ( PSA ) is a primary screening tool for prostate cancer .
The systematic review and meta- analysis aim ed to determine the effect of testosterone replacement therapy on PSA levels . | Purpose . We performed a r and omised controlled study regarding the effects of and rogen replacement therapy ( ART ) on lower urinary tract symptoms ( LUTS ) in hypogonadal men with benign prostate hypertrophy ( BPH ) . Methods . Fifty-two patients with hypogonadism and BPH were r and omly assigned to receive testosterone ( ART group ) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group . We compared International Prostate Symptom Score ( IPSS ) , uroflowmetry data , post-voiding residual volume ( PVR ) and systemic muscle volume at baseline and 12 months after treatment . Results . Forty-six patients ( ART group , n = 23 ; control , n = 23 ) were included in the analysis . At the 12-month visit , IPSS showed a significant decrease compared with baseline in the ART group ( 15.7 ± 8.7 vs. 12.5 ± 9.5 ; p < 0.05 ) . No significant changes were observed in the control group . The ART group also showed improvement in maximum flow rate and voided volume ( p < 0.05 ) , whereas no significant improvements were observed in the controls . PVR showed no significant changes in either group . In addition , the ART group showed significant enhancement of mean muscle volume ( p < 0.05 ) , whereas no significant changes were seen in the controls . Conclusion . ART improved LUTS in hypogonadal men with mild BPH Although weight loss associated with human immunodeficiency virus ( HIV ) infection is multifactorial in its pathogenesis , it has been speculated that hypogonadism , a common occurrence in HIV disease , contributes to depletion of lean tissue and muscle dysfunction . We , therefore , examined the effects of testosterone replacement by means of And roderm , a permeation-enhanced , nongenital transdermal system , on lean body mass , body weight , muscle strength , health-related quality of life , and HIV-disease markers . We r and omly assigned 41 HIV-infected , ambulatory men , 18 - 60 yr of age , with serum testosterone levels below 400 ng/dL , to 1 of 2 treatment groups : group I , two placebo patches ( n = 21 ) ; or group II , two testosterone patches design ed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment . Serum total and free testosterone and dihydrotestosterone levels increased , and LH and FSH levels decreased in the testosterone-treated , but not in the placebo-treated , men . Lean body mass and fat-free mass , measured by dual energy x-ray absorptiometry , increased significantly in men receiving testosterone patches [ change in lean body mass , + 1.345 + /- 0.533 kg ( P = 0.02 compared to no change ) ; change in fat-free mass , + 1.364 + /- 0.525 kg ( P = 0.02 compared to no change ) ] , but did not change in the placebo group [ change in lean body mass , 0.189 + /- 0.470 kg ( P = NS compared to no change ) ; change in fat-free mass , 0.186 + /- 0.470 kg ( P = NS compared to no change ) ] . However , there was no significant difference between the 2 treatment groups in the change in lean body mass . The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels ( r = 0.41 ; P = 0.02 ) . The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches ( P = 0.04 ) . There was no significant change in body weight in either treatment group . Changes in overall quality of life scores did not correlate with testosterone treatment ; however , in the subcategory of role limitation due to emotional problems , the men in the testosterone group improved an average of 43 points of a 0 - 100 possible score , whereas those in the placebo group did not change . Red cell count increased in the testosterone group ( change in red cell count , + 0.1 + /- 0.1 10(12)/L ) but decreased in the placebo group ( change in red cell count , -0.2 + /- 0.1 10(12)/L ) . CD4 + and CD8 + T cell counts and plasma HIV copy number did not significantly change during treatment . Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group . Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass , a significantly greater reduction in fat mass than that achieved with placebo treatment , an increased red cell count , and an improvement in role limitation due to emotional problems . Further studies are needed to assess whether testosterone supplementation can produce clinical ly meaningful changes in muscle function and disease outcome in HIV-infected men The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels . Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors . Tau protein deposition is also affected by and rogen supplementation in animals . We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition , in particular the visual-spatial domain . Thirty-six male patients with a new diagnosis of Alzheimer 's disease had their total and bioavailable testosterone levels measured . None of the patients had been on acetylcholinesterase inhibitors . Ten of the 36 patients ( 28 % ) were deemed biochemically hypogonadal ( total testosterone < 240 ng/dl or 7 nmol/l ) . Five of the hypogonadal patients were r and omized to testosterone and five to placebo . Initial Alzheimer 's Disease Assessment Scale cognitive subscale ( ADAScog ) and Mini Mental Status Examination ( MMSE ) ranged from 31 to 19 and from 17 to 22 , respectively . The clock drawing test ( CDT ) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities . Normal prostate-specific antigen ( PSA ) levels were essential before treatment with intramuscular testosterone , 200 mg every 2 weeks . Measurement of testosterone , complete blood count , lipids , PSA and neuropsychological cognitive tests were repeated at 3 , 6 , 9 and 12 months of treatment . In the testosterone-treated group , levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l ( p = 0.11 ) . Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l ( p = 0.10 ) . PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml ( p = 0.07 ) . ADAScog improved from a mean of 25 to 16.3 ( p = 0.02 ) ; MMSE improved from a mean of 19.4 to 23.2 ( p = 0.02 ) , CDT also improved from 2.2 to 3.2 ( p = 0.07 ) . One patient stopped treatment because of hypersexual behavior . The placebo-treated group deteriorated gradually . This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition , including visual-spatial skills in mild to moderate Alzheimer 's disease CONTEXT Prostate safety is a primary concern when aging men receive testosterone replacement therapy ( TRT ) , but little information is available regarding the effects of TRT on prostate tissue in men . OBJECTIVE To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 44 men , aged 44 to 78 years , with screening serum testosterone levels lower than 300 ng/dL ( < 10.4 nmol/L ) and related symptoms , conducted at a US community-based research center between February 2003 and November 2004 . INTERVENTION Participants were r and omly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months . MAIN OUTCOME MEASURES The primary outcome measure was the 6-month change in prostate tissue and rogen levels ( testosterone and dihydrotestosterone ) . Secondary outcome measures included 6-month changes in prostate-related clinical features , histology , biomarkers , and epithelial cell gene expression . RESULTS Of the 44 men r and omized , 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per- protocol analysis ( TRT , n = 21 ; placebo , n = 19 ) . Testosterone replacement therapy increased serum testosterone levels to the mid-normal range ( median at baseline , 282 ng/dL [ 9.8 nmol/L ] ; median at 6 months , 640 ng/dL [ 22.2 nmol/L ] ) with no significant change in serum testosterone levels in matched , placebo-treated men . However , median prostate tissue levels of testosterone ( 0.91 ng/g ) and dihydrotestosterone ( 6.79 ng/g ) did not change significantly in the TRT group . No treatment-related change was observed in prostate histology , tissue biomarkers ( and rogen receptor , Ki-67 , CD34 ) , gene expression ( including AR , PSA , PAP2A , VEGF , NXK3 , CLU [ Clusterin ] ) , or cancer incidence or severity . Treatment-related changes in prostate volume , serum prostate-specific antigen , voiding symptoms , and urinary flow were minor . CONCLUSIONS These preliminary data suggest that in aging men with late-onset hypogonadism , 6 months of TRT normalizes serum and rogen levels but appears to have little effect on prostate tissue and rogen levels and cellular functions . Establishment of prostate safety for large population s of older men undergoing longer duration of TRT requires further study . Trial Registration clinical trials.gov Identifier : NCT00161304 Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit . We evaluated the response to testosterone in men with borderline hypogonadism . A r and omized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level ( total testosterone < 10 nmol/L or free and rogen index < 30 % ) . Patients were r and omized to Testoderm TTS body patch ( 5 mg/day , n = 20 ) or a placebo patch ( n = 19 ) for 6 months , followed by open-label testosterone replacement for a further 6 months in all patients . During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment ( p = 0.004 ) ; this was associated with a decrease in total body fat mass ( p = 0.019 ) and increase in haemoglobin level ( p = 0.036 ) . There were no significant changes in lean body mass , markers of bone turnover , and measures of bone mineral density ( BMD ) . There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life question naire ( MEDQoL score , p = 0.017 ) , mainly accounted for by deterioration in the placebo arm . When the active treatment period was combined for placebo and testosterone groups , the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption ( uNTX/Cr , p = 0.007 ; iFDPD/Cr , p = 0.0006 ) and to increase lean body mass ( p = 0.001 ) . There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction . However , there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD OBJECTIVE To investigate the effect of testosterone treatment on insulin resistance , glycemic control , and dyslipidemia in Asian Indian men with type 2 diabetes mellitus ( T2DM ) and hypogonadism . METHODS We conducted a double-blind , placebo-controlled , crossover study in 22 men , 25 to 50 years old , with T2DM and hypogonadism . Patients were treated with intramuscularly administered testosterone ( 200 mg every 15 days ) or placebo for 3 months in r and om order , followed by a washout period of 1 month before the alternative treatment phase . The primary outcomes were changes in fasting insulin sensitivity ( as measured by homeostasis model assessment [ HOMA ] in those patients not receiving insulin ) , fasting blood glucose , and hemoglobin A1c . The secondary outcomes were changes in fasting lipids , blood pressure , body mass index , waist circumference , waist-to-hip ratio , and and rogen deficiency symptoms . Statistical analysis was performed on the delta values , with the treatment effect of placebo compared with the effect of testosterone . RESULTS Treatment with testosterone did not significantly influence insulin resistance measured by the HOMA index ( mean treatment effect , 1.67 + /- 4.29 ; confidence interval , -6.91 to 10.25 ; P>.05 ) . Mean change in hemoglobin A1c ( % ) ( -1.75 + /- 5.35 ; -12.46 to 8.95 ) and fasting blood glucose ( mg/dL ) ( 20.20 + /- 67.87 ; -115.54 to 155.94 ) also did not reach statistical significance . Testosterone treatment did not affect fasting lipids , blood pressure , and anthropometric determinations significantly . CONCLUSION In this study , testosterone treatment showed a neutral effect on insulin resistance and glycemic control and failed to improve dyslipidemia , control blood pressure , or reduce visceral fat significantly in Asian Indian men with T2DM and hypogonadism In a single-blind , placebo-controlled study , the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate ( And riol ® ) on the quality of life of men with testosterone deficiency were evaluated . The subjects included ten men with primary hypogonadism and 29 with and ropause with sexual dysfunction as the most common problem . The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Question naire for and rogen deficiency in aging males ( ADAM ) . Digital rectal examination ( DRE ) was performed and serum testosterone , prostate-specific antigen ( PSA ) and liver profile were monitored . Testosterone undecanoate treatment ( n = 33 ) significantly improved sexual dysfunction and symptom scores of metabolic , cardiopulmonary , musculo-skeletal and gastrointestinal functions compared to baseline and to placebo ( n = 6 ) . ADAM score also significantly improved after 3 months of treatment . Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group . In the placebo group , no significant changes compared to baseline were found for testosterone levels and QoL question naires . No abnormal findings were detected on DRE or laboratory findings in either group . Adverse events , such as gastrointestinal problems and fatigue , were mild and self-limiting . It is concluded that and rogen supplement therapy with oral testosterone undecanoate ( And riol ) restores the quality of life through improvement of general body functions in men with testosterone deficiency OBJECTIVE To assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism compared to hypogonadal men without replacement , and controls , during six months . METHODS We assessed , through ADAM , AMS , IIEF-5 and SF-36 question naires , and through clinical and laboratory examinations , 62 patients divided into three groups : 17 hypogonadal males ( HR ) used intramuscular testosterone every three weeks ; 14 hypogonadal males ( HV ) and 31 non-hypogonadal males ( CV ) used oral vitamins daily . RESULTS When compared to others , HR group obtained libido improvement assessed by ADAM 1 ( p = 0.004 ) , and borderline sexual potency improvement assessed by IIEF-5 ( p = 0.053 ) , besides a decrease in waist circumference after eight weeks ( p = 0.018 ) . The remaining parameters did not differ between the groups . PSA and hematocrit remained stable in those using testosterone . CONCLUSION Six months of testosterone replacement improved sexuality and body composition , with prostatic and hematological safety A decline in testicular function is recognized as a common occurrence in older men . However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines . This study was undertaken to examine the year-long effects of testosterone administration in this patient population . Fifteen hypogonadal men ( mean age 68 + /- 6 yr ) were r and omly assigned to receive a placebo , and 17 hypogonadal men ( mean age 65 + /- 7 yr ) were r and omly assigned to receive testosterone . Hypogonadism was defined as a bioavailable testosterone < 60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months . The main outcomes measured included grip strength , hemoglobin , prostate-specific antigen , leptin , and memory . Testosterone improved bilateral grip strength ( P < 0.05 by ANOVA ) and increased hemoglobin ( P < 0.001 by ANOVA ) . The men assigned to testosterone had greater decreases in leptin than those assigned to the control group ( mean + /- SEM : -2.0 + /- 0.9 ng/dL vs. 0.8 + /- 0.7 ng/dL ; P < 0.02 ) . There were no significant changes in prostate-specific antigen or memory . Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study . Three of those seven withdrew because of an abnormal elevation in hematocrit . Testosterone supplementation improved strength , increased hemoglobin , and lowered leptin levels in older hypogonadal men . Testosterone may have a role in the treatment of frailty in males with hypogonadism ; however , older men receiving testosterone must be carefully monitored because of its potential risks Transdermal testosterone ( T ) delivery represents an effective alternative to injectable and rogens . We studied 163 hypogonadal men who applied 5 , 7.5 , or 10 g And roGel ( T gel ) 1 % CIII per day for up to 42 months . Efficacy data were presented in 123 subjects considered evaluable . Continuous And roGel treatment normalized mean serum T and free T levels . Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased , mean serum estradiol/T ratio doubled , and mean serum FSH and LH levels were suppressed by T replacement . Sexual function and mood parameters improved rapidly and were maintained throughout T treatment . Lean body mass increased ( P = 0.0001 ) and fat mass decreased ( P = 0.0001 ) , and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength . Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine ( P = 0.0001 ) than the hip ( P = 0.0004 ) . Mild local skin irritation occurred in 12 subjects , result ing in discontinuation in only one subject . Except for the anticipated increase in hematocrit and hemoglobin , there were no clinical ly significant changes in blood counts or biochemistry . In three subjects with elevated serum prostate-specific antigen , prostate biopsies showed cancer . We conclude that continued application of And roGel result ed in beneficial effects similar to those with injectables and other transdermal preparations . This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk . Thus , monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men Abstract Background : Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities . Despite limitations , registries can provide an opportunity to accumulate data regarding disease management in a typical patient population , including diagnosis , treatment , and outcomes . Material s and Methods : The Testim Registry in the United States ( TRiUS ) was a prospect i ve , 12-month , observational cohort registry of men prescribed Testim ® ( 1 % testosterone gel ; Auxilium Pharmaceuticals , Inc. ) for the first time ; patients previously on other forms of testosterone replacement therapy ( TRT ) were eligible to participate in the study as well . The registry recorded total testosterone ( TT ) and free testosterone ( FT ) levels , prostate-specific antigen ( PSA ) , sexual function , mood/depression , and cardiometabolic and anthropometric criteria before and after TRT . Changes over time were analyzed by analysis of variance , and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables . Results : At baseline , 849 patients from 72 sites were enrolled , with 743 of 849 started on 5 g gel/day ( 50 mg testosterone/day ) and 106 of 849 started on 10 g gel/day ( 100 mg testosterone/day ) . Mean TT and FT levels increased significantly after 3 months of TRT ( TT level , 16.8 ± 9.87 nmol/L [ 485 ± 284 ng/dL ] , P < 0.001 ; FT level , 286.3 ± 224.9 pmol/L [ 82.5 ± 64.8 pg/mL ] , P < 0.001 ) and were maintained at eugonadal levels . Mean PSA levels increased significantly ( P = 0.004 ) from 1.12 ± 1.11 μg/L ( 1.12 + 1.11 ng/mL ) at baseline to 1.26 ± 1.22 μg/L ( 1.26 ± 1.22 ng/mL ) after 12 months of TRT , although changes were well within guidelines ( < 1.4 μg/L/year increase ) . Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months . Conclusion : Testosterone deficiency symptoms improved with TRT use in men ; sexual function and mood/depression improvements were seen before metabolic improvements . Prostate-specific antigen levels increased , although increases were within guideline -determined safety limits INTRODUCTION The effect of parenteral testosterone replacement therapy on prostatic specific antigen ( PSA ) level or the development or growth of prostate cancer is unclear . AIM To assess the effect of testosterone replacement on PSA level in patients with hypogonadism associated with erectile dysfunction ( ED ) . METHODS A total of 187 male patients above the age of 45 with hypogonadism associated with ED were enrolled in this study . Patients were screened for ED by the erectile function domain of the International Index of Erectile Function ( IIEF ) . Patients underwent routine laboratory investigations , plus total testosterone , and PSA assessment . Replacement treatment with parenteral testosterone every 2 - 4 weeks for 1 year was instituted . Total testosterone and PSA serum levels were assessed every 3 months during the treatment course . RESULTS Mean age + /- SD was 62.8 + /- 11.4 . Of the patients 87.7 % were sexually active . Of the patients 10.2 % had mild , 40.6 % had moderate and 49.2 % had severe ED . Of the study population , 62.5 % had ED complaints for less than 5 years and 84.5 % had gradual onset of their complaint . The majority of the patients ( 91.4 % ) had either progressive or stationary course while the minority reported regressive course and improvement of the condition . There was a significant increase of the post-treatment testosterone level in comparison to pretreatment level ( P < 0.05 ) . No significant increase in the post-treatment PSA level in comparison to pretreatment ( P > 0.05 ) . No significant difference between pre- and post-treatment categories of PSA level ( normal , borderline , high ) in relation to the severity of ED ( P > 0.05 ) . There was no significant association between PSA level and the duration of testosterone replacement therapy in the study population ( P > 0.05 ) . CONCLUSION The current study demonstrated that the level of PSA was not significantly changed after 1 year of testosterone replacement therapy in patients with hypogonadism associated with ED OBJECTIVES To use the International Index of Erectile Function ( IIEF ) to evaluate the improvement of erectile function and other sexual functions after testosterone monotherapy . Testosterone replacement therapy alone was reported to be effective for the improvement in sexual function in hypogonadal males . However , it is still unclear that which kind of the sexual function is most beneficial and to what extent the sexual function could be improved . METHODS A double-blind , r and omized , placebo-controlled study was conducted with a treatment group ( n = 20 ) and control group ( n = 20 ) . Using a critical review of the different sexual functional domain scores of the IIEF-15 and the scores of the IIEF-5 , we evaluated the sexual function of men in hypogonadal status before and after 3 months of testosterone gel treatment . Effect size was used to compare the drug effects for each sexual functional domain , and the results were confirmed by multivariate analysis . RESULTS A total of 30 men remained at the end of the study . After 3 months of testosterone gel therapy for the hypogonadal men , the most beneficial effect on sexual function was erectile function , with sexual desire and orgasmic satisfaction insignificantly affected . CONCLUSIONS The results of our study have shown that transdermal testosterone gel treatment for hypogonadal patients can improve their sexual dysfunction mainly through restoring erectile function Men with spinal cord injury are at an increased risk for secondary medical conditions , including metabolic disorders , accelerated musculoskeletal atrophy , and , for some , hypogonadism , a deficiency , which may further adversely affect metabolism and body composition . A prospect i ve , open label , controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury . Healthy eugonadal ( n = 11 ) and hypogonadal ( n = 11 ) out patients with chronic spinal cord injury were enrolled . Hypogonadal subjects received transdermal testosterone ( 5 or 10 mg ) daily for 12 months . Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months . The testosterone replacement therapy group increased lean tissue mass for total body ( 49.6 ± 7.6 vs. 53.1 ± 6.9 kg ; p < 0.0005 ) , trunk ( 24.1 ± 4.1 vs. 25.8 ± 3.8 kg ; p < 0.005 ) , leg ( 14.5 ± 2.7 vs. 15.8 ±2.6 kg ; p = 0.005 ) , and arm ( 7.6 ± 2.3 vs. 8.0 ± 2.2 kg ; p < 0.005 ) from baseline to month 12 . After testosterone replacement therapy , resting energy expenditure ( 1328 ± 262 vs. 1440 ± 262 kcal/d ; p < 0.01 ) and percent predicted basal energy expenditure ( 73 ± 9 vs. 79 ± 10 % ; p < 0.05 ) were significantly increased . In conclusion , testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury , findings that would be expected to influence the practice of clinical care , if confirmed . Larger , r and omized , controlled clinical trials should be performed to confirm and extend our preliminary findings OBJECTIVE To investigate the effects of oral testosterone undecanoate ( TU ) on symptoms associated with late-onset hypogonadism ( LOH ) . Design Multicenter , r and omized , double-blind , placebo-controlled . METHODS The study was performed in 14 study centers in seven European countries . Men > or = 50 years ( n=322 ) with symptoms of hypogonadism and testosterone deficiency ( calculated free testosterone < 0.26 nmol/l ) were r and omized and treated for 12 months with placebo or oral TU 80 , 160 or 240 mg/day . Primary outcome was the total score on the Aging Males ' Symptoms ( AMS ) rating scale after six months of treatment . RESULTS Treatment of mild-to-moderate LOH symptoms in subjects with borderline hypogonadism with oral TU result ed in an improved total AMS score at month 6 , but differences between groups were not statistically significant . There was greater improvement in subjects < 60 years when compared with subjects > or = 60 years ( P=0.001 ) , but baseline testosterone level had no influence on treatment response . The AMS sexual symptoms domain improved with oral TU 160 mg/day at months 6 ( P=0.008 ) and 12 ( P=0.012 ) compared with placebo , but not with 80 and 240 mg/day . Treatment was well-tolerated and there were no between-group differences in adverse events or drop-out rates . CONCLUSIONS In one of the largest placebo-controlled studies of testosterone therapy in LOH , oral TU did not improve total AMS score in subjects with mild-to-moderate symptoms compared with placebo , except the sexual symptom sub-domain where a modest improvement was reported with oral TU 160 mg/day |
11,323 | 11,699,978 | Estimates for the number of patients or tooth surfaces needed to treat to prevent a carious event suggest that the effects of these professional treatments are low in patients who are at reduced risk for dental caries . | This paper summarizes and rates the evidence for the effectiveness of methods available to dental professionals for their use in the primary prevention of dental caries . | This paper examines the evidence demonstrating the effectiveness of sealants in high-caries-risk children and discusses the Research Triangle Institute/University of North Carolina 's ( RTI/UNC ) systematic review . The strict RTI/UNC protocol limited the number of sealant studies that could be included . This analysis exp and ed their criteria to permit additional methods of determining caries risk ( for example , past caries experience , less than two pairs of sound first permanent molars available/child in half-mouth design s ) and outcome measures in addition to DMFS ( that is , percent sealant retention , survival rates , cost-effectiveness , changes in salivary S. mutans levels ) . Nine clinical studies with a r and omized , half-mouth , clinical trial design and seven studies with observational study design s were included . There is good evidence that sealants can be used efficaciously and effectively in high-risk children as long as the sealant is retained . Sealants are more effective in preventing further caries and providing cost savings in a shorter time span if placed in children who have high rather than low caries risk The aim of the investigation was to evaluate the effect of chlorhexidine gel treatment on caries development of approximal tooth surfaces and on salivary counts of Streptococcus mutans . 220 12-year-old schoolchildren , divided into three groups , participated : ( 1 ) chlorhexidine gel group ( n = 72 ) , ( 2 ) placebo gel group ( n = 77 ) , and ( 3 ) control group ( n = 71 ) . The study was carried out double blind with respect to the two gel groups . Group 1 was treated 4 times/year with 1 % chlorhexidine gel and group 2 with a placebo gel . Approximately 1 ml of gel was applied interdentally by means of a flat dental floss . The control group did not receive any gel treatment or flossing . Number of S. mutans in the saliva was estimated on five occasions during the study with the spatula method . After 3 years , the mean approximal caries increment , expressed as new DFS , was 2.50 in the chlorhexidine gel group and 4.30 in the placebo gel group ( p less than 0.05 ) . The corresponding figure in the control group was 5.25 ( p less than 0.001 when compared to group 1 ) . 44 % of the children in the chlorhexidine gel group and 32 % in the placebo gel group did not develop any new approximal caries lesion during the 3-year observation period compared to 18 % in the control group ( group 1 - 3 p less than 0.001 ; group 2 - 3 p less than 0.05 ) . The number of new approximal fillings ( FS ) was 0.24 in the chlorhexidine gel group , 0.75 in the placebo gel group and 0.82 in the control group ( group 1 - 3 p less than 0.01 ; group 2 - 3 p less than 0.05 ) . There was no statistically significant difference between the groups with respect to numbers of S. mutans in saliva . However , there were more individuals with low numbers of S. mutans in the chlorhexidine gel group at the final examination compared to the baseline level ( p less than 0.05 ) The present study compares visible-light Delton with Duraphat fluoride varnish for the prevention of occlusal caries in permanent first molars . A clinical trial was carried out in three groups of 6 - 8-yr-old schoolchildren : a sealant group ( 100 children ) , in which Delton light-polymerized fissure sealant was applied to permanent first molars ; a varnish group ( 98 children ) , in which Duraphat was applied to permanent first molars ; and a control group ( 116 children ) . Replacement ( sealant ) and reapplication ( varnish ) was carried out every 6 months . Percent effectiveness at 24 months ( percentage of saving from caries taking molars as analysis unit ) for those molars initially healthy and with complete occlusal eruption was analyzed . 272 , 252 and 238 molars met the inclusion criteria in the control , varnish and sealant groups , respectively . Of these , 45.2 % , 28.2 % and 10.5 % developed caries after 24 months . The effectiveness was greater in the sealed molars than in the varnished molars ( 62.7 % ) Results of a 3-year clinical trial of Delton fissure sealant resin are reported . 41 % of first molar fissures remained fully sealed after 3 years . Significant differences were found between the levels of resin retention produced by the two operators and retention was significantly better on m and ibular molars than on maxillary molars . In a separate group of 11-year-old children 77 % of fissures were full)’sealed after 3 years The effect of daily toothbrushing with 0.5 % chlorhexidine-containing gel for 12 months was evaluated in a double-blind study in 37 dental students . The active gel did not markedly influence plaque formation , gingival conditions , or caries as compared with placebo gel treatment . Salivary bacterial counts were performed on subgroups of six subjects using chlorhexidine gel and on six using placebo gel . No differences in the effect of treatment on the microorganisms studied in the two subgroups could be detected except for S. sanguis . The percentage of this species decrease in the placebo group and increased in the chlorhexidine group . The difference became significant after 2 weeks . A tendency to a greater reduction of S. mutans noted in the chlorhexidine group was most marked in individuals who had high initial counts of this species . The proportion of S. sanguis , which could grow on chlorhexidinei-containing mitis salivarius medium , increased and after 12 months of chlorhexidine treatment averaged 34 % of cultivable S. sanguis compared with 0.002 % prior to treatment . The number of less sensitive S. sanguis decreased in the 12 months following termination of treatment . There was no observed tendency for the selection or proliferation of other streptococci , gram-negative rods , yeasts , or staphylococci The objective of this study was to compare Delton visible-light fissure sealant with Duraphat fluoride varnish in the prevention of occlusal caries in permanent first molars . A 48-month clinical trial was carried out in three groups of 6- to 8-year-old schoolchildren : a sealant group ( 104 children ) , in which Delton was used ; a varnish group ( 112 children ) , in which Duraphat was used ; and a control group ( 128 children ) . Sealant or varnish was applied to all sound permanent first molars , according to group . Replacement ( sealant ) and reapplication ( varnish ) was carried out every 6 months . A survival analysis was used to describe the molar failures over time in the three groups . A Cox proportional hazards regression model was built to test the influence of group on molar failure . The median survival times were 28.6 months for the control molars and more than 48 months for both sealed and varnished molars . The Cox model indicated a hazard ratio of 0.177 for the sealant vs control comparison , 0.463 for varnish vs control and 0.382 for sealant vs varnish The effects of some oral hygiene measures on Streptococcus mutans and approximal dental caries were evaluated . One hundred and eighty-seven 13-year-old individuals with high levels of salivary S. mutans ( > 106/mL ) were selected . They were r and omly distributed into three groups . Group I initially received professional mechanical toothcleaning , tongue-scraping , chlorhexidine treatment , and oral hygiene instructions concentrated on the approximal surfaces most colonized by S. mutans . The treatment was given four times with intervals of two days , followed by one single treatment every six months throughout the experimental period . The initial treatment period for group II , also consisting of four visits , included the same oral hygiene instructions as for group 1 . The instructions were repeated every six months . Group III was maintained in the preventive program provided by the local Dental Health Office , based on mechanical plaque control and topical use of fluorides and chlorhexidine at individualized intervals . Group I showed a significant immediate reduction of S. mutans in saliva as well as on approximal tooth surfaces . After six months , there were no differences among the three groups regarding these variables . Compared with baseline , there was a significant reduction of S. mutans in all groups . There was no significant difference in caries progression among the three groups . However , the selected " high-risk " individuals in group I developed 0.25 new manifest caries lesions approximallylyear , compared with 0.27 for all children of the same age group in the area . Seventeen individuals had approximal surfaces with consistently high or consistently low S. mutans levels . Forty-six percent of the surfaces with high values developed new or progressive caries , compared with 2 % of the surfaces with low values A 3-year prospect i ve study was design ed to evaluate sealants in preventing the formation and progression of caries in a young adult military population . United States Navy dentists performed dental examinations on recruits being in-processed at the Naval Training Center , San Diego , California . Contralateral molar pairs ( same arch ) without caries or restorations were selected . Occlusal decalcification and lesions limited to enamel were also eligible , but teeth with proximal decalcification were disqualified . The sample consisted of 860 molar pairs in 529 Navy recruits , each contributing one or two pairs . Required annual dental examinations provided follow-up data , with results being recorded on postcards that were mailed back to the investigator . Yearly response rates were as follows : 1 year , 62.2 % ( 483 molar pairs ) ; 2 year , 47.8 % ( 378 molar pairs ) ; and 3 year , 41.4 % ( 317 molar pairs ) . The response rate for pairs having at least one observation during the 3-year follow-up was 72.6 % ( 563 molar pairs ) , with a caries conversion rate of 1.2 % ( 7 teeth ) on sealed teeth and 5.3 % ( 32 teeth ) on control teeth , yielding 35 discordant molar pairs on 33 recruits ( 30 on control teeth and 5 on sealed teeth ) ( p < 0.0001 ) . These results confirm the efficacy of sealants in significantly reducing the rate caries in a young adult military population The aim of this study was to evaluate the effect of professional flossing with NaF and SnF2 gels on caries development on approximal tooth surfaces . Two-hundred- and -eighty 13-year-old schoolchildren were divided into 3 groups : ( 1 ) NaF ( n = 97 ) , ( 2 ) SnF2 ( n = 85 ) , and ( 3 ) placebo gel group ( n = 98 ) . The investigation was carried out double-blind . The children were treated 4 times a year for 3 years with 1 % NaF gel , 1 % SnF2 gel , or placebo gel . The treatment was carried out by dental nurses and the time required per visit was approximately 10 min . After 3 years , the mean approximal caries increment , including initial caries lesions , was 2.8 in the NaF , 2.4 in the SnF2 , and 4.0 in the placebo gel group ( P < 0.05 for SnF2 vs placebo ) ; a reduction compared to the placebo of 30 % and 39 % in the NaF and SnF2 groups , respectively . Thus , professional flossing with NaF or SnF2 gel carried out 4 times a year may be considered as an interesting caries-preventing method for large-scale application in schoolchildren The aim of this study , performed in Bangkok , was to evaluate the possibility of reducing fissure caries development using an antimicrobial varnish , Cervitec . Children aged 7 - 8 years and 12 - 13 years , 251 in each age group , with at least 2 sound contra-lateral permanent molars , were selected . A split mouth method was used with one test and one control tooth within the same jaw . At baseline and after two years all children were investigated for DMFS and DMFT . In addition , the size of any cavities was estimated . From 200 children , plaque sample s of test and control occlusal surfaces were collected at baseline and after one year and processed to estimate the number of mutans streptococci . Mutans streptococci in saliva were estimated by the Strip mutans method . Cervitec varnish , containing 1 per cent chlorhexidine and thymol was applied at baseline , after 3 - 4 and after 8 - 9 months . The results showed that : Cervitec varnish reduced fissure caries development significantly ; the levels of salivary mutans streptococci at baseline were significantly correlated with caries status at baseline and with total caries increment over the two-year period ; caries development in a fissure was significantly correlated to the level of plaque mutans streptococci at that same site ; three months after the last varnish application , a certain reduction of mutans streptococci in plaque could be seen in the test teeth ; comparing the size of the lesions , more large cavities were found in the untreated teeth . It is concluded that varnishes should be considered as further options for prevention of fissure caries , possibly in more individualised programmes or in combination with already established methods A total of 220 children were examined at 4 1/2 years ( 54 months ) after a single application of a pit and fissure sealant . In 110 children , 177 permanent first molars were treated with Nuva-Seal ; and in 110 children , 168 permanent first molars were treated with Delton . Nuva-Seal was completely retained on 35 % of all paired permanent molars , partially retained on 21 % , and completely lost on 44 % of the study teeth . Delton was completely retained on 72 % of all paired permanent molars , partially retained on 14 % , and completely lost on 14 % of the study teeth . These data indicate that occlusal caries protection on permanent molars is assured if the sealant is completely retained on the tooth . Delton was four times more effective in providing protection against pit and fissure caries than Nuva-Seal A clinical field trial was conducted , over a 2-yr period , to evaluate the efficacy of bi-annual APF gel topical applications without previous prophylaxis in reducing dental caries among high-risk children living in non-fluori date d communities . 488 children 6 yr old , presenting at least three cavities on proximal surfaces of their primary teeth , were r and omly assigned to two groups . The experimental group received bi-annual topical APF gel applications and the control group received a placebo . All treatments were given at school without any prior toothcleaning . The APF gel provided a 34.3 % reduction in caries incidence ( P-value = 0.03 ) among the children with 3 - 14 cavities on their primary teeth at the beginning of the study . However , the treatment did not show any efficacy in reducing caries incidence among the higher-risk children having initially more than 14 cavities . These findings suggest that the efficacy of APF gel applications without previous prophylaxis varies according to the individual risk of the subjects and that more comprehensive programs should be targeted to very high-risk children The purpose of this double blind clinical trial was to determine the anticaries activity of a dentifrice containing 0.78 % sodium monofluorophosphate in a silica gel abrasive base compared with a placebo under conditions of supervised brushing . 1154 schoolchildren , ages 9 - 12 , were recruited in a non-fluori date d semi-rural area of northeastern Connecticut . Subjects were stratified according to school , grade and sex , and then r and omly divided into two groups . Each school day , children brushed their teeth for 1 min under supervision by project personnel . Weekend and vacation usage was ad libitum . Caries examinations and radiographic readings were performed by the same examiner ( J.R. ) . After 12 months , the 996 subjects examined showed that the group using the test dentifrice had significantly ( less than 0.05 ) lower DMFT ( 25.0 % ) and DMFS ( 19.1 % ) increments than the group using the placebo . After 24 months the 876 subjects examined showed that the test group continued to have significantly lower DMFT ( 24.5 % ) and DMFS ( 24.7 % ) increments than the placebo group . Surface protection after 24 months ranged from 22.1 % for occlusal to 37.1 % for interproximal surfaces This l and mark study of a pit and fissure sealant found 27.6 percent complete retention and 35.4 percent partial retention on permanent first molars . In the matched pair analysis , carious or restored surfaces made up 31.3 percent of the surfaces in the sealed group and 82.8 percent in the unsealed group The aim of the present study was to assess the caries-preventive effect of topical application of Duraphat on the occlusal surface of newly erupted first permanent molars . A base-line examination was performed on children aged 5 years and 9 months . The children were r and omly divided into a Duraphat group and a control group . In accordance with the anatomy of the fissure system , the molars were divided into shallow and deep fissures , respectively . From the time of eruption , 381 molars were examined every 3rd month during 24 months . Duraphat was applied every 6th month , altogether four times . The results showed that in the Duraphat group 35 % of the fissures were decayed compared with 80 % in the control group . Caries reduction amounted to 56 % , and the caries-preventive effect was found in molars with shallow and deep fissures A professionally applied two – stage chlorhexidine varnish , Chlorzoin ® , was developed to achieve sustained release and minimise the problems of staining and bad taste associated with chlorhexidine mouthrinses . The primary aim of this r and omised controlled clinical trial was to assess the efficacy of Chlorzoin in reducing the caries increment in high – caries – risk adolescents . Secondary aims included investigating the effect of compliance upon caries increment , the effect of Chlorzoin upon salivary mutans streptococci levels and assessing the benefit of individual dental health advice by dental auxiliaries in a community setting . 1,240 children , initially aged 11–13 years , assessed to be at high caries risk were recruited into the trial . The trial design involved four arms : an observational group , a control group , an active ( Chlorzoin ) varnish group and a placebo varnish group . All subjects were examined annually by a calibrated examiner who was blind to the group allocation . Three – year caries increments were calculated using clinical , clinical and fibre – optic transillumination , and clinical and bitewing data sets . The results indicated that the use of Chlorzoin had an initial effect on mutans streptococci levels but that no long – term reduction in caries increment or mutans streptococci infection could be detected . One reason for this lack of efficacy may have been the regimen of reduced frequency of varnish applications after the initial period . Children who followed the protocol and , therefore , were seen regularly by dental auxiliaries had a lower caries increment than those who did not . This finding was independent of varnish allocation . In summary , under this regimen , Chlorzoin has been found to be effective in decreasing salivary mutans streptococci but ineffective as a caries – preventive agent in high – risk Scottish children when applied pragmatically in a community setting An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices , one in a calcium pyrophosphate base and the other in a silica gel base , with a nonfluoride control dentifrice . The test dentifrice , stannous fluoride in a silica gel base , reduced caries to a significant extent when compared with the nonfluoride control dentifrice . The percentage of reductions ranged from 15 % to 25 % for whole mouth and interproximal surface indexes . There was no significant difference between the two fluoride dentifrices OBJECTIVES The aim of this study was to assess the effect of a chlorhexidine varnish on occlusal caries incidence when applied 6-monthly into the fissures of erupting and freshly erupted permanent molars . METHODS In a double-blind clinical trial , 332 children aged 5/6 and 11/12 years attending a Child Dental Health Centre were r and omly assigned to a control and an experimental group . Criteria for inclusion in the study were that all first permanent molars in 5 - 6-year-olds and all second permanent molars in 11 - 12-year-olds either had recently erupted , or were in a stage of eruption , or would erupt within half a year . At baseline , counts of dmfs/DMFS and mutans streptococci in saliva were recorded . During a maximum of 3 years , every 6 months the occlusal surfaces of molars in the experimental group received a 40 % chlorhexidine varnish application , whereas those in the control group received a placebo varnish application . RESULTS Data of 316 children were analysed and ANOVA showed no significant occlusal caries reduction in this sample of Dutch 5/6- and 11/12-year-old children . After stratification into low and high caries risk groups , a statistically significant caries-reducing effect on occlusal caries in permanent molars was found in the group of children with > or = 10(6 ) mutans streptococci per ml saliva ( P < 0.05 ) . CONCLUSION Six-monthly application of chlorhexidine varnish has no caries-reducing effect on occlusal caries in recently erupted permanent molars in a population with low caries prevalence This report presents final results obtained after the third annual follow-up survey in a study design ed to test the caries-inhibiting effect of a topically applied acidulated phosphate-fluoride solution and gel . The follow-up survey included 681 of the original 1,105 Hawaiian children , ages 10 through 12 years . Findings from the first examinations were used for base line data and for classifying the subjects according to sex , dental age , and previous caries experience . The participants were then assigned r and omly to one of the four study groups . Statistical analysis of the data is included to support the finding that acidulated phosphate-fluoride solution and gel are effective cariostatic agents Caries prevention by daily supervised use of a MFP gel dentifrice . Report of a 3-year clinical The aim of this community-oriented study was to evaluate different methods to prevent fissure caries . The following products and measures were tested : 1 ) glass ionomer cement ( GIC ) applied by dentist ; 2 ) same material applied by short term ( 3 days ) trained personnel ( teachers ) ; 3 ) application of a 0.5 % HF solution three times ; 4 ) an established autopolymerized resin based sealant ( Delton ) . The study was performed in Bangkok , Thail and , a city in a developing country experiencing increasing caries prevalence . Children with at least three sound permanent molars from two age groups , 7 - 8 and 12 - 13-yr-olds respectively were chosen from very low to medium socioeconomic level families . 1264 children were systematic ally assigned to experiment or control groups based on school and DMFT . For the younger age group , the 2 yr mean DFS occlusal increment in the Control group was 0.66 surfaces . Significantly lower increments were observed in the GIC experimental group : 0.17 surfaces applied by the teachers and 0.32 applied by dentist , corresponding to 74 % and 52 % reductions , respectively . The mean increment in the HF group was 0.44 surfaces , a 33 % reduction in relation to the Control group . For the 12 - 13-yr-olds , the mean occlusal surface DF increment was 0.70 surfaces in the Control group . Almost no occlusal increment was found in the Delton group , 0.05 DFS , a 93 % reduction . In the GIC Dentist group , the DFS increment was 0.48 and in the Teacher group 0.56 , corresponding to 31 % and 20 % reduction , respectively . A slight and nonsignificant increase of caries in relation to the Control group was observed in the HF group . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED It has been suggested that specific preventive programs be developed for children with high caries risk . One possibility is to consider whole classes in socially deprived schools as caries-risk groups and perform an intensified preventive program for the entire class . OBJECTIVE The purpose of this study was to evaluate the effectiveness of such a program which includes the application of a fluoride varnish ( Duraphat ) . METHODS The application of the varnish was offered three to four times a year in a community with low socio-economic status and a generally high caries level . Two hundred and sixty-nine children in six primary schools of Linden/Limmer , a district in Hannover , Germany , were allocated to a test or a control group . The test group received the fluoride varnish for 4 years whereas the control group received no professional fluoride application . DMFT was recorded at the beginning of the study and after 4 years . RESULTS At the end of the study , children who had received a minimum of two fluoride applications per year showed a significantly lower caries increment in comparison with the control group ( 0.88 DMFT vs 1.39 DMFT , P < 0.05 ) . CONCLUSIONS It can be concluded that a minimum of two applications of the fluoride varnish Duraphat per year may be an effective measure in preventing caries in socially deprived children with high caries activity The caries preventive effect of topical application of fluoride varnish ( Duraphat ) , ferric-aluminum-fluoride solution ( FeAlF ) and chlorhexidine gel was compared in 2-yr clinical study . Children with more than 10(6 ) mutans steptococci per ml saliva were selected and a total of 189 13-yr-old children participated in the study . The children in the fluoride groups were treated every third month with either Duraphat or FeAlF-solution . In the chlorhexidine group children with more than 2.5 x 10(5 ) mutans streptococci per ml of saliva were treated every third month . The mean number of new decayed and filled tooth surfaces was 3.06 in the chlorhexidine group , 5.88 in the Duraphat group , 5.33 in the FeAlF group , and 6.34 in the control group . Thus supervised antimicrobial treatment can significantly reduce the incidence of dental ( caries ) in children with high numbers of mutans streptococci Following a single application of a chemically polymerized fissure sealant ( Concise Enamel Bond System ) 60 % of the sealants were present after 2 years of examination . The effectiveness of the treatment was highly significant and the caries reduction , irrespective of the sealant status , was found to be about 50 % . The caries reduction was 98 % in sealed pairs where the material was fully retained Due to concerns about the potential for acute toxicity following professional application of topical fluoride , this clinical trial was undertaken to determine if half-strength acidulated phosphate fluoride ( APF ) would be as clinical ly effective in reducing caries as the currently used 1.23 % APF . Three hundred and sixteen junior high school students , 11 - 15 years of age , living in a nonfluori date d area were assigned r and omly to 1 of 3 groups : a 1.23 % APF thixotropic gel group , a 0.6 % APF thixotropic gel group , or a placebo gel control group . Visual and tactile dental examinations , toothbrush and floss prophylaxis , and topical application of assigned gel were performed twice annually for each child . After 24 months , both the 1.23 % APF group and the 0.6 % APF group experienced statistically significant ( p < .05 ) caries increment reductions when compared to the contro ! group . Although the 2 fluoride-treated groups experienced caries increment reductions that were not statistically different from each other , there was a tendency for the half-strength fluoride ( 0.6 % APF ) to be less effective , especially in reducing pit and fissure caries . Thus , while a half-strength fluoride gel may be effective in reducing caries in selected cases where acute fluoride toxicity is of special concern , these findings suggest hat some effectiveness in pit and fissure caries prevention may be sacrificed . Therefore , this clinical trial does not support widespread reduction of fluoride content to 0.6 % Fin twice-annual , professionally applied topical fluoride formulations . The results of previous clinical trials have shown that the use of acidulated phosphate fluoride ( APF ) gels containing 1.23 % fluoride ( F- ) on a twice-annual basis is effective in preventing dental caries . ~-3 However , recent studies have shown that a considerable amount of fluoride may be ingested during the course of a st and ard professional topical fluoride application 4,5 and that plasma fluoride levels achieved after such an application may reach potentially toxic levels . 6 - 8 Acute fluoride toxicity is of particular concern when administering a topical fluoride treatment to the small child patient because of the exposure to a relatively higher fluoride dose per body weight than in the case of an adult receiving the same treatment . Since most currently used gels are both flavored and acidulated , salivation is stimulated and swallowing of this excess saliva-fluoride mixture generally occurs during gel application . The amount ingested by a young child may be increased if the child is unable to use a saliva ejector effectively . This potential for toxicity would be diminished if the fluoride concentration of the currently used 1.23 % APF gels could be reduced without compromising clinical effectiveness . Due to differences in conditions under which clinical studies are conducted , the clinical effect of variations in fluoride concentration can not be determined by comparing the results obtained in independent trials . As a result , the lowest fluoride concentration that achieves optimum clinical effectiveness when applied twice annually has not been established . Evidence exists , however , to support the idea that a lower concentration than the current st and ard 1.23 % APF gel may be effective . All the current theories of mechanism of action of topical fluorides including remineralization , reduction of enamel solubility and antibacterial action , propose that lower concentrations of fluoride would suffice for these effects . 9 - 12 Fluoride gels of different concentrations ranging from 0.25 to 1.25 % Fhave been tested in the rat model and all were found to be significantly effective in inhibiting caries . 13 In a previously reported clinical trial PEDIATRIC DENTISTRY : September 1985/Vol . 7 No. 3 185 in which a high-release 1.23 % fluoride solution was compared with a gel that released only half as much fluoride , both agents were found to be equally effective in reducing caries when the agents were applied twice annually . 3 However , the vehicles were not the same and that variable may have been a factor . Although such supporting evidence exists , no clinical trials directly comparing the caries reducing effects of twice-annual , professionally applied topical gels of varying fluaride concentrations have been reported . This controlled clinical trial was design ed to compare directly the caries-preventive effects of an APF topical gel containing the st and ard 1.23 % Fwith those of a gel containing a reduced fluoride concentration ( 0.6 % F- ) when the agents were applied twice annually in a child population . Methods and Material s The initial study sample consisted of 428 seventh grade students in nonfluori date d ( < 0.2 ppm F- ) areas of Guilford County , North Carolina . Students undergoing fixed orthodontic appliance therapy were excluded from the study since the presence of b and ed appliances would not allow adequate examination and would interfere with the direct contact between enamel and fluoride . Students who returned a permission slip were assigned r and omly to 1 of 3 groups of equal size : those to be treated with a 1.23 % APF gel ( Group A ) ; those to be treated with a 0.6 % APF gel ( Group B ) ; and those to receive a placebo gel containing no fluoride ( Group C ) . At the beginning of the study in March , 1981 , each child received a dental prophylaxis , a dental examination , and an application of his assigned gel . These procedures were repeated every 6 months ( _ + 3 weeks ) for 2 years . To obtain subject demographic data and ascertain the extent of the child ’s dental care and past fluoride exposure , a question naire was mailed to the parents of each participant . Prior to examina ~ tion and gel application , each subject ’s teeth were stained with a disclosing solution . " ~ The stained plaque was removed with a soft bristle brushb and unwaxed dental floss b by dental hygiene students or dental assistants who were familiar with the study protocol . No prophylaxis paste or dentifrice was used in the prophylaxis procedure . A single examiner ( PH ) performed all dental examinations . Portable dental chairs and lights were set up in the schools for the procedures . The teeth were dried with compressed air prior to the examinations . Front surface mirrors and sharp # 23 explorers were Trace Dental Disclosing Solution -Lorvic Corp : St. Louis , MO . Oral B 40 Toothbrushes and Oral B Unwaxed Dental Floss -Coopercare , Inc : Fairfield , NJ . used to perform the visual and tactile examinations . Radiographs were not taken . The DMFS index was used as the measurement of caries experience . The examiner adhered to the DMFS criteria set forth by the Caries Measurement Task Group ~ a as modified by the NIDR for the National Dental Caries Prevalence Survey .~ s Only erupted , permanent teeth were included in the study . Third molars were excluded from the data . The data for each child were recorded by trained individuals on separate forms design ed for ease of recording as well as for facilitating subsequent data entry into a computer . Results from prior examinations were not available to the examiner during the course of the study . All data were edited before , during , and after entry into the computer by means of logical checks by a dentist ( PH ) . The edited data then were processed using a Statistical Analysis System ( SAS ) package . ~6 Following plaque removal and examination , the subjects received a 4-min topical application of their assigned gel . Approximately 2.5 ml of the appropriate gel was placed into the trough of disposable styrofoam trays~ by trained dental personnel . The study followed the classic double-blind protocol in that the examiner , subjects , and dental auxiliaries were unaware of which agent was applied in each subject . All gels were packaged in plain containers labeled only with an identifying code letter . The code was broken only after data collection was completed . Group A received an application of a 1.23 % FAPF thixotropic gel ; d Group B received an application of a 0.6 % Fo APF thixotropic gel ; a and Group C received an application of a placebo thixotropic gel . d To minimize potential bias , the placebo gel was similar to the fluoride gels in color , odor , and physical appearance but contained no fluoride or acid . Prior to placing the fluoride trays firmly onto the dental arches , the teeth were dried with compressed air or cotton gauze . A saliva ejector was placed sublingually to remove excess saliva and fluoride . Participants were allowed to expectorate into a disposable bowl after the trays were removed and each child then was instructed not to eat or drink for 30 min . Students were observed for at least 15 min following gel applications for any signs of acute toxicity such as nausea or vomiting . The data collected were evaluated statistically to determine the significance of DMFS increment difCentrays -Pacemaker Corp : ( Coopercare , lnc ) . All gels were manufactured for this study by Pacemaker Corp : ( Coopercare , |nc ) . The manufacturer of the gels used in this study had no regulatory or administrative role in the planning or implementation of the study or in the analysis of results . After receipt from the manufacturer , fluoride release from the gels was measured according to the flow dialysis method of Congleton et al. ~7 186 PREVENTIVE FFECTS OF TOPICAL FLUORIDE : Hagan et al. ferences using analysis of variance ( ANOVA ) . TM Differences were regarded as significant at the 95 % confidence level . Only data from subjects who finished the 2-year study were included in the data analysis The purpose of this study was to determine the types of fluorides and techniques used for the application of in-office fluorides in the Houston area . A telephone survey was conducted using a stratified r and om sample of 262 dentists . Approximately 39 % of the offices contacted chose to respond to the survey . Only one of the 101 dental offices responding was using an ADA approved professional fluoride product and technique : 1.23 % APF for 4 minutes . While 41.6 % or 42 of the respondents were using 1.23 % APF , they were administering the fluoride for 2 minutes or less with the majority ( 38 out of 42 ) administering for only 1 minute . The second most number of respondents ( 35.6 % ) reported using a dual rinse type product consisting of 0.31 % APF and 1.64 % SnF2 . Of the 101 respondents , 12.8 % reported the use of sodium fluoride gels and rinses . Of these 13 respondents , 9 were using 2.0 % NaF but for less than the recommended 4 minute application time . The other 4 were using 2.0 % rinse which is more appropriate as a weekly-use rinse . The remaining respondents ( 9.8 % ) reported the use of a stannous fluoride containing less fluoride than the approved 8.0 % . Of these 10 respondents , 3 were using 0.63 % SnF2 and 7 were using 0.4 % SnF2 . One office reported the use of a non-fluoride containing mouthrinse used as an in-office fluoride treatment . This response is not included in the data as it does not qualify as a type of fluoride product OBJECTIVE The aim of this two-year community demonstration trial was to study the caries inhibitory effects of semiannual applications of a fluoride varnish in preschool children . METHODS Twenty-four public dental health clinics in the county of Hall and , Sweden , with 5,137 preschool children , 4 and 5 years of age , were matched and equally allocated to a fluoride varnish group ( n = 2,535 ) and a reference group ( n = 2,602 ) . The children in the fluoride varnish group were treated every six months with topical applications of a silane fluoride varnish , Fluor Protector ( 0.1 % F ) , while no fluoride varnish was used in the reference group . Both groups received a basic preventive program at annual checkups consisting of dietary counseling and instructions to parents to brush their children 's teeth at least once daily with fluori date d dentifrice . Caries data were collected by clinical examinations at baseline and after one and two years . RESULTS Caries prevalence at baseline did not differ significantly between the groups . After two years , the mean caries incidence was low and no statistical difference was found in the total number of carious and filled surfaces ( dfs ) between the two groups . However , the incidence of approximal lesions ( dfsa ) was significantly lower ( P < .05 ) in the fluoride varnish group than the reference group . Children in the fluoride varnish group with dfs scores of 1 - 4 and > or = 5 at the start of the study exhibited a statistically significant ( P < .05 ) reduction in approximal caries incidence of 19 percent and 25 percent , respectively , when compared with the reference group . CONCLUSION Preschool children 4 and 5 years of age with clinical caries who receive semiannual applications of a silane fluoride varnish containing 0.1 percent F experience a reduced incidence of approximal caries over two years This report describes a clinical study carried out to compare the cariesinhibiting effect of the unsupervised home use of a sodium-monofluorophosphate-calcium-carbonate-based toothpaste formulation |
11,324 | 25,805,864 | Although the studies had small sample sizes and were of short duration , the current evidence suggests that moderate alcohol consumption may decrease fasting insulin and HbA1c concentrations among nondiabetic subjects .
Alcohol consumption might improve insulin sensitivity among women but did not do so overall | OBJECTIVE Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes .
This reduced risk might be explained by improved insulin sensitivity or improved glycemic status , but results of intervention studies on this relation are inconsistent .
The purpose of this study was to conduct a systematic review and meta- analysis of intervention studies investigating the effect of alcohol consumption on insulin sensitivity and glycemic status . | BACKGROUND : Patients on dietary , weight-reducing treatment commonly are advised against alcohol consumption . In light of the widespread use of alcoholic beverages and the well-established benefits of light to moderate alcohol consumption in risk reduction , a revision of dietary treatment recommendations may be warranted . OBJECTIVE : To investigate whether daily consumption of moderate amounts of alcohol influences the effectiveness of an energy-restricted diet in overweight and obese subjects . DESIGN : A prospect i ve r and omized clinical trial was conducted , with a 3-months intervention period and two isocaloric dietary regimens containing 6.3 MJ ( 1500 kcal ) each , one with 10 % of energy from white wine and one with 10 % of energy from grape juice . The trial was performed in obese subjects being recruited from the Obesity Outpatient Clinic at the University Hospital , Ulm , who all habitually consumed moderate amounts of alcohol . Out of 87 patients , 49 were eligible to participate and 40 completed the study ( age 48.1±11.4 y , BMI 34.2±6.4 kg/m2 ) . Efficacy parameters were body weight and biomarkers of good health . RESULTS : All subjects achieved significant body weight reduction . Weight loss in the grape juice group and white wine group was 3.75±0.46 and 4.73±0.53 kg , respectively . Percent body fat , waist circumference , blood pressure , blood glucose , insulin , triglycerides , and cholesterol were reduced . The antioxidant status was unchanged , as were liver enzyme activities and other safety parameters . There were no significant differences between the groups . CONCLUSIONS : An energy-restricted diet is effective in overweight and obese subjects used to drinking moderate amounts of alcohol . A diet with 10 % of energy derived from white wine is as effective as an isocaloric diet with 10 % of energy derived from grape juice CONTEXT Epidemiologic data demonstrate that moderate alcohol intake is associated with improved insulin sensitivity in nondiabetic individuals . No controlled-diet studies have addressed the effects of daily moderate alcohol consumption on fasting insulin and glucose concentrations and insulin sensitivity . OBJECTIVE To determine whether daily consumption of low to moderate amounts of alcohol influences fasting insulin and glucose concentrations and insulin sensitivity in nondiabetic postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled crossover trial of 63 healthy postmenopausal women , conducted at a clinical research center in Maryl and between 1998 and 1999 . INTERVENTIONS Participants were r and omly assigned to consume 0 , 15 , or 30 g/d of alcohol for 8 weeks each as part of a controlled diet . All foods and beverages were provided during the intervention . An isocaloric beverage was provided in the 0-g/d arm . Energy intake was adjusted to maintain constant body weight . MAIN OUTCOME MEASURES Fasting insulin , triglyceride , and glucose concentrations , measured at the end of each dietary period ; insulin sensitivity , estimated with a published index of glucose disposal rate corrected for fat-free mass based on fasting insulin and fasting triglyceride concentrations , compared among treatments with a mixed-model analysis of variance . RESULTS A complete set of plasma sample s was collected and analyzed for 51 women who completed all diet treatments . Consumption of 30 g/d of alcohol compared with 0 g/d reduced fasting insulin concentration by 19.2 % ( P = .004 ) and triglyceride concentration by 10.3 % ( P = .001 ) , and increased insulin sensitivity by 7.2 % ( P = .002 ) . Normal-weight , overweight , and obese individuals responded similarly . Only fasting triglyceride concentration was significantly reduced when comparing 0 and 15 g/d of alcohol ( 7.8 % ; P = .03 ) , and no difference was found between consumption of 15 and 30 g/d of alcohol ; however , there was a significant linear trend ( P = .001 ) . Fasting glucose concentrations were not different across treatments . CONCLUSIONS Consumption of 30 g/d of alcohol ( 2 drinks per day ) has beneficial effects on insulin and triglyceride concentrations and insulin sensitivity in nondiabetic postmenopausal women Epidemiologic studies indicate that alcohol consumption is associated with improved insulin sensitivity ; however , scant experimental evidence confirms this observation . To determine the effects of regular moderate wine consumption on insulin sensitivity , 20 overweight women ( body mass index [ BMI ] , 29.8 + /- 2.2 kg/m2 ) participated in a 20-week free-living r and omized crossover trial . The subjects , serving as their own controls , consumed wine ( 190 mL red wine , 13 % vol/vol ethanol , 5 days per week ) for 10 weeks and abstained for 10 weeks or vice versa . The dependent variables ( body weight , BMI , percent body fat , blood pressure , fasting blood glucose and insulin , blood lipids , dietary intake , and insulin sensitivity by intravenous glucose tolerance test [ IVGTT ] ) were measured at the pretest , at the 10-week crossover , and at the 20-week completion of the study . Data were analyzed at the pretest and at completion of the wine drinking and abstention periods of the study using ANOVA by order of treatment . Fasting glucose remained unchanged ( mean + /- SD ; P > .05 ) throughout the experiment ( pretest , drinking , and abstention , 91.1 + /- 9.2 , 91.6 + /- 9.1 , and 88.5 + /- 11.2 mg/dL ) , as did the measures of insulin sensitivity , fasting insulin ( pretest , drinking , and abstention , 8.6 + /- 3.3 , 8.6 + /- 4.1 , and 9.1 + /- 4.7 microU/mg ) and the insulin sensitivity index ( 3.60 + /- 2.96 , 3.25 + /- 2.17 , and 3.30 + /- 1.84 ) . Body composition and blood lipids also remained unchanged ( P > .05 ) during treatment . Moderate wine consumption at this dose in overweight women did not improve or impair insulin sensitivity , nor did it change any of the known correlates of insulin sensitivity , including body weight and composition , blood lipids , and blood pressure OBJECTIVE To investigate the effect of moderate alcohol consumption on fat distribution , adipose tissue secreted proteins ( adiponectin and resistin ) , and insulin sensitivity in healthy middle-aged men with abdominal obesity . RESEARCH METHODS AND PROCEDURES Thirty-four healthy men between 35 and 70 years old , with increased waist circumference ( > or = 94 cm ) , participated in a r and omized , controlled cross-over design trial . They drank 450 mL of red wine ( 40 grams of alcohol ) or 450 mL of de-alcoholized red wine daily during 4 weeks . At the end of each treatment period , fat distribution , adipose tissue proteins , and insulin sensitivity index ( ISI ) were measured . RESULTS Subcutaneous and abdominal fat contents and body weight did not change after 4 weeks of moderate alcohol consumption . Liver fat ( quip index ) was slightly higher after consumption of red wine ( 6.8 + /- 0.1 ) as compared with de-alcoholized red wine ( 6.5 + /- 0.1 ) but not significantly different ( p = 0.09 ) . Plasma adiponectin concentration increased ( p < 0.01 ) to 6.0 + /- 0.1 microg/mL after 28 days of moderate alcohol consumption compared with de-alcoholized red wine ( 5.5 + /- 0.1 microg/mL ) . Serum resistin concentrations and ISI were not affected by alcohol consumption . Percentage changes in serum resistin correlated significantly with changes in ISI ( r = -0.69 , p < 0.01 ) , whereas this correlation was not present between changes in plasma adiponectin and ISI ( r = 0.31 , p = 0.22 ) . DISCUSSION Moderate alcohol consumption for 4 weeks is not associated with differences in subcutaneous and abdominal fat contents or body weight . Thus , the 10 % increase in adiponectin was not associated with a change in fat distribution or body weight change Objectives . To eluci date whether consumption of two Chinese liquors , tea-flavor liquor ( TFL ) and traditional Chinese liquor ( TCL ) have protective effects on cardiovascular disease ( CVD ) risk factors in healthy human subjects . Methods . Forty-five healthy subjects ( 23 men , 22 women ) , aged 23–28 , were recruited and r and omized into two groups : TFL and TCL , and consumed 30 mL/day ( 45 % ( v/v ) alcohol ) of either liquor for 28 days . Results . Serum high-density lipoprotein cholesterol/low-density lipoprotein cholesterol ( HDL-C/LDL-C ) and apolipoprotein A1 were significantly increased , and total cholesterol ( TC ) and TC/HDL-C were significantly decreased after the intervention in both groups ( P < 0.05 ) . Serum uric acid ( P = 0.004 for TFL , P = 0.001 for TCL ) , glucose ( P < 0.001 for TFL , P < 0.001 for TCL ) and endothelial adhesion molecules ( P < 0.05 ) were significantly decreased after the intervention . ADP-induced whole blood platelet aggregation was also significantly decreased after the intervention in both TFL and TCL groups ( P < 0.05 ) . Conclusions . TFL and TCL consumption had protective effects on CVD risk factors in young humans . However , the results were valid only for 28 days , and that the possibility of adverse effect ( liver , kidney ) of chronic alcohol consumption should be considered Moderate alcohol consumption is associated with increased concentrations of adiponectin . Whether this is the case for both total and high-molecular-weight ( HMW ) adiponectin is uncertain . Furthermore , the rate at which this increase occurs is unclear . Therefore , we examined the effect of moderate alcohol consumption on total and HMW adiponectin . In a r and omized , crossover trial , 24 premenopausal women who were regular alcohol consumers received beer ( ∼26 g alcohol ) or alcohol-free beer daily for 3 weeks preceded by a 1-week washout . Blood sample s were collected weekly after an overnight fast for measurement of total and HMW adiponectin and markers of glucose and lipid metabolism . There was a significant interaction ( P < .05 ) between the 2 treatments over time for both plasma HMW and total adiponectin concentrations . Within 3 weeks , plasma total ( 8.2 % , P = .01 ) and HMW ( 8.2 % , P = .02 ) adiponectin levels were higher after moderate alcohol consumption compared with abstention . Changes over time in total adiponectin were positively associated with changes in HMW adiponectin during the nonalcoholic beer ( r = 0.80 ; 95 % confidence interval , 0.55 - 0.92 ) and beer ( r = 0.82 ; 0.58 - 0.93 ) intervention . Alcohol consumption did not affect the ratio of HMW to total adiponectin or the serum glucose , insulin , hemoglobin A(1c ) , or triglyceride levels compared with abstention during the intervention periods . Both total and HMW adiponectin concentrations are higher after moderate alcohol consumption compared with abstention in premenopausal women . These effects were evident after at least 3 weeks of consumption and occurred concomitantly OBJECTIVE —In a r and omized controlled trial , we assessed the effect of daily moderate alcohol intake on glycemic control in the fasting and postpr and ial states in patients with type 2 diabetes who previously had abstained from alcohol . RESEARCH DESIGN AND METHODS —We r and omly assigned 109 patients ( 41–74 years old ) with established type 2 diabetes who abstained from alcohol to receive 150 ml wine ( 13 g alcohol ) or nonalcoholic diet beer ( control ) each day during a 3-month multicenter trial . The beverages were consumed during dinner . Diet and alcohol consumption were monitored . RESULTS —During the intervention , 17 % of participants ( 12 % from the alcohol group ) dropped out , leaving 91 who completed the trial . Within the alcohol group , fasting plasma glucose ( FPG ) decreased from 139.6 ± 41 to 118.0 ± 32.5 mg/dl after 3 months compared with 136.7 ± 15.4 to 138.6 ± 27.8 mg/dl in the control subjects ( Pv = 0.015 ) . However , alcohol consumption had no effect on 2-h postpr and ial glucose levels ( difference of 18.5 mg/dl in the control group vs. 17.7 mg/dl in the alcohol group , Pv = 0.97 ) . Patients in the alcohol group with higher baseline A1C levels had greater reductions in FPG ( age-adjusted correlation −0.57 , Pv < 0.001 ) . No significant changes were observed in the levels of bilirubin , alkaline phosphatase , alanine aminotransferase , or aspartate aminotransferase , and no notable adverse effects were reported . Participants in the alcohol group reported an improvement in the ability to fall asleep ( Pv < 0.001 ) . CONCLUSIONS —Among patients with type 2 diabetes who had previously abstained from alcohol , initiation of moderate daily alcohol consumption reduced FPG but not postpr and ial glucose . Patients with higher A1C may benefit more from the favorable glycemic effect of alcohol . Further intervention studies are needed to confirm the long-term effect of moderate alcohol intake OBJECTIVE Population data suggest that alcohol consumption may influence the risk of diabetes in a biphasic manner , but this has not been tested by any controlled interventions . The object of this study was to determine whether reducing alcohol intake in moderate-to-heavy drinkers ( 40 - 110 g/day ) results in improvement in insulin sensitivity . RESEARCH DESIGN AND METHODS A 4-week run-in period where subjects maintained their usual drinking pattern was followed by r and omization to a two-way cross-over intervention study . In each of two 4-week treatment interventions , subjects either substituted their usual alcohol intake with a 0.9 % alcohol beer or maintained their usual alcohol intake . At the end of each 4-week period , insulin sensitivity as determined by the low-dose insulin glucose infusion test and the homeostasis model assessment ( HOMA ) score , and biomarkers of alcohol consumption ( gamma-glutamyl transpeptidase [ gamma-GT ] and HDL cholesterol ) were measured . RESULTS A total of 16 healthy men aged 51.0 + /- 2.7 ( mean + /- SEM ) years with a BMI of 26.4 + /- 0.61 kg/m(2 ) completed the study . There was a large reduction in alcohol intake ( 72.4 + /- 5.0 vs. 7.9 + /- 1.6 g/day , P < 0.001 ) and significant reductions in gamma-GT ( geometric mean 24.4 units/l [ 95 % CI 19.7 - 30.2 ] vs. 18.6 units/l [ 15.5 - 22.2 ] , P < 0.01 ) and HDL cholesterol ( 1.36 + /- 0.07 vs. 1.13 + /- 0.07 mmol/l , P < 0.001 ) . There was no effect of alcohol on insulin sensitivity index ( ISI ) , fasting insulin , glucose , or HOMA score . CONCLUSIONS A substantial reduction in alcohol intake from 7.2 to 0.8 st and ard drinks per day in healthy men did not change insulin sensitivity as measured by ISI or HOMA score OBJECTIVE Little research has explored associations of drinking patterns with glycemic control , especially among women . Our objective was to determine the relationship of patterns of alcohol consumption-including average daily consumption , weekly frequency of consumption , drinking with meals , and beverage type-with biologic markers of insulin resistance in young women . RESEARCH DESIGN AND METHODS This study was cross-sectional in design . The subjects consisted of a stratified r and om sub population of 459 U.S. normal-weight and overweight female nurses , 33 - 50 years of age , drawn from the Nurses ' Health Study II and sample d for distinct drinking patterns . Women provided blood sample s and detailed information on dietary and lifestyle factors between 1995 and 1999 . The main outcome measures were fasting insulin , C-peptide , and HbA(1c ) . RESULTS Adjusting for age , smoking , physical activity , television watching , BMI , and several dietary factors , average alcohol intake was inversely associated with HbA(1c ) ( units in percentage of HbA(1c ) ) : 0 g/day ( reference = 5.36 % ) , 0.1 to < 5.0 g/day ( -0.04 % ) , 5.0 to < 15.0 g/day ( -0.09 % ) , 15.0 to < 25.0 g/day ( -0.10 % ) , and > or = 25.0 g/day ( -0.17 % ) ( P value , test for trend < 0.001 ) . We found an inverse association of alcohol intake and insulin , but only for women with a BMI > or = 25 kg/m(2 ) . Specifically , insulin levels were lowest for episodic drinkers consuming > or = 2 drinks per day on 0 - 3 days per week . Consumption with meals and type of alcoholic beverage did not further influence these results . CONCLUSIONS Moderate alcohol consumption of 1 - 2 drinks per day on a few to several days of the week may have a beneficial glycemic effect , particularly among overweight women Aims /hypothesisThe aim of this study was to investigate whether moderate alcohol consumption increases plasma high molecular weight ( HMW ) adiponectin and /or muscle oxidative capacity . Material s and methods Eleven lean ( BMI 18–25 kg/m2 ) and eight overweight ( BMI ≥27 kg/m2 ) men consumed 100 ml whisky ( ∼32 g alcohol ) or water daily for 4 weeks in a r and omised , controlled , crossover trial . After each treatment period , muscle biopsies and fasting blood sample s were collected . Results Adiponectin concentrations increased ( p < 0.001 ) by 12.5 % after 4 weeks of moderate alcohol consumption . Moderate alcohol consumption tended to increase HMW adiponectin by 57 % ( p = 0.07 ) and medium molecular weight adiponectin by 12.5 % ( p = 0.07 ) , but not low molecular weight ( LMW ) adiponectin . Skeletal muscle citrate synthase , cytochrome c oxidase and β-3-hydroxyacyl coenzyme A dehydrogenase ( β-HAD ) activity were not changed after moderate alcohol consumption , but an interaction between alcohol consumption and BMI was observed for cytochrome c oxidase ( p = 0.072 ) and citrate synthase ( p = 0.102 ) activity . Among lean men , moderate alcohol consumption tended to increase cytochrome c oxidase ( p = 0.08 ) and citrate synthase activity ( p = 0.12 ) by 23 and 26 % , respectively , but not among overweight men . In particular , plasma HMW adiponectin correlated positively with activities of skeletal muscle citrate synthase ( r = 0.64 , p = 0.009 ) , cytochrome c oxidase ( p = 0.59 , p = 0.009 ) and β-HAD ( r = 0.46 , p = 0.056 ) , while such correlation was not present for LMW adiponectin . Whole-body insulin sensitivity and intramyocellular triacylglycerol content were not affected by moderate alcohol consumption . Conclusions /interpretationModerate alcohol consumption increases adiponectin concentrations , and in particular HMW adiponectin . Concentrations of HMW adiponectin in particular were positively associated with skeletal muscle oxidative capacity Background Fetuin-A , a liver-derived glycoprotein that impairs insulin-signalling , has emerged as a biomarker for diabetes risk . Although moderate alcohol consumption has been inversely associated with fetuin-A , data from clinical trials are lacking . Thus , we evaluated whether moderate alcohol consumption decreases circulating levels of fetuin-A. Methods We analyzed data of three separate open-label , r and omized , crossover trials : 1 ) 36 postmenopausal women consuming 250 ml white wine ( 25 g alcohol ) or white grape juice daily for 6 weeks , 2 ) 24 premenopausal women consuming 660 ml beer ( 26 g alcohol ) or alcohol-free beer daily for 3 weeks , and 3 ) 24 young men consuming 100 ml vodka ( 30 g alcohol ) orange juice or only orange juice daily for 4 weeks . After each treatment period fasting blood sample s were collected . Results Circulating fetuin-A concentrations decreased in men after vodka consumption ( Mean ± SEM : 441 ± 11 to 426 ± 11 μg/ml , p = 0.02 ) , but not in women after wine ( 448 ± 17 to 437 ± 17 μg/ml , p = 0.16 ) or beer consumption ( 498 ± 15 to 492 ± 15 μg/ml , p = 0.48 ) compared to levels after each corresponding alcohol-free treatment . Post-hoc power analyses indicated that the statistical power to detect a similar effect as observed in men was 30 % among the postmenopausal women and 31 % among the premenopausal women . Conclusions In these r and omized crossover trials , moderate alcohol consumption decreased fetuin-A in men but not in women . This sex-specific effect may be explained by the relatively short intervention periods or the low statistical power in the trials among women . Trials registration Clinical Trials.gov ID no ’s : NCT00285909 , NCT00524550 , NCT00918918 Aims /hypothesisTo determine whether 6 weeks of daily , moderate alcohol consumption increases expression of the gene encoding adiponectin ( ADIPOQ ) and plasma levels of the protein , and improves insulin sensitivity in postmenopausal women . Methods In a r and omised , open-label , crossover trial conducted in the Netherl and s , 36 apparently healthy postmenopausal women who were habitual alcohol consumers , received 250 ml white wine ( ∼25 g alcohol/day ) or 250 ml of white grape juice ( control ) daily during dinner for 6 weeks . R and omisation to treatment allocation occurred according to BMI . Insulin sensitivity and ADIPOQ mRNA and plasma adiponectin levels were measured at the end of both periods . Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance ( HOMA-IR ) . Levels of ADIPOQ mRNA in subcutaneous adipose tissue were determined by RT-PCR . Results All subjects completed the study . Six weeks of white wine consumption reduced fasting insulin ( mean ± SEM 40.0 ± 3.4 vs 46.5 ± 3.4 pmol/l ; p < 0.01 ) and HOMA-IR ( 1.42 ± 0.13 vs 1.64 ± 0.13 ; p = 0.02 ) compared with 6 weeks of grape juice consumption . ADIPOQ mRNA levels ( 1.09 ± 0.15 vs 0.98 ± 0.15 ; p = 0.04 ) and plasma levels of total ( 13.1 ± 0.8 vs 12.0 ± 0.8 μg/ml ; p < 0.001 ) and high molecular weight ( HMW ) adiponectin ( 9.9 ± 1.2 vs 8.8 ± 1.2 μg/ml ; p = 0.02 ) significantly increased after alcohol compared with juice consumption . Changes in ADIPOQ mRNA levels correlated with changes in plasma levels of total adiponectin ( ρ = 0.46 ; p < 0.01 ) . Both fasting triacylglycerol ( 8.2 % ; p = 0.04 ) and LDL-cholesterol levels ( 7.8 % ; p < 0.0001 ) decreased , whereas HDL-cholesterol increased ( 7.0 % ; p < 0.0001 ) after prolonged moderate alcohol intake . No notable adverse effects were reported . Conclusions /interpretationModerate alcohol consumption for 6 weeks improves insulin sensitivity , adiponectin levels and lipid profile in postmenopausal women . Furthermore , these data suggest a transcriptional mechanism leading to the alcohol-induced increase in adiponectin plasma levels . Trial registration : Clinical Trials.gov ID no. : NCT00285909 Funding : Partly funded by the Dutch Foundation for Alcohol Research ( SAR ) BACKGROUND Alcohol may have a cardioprotective effect . One possible mechanism is by modifying insulin resistance/secretion . The aims of this study were : ( i ) to examine the effect of short-term alcohol consumption on the metabolic control of glucose tolerance ; ( ii ) to study the influence of short-term alcohol consumption on cardiac autonomic activity using spectral analysis of heart rate variability . METHODS Twenty-one healthy subjects , in a r and omized crossover design , either received three units of ethanol daily for 1 week or abstained from ethanol . The control of glucose tolerance was assessed using the intravenous glucose tolerance test with minimal modelling . RESULTS There was no difference in fasting glucose , fasting insulin or insulin sensitivity between the two groups . Alcohol showed a lower insulin first phase insulin response ( no alcohol 659.0 + /- 394.1 SD , alcohol 535.2 + /- 309.1 ) pmol L-1 min-1 , P = 0.027 ) . There was no difference in heart rate or blood pressure but a significant difference in the ratio of high to low frequency spectral power of heart rate variability ; ( no alcohol 4.55 + /- 3.78 , alcohol 8.16 + /- 6.77 , P = 0.033 ) . This suggests decreased sympathetic and /or increased vagal modulation of heart rate in the alcohol group . CONCLUSION The finding of no difference in insulin sensitivity between the two groups contrasts with , but does not entirely contradict , the results of previous epidemiological studies --perhaps suggesting that longer term changes such as liver enzyme induction may be important . The difference in insulin secretion questions the validity of previous studies of the influence of alcohol on insulin sensitivity , where insulin levels were used as a surrogate for insulin resistance BACKGROUND Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota , and they focused mainly on single polyphenol molecules and select bacterial population s. OBJECTIVE The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits . DESIGN Ten healthy male volunteers underwent a r and omized , crossover , controlled intervention study . After a washout period , all of the subjects received red wine , the equivalent amount of de-alcoholized red wine , or gin for 20 d each . Total fecal DNA was su bmi tted to polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota . Several biochemical markers were measured . RESULTS The dominant bacterial composition did not remain constant over the different intake periods . Compared with baseline , the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus , Prevotella , Bacteroides , Bifidobacterium , Bacteroides uniformis , Eggerthella lenta , and Blautia coccoides-Eubacterium rectale groups ( P < 0.05 ) . In parallel , systolic and diastolic blood pressures and triglyceride , total cholesterol , HDL cholesterol , and C-reactive protein concentrations decreased significantly ( P < 0.05 ) . Moreover , changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number . CONCLUSION This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans , which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet . This trial was registered at controlled-trials.com as IS RCT N88720134 OBJECTIVE Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes . Adiponectin , an adipocyte-derived plasma protein , has been found to be negatively associated with adiposity and positively associated with insulin sensitivity . Moderate alcohol consumption may increase adiponectin , which in turn causes a decrease of tumor necrosis factor (TNF)-alpha . A decreased TNF-alpha level may consequently increase insulin sensitivity . RESEARCH DESIGN AND METHODS To test this hypothesis , we performed a r and omized crossover partially diet-controlled study . A total of 23 healthy middle-aged male subjects consumed daily four glasses of whisky ( 40 g ethanol ) or tap water with dinner during two successive periods of 17 days . RESULTS Moderate alcohol consumption increased plasma adiponectin level ( 11 % ; P = 0.0002 ) but did not affect plasma TNF-alpha level . An increase in insulin sensitivity index was observed in an insulin-resistant subgroup ( 21 % ; P = 0.11 ) , which positively correlated with the relative alcohol-induced increase in plasma adiponectin level ( r = 0.73 , P = 0.02 ) . CONCLUSIONS The experimental results are in agreement with observational data . Moderate alcohol consumption improved insulin sensitivity in relatively insulin-resistant middle-aged men , an effect that may be mediated through alcohol-induced increases in adiponectin Objective : Moderate alcohol consumption is associated with a decreased risk of type II diabetes . This study investigates the effect of moderate alcohol consumption on adipokines and insulin sensitivity . Subjects : Twenty healthy , lean ( body mass index ( BMI ) 18.5–25 kg/m2 ; n=11 ) or overweight ( BMI > 27 kg/m2 ; n=9 ) men ( 18–25 years ) . Methods : Three cans of beer ( 40 g alcohol ) or alcohol-free beer daily during 3 weeks . Results : Adiponectin and ghrelin concentrations increased ( P<0.01 ) by 11 and 8 % , while acylation-stimulating protein ( ASP ) concentrations decreased by 12 % ( P=0.04 ) after moderate alcohol consumption . Concentrations of leptin and resistin remained unchanged . Insulin sensitivity by an oral glucose tolerance test ( OGTT ) was not affected by moderate alcohol consumption , but 2 h glucose concentrations were lower ( P=0.01 ) after beer ( 4.5±0.1 mmol/l ) than alcohol-free beer ( 4.9±0.1 mmol/l ) . Both free fatty acids and glucagon concentrations showed a stronger increase ( P<0.01 ) after 90 min during OGTT after beer than alcohol-free beer . Changes of adiponectin were positively correlated ( r=0.69 , P<0.001 ) , and changes of leptin ( r=−0.53 , P=0.016 ) and ASP ( r=−0.43 , P=0.067 ) were negatively correlated with changes of insulin sensitivity index . All these results did not differ between lean and overweight men . Conclusions : Moderate alcohol consumption increased adiponectin and ghrelin , while it decreased ASP concentrations both in lean and overweight men . These changes are in line with the hypothesized improvement of insulin sensitivity , but did not affect insulin sensitivity within 3 weeks of moderate alcohol consumption 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 Epidemiologic studies have correlated fasting and postload insulin levels with the risk of coronary heart disease , assuming that insulin levels are reliable markers of insulin resistance . However , this assumption has not been systematic ally studied . The author measured insulin response to an oral glucose load and quantitated insulin resistance using the euglycemic hyperinsulinemic clamp technique to evaluate the correlation between insulin level and the degree of insulin resistance in individuals with varying degrees of glucose tolerance . Subjects were r and omly selected from previous population studies done in 1987 - 1989 at the Department of Medicine of the University of Kuopio in east Finl and . Altogether , 50 subjects with normal glucose tolerance , 28 with impaired glucose tolerance , and 54 with non-insulin-dependent diabetes mellitus were studied . Correlations of insulin resistance ( whole-body glucose uptake in clamp studies ) with fasting or postload insulin levels were remarkably consistent , ranging from -0.58 to -0.74 ( p < 0.01 ) in subjects with normoglycemia . In contrast , corresponding correlations were substantially weaker in subjects with impaired glucose tolerance and non-insulin-dependent diabetes . Among these subjects , only the fasting insulin level correlated significantly with insulin resistance ( -0.47 , p < 0.05 and -0.48 , p < 0.01 , respectively ) . The authors conclude that in population studies , only the fasting insulin level should be used as a marker of insulin resistance , particularly in subjects with abnormal glucose tolerance BACKGROUND AND AIMS To analyse the association of moderate beer consumption on the blood lipid profile in healthy Spanish adults . METHODS AND RESULTS The study had an intervention longitudinal design in which each subject established their own control with a previous wash-out phase . After a 30-day alcohol abstinence period , 57 healthy volunteers were su bmi tted to a daily moderate intake of beer for 30 days . Serum total cholesterol , HDL-cholesterol , triacylglycerols , GOT , GPT , GGT and glucose values , as well as blood erythrocytes , haemoglobin , haematocrit and MCV levels , together with anthropometric parameters were determined at the beginning of the study ( baseline levels ) ( a ) , after 1 month of alcoholic abstinence ( b ) and after 1 month of moderate beer consumption ( c ) . Dietary intake was assessed twice by a 7-day dietary record . HDL-cholesterol , erythrocytes , haematocrit and MCV levels increased significantly ( p<0.05 ) after moderate beer consumption in women . In men , a decrease in HDL-cholesterol levels was observed after alcohol abstention . Haematocrit and MCV counts also increased significantly ( p<0.05 ) in men after moderate beer consumption . There were no dietary changes during the study . CONCLUSION In healthy Spanish adults , the effects of moderate beer consumption during 1 month were associated with favourable changes on the blood lipid profile BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin Alcohol consumption is associated with a decreased risk of type II diabetes and cardiovascular diseases . However , there is a great deal of controversy concerning the relationship between alcohol consumption and insulin resistance . This association may be further confounded by an increase in body weight levels . The aim of this study was to determine whether alcohol consumption promotes insulin resistance according to body weight levels in community-dwelling men . Study participants without a clinical history of stroke , transient ischemic attack , myocardial infa rct ion , angina or diabetes were r and omly recruited from a single community at the time of their annual health examination ( 678 men aged 59 + /- 14 years ) . They were classified into never drinkers , light drinkers [ < 1 unit ( 22.9 g ethanol)/day ] , moderate drinkers ( 1 - 1.9 unit/day ) , and heavy drinkers ( > or = 2 unit/day ) , and further divided into underweight [ body mass index ( BMI ) < 23 kg/m(2 ) ] or overweight ( BMI > or = 23.0 kg/m(2 ) ) . Insulin resistance was estimated on the basis of the homeostasis model assessment of insulin resistance ( HOMA-IR ) , and HOMA-IR and potential confounders were compared between the groups . The confounders included age , BMI , smoking status , serum gamma glutamyltransferase , and high molecular-weight adiponectin . In the overall , HOMA-IR is significantly correlated with age , BMI , serum gamma glutamyltransferase , and high molecular-weight adiponectin . After adjustment for potential confounders , mean log HOMA-IR is significantly lower in the heavy drinkers irrespective of BMI categories . In conclusion , alcohol consumption is associated with decreased insulin resistance independent of BMI in Japanese community-dwelling men Abstract Objectives : To assess the relation between regular alcohol consumption and insulin sensitivity , and to estimate the importance of insulin in the association of alcohol with multiple vascular risk factors and cardiovascular disease . Design : Prospect i ve and cross sectional study of a large r and omly selected population sample . Setting : Part of the Bruneck study 1990–5 ( Bolzano province , Italy ) . Subjects : 820 healthy non-diabetic women and men aged 40–79 years . Main outcome measure : Concentrations of fasting and post-glucose insulin , cholesterol , apolipoproteins , triglycerides , Lp(a ) lipoprotein , glucose , fibrinogen , and antithrombin III ; blood pressure ; insulin resistance estimated by the homeostasis model assessment . Results : Fasting insulin concentrations in those who did not drink alcohol and subjects reporting low ( 1–50 g/day ) , moderate ( 51–99 g/day ) , and heavy ( > /=100 g/day ) alcohol intake were 12.4 , 10.0 , 8.7 , and 7.1 mU/l ( P<0.001 ) . Likewise , post-glucose insulin concentrations and estimates for insulin resistance assessed by the homeostasis model assessment decreased significantly with increasing amounts of regular alcohol consumption . These trends were independent of sex , body mass index , physical activity , cigarette smoking , medication , and diet ( P<0.001 ) . Regular alcohol intake predicted multiple changes in vascular risk factors over a five year period including increased concentrations of high density lipoprotein cholesterol and apolipoprotein A I ; higher blood pressure ; and decreased concentration of antithrombin III . These associations were in part attributable to the decrease in insulin concentrations observed among alcohol consumers . Conclusions : Low to moderate amounts of alcohol , when taken on a regular basis , improve insulin sensitivity . Insulin is a potential intermediate component in the association between alcohol consumption and vascular risk factors ( metabolic syndrome ) . Key messages Regular alcohol consumption predicted multiple changes of vascular risk factors over a five year period This alcohol associated metabolic syndrome is in part attributable to the decline in insulin Insulin resistance and beta-cell dysfunction , two factors central to the pathogenesis of type 2 diabetes , were studied in relation to the development of diabetes in a group of participants with impaired glucose tolerance in the Diabetes Prevention Program ( DPP ) at baseline and after specific interventions design ed to prevent diabetes . Participants were r and omly assigned to placebo ( n = 1,082 ) , metformin ( 850 mg twice a day ) ( n = 1,073 ) , or intensive lifestyle intervention ( n = 1,079 ) . The diabetes hazard rate was negatively associated with baseline insulin sensitivity ( hazard rate ratio = 0.62 - 0.94 per SD difference , depending on treatment group and measure of sensitivity ) and with baseline insulin secretion ( hazard rate ratio = 0.57 - 0.76 per SD ) . Improvements in insulin secretion and insulin sensitivity were associated with lower hazard rates in all treatment arms ( hazard rate ratio = 0.46 - 0.95 per SD increase and 0.29 - 0.79 per SD increase , respectively ) . In multivariate models that included the three metabolic variables ( changes in body weight , insulin sensitivity , and insulin secretion ) each significantly and independently predicted progression to diabetes when adjusted for the other two variables . The intensive lifestyle intervention , which elicited the greatest reduction in diabetes incidence , produced the greatest improvement in insulin sensitivity and the best preservation of beta-cell function after 1 year , whereas the placebo group , which had the highest diabetes incidence , had no significant change in insulin sensitivity and beta-cell function after 1 year . In the metformin group , diabetes risk , insulin sensitivity , and beta-cell function at 1 year were intermediate between those in the intensive lifestyle and placebo groups . In conclusion , higher insulin secretion and sensitivity at baseline and improvements in response to treatment were associated with lower diabetes risk in the DPP . The better preventive effectiveness of intensive lifestyle may be due to improved insulin sensitivity concomitant with preservation of beta-cell function |
11,325 | 15,846,625 | Protein supplementation may have reduced the number of long term complications and days spent in rehabilitation wards .
While some evidence exists for the effectiveness of oral protein and energy feeds , overall the evidence for the effectiveness of nutritional supplementation remains weak . | BACKGROUND Fractures of the hip are an important cause of later ill health and mortality in older people .
People with hip fractures are often malnourished at the time of fracture , and have poor food intake in hospital .
OBJECTIVES This review assesses the effects of nutritional interventions in older people recovering from hip fracture . | BACKGROUND Undernutrition and weight loss are important determinants of clinical outcome in older patients after hip fracture but the effectiveness of nutritional support programs in routine clinical practice remains controversial . AIMS OF THE PROJECT : To determine if oral nutritional supplements given daily for 28 days after hip fracture surgery could prevent weight loss and /or lead to improved clinical outcomes ( mortality rates , discharge destination , activities of daily living or length of hospital stay ) in non-malnourished community-dwelling older women with hip fracture . METHODS One hundred and nine women with BMI range 20 - 30 kg/m(2 ) were allocated to either nutritional supplements ( 352 kcal/day ) or usual hospital nutrition using a quasi-r and omisation technique . Body weight changes were monitored at 4 and 8 weeks and clinical outcomes were recorded at discharge and at 6 months . RESULTS No significant differences in weight change or clinical outcomes were seen between the two groups . Compliance with consuming the nutritional supplements was quite variable and there was a significant negative correlation between the amount of supplement consumed and subsequent weight change ( r=-0.36 , P=0.019 ) . CONCLUSIONS Poor compliance with oral nutritional supplements is an important determinant of the effectiveness of oral nutritional interventions in preventing weight loss after hip fracture . Whilst this may explain the lack of clinical improvements seen , our data do not support the routine use of oral nutritional supplements in non-malnourished hip fracture patients To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results AIMS To investigate whether a nutritional intervention in older women and men with femoral neck fracture had an effect on postoperative complications during hospitalization and on nutritional status at a four-month follow-up . METHODS The design was a r and omized controlled trial . The present study sample consisted of 157 patients aged 70 years and above with femoral neck fracture . The nutritional intervention included , among other things , a nutritional journal to detect nutrition deficiencies and protein-enriched meals for at least four days postoperatively . Further , at least two nutritional and protein drinks were served each day during the whole hospitalization and other factors that would influence the patient 's nutrition were also considered and dealt with . Postoperative complications were registered and patients were assessed using the Mini Nutritional Assessment ( MNA ) scale , including body mass index ( BMI ) , on admission and at a four-month follow-up . RESULTS Malnutrition was common and low MNA scores were associated with postoperative complications such as delirium and decubitus ulcers . There were significantly fewer days of delirium in the intervention group , seven patients in the intervention group developed decubitus ulcers vs. 14 patients in the control group and the total length of hospitalization was shorter . There were no detectable significant improvements regarding nutritional parameters between the intervention and the control group at the four-month follow-up but men improved their mean BMI , body weight and MNA scores in both the intervention and the control groups while women deteriorated in both groups . CONCLUSIONS Malnutrition was common among older people with hip fractures admitted to hospital . The nutritional intervention might have contributed to the patients suffering fewer days with delirium , fewer decubitus ulcers and shorter hospitalization but did not improve the long-term nutritional status , at least not in women . RELEVANCE TO CLINICAL PRACTICE This nutritional intervention , which was included in a multifactorial multidisciplinary intervention , is inexpensive and relatively easy to implement . It has significant effects on complications but no long-term effect on nutritional parameters , at least not in women AIM To evaluate the effects of a protein-rich liquid supplementation , alone or in combination with the anabolic steroid n and rolone decanoate , on body composition , activities of daily living ( ADL ) status and the health-related quality of life ( HRQoL ) after a femoral neck fracture . METHODS Sixty women , aged 83 + /- 5 years ( mean + /- SD ) , BMI < 24 kg/m2 ( 20.4 + /- 2 kg/m2 ) and capable of co-operating , with a femoral neck fracture treated with internal fixation , were r and omised to open treatment during 6 months with a protein-rich liquid formula alone ( PR , Fortimel , 200 ml/day , 20 g protein/day ) or in combination with n and rolone decanoate ( PR/N , Deca-Durabol 25 mg i.m./3 weeks ) or to a control group ( C ) . The patients were re-examined after 6 and 12 months regarding body weight ( BW ) , lean body mass ( LBM , DXA ) , ADL status according to Katz , HRQoL according to EQ 5-D and fracture healing . RESULTS LBM decreased in the C ( -1.2 + /- 2 kg ) and PR groups ( -1.2 + /- 1 kg ) but remained the same in the PR/N group ( 0.3 + /- 1 kg ) ( P < 0.05 between groups ) . ADL remained at a high level in the two intervention groups but declined significantly in the C group ( P < 0.005 between groups ) . The decline in HRQoL was least pronounced in the PR/N group at 6 months ( P < 0.05 between groups ) . Patients with fracture healing complications lost more BW ( P < 0.05 ) and LBM ( P < 0.01 ) than patients with uneventful fracture healing . CONCLUSION Protein-rich liquid supplementation in combination with n and rolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM , ADL and A double-blind comparative study of 1 alpha-OHD3 and placebo was performed on 37 patients with osteoporotic hip fracture without clinical osteomalacia . 1 alpha-OHD3 , in a dose of 1 microgram/day together with 2.5 g CaCO3 , did not heal osteoporosis as judged from determinations of bone mineral density and histomorphometric analyses during four months of treatment . However , 1 alpha-OHD3 seemed to have an effect on fracture healing as concluded from the posttreatment alkaline phosphatase level . Hypercalcemia was common , occurring in six out of 19 patients treated with 1 alpha-OHD3 . It is concluded that treatment of osteoporosis with 1 alpha-OHD3 and calcium is ineffective and potentially dangerous because it frequently causes hypercalcemia Twenty patients underwent simultaneous bilateral medial unicompartmental knee arthroplasty . Pre-operative hip-knee-ankle alignment and valgus stress radiographs were used to plan the desired post-operative alignment of the limb in accordance with established principles for unicompartmental arthroplasty . In each patient the planned alignment was the same for both knees . Overall , the mean planned post-operative alignment was to 2.3 degrees of varus ( 0 degrees to 5 degrees ) . The side and starting order of surgery were r and omised , using conventional instrumentation for one knee and computer-assisted surgery for the opposite side . The mean variation between the pre-operative plan and the achieved correction in the navigated and the non-navigated limb was 0.9 degrees ( sd 1.1 ; 0 degrees to 4 degrees ) and 2.8 degrees ( sd 1.4 ; 1 degrees to 7 degrees ) , respectively . Using the Wilcoxon signed rank test , we found the difference in variation statistically significant ( p < 0.001 ) . Assessment of lower limb alignment in the non-navigated group revealed that 12 ( 60 % ) were within + /- 2 degrees of the pre-operative plan , compared to 17 ( 87 % ) of the navigated cases . Computer-assisted surgery significantly improves the post-operative alignment of medial unicompartmental knee arthroplasty compared to conventional techniques in patients undergoing bilateral simultaneous arthroplasty . Improved alignment after arthroplasty is associated with better function and increased longevity In a double-blind trial , 194 ambulatory elderly patients ( mean age , 74 + /- 8 years ) recovering from acute illnesses were r and omly assigned to receive either ornithine oxoglutarate ( OGO ) or a placebo . Nine subjects withdrew during the study , six in the OGO group and three in the placebo group . OGO and the placebo were administered once daily at a dose of 10 g after lunch for 2 months ; the patients were monitored for a total of 4 months . Efficacy was evaluated in terms of nutritional variables , quality of life and total cost of medical treatment . The analysis involved a total of 185 patients ( 93 in the placebo group and 92 in the OGO group ) . The two groups were comparable at inclusion . After 30 and 60 days of treatment , there was a significant improvement in the following variables in the OGO group relative to the placebo group : appetite ( p < 0.001 ) , body weight ( p < 0.001 ) and independence ( p < 0.01 ) . Two months after the end of treatment , there was still a significant improvement in the quality -of-life index ( p < 0.001 ) and the medical-cost index ( p < 0.03 ) in the OGO group , with an overall cost saving of 37 % . We conclude that OGO seems to be a cost-effective nutritional supplement for elderly convalescent patients OBJECTIVE To investigate the short- and long-term effects of a multidisciplinary postoperative rehabilitation programme in patients with femoral neck fracture . DESIGN AND SUBJECTS A r and omized controlled trial in patients ( n = 199 ) with femoral neck fracture , aged > or= 70 years . METHODS The primary outcomes were : living conditions , walking ability and activities of daily living performance on discharge , 4 and 12 months postoperatively . The intervention consisted of staff education , individualized care planning and rehabilitation , active prevention , detection and treatment of postoperative complications . The staff worked in teams to apply comprehensive geriatric assessment , management and rehabilitation . A geriatric team assessed those in the intervention group 4 months postoperatively , in order to detect and treat any complications . The control group followed conventional postoperative routines . RESULTS Despite shorter hospitalization , significantly more people from the intervention group had regained independence in personal activities of daily living performance at the 4- and 12-month follow-ups ; odds ratios ( 95 % confidence interval ( CI ) ) 2.51 ( 1.00 - 6.30 ) and 3.49 ( 1.31 - 9.23 ) , respectively . More patients in the intervention group had also regained the ability to walk independently indoors without walking aids by the end of the study period , odds ratio ( 95 % confidence interval ) 3.01 ( 1.18 - 7.61 ) . CONCLUSION A multidisciplinary postoperative intervention programme enhances activities of daily living performance and mobility after hip fracture , from both a short-term and long-term perspective BACKGROUND Low-energy fractures of the hip , forearm , shoulder , and spine are known consequences of osteoporosis . OBJECTIVE We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density ( BMD ) and bone markers in patients with a recent low-energy fracture . DESIGN In a double-blinded design , patients with fracture of the hip ( lower-extremity fracture , or LEF ) or upper extremity ( UEF ) were r and omly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo ( 200 IU cholecalciferol ) . BMD of the hip ( HBMD ) and lumbar spine ( LBMD ) were evaluated by dual-energy X-ray absorptiometry , and physical performance was assessed by the timed Up & Go test . Serum concentrations of 25-hydroxycholecalciferol , parathyroid hormone ( PTH ) , telepeptide of type I collagen ( ICTP ) , osteocalcin , and N-terminal propeptide of collagen type I were measured . RESULTS A total of 122 patients were included ( 84 % women ; x + /- SD age : 70 + /- 11 y ) ; 68 % completed the study . In an intention-to-treat analysis , LBMD increased in the intervention group and decreased in the placebo group , and the difference between the groups was significant after 12 mo : 0.931 + /- 0.211 compared with 0.848 + /- 0.194 ( P<0.05 ) . No significant change was shown for HBMD . The effect of treatment was more pronounced in patients aged < 70 y. The intervention decreased bone turnover . PTH was significantly lower in the intervention group ( P<0.01 ) for the LEF patients . ICTP and change in LBMD were significantly related to physical performance . CONCLUSIONS A 1-y intervention with calcium and vitamin D reduced bone turnover , significantly increased BMD in patients younger than 70 y , and decreased bone loss in older patients . The effect of treatment was related to physical performance Pressure sores are a frequent problem , especially in elderly patients . Nutritional status may influence the incidence , progression and severity of pressure sores , data , however , are contradictory ( 1 ) . The purpose of this study was to determine the effect of supplemental feeding on the nutritional status and the development and severity of pressure sores . The effect of supplemental feeding overnight ( tube + ) on patients with a fracture of the hip and a high pressure-sore risk score , was studied in a r and omized clinical trial . The control group ( tube - ) had no supplemental feeding . After informed consent , 140 patients were r and omized , and 129 of these took part in the trial ( 62 tube + , and 67 tube - ) . Protein and energy intake , haemoglobin , serum albumin , total serum protein and pressure-sore grade were measured at admission and after 1 and 2 weeks . Of the 62 patients r and omized for tube feeding ( tube + ) , only 25 tolerated their tube for more than 1 week and 16 for 2 weeks . Nevertheless , energy and protein intake was significantly higher in the tube + group ( P < 0.001 ) . This , however , did not significantly influence total serum protein , serum albumin and development and severity of pressure sores after 1 and 2 weeks . Comparison of the actually tube fed group ( n=25 at 1 week , n = 16 at 2 weeks ) and the control group showed a 2 - 3 times higher protein and energy intake ( P < 0.0001 ) , and a significantly higher total serum protein and serum albumin after 1 and 2 weeks in the actually tube fed group ( all P < 0.001 ) . Pressure-sore development and severity were not significantly influenced in the actually tube fed group . We conclude that we were not able to show a significant decrease in development and severity of pressure sores , because the nasogastric tube for supplemental feeding was not well tolerated in this patient group . Nevertheless , tube feeding overnight does result in a significant higher protein and energy intake , and has a significant effect on nutritional status in the actually tube-fed group . Other means of supplemental feeding will have to be used in order to answer the question of whether supplemental feeding can decrease development and severity of pressure sores This study aim ed to evaluate whether food fortification and snacks could increase the energy and protein intakes of hospital patients . The control group of 82 consecutive admissions on medical , elderly care and orthopaedic wards ate freely from the hospital menu . Subsequently , an intervention group of 62 patients were offered fortified food and snacks , providing an extra 22.2|g protein/day and 966 kcal/day in addition to the st and ard menu . Fortification significantly increased energy intake in the intervention group ( P = 0.007 , independent sample s t-test ) , having the greatest effect on groups with the lowest energy intake , that is male and female orthopaedic , female medical and female elderly patients ( 84 cent of total ) . The increases in energy intake were 21.3 cent , 21.4 cent , 23 cent and 19.6 cent respectively . Although the increased energy and protein intake represented 25.6 cent and 22.5 cent respectively , of the supplements given , and suggested that wastage was high , it was nevertheless sufficient to remove energy deficit . We therefore propose that provision of fortified food and snacks is a convenient method of improving the nutritional intakes of hospital patients 59 elderly patients ( mean age 82 ) with femoral neck fractures were r and omised into two groups . 27 patients received daily an oral nutrition supplement ( 250 ml , 20 g protein , 254 kcal ) for a mean of 32 days ; 32 patients acted as controls . On admission most patients had nutritional deficiencies . Despite being offered adequate quantities , nutritional requirements were not met during the hospital stay . Clinical outcome was significantly better in the supplemented group ( 56 % favourable course vs 13 % in controls ) during the stay in the convalescent hospital . The rates of complications and deaths were also significantly lower in supplemented patients ( 44 % vs 87 % ) . 6 months after the fracture the rates of complications and mortality were significantly lower in supplemented patients ( 40 % vs 74 % ) . The median duration of hospital stay was significantly shorter in the supplemented group ( 24 vs 40 days ) . Thus the clinical outcome of elderly patients with femoral neck fracture can be improved by once daily dietary oral supplementation The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9 ) and 25 μg calcitonin given subcutaneously 30 times ( n=10 ) in 10 weeks were studied against a control ( n = ll ) . Bone histology and histomorphometry showed non-age related osteoporosis in 30 % and osteomalacia in 22 % of the patients studied . Impaired serum vitamin D status was found in 47 – 88 % of patients , secondary hyperparathyroidism and increased serum parathyroid hormone in 59 % and decreased serum calcitonin levels in 69 % . On histology , normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3 . Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia . Calcitonin improved calcium balance , reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia . Vitamin D reduced osteomalacia , slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone . Both treatments gave a similar slight decrease in serum calcitonin concentrations . A mechanism of action for the treatments is suggested A total of 744 elderly women with fractured neck of femur were classified into three groups according to anthropometric measurements on admission : group 1 , well nourished ; group 2 , thin ; group 3 , very thin . Group 1 ate well and had a low mortality and a short rehabilitation time . The thinner the patients the lower their voluntary food intake , the higher their mortality and the longer their rehabilitation time . A series of 122 patients from groups 2 and 3 were entered postoperatively into a r and omised controlled trial of overnight supplementary nasogastric tube feeding ( 4.2 MJ ( 1000 kcal ) , including 28 g protein ) in addition to their normal ward diet . This treatment was associated with improvements not only in anthropometric and plasma protein measurements but also in clinical outcome , especially in the very thin group 3 patients . Rehabilitation time and hospital stay were shortened . Mortality in group 3 was less in the tube fed patients ( 8 % ) than in the controls ( 22 % ) but this difference did not reach statistical significance . One in five patients could not tolerate the nasogastric tube , but in the remainder the treatment caused no side effects and did not seriously diminish voluntary oral food intake by day A total of 63 women who had an operation for a fracture of the hip was r and omly allocated to one year of treatment either with anabolic steroids , vitamin D and calcium ( anabolic group ) or with calcium only ( control group ) . The thigh muscle volume was measured by quantitative CT . The bone mineral density of the hip , femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound . Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did ( p<0.01 ) . There was less bone loss in the proximal tibia in the anabolic group than in the control group . The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months . Anabolic steroids , even in this moderate dose , given in combination with vitamin D and calcium had a beneficial effect on muscle volume , bone mineral density and clinical function in this group of elderly women Protein energy malnutrition is an important determinant of clinical outcome in older patients after hip fracture , but the effectiveness of nutritional support programs in routine clinical practice is controversial . We performed a prospect i ve , r and omized , controlled clinical trial to determine if nutritional supplementation decreased fracture-related complications in a selection of otherwise healthy patients with hip fractures . Patients were r and omized to intervention or control groups . The control group ( n = 40 ) was given ordinary hospital food and beverage . The intervention group ( n = 40 ) also was administered a 1000 kcal daily intravenous supplement for 3 days , followed by a 400 kcal oral nutritional supplement for 7 days . We recorded daily fluid and energy intake during the first 10 days of hospitalization and fracture-related complications up to 4 months . The total fluid and energy intake in the intervention group neared optimal levels . The control group received 54 % and 64 % of optimal energy and fluid intake , respectively . The risk of fracture- related complications was greater in the control group ( 70 % ) than in the intervention group ( 15 % ) . Four patients in the control group died within 120 days postoperatively . The comprehensive balanced nutrition supplement result ed in lower complication rates and mortality at 120 days postoperatively . Level of Evidence : Therapeutic Level I. See the Guidelines for Authors for a complete description of levels of evidence OBJECTIVE We compared clinical outcomes with a st and ard ( Ensure ) or a high-protein ( Boost HP ) liquid nutritional supplement for older adults recovering from hip fracture surgery in a rehabilitation hospital . METHODS This r and omized , double-blind , parallel-group study compared the clinical effectiveness of a st and ard ( Ensure ) with a high-protein ( Boost HP ) liquid nutritional supplement among patients ( n = 46 ) 60 y or older who recently underwent surgical repair of a hip fracture . Patients were encouraged to drink at least two 8-oz cans ( 17.8 g/d protein for Ensure versus 30 g/d protein for Boost HP ) per day for 28 d. Study measurements included change in Functional Independence Measure between rehabilitation admission and discharge , length of rehabilitation stay , laboratory measures ( i.e. , serum albumin , prealbumin , and C-reactive protein ) , physical activity energy expenditure by 7-d triaxial accelerometry , and dietary intake by three r and om , telephonic , 24-h dietary recalls . RESULTS There were no significant group differences with respect to age , sex , acute hospital days , hip fracture assessment parameters , or surgical treatment . Consumption of supplement ( 260 oz/28 d of Ensure versus 239 oz/28 d of Boost HP ) was comparable . There were no differences in complication or adverse event rates during the study . The Boost HP group consumed more protein than the Ensure group ( 63 versus 50 g , P < 0.048 ) and had a greater improvement in serum albumin over the 28-d supplementation period ( + 0.7 versus + 0.2 g/dL , P < 0.019 ) . The Boost HP group also consumed more fiber ( 12 versus 8 g ) , calcium ( 821 versus 639 mg ) , vitamin K ( 66 versus 45 microg ) , and phosphorus ( 1035 versus 833 mg ) than did the Ensure group . Rehabilitation length of stay was shorter in the Boost HP than in the Ensure group , although this trend did not reach statistical significance ( 23 versus 28 d , P = 0.27 ) . Outcome differences were not detected in the Functional Independence Measure . CONCLUSIONS Supplementation was well tolerated in this population and contributed significantly to total dietary intake . Consumption of a high-protein liquid nutritional supplement may offer some benefits by improving visceral protein status In a prospect i ve double-blind controlled trial the effect of large doses of ascorbic acid on the healing of pressure-sores has been assessed . 20 surgical patients were studied , the pressure areas being assessed by serial photography and ulcer tracings . The mean ascorbic-acid levels in treated and non-treated groups one month after the start of treatment were 65.6 and 25.8 mug per 10 - 8 white blood-cells . In the group treated with ascorbic acid there was a mean reduction in pressure-sore area of 84 % after one month compared with 42.7 % in the placebo group . These findings are statistically significant ( P less than 0.005 ) and suggest that ascorbic acid may accelerate the healing of pressure-sores OBJECTIVE To examine how improved attention to nutritional status and dietary intake , achieved through the employment of dietetic assistants ( DAs ) , will affect postoperative clinical outcome among elderly women with hip fracture . DESIGN Open prospect i ve r and omised controlled trial , comparing conventional nursing care with the additional nutritional support provided by DA . SETTING Thirty-eight bedded acute trauma ward in a teaching hospital . PARTICIPANTS All but 11 of 344 consecutive admissions with acute nonpathological hip fracture were approached . Three hundred and eighteen ( 93 % ) agreed to inclusion . Sixteen were ineligible as they were immediately transferred to another acute ward , were managed conservatively or died preoperatively . PRIMARY OUTCOME MEASURE Postoperative mortality in the acute trauma unit . SECONDARY OUTCOME MEASURES Postoperative mortality at 4 months after fracture , length of stay , energy intake and nutritional status . RESULTS DA-supported participants were less likely to die in the acute ward ( 4.1 versus 10.1 % , P = 0.048 ) . This effect was still apparent at 4 month follow-up ( 13.1 versus 22.9 % , P = 0.036 ) . DA-supported subjects had significantly better mean daily energy intake ( 1,105 kcal versus 756 kcal/24 h , 95 % CI 259 - 440 kcal/24 h , P<0.001 ) , significantly smaller reduction in mid-arm circumference during their inpatient stay ( 0.39 cm , P = 0.002 ) and nonsignificantly favourable results for other anthropometric and laboratory measurements . CONCLUSION Dietetic or nutrition assistants are being introduced in units across the UK . This , the largest ever study of nutritional support after hip fracture , shows that their employment significantly reduced patients ' risk of dying in the acute trauma unit ; an effect that persisted at 4 month follow-up Objectives : Assess whether postoperative nightly enteral nutrition support improves outcomes of elderly patients with an acute hip fracture Design : R and omized controlled trial Setting : A University and a Department of Veteran ’s Affairs Hospital Subjects : Adults > 64 years of age who underwent surgical repair of an acute hip fracture Interventions : Subjects r and omized to the control ( Ctrl ) group received st and ard care while the treatment ( Tx ) group received st and ard care plus up to 1,375 Kcal [ 5,755 kJ/d ] of nasoenteral tube feedings each night . When tube feedings had to be discontinued , Tx subjects were asked to drink an equivalent amount of the nutritional supplement each night . Measures of Outcome : Rate of postoperative complications and 6-month postoperative survival Results : Fifty-seven patients were r and omized to the Tx ( n = 27 , mean age 75.9 ± 7.4 yrs ) or Ctrl groups ( age 81.7 ± 7.7 yrs ) . All subjects had reduced volitional nutrient intakes after surgery . During the first week subsequent to surgery , there was no difference between the treatment and control groups in the amount of nutrients that they volitionally consumed during the day . However , the treatment subjects had a greater total daily nutrient intake ( Median 5,866 ( IQR 5,024 to 7,335 ) kJ/d vs. 3,965 ( IQR 2,968 to 4,664 ) kJ/d , p < 0.001 ) . However , by the second postoperative week this difference was no longer statistically significant . Intolerance to the tube feedings developed commonly . There was no difference between the groups in the rate of postoperative life-threatening complications or mortality within six months subsequent to surgery . Conclusions : This study failed to confirm findings from a prior study of improved postoperative survival with nutrition support . However , it was conducted on multiple hospital wards which may have contributed to the higher rate of tube-related problems and less nutrient delivery signifying the need for further study A group of 40 consecutive patients with hip fractures were studied and confirmed to have a high incidence of protein-calorie malnutrition . The prospect i ve nutritional assessment performed for this study included : serum albumin , serum transferrin , anthropometric measurements , skin testing for delayed hypersensitivity , total lymphocyte count , and a 24-h urine collection for metabolic and nitrogen balance determinations . At 3 months after their hip fracture , 37.5 % returned to their premorbid ambulatory status ; 42.5 % sustained a decrement in their ambulatory status or independence ; 12.5 % died ; 7.5 % were lost to follow-up . Of the nutritional parameters studied , albumin was significantly associated with mortality ( p = 0.004 ) . Considering those patients with an albumin less than 3.0 , a mortality rate of 70 % was observed in follow-up ( maximum of 11 months ) , compared with a mortality rate of 18 % in patients with an albumin greater than or equal to 3.0 . It is concluded that the serum albumin has value as a nutritional index without specialized nutritional parameters , and that a more aggressive approach to nutritional support is needed for the hypoalbuminemic patient with a hip fracture , particularly for those with a serum albumin below 3.0 OBJECTIVES To vali date a nutritional intervention programme for elderly people living in nursing homes . DESIGN In a prospect i ve , r and omized , controlled study of 88 residents , we determined nutritional status at day 0 and day 60 using a record of dietary intake , anthropometry , h and -grip strength and mini-nutritional assessment . Dietary intake , grip strength and body weight were also recorded at day 30 . We divided subjects into four groups according to their mini-nutritional assessment score . Those with a score 24 received no oral supplementation . Those at risk of malnutrition ( with a score of 17 - 23.5 ) were r and omized to oral supplementation . Those with a score < 17 received oral supplementation . We recorded the amount of oral supplements consumed daily . RESULTS Compliance with oral supplementation was good , and daily intake averaged about 400 kcal . The total energy intake on day 60 was significantly higher in both of the groups that received supplements . Following supplementation , most subjects at risk of malnutrition improved their mini-nutritional assessment score and increased their weight ( by 1.4 + /- 0.5 kg ) . Neither the mini-nutritional assessment score nor weight improved in subjects at risk of malnutrition who did not receive supplements . Supplementation in the malnourished group result ed in a mean mini-nutritional assessment score increase ( from 13.9 + /- 2.6 to 17.1 + /- 3.9 ) and a mean weight gain of 1.5 + /- 0.4 kg . CONCLUSION Oral nutritional supplements are well accepted and result in increased daily protein and energy intake , body weight and nutritional status in most malnourished patients and in those at risk of malnutrition Background and aims : Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs . We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures . Methods : One hundred and ninety-nine patients , aged 70 years and over ( mean age±SD , 82±6 , 74 % women ) , were r and omly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward . The intervention consisted of staff education focusing on the assessment , prevention and treatment of delirium and associated complications . The staff worked as a team , applying comprehensive geriatric assessment , management and rehabilitation . Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale , and delirium was diagnosed according to DSM-IV criteria . Results : The number of days of postoperative delirium among intervention patients was fewer ( 5.0±7.1 days vs 10.2±13.3 days , p=0.009 ) compared with controls . A lower proportion of intervention patients were delirious postoperatively than controls ( 56/102 , 54.9 % vs 73/97 , 75.3 % , p=0.003 ) . Eighteen percent in the intervention ward and 52 % of controls were delirious after the seventh postoperative day ( p<0.001 ) . Intervention patients suffered from fewer complications , such as decubitus ulcers , urinary tract infections , nutritional complications , sleeping problems and falls , than controls . Total postoperative hospitalization was shorter in the intervention ward ( 28.0±17.9 days vs 38.0±40.6 days , p=0.028 ) . Conclusions : Patients with postoperative delirium can be successfully treated , result ing in fewer days of delirium , fewer other complications , and shorter length of hospitalization OBJECTIVE Hip fractures are a major cause of morbidity for older women , which result in impaired health related quality of life ( HRQOL ) . Few studies have prospect ively evaluated the effect of hip fractures in women on HRQOL with different health state preference measures . We compared how 4 different preference measures change in women post-hip fracture and evaluated the responsiveness of the preference measures . We also compared HRQOL in women with recent hip fractures to a control sample at baseline and to normative Canadian data at followup . METHODS Health status measures [ the Medical Outcomes Study Short Form-36 ( SF-36 ) ] and preferences ( direct and indirect ) of women over age 50 years with hip fractures were measured at baseline and at 3 and 9 months . Baseline preferences [ Health Utilities Index ( HUI ) , Feeling Thermometer , St and ard Gamble , and SF-36 ] were obtained from women without hip fractures for comparison . Independent sample t tests were used to compare baseline scores of fracture and nonfracture controls . Correlations between preference and health status measures were assessed and repeated measures ANOVA was used to assess change in health status and preferences over time . RESULTS Health status and preference measures were lower in women with hip fractures in comparison to nonfracture controls . After 9 months , the SF-36 , HUI , Feeling Thermometer , and SF-6D scores improved significantly . Values for the SF-36 remained lower than an age-matched normative sample . The HUI and SF-6D were sensitive to change over time , but the St and ard Gamble was not . CONCLUSION HRQOL and preference measures improve over time in women with recent hip fractures , with the majority of the change occurring in the initial 3 months . Our results suggest that the HUI and SF-6D are valid measures to assess change over time post-hip fracture The present study was design ed to evaluate to the effect of dietary supplements on clinical outcome and nutritional status in a large group of geriatric patients ( n = 501 ) . The patients were r and omised into an experimental group which received nutritional supplementation ( 400 kcal ) as well as a st and ard hospital diet , and a control group on hospital diet alone . The nutritional state was measured on admission and after 8 and 26 weeks by anthropometry , serum protein analysis and a delayed hypersensitivity skin test . Protein energy malnutrition was defined as the presence of three or more abnormal parameters . 28.5 % of patients showed evidence of malnutrition on admission . Hospitalisation itself result ed in a gradual deterioration in nutritional status . Nutritional supplementation generally improved nutritional state . Among those patients who were well nourished on admission , and subsequently receiving dietary supplementation , 8.3 % fulfilled malnutrition criteria after 26 weeks , while 21.1 % were considered malnourished in the control group ( p < 0.05 ) . The improvement observed in transport proteins was probably related to nutritional support and not just to the reversal of inflammation . In the initially well nourished group of more than 300 patients , the mortality rate was 8.6 % in those given nutritional support compared to 18.6 % in the control group ( p < 0.02 ) BACKGROUND Studies have shown clinical benefits of nutritional supplementation in orthopaedic and elderly patients in both under and well nourished groups . However , patient compliance with the supplementation has not been reported . AIM To assess level of patient compliance with nutritional supplementation when prescribed postoperatively to unselected orthopaedic patients as part of a large controlled trial research ing the clinical benefits of non-targeted nutritional supplementation . METHODS Patients in the intervention group were prescribed two oral supplements each day of their hospital stay , in addition to usual meals . Information describing the supplements was given by the dietitian . Supplements were issued on drug rounds and the proportion of each drink consumed was recorded and collated . Patients could choose to change the type of drink or to discontinue the supplements completely at any time . Twenty-four hour food intake was analysed for a r and om sub- sample of 48 patients . RESULTS Eighty-four patients ( 27 men , 57 women ; mean age , 72 years ) were prescribed supplements . Median length of stay was 14.4 days . Supplements were taken for a mean of 6.7 days . Median compliance was 14.9 % . Despite this , median energy intake in the study group was 1523 kcal/day and 1289 kcal/day in the control ( P= 0 . 0214 ) . CONCLUSION Compliance with non-targeted , postoperative nutritional supplementation is poor in unselected orthopaedic patients but even low levels of supplementation significantly increase energy intake AIMS Evaluate nutritional status and fluid and energy intake during the first ten days of hospitalisation in a selection of otherwise healthy patients with a hip fracture . METHODS A prospect i ve r and omised controlled study of 80 patients . Nutritional status was assessed at inclusion . The energy and fluid intake was recorded and calculated daily whilst hospitalised . All patients were given ordinary hospital food and beverage . In the treatment group ( n = 40 ) patients also received intraveneous supplementary nutrition ( 1000 kcal/day ) for three days followed by oral supplementary nutrition ( 400 kcal/day ) for seven days or until discharge . RESULTS One third of patients were classified as malnourished in both groups . The average daily fluid intake/patient was 1300 ml in the control group compared to 1856 ml in the treatment group ( P<0.0001 ) . The average daily energy intake/patient was 916 kcal in the control group compared to 1296 kcal in the treatment group ( P = 0.003 ) . The mean difference between actual and needed daily fluid intake was -739 ml in the control group and + 27 ml in the treatment group ( P<0.0001 ) . Corresponding numbers for energy intake was -783 kcal/day in the control group and -228 kcal/day in the treatment group ( P = 0.0003 ) . CONCLUSIONS Malnutrition is common even in a selection of healthy patients with hip fractures . During hospital stay the fluid and energy intake was considerably lower than that needed in the control group . Supplementary nutritional intake for ten days increased the total fluid and energy intake in the treatment group to near needed levels The primary aim of this study was to evaluate the effect of two different surgical methods on nutritional status and functional capacity during the first postoperative year in patients with displaced femoral neck fractures . A further aim was to evaluate the effect of nutritional support . One hundred patients were r and omly assigned to treatment with either primary total hip arthroplasty ( THA ) or osteo synthesis . Half of the patients in each treatment group received protein- and energy-enriched food in the hospital in addition to individual nutritional advice in order to optimize their intake of protein- and energy-rich food . Nutritional state and functional capacity were examined at baseline , one and three months , and one year after the operation . Pain was examined at three months and one year . The effect of nutritional intervention was equal within both surgical groups . Logistic regression showed that the dependent variable “ living at one year ” was significantly associated with serum albumin levels at one month . Advanced age , mental impairment and deteriorated nutritional status were predominant in the non-survivors . Overall , the primary THA group performed better compared with the osteo synthesis group concerning weight change over time , locomotion and pain . This study also showed that primary THA could safely be performed in the elderly without an increased postoperative mortality rate AIMS AND OBJECTIVES The purpose of the study was to test the effectiveness of nursing care based on active involvement of patients in their nutritional care . It was hypothesized that this type of care could improve energy and protein intake in elder orthopaedic patients . BACKGROUND Protein and energy malnutrition and deterioration in nutritional status is a common but neglected problem in hospital patients . METHODS The design was quasi-experimental with an intervention and control group . The study included 253 patients aged 65 and above admitted for hip fracture , hip or knee replacement . Food intake was recorded on a daily basis during the hospital stay . RESULTS The daily intake of energy increased with 23 % ( P = 0.001 ) and of protein with 45 % ( P = 0.001 ) . The intake increased from the very first day after the operation . The intake of energy and protein was not correlated with the patient 's age , body mass index or type of surgery . CONCLUSIONS The care based on patients ' active involvement in their own nutritional care and was found to be an effective method to raise the intake of energy and protein among elder orthopaedic patients . RELEVANCE TO CLINICAL PRACTICE This way of organizing the care identifies patients who do not consume enough energy and protein according to their current requirements and to take appropriate actions to prevent further malnutrition AIM The purpose of the study was to evaluate the effectiveness of planned nursing interventions , including bran supplement , on the bowel management of older orthopaedic patients . BACKGROUND Constipation is prevalent among older people . Constipation is also well-known to be a problem for a range of orthopaedic patients . Orthopaedic diseases or conditions may , because of the specific problems , cause this . The problem may also arise as a result of the orthopaedic treatment options undertaken by patients . DESIGN A quasiexperimental design was employed . METHODS The patients were recruited from an orthopaedic clinic at a university hospital in Erzurum , eastern Turkey . Descriptive statistics , independent sample test t-test , chi-square and McNemar test were used to analyse the data . Constipation problems were identified through interviews by using the Constipation Diagnosis Form . Interviews were performed within the fourth postoperative day . After that , while the patients in the control group received routine nursing care according to clinic routine , the patients in the experimental group received bran supplement together with planned nursing interventions . The patents in both groups were followed by using the Constipation Follow Form . RESULTS While patients in the experimental group showed significant improvements in most characteristics of bowel elimination such as time of defecation , intensity of faeces , colour of faeces and amount of faeces , the control group showed a significant improvement in only duration of defecation . CONCLUSIONS The results of the study indicate planned nursing interventions including bran supplement are more effective than routine nursing interventions for management of constipation problems in older orthopaedic patients . RELEVANCE TO CLINICAL PRACTICE Nurses have an important part to play in both prevention and management of constipation . Constipation is a problem especially for older orthopaedic patients . Planned nursing interventions that include bran supplements may be more effective than routine nursing interventions for management of constipation problems in older orthopaedic patients OBJECTIVE This non-blinded r and omized controlled trial was the first phase of a planned series of investigations design ed to test the efficacy of aggressive post-operative enteral nutrition support to decrease the rate of post-operative complications or improve long-term outcomes in specifically defined subgroups of elderly patients who have sustained a hip fracture requiring surgery . METHODS Eighteen patients ( 17 males ) were r and omized to the treatment ( eight male subjects ) or control groups . The control group ( mean age 76.5+/-6.1 years ) received st and ard post-operative care . Subjects in the treatment group ( mean age 74.5+/-2.1 years ) received 125 cc/hour of nasoenteral tube feedings over 11 hours each night in addition to st and ard post-operative nutritional care . RESULTS Both the treatment and control groups had reduced volitional nutrient intakes for the first 7 post-operative days ( 3,966+/-2,238 vs. 4,263+/-2,916 kJ/day [ 948+/-535 vs. 1019+/-697 kcal/day ] , p=0.815 ) , but the treatment subjects had a greater total nutrient intake ( 7,719+/-2,109 vs. 4,301+/-2,858 kJ/day [ 1845+/-504 vs. 1028+/-683 kcal ] , p=0.012 ) . On average , treatment subjects were tube fed for 15.8+/-16.4 days . There was no difference between the groups ( treatment vs. controls ) in the rate of post-operative life-threatening complications ( 25 vs. 30 % , p=1.00 ) or in-hospital mortality ( 0 vs. 30 % , p=0.216 ) . Mortality within 6 months subsequent to surgery was lower in the treatment group compared to the controls ( 0 vs. 50 % , p=0.036 ) . DISCUSSION We conclude that nightly enteral feedings are a safe and effective means of supplementing nutrient intake . The greatest impact of nutrition support may be to reduce mortality Malnutrition has been often suggested as contributing to both the high incidence of hip fracture in elderly people and its complications . In a recent prospect i ve controlled r and omized study , the clinical outcome of elderly patients with osteoporotic fracture of the proximal femur ( hip fracture ) improved by giving a simple oral dietary supplement . This study , however , did not prove that protein was responsible for the clinical improvement since the supplement also contained vitamins and minerals . We addressed this question by comparing the clinical outcome and bone mineral density ( BMD ) changes in elderly patients with hip fracture , receiving two different dietary supplements with different protein contents . Sixty-two patients ( mean age 82 ) admitted into the orthopedic ward for fracture of the proximal femur were r and omized into two groups . One group ( n = 33 ) received 250 ml/day of an oral nutritional supplement containing protein ( 20.4 g ) , mineral salts ( Ca : 0.525 g ) and vitamins A = 750 IU ; D3 = 25 IU ) for a mean of 38 days . A control group ( n = 29 ) received the same supplement dose , but with no protein , for the same period of time . The clinical course was significantly better in the group receiving protein , with 79 % having a favorable course as compared to 36 % ( p less than 0.02 ) in the control group during the stay in the recovery hospital . The rate of complications and deaths was also significantly lower in the protein-supplemented vs the control group ( 52 vs 80 % , p less than 0.05 ) 7 months after hip fracture . The median hospital stay was significantly lower in the protein-supplemented group ( 69 vs 102 days , p less than 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND undernourishment is common in elderly hip fracture patients and has been linked to poorer recovery and increased post-operative complications . OBJECTIVE to determine whether a nutritional supplement may ( i ) help elderly patients return to pre-fracture functional levels 6 months post-fracture and ( ii ) decrease fracture-related complications and mortality . DESIGN a double-blind , r and omized , placebo-controlled clinical trial . SETTING a county hospital near Barcelona . SUBJECTS 171 patients , aged 70 and older , hospitalized for hip fracture between July 1994 and July 1996 . METHODS we r and omized patients to intervention ( n = 85 ) or control ( n = 86 ) group . Patients received a nutritional supplement containing 20 g of protein and 800 mg of calcium or placebo for 60 days . We determined functional levels by the Barthel index , the mobility index and by the use of walking aids . We performed assessment s during hospitalization and at 2 and 6 months post-fracture . FINDINGS the two groups were comparable at study entry . We observed no differences in return to functional status 6 months post-fracture ( 61 % intervention group vs 55 % in control group ) nor in fracture-related mortality ( 13 % in intervention group vs 10 % in control group ) . The intervention group suffered fewer in-hospital [ odds ratio 1.88 ( 95 % CI 1.01 - 3.53 ) , P = 0.05 ] and total complications [ odds ratio 1.94 ( 95 % CI 1.02 - 3.7 ) , P = 0.04 ] than the control group . CONCLUSION based on our results , we can not recommend routine nutritional supplementation of all elderly hip fracture patients . While nutritional supplementation may be useful in decreasing complications , this reduction does not result in improvement in functional recovery and nor does it decrease fracture-related mortality . Selected patients may , however , benefit from nutritional supplementation BACKGROUND & AIMS Malnutrition is a risk factor for development of pressure ulcers ( PU ) . Nutritional supplementation may thus reduce the incidence of PU . We investigated the effect of nutritional supplementation on incidence of PU in hip-fracture patients at risk of developing PU . METHODS Hip-fracture patients ( n=103 ) were included in this double-blind , r and omised , placebo-controlled trial . They received 400 ml daily of a supplement enriched with protein , arginine , zinc and antioxidants ( n=51 ) or a non-caloric , water-based placebo supplement ( n=52 ) . Presence and stage of PU were assessed daily for 28 days or until discharge ( median : 10 days during supplementation ) . RESULTS Incidence of PU was not different between supplement ( 55 % ) and placebo ( 59 % ) , but incidence of PU stage II showed a 9 % difference ( difference : 0.091 ; 95 % CI : 0.07 - 0.25 ) between supplement ( 18 % ) and placebo ( 28 % ) . Of patients developing PU 57 % developed it by the second day . Time of onset ( days ) showed a trend ( P=0.090 ) towards later onset of PU with supplement ( 3.6+/-0.9 ) than placebo ( 1.6+/-0.9 ) . CONCLUSIONS Hip-fracture patients develop PU at an early stage . Nutritional supplementation may not prevent PU at this stage , but contributes possibly to a delayed onset and progression of PU . Nutritional supplementation may be more effective if initiated earlier The role of calcitonin in the aetiology of postmenopausal osteoporosis remains uncertain . Oestrogen , an established therapy for postmenopausal osteoporosis , has been shown to enhance calcitonin secretion . In order to assess whether two other osteoporotic drug treatments , oral calcium and stanozolol ( an anabolic steroid ) , may also affect calcitonin secretion , 20 elderly women with femoral neck fracture were r and omly selected to receive either 880 mg calcium or 5 mg stanozolol daily for 12 weeks . Basal calcitonin and serum calcium were not altered significantly by either treatment . The calcitonin response to a 10 min infusion of calcium was enhanced following treatment with oral calcium but not stanozolol . This suggests one possible mechanism of action whereby calcium may exert its antiresorptive effect on bone and supports the use of oral calcium in the treatment of postmenopausal osteoporosis BACKGROUND AND AIMS Nutritional supplements are widely administered in hospitals and can benefit clinical outcome . The aim here was to determine the effect of routine post-operative nutritional supplementation on the nutritional status and clinical outcome of adult orthopaedic patients . METHODS A prospect i ve controlled study was conducted on two adult orthopaedic wards . Patients in the study group were prescribed two nutritional supplements/day post-operatively . Nutritional and biochemical indices and incidence of clinical complications were observed . RESULTS Of 181 patients studied , 14 in the supplemented group and 34 in the control ( P=0.005 ) developed major complications . There were 22 occurrences of major complications in the supplemented group and 55 in the control ( P=0.0002 ) . There was no significant difference in the number of minor complications between the two groups ( P=0.2 ) . There was no statistical difference in changes in nutritional parameters or in albumin or CRP between the two groups . There were significantly greater reductions in transferrin ( P=0.002 ) and in haemoglobin ( P=0.002 ) in the control group at week 1 . The median costs of hospital stay were 2068 UK pounds in the supplemented group and 2199 UK pounds in the control . The median cost of additional treatments was 30.16 UK pounds in the supplemented group and 46.23 UK pounds in the control . CONCLUSION A significant reduction in major complications and in number and costs of additional treatments was seen in the supplemented group Objective : To describe the independent and combined effects of oral nutrition supplementation and resistance training on health outcomes in nutritionally at risk older adults following lower limb fracture . Design : R and omized controlled trial with 12-week masked outcome assessment . Setting : Teaching hospital . Participants : One hundred nutritionally at risk older adults hospitalized following a fall-related lower limb fracture . Intervention : Commenced seven days after injury . Consisted of daily multinutrient energy-dense oral supplement ( 6.3 kJ/mL ) individually prescribed for six weeks ( n = 25 ) , tri-weekly resistance training for 12 weeks ( n = 25 ) , combined treatment ( n = 24 ) or attention control plus usual care and general nutrition and exercise advice ( n = 26 ) . Measurements : Weight change , quadriceps strength , gait speed , quality of life and health care utilization at completion of the 12-week intervention . Results : At 12 weeks , all groups lost weight : nutrition -6.2 % ( -8.4 , -4.0 ) ; resistance training -6.3 % ( -8.3 , -4.3 ) ; nutrition and resistance training -4.7 % ( -7.4 , -2.0 ) ; attention control -5.2 % ( -9.0 , -1.5 ) . Those receiving resistance training alone lost more weight than those receiving the combined treatment ( P = 0.029 ) . Significant weight loss was prevented if supplement was consumed for at least 35 days . Groups were no different at 12 weeks for any other outcome . Conclusion : Frail , undernourished older adults with a fall-related lower limb fracture experience clinical ly significant weight loss that is unable to be reversed with oral nutritional supplements . Those receiving a programme of resistance training without concurrent nutrition support are at increased risk of weight loss compared with those who receive a combined nutrition and resistance training intervention . In this high-risk patient group it is possible to prevent further decline in nutritional status using oral nutritional supplements if strategies are implemented to ensure prescription is adequate to meet energy requirements and levels of adherence are high BACKGROUND & AIMS Osteoporosis is a major health problem worldwide . Low weight is a major risk factor for low bone mass and fractures . The aim of this study was to investigate the effects on bone tissue of protein-rich supplementation alone or in combination with n and rolone decanoate in lean elderly women after a hip fracture . METHODS Sixty elderly women with BMI < 24 kg/m(2 ) admitted to hospital due to a femoral neck fracture were r and omised to a control group , to receive a protein-rich formula or to receive the same formula with an addition of n and rolone decanoate for 6 months . All patients received additional calcium and vitamin D. The effects after 6 and 12 months were measured by means of bone mineral density ( BMD ) using dual-energy X-ray absorptiometry ( DXA ) , and with biochemical bone markers . Osteocalcin and C-terminal telopeptide of collagen-1 ( CTX ) were used to estimate bone formation and bone resorption , respectively . RESULTS The analyses showed an increase in total body BMD at 6 and 12 months in patients who received protein-rich supplementation . N and rolone decanoate did not appear to have any additional effect on BMD . Osteocalcin increased in all groups while no significant changes were found for CTX . CONCLUSION The overall results of the study indicated that protein-rich supplementation given to lean elderly female hip fracture patients increased the total body BMD To determine the feasibility of increasing the calcium , protein and calorie intake of osteoporotic fracture patients by repeated dietary counselling delivered by a dietitian , a r and omized controlled trial was conducted . Among 189 patients presenting with osteoporotic fractures to an Orthopaedics and Traumatology Department of a large regional hospital , 98 patients were r and omized to the intervention group and 91 were r and omized to the control group ( with usual care ) . Intervention group received three sessions of dietary counselling with tailored made recommendations over a period of 4 months , while the control group only received dietary assessment and pamphlets on the prevention of osteoporosis . Almost all subjects in both intervention and control groups had calcium intake below the recommended level of 1000 mg at baseline . Half and 60 % of subjects in both groups had total energy and protein intake below recommended levels respectively . The mean weights of control and intervention groups at baseline were 51.5 and 50.9 kg respectively , while the body mass index ( BMI ) were 22.6 ( kg m(-2 ) ) and 22.6 ( kg m(-2 ) ) respectively . After dietary intervention , significant increase of intake was seen in calcium intake ( P = 0.0095 by t-test ) in the intervention group . No significant increase was seen in protein or calorie intake . No significant change was observed in the body weight or BMI although there was a positive trend in the intervention group for all these parameters . We concluded that there was general malnutrition in Chinese elderly who presented with osteoporotic fractures . Dietary calcium could be increased by repeated professional dietary counselling . Future studies with longer duration and more objective clinical outcomes will be helpful to further demonstrate the long-term effects of dietary intervention on osteoporosis and other chronic diseases The potential nutritional and clinical benefits of sip-feed supplements were investigated by means of a controlled trial in elderly female patients admitted for orthopaedic surgery . A nutritional risk assessment procedure ( Nutritional Risk Question naire , NRQ ) was used to identify patients who might benefit from supplementation . Patients identified as high risk who did not receive supplements showed significant losses in triceps skinfold thickness ( TSF ) and mid-upper arm muscle circumference ( MUAMC ) measurements during hospitalization . Such changes were not observed in high-risk supplemented patients , but significant losses of MUAMC were also recorded in a group of patients who failed to comply with the supplement . No differences in biochemical parameters , muscle function , or clinical outcome were observed between supplemented and unsupplemented and non-compliant patients . The problems of poor compliance to sip-feed supplements and failure to observe clinical benefit in supplemented patients are discussed 1 . This study examined the effects of a geriatric orthopaedic nursing education program of care for the elderly hip fractured patient on select patient outcomes using a post-test nonequivalent control group design . 2 . Nursing staff of a 26-bed orthopaedic unit attended a day long education workshop focusing on common clinical problems the elderly patient experiences in the acute care setting . 3 . This program provided nursing staff with sound knowledge for the provision of effective care to the acutely ill elderly patient , which result ed in improved patient outcomes and use of health care re sources The worldwide increase in hip fractures is a major challenge to the health care system and society . The proper treatment of femoral neck fractures in the elderly is still controversial , and even more so from an international perspective . Optimising the treatment for improved outcomes and a reduced need for secondary surgery is m and atory for humanitarian and economical reasons . The importance of incorporating the patient 's perspective of the outcome in clinical trials has been acknowledged and there are now numerous instruments for assessing the quality of life . We evaluated two quality of life instruments , the EQ-5D and the SF-36 , in patients with femoral neck fractures and also measured the quality of life two years after different interventions . The EQ-5D was vali date d in two prospect i ve studies and it appeared to be an appropriate quality of life instrument in elderly patients with femoral neck fractures . There was a good correlation between the quality of life ( EQ-5D index scores ) and other outcome measures such as pain , mobility and independence in activities of daily living ( ADL ) . The results also showed high responsiveness , i.e. , ability to capture clinical ly important changes , for both the EQ-5D and the SF-36 . The question naire response rate for both instruments was high . The rated prefracture EQ-5D index scores showed good correspondence with the scores of an age-matched Swedish reference population . The quality of life in patients with femoral neck fractures treated with internal fixation ( IF ) decreased , particularly in patients with fracture healing complications . The fracture healing complications rate at two years in patients with displaced femoral neck fractures treated with IF was 36 % compared with 7 % in patients with undisplaced fractures . The quality of life of patients with uneventfully healed fractures at two year was lower in patients with primary displaced fractures than in patients with primary undisplaced fractures . In a prospect i ve r and omised trial , patients with displaced femoral neck fractures were r and omised to IF or total hip replacement ( THR ) . IF result ed in more complications than THR , 36 % versus 4 % , and necessitated more reoperations , 42 % versus 4 % . Hip function and quality of life ( EQ-5D ) were generally better in the THR group . In summary , THR yielded a better outcome than IF for an elderly , relatively healthy , lucid patient with a displaced femoral neck fracture . In a study of elderly women with femoral neck fractures , nearly half of the patients displayed signs of protein-energy malnutrition . Underweight was associated with muscle fatigue , cognitive dysfunction and a low quality of life ( Nottingham Health Profile ) . In a prospect i ve r and omised trial , protein-rich liquid supplementation in combination with an anabolic steroid given for 6 months to lean elderly women after a femoral neck fracture was shown to positively affect lean body mass , ADL and quality of life ( EQ-5D ) . Fracture healing complications had a negative impact on body weight , lean body mass and quality of life BACKGROUND The purpose of this study was to provide a detailed evaluation of adherence to nutrition supplements by patients with a lower limb fracture . METHODS These descriptive data are from 49 nutritionally " at-risk " patients aged 70 + years admitted to the hospital after a fall-related lower limb fracture and allocated to receive supplementation as part of a r and omized , controlled trial . Supplementation commenced on day 7 and continued for 42 days . Prescribed volumes aim ed to meet 45 % of individually estimated theoretical energy requirements to meet the shortfall between literature estimates of energy intake and requirements . The supplement was administered by nursing staff on medication rounds in the acute or residential care setting s and supervised through thrice-weekly home visits postdischarge . RESULTS Median daily percent of the prescribed volume of nutrition supplement consumed averaged over the 42 days was 67 % ( interquartile range [ IQR ] , 31 - 89 , n = 49 ) . There was no difference in adherence for gender , accommodation , cognition , or whether the supplement was self-administered or supervised . Twenty-three participants took some supplement every day , and a further 12 missed < 5 days . For these 35 " nonrefusers , " adherence was 82 % ( IQR , 65 - 93 ) , and they lost on average 0.7 % ( SD , 4.0 % ) of baseline weight over the 6 weeks of supplementation compared with a loss of 5.5 % ( SD , 5.4 % ) in the " refusers " ( n = 14 , 29 % ) , p = .003 . CONCLUSIONS We achieved better volume and energy consumption than previous studies of hip fracture patients but still failed to meet target supplement volumes prescribed to meet 45 % of theoretical energy requirements . Clinicians should consider alternative methods of feeding such as a nasogastric tube , particularly in those patients where adherence to oral nutrition supplements is poor and dietary intake alone is insufficient to meet estimated energy requirements OBJECTIVE To study appetite and food choices in lean elderly women at the time of a femoral neck fracture and after 6 months of nutritional and anabolic intervention . SUBJECTS AND METHODS Forty-five nondemented women > 70 years of age ( mean + /- SD : 83 + /- 5 years ) with a recent hip fracture and body mass index < 24 kg/m2 ( mean : 20.5 + /- 2.3 ) were interviewed about their appetite and dietary habits prior to fracture . The patients were r and omized to treatment with a protein-rich liquid supplement ( PR ; 200 kcal and 20 g protein day(-1 ) ) alone or in combination with n and rolone decanoate injections ( PR/N ) 25 mg i.m . every third week or to a control group ( C ) . A second interview was conducted 6 months later . RESULTS Reduced appetite before the fracture was reported by 60 % . Half of the patients did not have dessert with any of their daily meals , one-third used low-fat margarines and one-third drank water with their meals . The estimated mean daily energy intake was 6.4 + /- 1.2 MJ ( 1541 + /- 304 kcal ) indicating that three of four subjects did not meet their energy needs . At 6 months , 40 % reported reduced appetite . There was no difference in the change of appetite between the three r and omized groups . Still , half of the subjects appeared to not meet their energy needs . Protein intake increased in the PR and PR/N groups , in contrast to the controls ( P = 0.002 ) . CONCLUSION Reduced appetite and insufficient energy intake was recorded in lean elderly women with a femoral neck fracture . Nutritional supplementation alone or in combination with an anabolic steroid increased protein intake without adversely affecting appetite In a prospect i ve , r and omized , controlled study an intravenous vitamin B complex and vitamin C preparation was administered pre- and post-operatively to 28 elderly patients with a fractured proximal femur and compared with 32 nonsupplemented postoperative controls . Vitamin supplementation significantly , though only transiently , improved postoperative thiamine status ( P less than 0.001 ) , but had no influence on mental state or outcome during the postsurgical period . Therefore , the use of parenteral vitamins for postoperative confusion can not be justified on a routine basis Wound-care journals contain abundant reports of trials , but not all report a satisfactory methodology . Systematic review s of wound-care trials have highlighted many areas for improvement , and the National Institute for Clinical Excellence ( NICE ) guidelines recommend that primary research in the field of pressure ulcer prevention should adhere more closely to current method ological st and ards in terms of conduct and reporting . The CONSORT tool was developed to help achieve these improvements in the design and reporting of r and omised controlled trials ( RCTs ) Fracture of the proximal femur is the most dramatic clinical sequela of osteoporosis [ 1 , 2 ] . It is associated with a high mortality rate , need for long-term medical care , and prolonged disability [ 3 - 5 ] . Protein malnutrition is often seen in elderly persons and is more severe in patients with hip fracture [ 6 - 11 ] . Protein deficiency may contribute to the occurrence of hip fracture by reducing muscle strength , impairing movement coordination , and diminishing the protective layer of soft tissue padding [ 9 , 10 , 12 - 14 ] It may also be associated with lower bone mineral density at the proximal femur [ 15 ] . Furthermore , malnutrition in general and protein deficiency in particular at admission and during recovery may adversely influence clinical outcome after hip fracture [ 7 , 9 , 10 , 16 - 18 ] . Protein restriction has been shown to reduce plasma levels of insulin-like growth factor-I ( IGF-I ) by inducing resistance to the action of growth hormone in the liver and increasing the metabolic clearance rate of the growth factor [ 19 - 23 ] . Furthermore , evidence shows that protein depletion may blunt the effect of IGF-I on target organs [ 20 ] . Thus , low protein intake in elderly persons may be detrimental to skeletal integrity , muscle strength , and immune response [ 11 , 24 - 27 ] because of decreased production and action of IGF-I , which favorably influences these systems [ 28 - 33 ] . Previous studies [ 16 , 17 ] have shown that a 5-week course of protein supplements can reduce the medical complication rate and duration of hospital stay in patients with recent hip fracture . These findings were independent of energy , calcium , and vitamin D intake [ 17 ] . Whether these observations were related to the restoration of decreased IGF-I levels and whether bone may benefit from long-term protein supplementation are not known . We investigated whether protein supplements in vitamin D-replete patients with a recent hip fracture who were receiving calcium supplements could increase circulating IGF-I levels and favorably influence bone mineral density . Methods Patients Patients were recruited in the orthopedic ward of Geneva University Hospital , the referral center that receives 94.6 % of all patients with hip fracture from an area with a population of approximately 400 000 persons [ 5 ] . The protocol was approved by the ethical committee of the Geneva University Hospital Department of Surgery . Inclusion criteria were age greater than 60 years ; recent hip fracture ( within 2 weeks ) attributable to osteoporosis ( that is , a fracture after a minor trauma , such as a fall from st and ing height ) ; and the ability to give written , informed consent . Exclusion criteria were pathologic fracture ; fracture caused by severe trauma ; history of contralateral hip fracture ; severe mental impairment ; active metabolic bone disease ; renal failure ( plasma creatinine concentration 200 mol/L ) ; acute illness that could interfere with the study protocol ; severe malnutrition ( serum albumin level < 15 g/L ) ; consumption of drugs known to alter bone metabolism , such as calcitonin , fluoride , sex hormones , corticosteroids , or bisphosphonates ; and life expectancy of less than 1 year . Using a r and om number table , we assigned patients to receive an oral protein supplement composed of 90 % milk proteins or a placebo made isocaloric by the addition of maltodextrins . Patients took the assigned intervention 5 days a week for 6 months in addition to their regular diet . All patients received one oral dose of vitamin D3 , 200 000 IU ( vitamine D3B.O.N. , Doms-Adrian , Courbevoie , France ) , to correct any possible vitamin D deficiency [ 34 ] . The daily protein supplement ( Meritene , S and oz Nutrition Ltd. , Berne , Switzerl and ) provided 1050 kJ ( 250 kcal ) of energy in the form of 20 g of proteins , 3.1 g of lipids , and 35.7 g of carbohydrates ( 54.4 g in placebo ) . The other constituents of the 65 g powder supplement were vitamin A ( 1000 IU ) , vitamin K1 ( 30 g ) , vitamin C ( 20 mg ) , calcium ( 550 mg ) , magnesium ( 91 mg ) , phosphorus ( 429 mg ) , and sodium ( 228 mg ) . The supplement is design ed to normalize but not overcompensate for the insufficient dietary intake of protein of elderly persons with a recent fracture of the proximal femur [ 16 ] . Compliance was verified by weekly phone calls and by counting the remaining nutritional supplement bags , which were forwarded monthly by mail . Clinical Data Medical history , clinical characteristics , anthropometric data , and performance status according to an Activities of Daily Living score [ 35 ] were evaluated . Dietary intakes were recorded by using a food-frequency question naire [ 36 ] about the week before the fracture . Food intakes were analyzed by using a nutrient software system ( Fruitdor , Astra-Calve , Paris , France ) . Dietary intake of calcium , phosphorus , and protein was calculated from intake of dairy products , meat , fish , and vegetables . Because many patients were unable to st and a few days after hip fracture , their height was determined with a fathom measure while they were recumbent . Body weight was determined with a scale that correlated highly with that provided by measurement of whole body bone , fat , and lean mass as assessed by dual x-ray absorptiometry [ 37 ] . Mid-arm circumference was measured with a tape measure ( coefficient of variation , 2 % ) . Isometric muscle strength of the biceps of the dominant arm was evaluated with a dynamometer ( Lido , Lidoactive Isokinetic System , Loredan Biomedical Inc. , West Sacramento , California ) , which measures the peak torque ( coefficient of variation < 5 % ) . The grip strength of the same arm was measured with a dynamometer ( Vigorimeter , Martin Medizin-Technik , Tuttlingen , Germany ) [ 38 ] . The mean of three measurements was used for calculation . Biochemical Data Within 120 hours after surgery , we used st and ard methods to analyze venous blood sample s for protein-corrected plasma levels of calcium , phosphate , creatinine , total proteins , albumin , and prealbumin . We also measured levels of IGF-I ( Nichols Institute , San Juan Capistrano , California ) after acid-ethanol extraction and cryoprecipitation [ 39 ] , intact parathyroid hormone ( Immulite , Diagnostic Products , Los Angeles , California ) , calcitriol , calcidiol ( Incstar , Stillwater , Minnesota ) , and osteocalcin ( CIS-BIO International , Gif-sur-Yvette , France ) . Biochemical measurements were repeated 6 and 12 months after the fracture . Serum IGF-I binding proteins were measured by Western lig and blot analysis [ 40 ] . Briefly , 3 L of serum was boiled and separated onto 15 % sodium dodecylsulfate polyacrilamide gel electrophoresis under nonreducing conditions . Proteins were electrically blotted onto a nitrocellulose membrane , and IGF-I binding proteins were detected after incubating the membranes with radioiodinated IGF-I at 4C for 24 hours . Insulin-like growth factor binding proteins were quantified by phosphorimaging ( Molecular Dynamics , Sunnyvale , California ) . The intensity of the b and s corresponding to the appropriate molecular weights [ 40 ] was expressed as the percentage of total bound radioactive IGF-I. Measurements of calcium , phosphate , and creatinine were obtained from the second fasting morning urine . The ratio of hydroxyproline to creatinine in the same sample was taken as a reflection of bone resorption . Markers of bone resorption ( pyridinoline and deoxypyridinoline ) in the first morning spot urine were measured by detecting fluorescence emission after acid hydrolysis and separation with isocratic reverse-phase high-performance liquid chromatography ( BioRad System , Munich , Germany ) , and the values were adjusted to the creatinine concentration . Immunologic Data Concentrations of IgA , IgG , IgM , and isohemagglutinins were measured by using st and ard methods . Cell-mediated immunity was assessed by using a skin-test antigens for cellular hypersensitivity system ( STACH , Institut Merieux , Lyon , France ) , which evaluates the size of the skin reaction to various antigens injected intradermally [ 41 ] . Bone Mass Assessment We measured areal bone mineral density at the lumbar spine ( anteroposterior and lateral views ) , the contralateral proximal femur ( femoral neck and trochanter ) , and the contralateral mid-femoral shaft . We also measured whole-body bone mineral content , fat , and lean mass by using dual x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . The coefficients of variation of these measurements are reported elsewhere [ 37 , 42 ] . Vertebral Deformity Two series of lateral radiography of the thoracic and lumbar spine were taken at the start of the study and at 12 months . The films were examined by a single investigator ( who was unaware of treatment group assignment ) according to a 6-point analysis procedure for each vertebral body from T4 to L4 [ 43 , 44 ] ( intra-observer coefficient of variation , 1.8 % to 3.1 % ) . At baseline , fracture was defined by a decrease of 20 % in the ratio of anterior or middle height to posterior height . Patients were considered to have a new vertebral deformity if the anterior , middle , or posterior height decreased by more than 20 % between the two examinations . Statistical Analysis All values are given as the mean SD for baseline measurement and the mean SE for comparisons of outcome results . All analyses were performed by using the SAS procedure ( Cary , North Carolina ) . One-way analysis of variance was used . A two-tailed P value less than 0.05 was considered significant . Role of the Funding Sources This study was supported by grants from S and oz Nutrition Ltd. , Berne , Switzerl and , and the Swiss National Research Science Foundation . The skin-test antigens for cellular hypersensitivity system was supplied by Rhone-Poulenc , Thalwil , Switzerl and . No organization influenced the design , conduct , or reporting of the study . Results Of 842 patients evaluated from April 1992 to February 1994 , 82 were recruited into the r and omized , double-blind , placebo-controlled trial . This low enrollment rate was due to patients ' poor medical or cognitive conditions and reluctance to give informed consent . BACKGROUND & AIMS The aim of this study of women with hip fracture was to describe nutritional status with biochemical markers and anthropometric variables , and to evaluate the effect of nutritional intervention with the intention of increasing protein and energy intake . METHODS The first consecutive 44 women were included , and used as controls . The next 44 were matched for age , fracture and mental state . Anthropometric variables , IGF-I , hormones and serum albumin were collected 4 - -6 days ( baseline ) , 1 and 3 months after surgery . Twenty-four women filled out a 7-day food record . RESULTS At baseline , one fourth had BMI < 20 kg/m(2 ) and subnormal triceps skinfold thickness . Baseline serum albumin , IGF-I and growth hormone levels were low , probably as an acute response to trauma . Women with BMI < 20 kg/m(2)had lower IGF-I levels compared to those with higher BMI . At 3 months , one-third of both groups were protein and energy malnourished . The intervention group obtained higher daily energy percentage from fat but none of the groups reached their calculated energy need . CONCLUSIONS Using biochemical markers in the acute postoperative situation to assess nutritional status is not recommended . The intervention had no impact on anthropometric or biochemical variables BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year 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 this study , design ed as a r and omized controlled prospect i ve intervention study , was to evaluate the effect of nutritional supplementation on functional status and need of care in undernourished geriatric patients during hospitalization , and up to 6 months after discharge . Participants consisted of 46 undernourished geriatric patients from a geriatric acute care hospital aged 75 years or older without malignant disease , or need for tube feeding or parenteral nutrition . Patients in the supplement group ( SG , N=20 ) were offered 400 mL ( 2100 kJ ) daily of a liquid supplement during hospital stay and 200 mL ( 1050 kJ ) per day for the following 6 months at home . Patients in the control group ( CG , N=26 ) had usual care without supplements . The main outcome measure was functional status based on the Barthel Activities of Daily Living score ( ADL ) at hospital admission , discharge and after 6 months , with higher scores indicating greater independence and a maximum score of 100 points . In supplemented patients with good acceptance ( SG+ , N=11 ) , a median improvement of 20 points was observed between admission and discharge , and a further improvement of 5 points at home . Median changes were 0 and −10 points in supplemented patients with poor acceptance ( SG- , N=9 ) and 5 and 2.5 points in CG , respectively . In SG+ , the proportion of independent patients ( > 65 points ) increased continuously from 36 % at admission to 63 % at discharge , to 72 % after 6 months , and was significantly higher compared to CG at discharge ( 63 % vs 19 % , pš 0.05 ) and after 6 months ( 72 % vs 39 % , p<0.05 ) . 64 % of the patients in SG+ improved during hospitalization , compared to 23 % in CG ( p<0.05 ) . In the six months at home , 18 % of SG+ improved ; none of SG+ deteriorated in hospital or at home . In contrast , deterioration of the ADL score occurred in considerable proportions of SG− ( 22 % in hospital , 22 % at home ) and CG ( 4 % at hospital , 12 % at home ) patients . The proportion of patients who improved was smaller in SG− ( 44 % at hospital , 22 % at home ) as well as in CG ( 23 % at hospital , 35 % at home ) , compared to SG+ . In conclusion , a positive functional course was evident in supplemented patients with good acceptance during hospitalization , and further improvement was observed during the following 6 months at home . Nutritional support may contribute to reconvalescence and recovery of undernourished geriatric patients To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results |
11,326 | 31,388,965 | In atherosclerosis , most studies report a positive correlation with the burden of CV risk factors and vascular calcification .
A higher uptake was found in culprit plaques/rupture sites in coronary and carotid arteries and it was also linked to high-risk features in histology and intravascular imaging analysis of the plaques .
In aortic stenosis , this tracer displayed an increasing uptake with disease severity .
Sodium fluoride positron emission tomography is a promising non-invasive technique to identify high-risk plaques , which sets ground to a potential use of this tracer in evaluating atherosclerotic disease progression and degenerative changes in aortic valve stenosis . | 18-Fluorine sodium fluoride is a well-known radiotracer used for bone metastasis diagnosis .
Its uptake correlation with cardiovascular ( CV ) risk was primarily suggested in oncological patients .
Moreover , as a specific marker of microcalcification , it seems to correlate with CV disease progression and plaque instability .
Our purpose was to systematic ally review clinical studies that characterized the use of this marker in CV conditions . | AIM To assess the calcification process of the carotid plaque by (18)F-sodium fluoride PET/CT imaging . MATERIAL AND METHODS A prospect ively design ed study including 15 patients in whom an atheroma plaque was detected by contrast enhanced CT scan during a neurological work-up was performed . A total of 29 plaques , 19 asymptomatic and 10 symptomatic , were studied . An (18)F-sodium fluoride PET/CT scan was acquired 180min after the i.v . injection of 370 MBq of (18)F-sodium fluoride in all the patients . The images obtained were analyzed visually according to the intensity of the uptake . RESULTS All the plaques showed (18)F-sodium fluoride uptake , regardless of the intensity . However , the plaques of the symptomatic group showed a level of 2 or greater intensity while the intensity in 6 of the 19 in the asymptomatic group was lower than 2 . CONCLUSIONS Although the study is limited by the small number of cases , the results show the feasibility of the technique to study the calcification of the atheroma using (18)F-sodium fluoride and suggest an association between symptomatology and higher uptake of (18)F-sodium fluoride . Thus , these results encourage us to continue this study , with the inclusion of a larger number of patients Background — The pathophysiology of aortic stenosis is incompletely understood , and the relative contributions of valvular calcification and inflammation to disease progression are unknown . Methods and Results — Patients with aortic sclerosis and mild , moderate , and severe stenosis were compared prospect ively with age- and sex-matched control subjects . Aortic valve severity was determined by echocardiography . Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride ( 18F-NaF ) and 18F-fluorodeoxyglucose ( 18F-FDG ) uptake with the use of positron emission tomography . One hundred twenty-one subjects ( 20 controls ; 20 aortic sclerosis ; 25 mild , 33 moderate , and 23 severe aortic stenosis ) were administered both 18F-NaF and 18F-FDG . Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 ( 18F-NaF ) and ±0.13 ( 18F-FDG ) for maximum tissue-to- background ratios . Activity of both tracers was higher in patients with aortic stenosis than in control subjects ( 18F-NaF : 2.87±0.82 versus 1.55±0.17 ; 18F-FDG : 1.58±0.21 versus 1.30±0.13 ; both P<0.001 ) . 18F-NaF uptake displayed a progressive rise with valve severity ( r2=0.540 , P<0.001 ) , with a more modest increase observed for 18F-FDG ( r2=0.218 , P<0.001 ) . Among patients with aortic stenosis , 91 % had increased 18F-NaF uptake ( > 1.97 ) , and 35 % had increased 18F-FDG uptake ( > 1.63 ) . A weak correlation between the activities of these tracers was observed ( r2=0.174 , P<0.001 ) . Conclusions — Positron emission tomography is a novel , feasible , and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis . The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT01358513 BACKGROUND The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease . We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ( (18)F-NaF ) and (18)F-fluorodeoxyglucose ( (18)F-FDG ) . METHODS In this prospect i ve clinical trial , patients with myocardial infa rct ion ( n=40 ) and stable angina ( n=40 ) underwent (18)F-NaF and (18)F-FDG PET-CT , and invasive coronary angiography . (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease , and with intravascular ultrasound in patients with stable angina . The primary endpoint was the comparison of (18)F-fluoride tissue-to- background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infa rct ion . FINDINGS In 37 ( 93 % ) patients with myocardial infa rct ion , the highest coronary (18)F-NaF uptake was seen in the culprit plaque ( median maximum tissue-to- background ratio : culprit 1·66 [ IQR 1·40 - 2·25 ] vs highest non-culprit 1·24 [ 1·06 - 1·38 ] , p<0·0001 ) . By contrast , coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible , there were no differences between culprit and non-culprit plaques ( 1·71 [ 1·40 - 2·13 ] vs 1·58 [ 1·28 - 2·01 ] , p=0·34 ) . Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification , macrophage infiltration , apoptosis , and necrosis . 18 ( 45 % ) patients with stable angina had plaques with focal (18)F-NaF uptake ( maximum tissue-to- background ratio 1·90 [ IQR 1·61 - 2·17 ] ) that were associated with more high-risk features on intravascular ultrasound than those without uptake : positive remodelling ( remodelling index 1·12 [ 1·09 - 1·19 ] vs 1·01 [ 0·94 - 1·06 ] ; p=0·0004 ) , microcalcification ( 73 % vs 21 % , p=0·002 ) , and necrotic core ( 25 % [ 21 - 29 ] vs 18 % [ 14 - 22 ] , p=0·001 ) . INTERPRETATION (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque . Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease . FUNDING Chief Scientist Office Scotl and and British Heart Foundation The purpose of this study was to correlate 18F-sodium fluoride accumulation in the common carotid arteries of neurologically asymptomatic patients with cardiovascular risk factors and carotid calcified plaque burden . Methods : Two hundred sixty-nine oncologic patients were examined by 18F-sodium fluoride PET/CT . Tracer accumulation in the common carotid arteries was analyzed both qualitatively and semiquantitatively by measuring the blood-pool – corrected st and ardized uptake value ( target-to- background ratio ) and comparing it with cardiovascular risk factors and calcified plaque burden . Results : 18F-sodium fluoride uptake was observed at 141 sites in 94 ( 34.9 % ) patients . Radiotracer accumulation was colocalized with calcification in all atherosclerotic lesions . 18F-sodium fluoride uptake was significantly associated with age ( P < 0.0001 ) , male sex ( P < 0.0001 ) , hypertension ( P < 0.002 ) , and hypercholesterolemia ( P < 0.05 ) . The presence of calcified plaque correlated significantly with these risk factors but also with diabetes ( P < 0.0001 ) , history of smoking ( P = 0.03 ) , and prior cardiovascular events ( P < 0.01 ) . There was a highly significant correlation between the presence of 18F-sodium fluoride uptake and number of present cardiovascular risk factors ( r = 0.30 , P < 0.0001 ) . Conclusion : Carotid 18F-sodium fluoride uptake is a surrogate measure of calcifying carotid plaque , correlates with cardiovascular risk factors , and is more frequent in patients with a high-risk profile for atherothrombotic events but demonstrates a weaker correlation with risk factors than does calcified plaque burden . This study provides a rationale to conduct further prospect i ve studies to determine whether 18F-sodium fluoride uptake can predict vascular events , or if it may be used to monitor pharmacologic therapy Purpose Arterial inflammation and vascular calcification are regarded as early prognostic markers of cardiovascular disease ( CVD ) . In this study we investigated the relationship between CVD risk and arterial inflammation ( 18F-FDG PET/CT imaging ) , vascular calcification metabolism ( Na18F PET/CT imaging ) , and vascular calcium burden ( CT imaging ) of the thoracic aorta in a population at low CVD risk . Methods Study participants underwent blood pressure measurements , blood analyses , and 18F-FDG and Na18F PET/CT imaging . In addition , the 10-year risk for development of CVD , based on the Framingham risk score ( FRS ) , was estimated . CVD risk was compared across quartiles of thoracic aorta 18F-FDG uptake , Na18F uptake , and calcium burden on CT . Results A total of 139 subjects ( 52 % men , mean age 49 years , age range 21 – 75 years , median FRS 6 % ) were evaluated . CVD risk was , on average , 3.7 times higher among subjects with thoracic aorta Na18F uptake in the highest quartile compared with those in the lowest quartile of the distribution ( 15.5 % vs. 4.2 % ; P < 0.001 ) . CVD risk was on average , 3.7 times higher among subjects with a thoracic aorta calcium burden on CT in the highest quartile compared with those in the lowest two quartiles of the distribution ( 18.0 % vs. 4.9 % ; P < 0.001 ) . CVD risk was similar in subjects in all quartiles of thoracic aorta 18F-FDG uptake . Conclusion Our findings indicate that an unfavourable CVD risk profile is associated with marked increases in vascular calcification metabolism and vascular calcium burden of the thoracic aorta , but not with arterial inflammation Background — 18F-sodium fluoride ( 18F-NaF ) positron-emission tomography has been introduced as a potential noninvasive imaging tool to identify plaques with high-risk characteristics in patients with coronary artery disease . We sought to evaluate the clinical relevance of 18F-NaF uptake using optical coherence tomography ( OCT ) , intravascular ultrasound ( IVUS ) , and coronary computed tomography angiography in patients with coronary artery disease . Methods and Results — The target population consisted of 51 prospect ively enrolled patients ( 93 stenoses ) who underwent 18F-NaF positron-emission tomography before invasive coronary angiography . 18F-NaF uptake was compared with IVUS- and OCT-derived plaque characteristics . In the coronary computed tomography angiography subgroup ( 46 lesions ) , qualitative lesion characteristics were compared between 18F-NaF – positive and 18F-NaF – negative plaques using adverse plaque characteristics . The plaques with 18F-NaF uptake showed significantly higher plaque burden , more frequent posterior attenuation and positive remodeling in IVUS , and significantly higher maximum lipid arc and more frequent microvessels in OCT ( all P<0.05 ) . There were no differences in minimum lumen area and area of calcium between 18F-NaF – positive and 18F-NaF – negative lesions . Among 51 lesions with 18F-NaF – positive uptake , 48 lesions ( 94.1 % ) had at least one of high-risk characteristics . The 18F-NaF tissue-to- background ratio in plaques with high-risk characteristics was significantly higher than in those without ( 1.09 [ 95 % confidence interval , 0.85–1.34 ] versus 0.62 [ 95 % confidence interval , 0.42–0.82 ] , P<0.001 for IVUS definition ; 0.76 [ 95 % confidence interval , 0.54–0.98 ] versus 0.42 [ 95 % confidence interval , 0.21–0.62 ] , P=0.014 for OCT definition ) . Among the 15 lesions that met both IVUS- and OCT-defined criteria for high-risk plaque , 14 ( 93.3 % ) showed 18F-NaF – positive uptake . There was no difference in the prevalence of plaques with any adverse plaque characteristics between 18F-NaF – positive and 18F-NaF – negative plaques in the coronary computed tomography angiography subgroup ( 85.2 % versus 78.9 % ; P=0.583 ) . Conclusions — This study ’s results suggest that 18F-NaF positron-emission tomography can be a useful noninvasive diagnostic tool to identify and localize plaque with high-risk characteristics . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT02388412 OBJECTIVES With combined positron emission tomography and computed tomography ( CT ) , we investigated coronary arterial uptake of 18F-sodium fluoride ( 18F-NaF ) and 18F-fluorodeoxyglucose ( 18F-FDG ) as markers of active plaque calcification and inflammation , respectively . BACKGROUND The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques , which are associated with specific pathological characteristics , including micro-calcification and inflammation . METHODS We prospect ively recruited 119 volunteers ( 72 ± 8 years of age , 68 % men ) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake . Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis ( calcium score > 0 ) . RESULTS Inter-observer repeatability of coronary 18F-NaF uptake measurements ( maximum tissue/ background ratio ) was excellent ( intra-class coefficient 0.99 ) . Activity was higher in patients with coronary atherosclerosis ( n = 106 ) versus control subjects ( 1.64 ± 0.49 vs. 1.23 ± 0.24 ; p = 0.003 ) and correlated with the calcium score ( r = 0.652 , p < 0.001 ) , although 40 % of those with scores > 1,000 displayed normal uptake . Patients with increased coronary 18F-NaF activity ( n = 40 ) had higher rates of prior cardiovascular events ( p = 0.016 ) and angina ( p = 0.023 ) and higher Framingham risk scores ( p = 0.011 ) . Quantification of coronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects ( p = 0.498 ) . CONCLUSIONS 18F-NaF is a promising new approach for the assessment of coronary artery plaque biology . Prospect i ve studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability , recent plaque rupture , and future cardiovascular risk . ( An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis ; NCT01358513 ) 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 . ) AIMS The pathophysiology of aortic stenosis shares many similarities with atherosclerosis and skeletal bone formation . Using non-invasive imaging , we compared aortic valve calcification and inflammation activity with that measured in atherosclerosis and bone . METHODS AND RESULTS Positron emission and computed tomography was performed using 18F-sodium fluoride ( 18F-NaF , calcification ) and 18F-fluorodeoxyglucose ( 18F-FDG , inflammation ) in 101 patients with calcific aortic valve disease ( 81 aortic stenosis and 20 aortic sclerosis ) . Calcium scores and positron emission tomography tracer activity ( tissue-to- background ratio ; TBR ) were measured in the aortic valve , coronary arteries , thoracic aorta , and bone . Over 90 % of the cohort had coexistent calcific atheroma , yet correlations between calcium scores were weak or absent ( valve vs. aorta r(2 ) = 0.015 , P = 0.222 ; valve vs. coronaries r(2 ) = 0.039 , P = 0.049 ) as were associations between calcium scores and bone mineral density ( BMD vs. valve r(2 ) = 0.000 , P = 0.766 ; vs. aorta r(2 ) = 0.052 , P = 0.025 ; vs. coronaries r(2 ) = 0.016 , P = 0.210 ) . 18F-NaF activity in the valve was 28 % higher than in the aorta ( TBR : 2.66 ± 0.84 vs. 2.11 ± 0.31 , respectively , P < 0.001 ) and correlated more strongly with the severity of aortic stenosis ( r(2 ) = 0.419 , P < 0.001 ) than 18F-NaF activity outwith the valve ( valve vs. aorta r(2 ) = 0.167 , P < 0.001 ; valve vs. coronary arteries r(2 ) = 0.174 , P < 0.001 ; valve vs. bone r(2 ) = 0.001 , P = 0.806 ) . In contrast , 18F-FDG activity was lower in the aortic valve than the aortic atheroma ( TBR : 1.56 ± 0.21 vs. 1.81 ± 0.24 , respectively , P < 0.001 ) and more closely associated with uptake outwith the valve ( valve vs. aorta r(2 ) = 0.327 , P < 0.001 ) . CONCLUSION In patients with aortic stenosis , disease activity appears to be determined by local calcific processes within the valve that are distinct from atherosclerosis and skeletal bone metabolism |
11,327 | 26,804,368 | Neither iloprost nor pentoxifylline had a significant effect on amputation rate compared with conventional therapy .
There is low- to moderate- quality evidence supporting the use of HBOT as an adjunctive therapy to enhance diabetic foot ulcer healing and potentially prevent amputation .
However , there are only sparse data regarding the efficacy of arterial pump devices and pharmacologic interventions | BACKGROUND Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers .
The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy ( HBOT ) , arterial pump devices , and pharmacologic agents ( pentoxifylline , cilostazol , and iloprost ) in this setting . | BACKGROUND Infected foot wounds in patients with diabetes are the most common reason for diabetes-related hospital admission in the United States . Nonhealing foot wounds are the major precipitant of lower-extremity amputation in the diabetic population . HYPOTHESIS The null hypothesis was that there would be no difference in proportion of healing with or without use of a foot-level mechanical compression device . DESIGN Twelve-week , double-blind , r and omized , controlled trial . SETTING A university teaching hospital and related clinics . PATIENTS One hundred fifteen patients with diabetes , 74 % male , with foot infections requiring incision and debridement . INTERVENTION All patients received either a functioning or placebo ( nonfunctioning ) foot compression device ( Kinetic Concepts Inc , San Antonio , Tex ) . Patients and investigators were blinded to the functionality of the device . PRIMARY OUTCOME MEASURE Proportion of wound healing in each group . RESULTS There was a significantly higher proportion of healing in the active group than in the placebo group ( 39 [ 75 % ] of 52 patients vs 23 [ 51 % ] of 45 ; chi(2 ) = 6.0 ; P<.02 ; odds ratio , 2.9 ; 95 % confidence interval , 1 . 2 - 6.8 ) . In the placebo group , there was no difference in proportion of healing between those identified as compliant ( > /=50 hours of use per week ) vs noncompliant ( P = .10 ) . In patients receiving active units , more patients in the compliant subgroup experienced wound healing ( P<.03 ) . When compared as a whole , there was a significant trend toward an increasing proportion of healing from the placebo-noncompliant to the placebo-compliant to the active-noncompliant to the active-compliant groups ( chi(2)(trend ) = 8.3 ; P<.005 ) . CONCLUSIONS Edema reduction achieved in this study by way of a pump and wrap system may increase the proportion of wound healing in patients after debridement of foot infections in patients with diabetes . Furthermore , the data suggest a potential association between increased compliance with use of the device and an increased trend toward wound healing . Arch Surg . 2000;135:1405 - OBJECTIVE Chronic diabetic foot ulcers are a source of major concern for both patients and health care systems . The aim of this study was to evaluate the effect of hyperbaric oxygen therapy ( HBOT ) in the management of chronic diabetic foot ulcers . RESEARCH DESIGN AND METHODS The Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers ( HODFU ) study was a r and omized , single-center , double-blinded , placebo-controlled clinical trial . The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air . Treatments were given in a multi-place hyperbaric chamber for 85-min daily ( session duration 95 min ) , five days a week for eight weeks ( 40 treatment sessions ) . The study was performed in an ambulatory setting . RESULTS Ninety-four patients with Wagner grade 2 , 3 , or 4 ulcers , which had been present for > 3 months , were studied . In the intention-to-treat analysis , complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up : 25/48 ( 52 % ) in the HBOT group and 12/42 ( 29 % ) in the placebo group ( P = 0.03 ) . In a sub- analysis of those patients completing > 35 HBOT sessions , healing of the index ulcer occurred in 23/38 ( 61 % ) in the HBOT group and 10/37 ( 27 % ) in the placebo group ( P = 0.009 ) . The frequency of adverse events was low . CONCLUSIONS The HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes OBJECTIVE To evaluate the effectiveness of systemic hyperbaric oxygen therapy ( s HBOT ) in addition to a comprehensive protocol in decreasing major amputation rate in diabetic patients hospitalized for severe foot ulcer . RESEARCH DESIGN AND METHODS From August 1993 to August 1995 , 70 diabetic subjects were consecutively admitted into our diabetologic unit for foot ulcers . All the subjects underwent our diagnostic-therapeutic protocol and were r and omized to undergo s-HBOT . Two subjects , one in the arm of the treated group and one in the arm of nontreated group , did not complete the protocol and were therefore excluded from the analysis of the results . Finally , 35 subjects received s-HBOT and another 33 did not . RESULTS Of the treated group ( mean session = 38.8 ± 8) , three subjects ( 8.6 % ) underwent major amputation : two below the knee and one above the knee . In the nontreated group , 11 subjects ( 33.3 % ) underwent major amputation : 7 below the knee and 4 above the knee . The difference is statistically significant ( P = 0.016 ) . The relative risk for the treated group was 0.26 ( 95 % CI 0.08–0.84 ) . The transcutaneous oxygen tension measured on the dorsum of the foot significantly increased in subjects treated with hyperbaric oxygen therapy : 14.0 ± 11.8 mmHg in treated group , 5.0 ± 5.4 mmHg in nontreated group ( P = 0.0002 ) . Multivariate analysis of major amputation on all the considered variables confirmed the protective role of s-HBOT ( odds ratio 0.084 , P = 0.033 , 95 % CI 0.008–0.821 ) and indicated as negative prognostic determinants low ankle-brachial index values ( odds ratio 1.715 , P = 0.013 , 95 % CI 1.121–2.626 ) and high Wagner grade ( odds ratio 11.199 , P = 0.022 , 95 % CI 1.406–89.146 ) . CONCLUSIONS s-HBOT , in conjunction with an aggressive multidisciplinary therapeutic protocol , is effective in decreasing major amputations in diabetic patients with severe prevalently ischemic foot ulcers BACKGROUND The cause of diabetic foot ulcers is multifactorial , e.g. , neuropathy and angiopathy , leading to functional disturbances in the macrocirculation and skin microcirculation . Adequate tissue oxygen tension is an essential factor in infection control and wound healing . Hyperbaric oxygen ( HBO ) therapy , daily sessions of oxygen breathing at 2.5-bar increased pressure in a hyperbaric chamber , has beneficial actions on wound healing including antimicrobial action , prevention of edema and stimulation of fibroblasts . The aim of the present study was to investigate the long-term effect of HBO in treatment of diabetic foot ulcers . METHODS Thirty-eight diabetic patients ( 30 males ) with chronic foot ulcers were investigated in a prospect i ve study . The mean age was 60+/-13 years and the mean diabetes duration 27+/-14 years . All patients were evaluated with measurements of transcutaneous oxygen tension ( tcPO(2 ) ) , peripheral blood pressure , and HbA(1c ) . All patients had a basal tcPO(2 ) value lower than 40 mmHg , which increased to > /=100 mmHg , or at least three times the basic value , during inhalation of pure oxygen . Seventeen patients underwent 40 - 60 sessions of HBO therapy , while 21 patients were treated conventionally . The follow-up time was 3 years . RESULTS 76 % of the patients treated with HBO ( Group A ) had healed with intact skin at a follow-up time of 3 years . The corresponding value for patients treated conventionally ( Group B ) was 48 % . Seven patients ( 33 % ) in Group B compared to two patients ( 12 % ) in Group A went to amputation . Peripheral blood pressure , HbA(1c ) , diabetes duration , and basal values of tcPO(2 ) were similar in both groups . CONCLUSIONS Adjunctive HBO therapy can be valuable for treating selected cases of hypoxic diabetic foot ulcers . It seems to accelerate the rate of healing , reduce the need for amputation , and increase the number of wounds that are completely healed on long-term follow-up . Additional studies are needed to further define the role of HBO , as part of a multidisciplinary program , to preserve a functional extremity , and reduce the short- and long-term costs of amputation and disability OBJECTIVE To study the effect of systemic hyperbaric oxygenation ( HBO ) therapy on the healing course of nonischemic chronic diabetic foot ulcers . RESEARCH DESIGN AND METHODS From 1999 to 2000 , 28 patients ( average age 60.2 + /- 9.7 years , diabetes duration 18.2 + /- 6.6 years ) , of whom 87 % had type 2 diabetes , demonstrating chronic Wagner grade s I-III foot ulcers without clinical symptoms of arteriopathy , were studied . They were r and omized to undergo HBO because their ulcers did not improve over 3 months of full st and ard treatment . All the patients demonstrated signs of neuropathy . HBO was applied twice a day , 5 days a week for 2 weeks ; each session lasted 90 min at 2.5 ATA ( absolute temperature air ) . The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer . It was evaluated before HBO and at day 15 and 30 after the baseline . RESULTS HBO was well tolerated in all but one patient ( barotraumatic otitis ) . The transcutaneous oxygen pressure ( TcPO(2 ) ) measured on the dorsum of the feet of the patients was 45.6 + /- 18.1 mmHg ( room air ) . During HBO , the TcPO(2 ) measured around the ulcer increased significantly from 21.9 + /- 12.1 to 454.2 + /- 128.1 mmHg ( P < 0.001 ) . At day 15 ( i.e. , after completion of HBO ) , the size of ulcers decreased significantly in the HBO group ( 41.8 + /- 25.5 vs. 21.7 + /- 16.9 % in the control group [ P = 0.037 ] ) . Such a difference could no longer be observed at day 30 ( 48.1 + /- 30.3 vs. 41.7 + /- 27.3 % ) . Four weeks later , complete healing was observed in two patients having undergone HBO and none in the control group . CONCLUSIONS In addition to st and ard multidisciplinary management , HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients . The time dependence of the effect of HBO warrants further investigations OBJECTIVE ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications . The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers . METHOD eighteen diabetic patients with ischaemic , non-healing lower-extremity ulcers were recruited in a double-blind study . Patients were r and omly assigned either to receive 100 % oxygen ( treatment group ) or air ( control group ) , at 2.4 atmospheres of absolute pressure for 90 min daily ( total of 30 treatments ) . RESULTS healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group . The median decrease of the wound areas in the treatment group was 100 % and in the control group was 52 % ( p=0.027 ) . Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen , there was a potential saving in the total cost of treatment for each patient during the study . CONCLUSION hyperbaric oxygen enhanced the healing of ischaemic , non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible CONTEXT Concerns about the safety and efficacy of diabetes interventions persist , in part because r and omized clinical trials ( RCTs ) have not measured their effect on patient-important outcomes , ie , death and quality of life ( morbidity , pain , function ) . OBJECTIVE To systematic ally determine the extent to which ongoing and future RCTs in diabetes will ascertain patient-important outcomes . DATA SOURCES On November 10 , 2007 , we search ed primary RCT registries Clinical Trials.gov ( http://www . clinical trials.gov ) , International St and ard R and omized Controlled Trial Number Register ( http://is rct n.org ) , and Australian New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au ) . STUDY SELECTION We identified phase 2 through 4 RCTs enrolling patients with diabetes . Of 2019 RCTs , 1054 proved eligible . We r and omly sample d 50 % of the eligible RCTs ( 527 of 1054 ) and selected 436 registered since registration became m and atory ( 2004 ) . DATA EXTRACTION Pairs of review ers working independently collected study characteristics and determined the outcomes measured and their type ( physiological outcomes , surrogate outcomes thought to reflect an increased risk for patient-important outcomes , and patient-important outcomes ) . RESULTS Of the 436 registered RCTs included in this analysis , 24 ( 6 % ) had not started enrollment , 109 ( 25 % ) were actively enrolling , and 303 ( 69 % ) had completed enrollment . Primary outcomes were patient-important outcomes in only 78 of 436 RCTs ( 18 % ; 95 % confidence interval [ CI ] , 14%-22 % ) , physiological and laboratory outcomes in 69 of 436 ( 16 % ; 95 % CI , 13%-20 % ) , and surrogate outcomes in 268 of 436 ( 61 % ; 95 % CI , 57%-66 % ) . Patient-important outcomes were reported as primary or secondary outcomes in 201 of 436 ( 46 % ; 95 % CI , 41%-51 % ) . In multivariate analysis , large trials ( odds ratio [ OR ] , 1.10 ; 95 % CI , 1.02 - 1.19 for every additional 100 patients ) and trials of longer duration ( OR , 1.03 ; 95 % CI , 1.01 - 1.06 for every additional 30 days ) were more likely while parallel design RCTs ( OR , 0.15 ; 95 % CI , 0.05 - 0.44 ) and type 2 diabetes trials ( OR , 0.23 ; 95 % CI , 0.09 - 0.61 ) were less likely to assess patient-important outcomes as a primary outcome . CONCLUSION In this sample of registered ongoing RCTs in diabetes , only 18 % included patient-important outcomes as primary outcomes To study the effect of hyperbaric oxygen therapy in chronic diabetic foot lesions , a prospect i ve controlled study was undertaken . Thirty diabetics with chronic foot lesions were r and omised to study group ( conventional management and 4 sessions of hyperbaric oxygen therapy ) and control group ( conventional management ) . The patients were assessed for average hospital stay , control of infection and wound healing . The control of infection spread was quicker . Positive cultures decreased from initial 19 to 3 in study group as against from 16 to 12 in the control group . ( p < 0.05 ) . This difference was most pronounced for Escherichia coli . Also , the need for major amputation was significantly less in the study group ( n = 2 ) as against the control group ( n = 7 ) ( p < 0.05 ) . The average hospital stay was not affected . We conclude that hyperbaric oxygen therapy can be safely used and is beneficial as an adjuvant therapy in chronic diabetic foot lesions Hyperbaric oxygen therapy can be used as an adjunct to st and ard wound care in the treatment of diabetic patients with foot ulcers . We undertook a prospect i ve , r and omized investigation of the use of hyperbaric oxygen therapy versus st and ard therapy for the treatment of foot ulcers in diabetic patients . A number of demographic variables were analyzed in regard to wound healing . We noted that foot ulcers in patients in the hyperbaric oxygen therapy group were more likely to heal , and were more likely to undergo amputation distal to the metatarsophalangeal joint compared with those patients receiving st and ard therapy without hyperbaric oxygen . We feel that hyperbaric oxygen therapy should be considered a useful adjunct in the management of foot ulcers in diabetic patients The purpose of this study was to prospect ively evaluate the effect of hyperbaric oxygen ( HBO2 ) on the healing of diabetic lower extremity wounds . Ten consecutive insulin-dependent diabetic patients with chronic lower extremity wounds were referred for HBO2 treatment . The control group consisted of five patients , two claustrophobic and three rural . The latter refused HBO2 treatments because of logistic reasons . Five patients underwent 30 HBO2 treatments in the problem wound protocol ( 100 % oxygen , 2 atm abs , 2 h/day , 5 days/wk ) . All patients were evaluated with transcutaneous oxygen measurements and had an initial surgical debridement of the wound . Weekly tracings of the wound surface area were made by a nurse or resident who was blinded to the group assignment . At the end of 7 wk , the mean wound area expressed as a percentage of pretreatment baseline area was compared between groups ( analysis of variance , Duncan 's post hoc ) . No significant differences were noted between groups with respect to age , gender , baseline wound area , wound site O2 tension , or presence of osteomyelitis . At the completion of each of the 7-wk treatment periods , a significantly greater reduction in wound surface area was noted in the HBO2 vs. the control group ( P < 0.05 ) . HBO2 treatment significantly reduced wound size compared to controls in this small , non-r and omized prospect i ve study . These results should serve as a basis for larger multicenter prospect i ve , r and omized , double-blind controlled studies to definitively evaluate the effect of HBO2 on the healing of diabetic foot wounds |
11,328 | 18,922,696 | Some evidence exists that : ( i ) pronated feet demonstrate greater electromyographic activation of invertor musculature and decreased activation of evertor musculature ; ( ii ) foot orthoses increase activation of tibialis anterior and peroneus longus , and may alter low back muscle activity ; and ( iii ) shoes with elevated heels alter lower limb and back muscle activation .
Most studies reported statistically significant changes in electromyographic activation , although these findings were often not well supported when confidence intervals were calculated . | The aim of this systematic review was to evaluate the literature pertaining to the effect of foot posture , foot orthoses and footwear on lower limb muscle activity during walking and running . | Muscle activity has previously been suggested to minimize soft-tissue resonance which occurs at heel-strike during walking and running . If this concept were true then the greatest vibration damping would occur when the input force was closest to the resonant frequency of the soft-tissues at heel-strike . However , this idea has not been tested . The purpose of this study was to test whether muscle activity in the lower extremity is used to damp soft-tissue resonance which occurs at heel-strike during walking . Hard and soft shoe conditions were tested in a r and omized block design . Ground reaction forces , soft-tissue accelerations and myoelectric activity were measured during walking for 40 subjects . Soft-tissue mass was estimated from anthropologic measurements , allowing inertial forces in the soft-tissues to be calculated . The force transfer from the ground to the tissues was compared with changes in the muscle activity . The soft condition result ed in relative frequencies ( input/tissue ) to be closer to resonance for the main soft-tissue groups . However , no increase in force transmission was observed . Therefore , the vibration damping in the tissues must have increased . This increase concurred with increases in the muscle activity for the biceps femoris and lateral gastrocnemius . The evidence supports the proposal that muscle activity damps soft-tissue resonance at heel-strike . Muscles generate forces which act across the joints and , therefore , shoe design may be used to modify muscle activity and thus joint loading during walking and running The foot provides an important source of afferent feedback for balance and locomotion . Sensory feedback from the feet can be altered by st and ing or walking on different surfaces . The purpose was to determine the effects of textured footwear on lower extremity muscle activity , limb kinematics , and joint kinetics while walking . Three-dimensional kinematics and kinetics , as well as muscle EMG , were collected as subjects walked with a smooth and textured shoe insert . Muscle activity was analyzed using a wavelet technique . The textured shoe insert caused a significant reduction in both soleus and tibialis anterior intensity during periods when these muscles are most active . Furthermore , the changes in muscle activity were only seen in the low frequency content of the EMG signal . The foot was significantly more plantar flexed at heel strike with the textured inserts . Small changes were also seen in vertical ground reaction forces and joint moments . It was assumed that the changes in gait patterns were due to a change in sensory feedback caused by the textured shoe insert . The possibilities of altered sensory feedback with footwear are discussed . Sensory feedback from the feet may affect specific motor unit pools during different activities . Changing the texture , without changing the geometry , of a shoe insert can alter muscle activity during walking . This may be useful in the prescription of footwear interventions and suggests that footwear may have sensory as well as mechanical effects Chronic Ankle Instability sprain causes are unclear and many factors or mechanisms may contribute to recurrence of this injury . The aim of the study was to investigate how an ankle destabilization device affects the EMG patterns of the ankle muscles during ankle stabilization against inversion . The left foot was equipped with a mechanical device mounted under the heel of the shoe . This mechanical device induces subtalar joint destabilization necessitating the control of ankle muscles . Surface electrodes were placed over the tibialis anterior , the peroneus longus , the peroneus brevis , the gastrocnemius lateral , and the gastrocnemius medial . Nine healthy subjects ( mean age 37+/-12 yr ; mean mass 68+/-17 kg ; mean height 1.73+/-0.7 m ) were instructed to walk normally along a tape fixed on the floor . The ankle destabilization device altered the walking pattern of all subjects . More specifically , the walking pattern is disturbed result ing in higher amplitude of the EMG activity of the peroneal muscles and the Tibialis Anterior and anticipatory reactions in the peroneal muscles . The results suggest that the ankle destabilization device could be beneficial for rehabilitation programs especially during the training of walking . Using this material may help to a specific reinforcement of muscles involved in anti-inversion ankle movement BACKGROUND To compare kinematics , kinetics and muscle activity during st and ing and walking for healthy subjects using an unstable test shoe ( Masai Barefoot Technology , MBT ) and a stable control shoe . METHODS Eight subjects volunteered for this study . During quiet st and ing , center of pressure excursion and muscle activity were determined . During walking , lower extremity kinematics , kinetics , and muscle electromyographic ( EMG ) signals were determined . Data were collected for the two shoe conditions after a 2week accommodation period . Statistics included repeated measures ANOVAs ( alpha = 0.05 ) and post hoc tests where appropriate . FINDINGS During quiet st and ing , the center of pressure excursion was significantly and substantially greater in the unstable compared to the control shoe . Electromyographic intensity increased in the unstable test shoe for all tested muscles , but only significantly for the tibialis anterior . During locomotion , kinematics were similar in the two shoe conditions except for the initial plantar-dorsiflexion , which showed a significant more dorsiflexed position during the first half of stance in the unstable test shoe compared to the stable control shoe . The angular impulses did not show any significant differences between the two shoe conditions for all three joints but some trends towards a reduction for the knee and hip joint . There were no significant differences in electromyographic activities between the control and the unstable shoe . However , several muscles showed some trends . INTERPRETATION The unstable shoe produced changes and trends in kinematic , kinetic and electromyographic characteristics that seemed to be advantageous for the locomotor system . Further studies should investigate muscle strength , dynamic stability , pain reduction for arthritic knees and injury prevention for high performance athletes when using the unstable shoes OBJECTIVE The purpose of this study was to determine if high-arched and low-arched runners exhibit different injury patterns . DESIGN Non-r and omized , two-group injury survey . BACKGROUND Running-related injuries are thought to be related , in part , to lower extremity structure . High-arched and low-arched runners with their different bony architecture may exhibit very different lower extremity mechanics and , consequently , different injury patterns . It was hypothesized that high-arched runners will exhibit a greater incidence of lateral injuries , skeletal injuries and knee injuries while low-arched runners will show a greater incidence of medial injuries , soft tissue injuries and foot injuries . METHODS Twenty high-arched and 20 low-arched runners were included in this study . Running-related injuries were recorded and divided into injury patterns of medial/lateral , bony/soft tissue and knee/foot and ankle for both high-arched and low-arched runners . A chi(2 ) analysis was then employed in an attempt to associate injury patterns with arch structure . RESULTS High-arched runners reported a greater incidence of ankle injuries , bony injuries and lateral injuries . Low-arched runners exhibited more knee injuries , soft tissue injuries and medial injuries . CONCLUSIONS Based on these results , high and low arch structure is associated with different injury patterns in runners . Relevance . Different injury patterns are present in individuals with extreme high arches when compared to those with extremely low arches . These relationships may lead to improved treatment and intervention strategies for runners based on their predisposing foot structure Abnormal foot morphology has been suggested to contribute to overuse injuries in athletes . This study investigated the relationship between foot type and injury incidence in a large sample of competitive triathletes not wearing foot orthoses during a 6-month retrospective analysis and a 10-week prospect i ve cohort study . Foot alignment was measured using the Foot Posture Index and the Valgus Index , and participants were assigned to supinated , pronated , and normal foot-type groups . Overall , 131 triathletes sustained 155 injuries during the study . Generally , foot type was not a major risk factor for injury ; however , there was a fourfold increased risk of overuse injury during the competition season in athletes with a supinated foot type . The results of this study show that triathletes with a supinated foot type are more likely to sustain an overuse injury 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 Over-pronation has been cited as a key contributor to many types of running injuries . However , the roles of the extrinsic foot muscles during running have not been adequately identified . The purpose of this study was to examine the muscle functional ( mf ) MRI and EMG responses to perturbations of the foot by running in varus , neutral and valgus wedged shoes . Ten males ran at 3.6 m/s in specially constructed shoes for 5 min with T2-weighted mfMRI collected before and after each run . The change in T2 from before to after each run characterized the level of metabolic activity in each of muscle . Kinematic and EMG data were also collected while subjects ran on a treadmill . There were no T2 differences across the three shoe conditions . In contrast , there was significantly less EMG activity in the tibialis anterior and soleus while wearing the neutral shoe . Overall , the results did not support the theory that muscle activity would increase as the degree of eversion increased . It also appears that surface EMG was more sensitive to differences between conditions than mfMRI . However , this study illustrated that mfMRI may be a useful tool for quantifying muscle activity in cases where surface EMG is inadequate OBJECTIVE To compare walking stance phase rearfoot and forefoot motion , ankle joint moments and extrinsic foot muscle EMG profiles between normal and pes planus feet . DESIGN A cross-sectional comparative study . BACKGROUND Musculoskeletal conditions are often attributed to pes planus , in which motion is assumed to be excessive and the muscle control inadequate . However , many of the speculated differences in mechanics and control between the normal and the pes planus foot have not been quantified . METHODS Kinematic and kinetic data were obtained from video recordings of skin surface markers and a force plate , and EMG was recorded with surface electrodes . Analysis of variance was carried out to compare the group profiles . RESULTS In the pes planus group : the forefoot was less adducted ( P < .05 ) at toe-off , and total transverse plane range of motion , at 8 degrees versus 10 degrees , was less ( P < .01 ) ; the peak plantarflexor ankle moment at push-off was greater ( P < .05 ) ; the invertor moment was greater at foot flat ( P < .05 ) ; for the EMG profiles , activity early in stance , relative to the mean stance phase activity was higher ( P < .01 ) in tibialis anterior and lower ( P < .05 ) in the peronei , soleus and medial and lateral gastrocnemius . CONCLUSIONS Despite reaching statistical significance , the group differences were small for the task of laboratory walking at a natural pace . The main implication s of the differences were for restraint of motion . The expectations of excessive motion and muscle effort in the pes planus group were therefore not substantiated . RELEVANCE Symptomatic pes planus subjects did not reveal the expected biomechanical differences from normal subjects . The underlying causes of symptoms were not identifiable Purpose To identify the incidence of medial tibial stress syndrome ( MTSS ) in a group of naval recruits undergoing a 10-week basic training period and to determine potential risk factors . Method One hundred and twenty-four recruits ( 84 men and 40 women ) were followed prospect ively during basic training . Anthropometric and lower limb biomechanical data were recorded at the start of the program along with injury history and previous sporting activity for the 3 months prior to enlisting . Recruits were monitored during training for development of medial tibial strees syndrome and were asked to complete an exit interview at the end of the program . Results Forty recruits ( 22 men and 18 women ) developed medial tibial stress syndrome , giving an incidence of 35 % . A significant relationship existed between gender and medial tibial stress syndrome ( P= .012 ) , with female recruits more likely to develop medial tibial stress syndrome than male recruits ( 53 % vs 28 % ) . A risk estimate revealed a relative risk of 2.03 . The biomechanical results indicated a more pronated foot type ( P= .002 ) in the medial tibial stress syndrome group when compared to the control group . A risk estimate established that recruits with a more pronated foot type had a relative risk of 1.70 . Conclusion Identifying a pronated foot type prior to training may help reduce the incidence of medial tibial stress syndrome by early intervention to control abnormal pronation . Findings of a higher incidence of medial tibial stress syndrome among female recruits require further investigation Background : Immobilization to limit muscle activity is a common therapeutic and posttreatment event . There are potential time and re source savings if a prefabricated boot can replace a custom applied cast . The purpose of this study was to determine if muscle activity reduction is similar using a fiberglass cast versus a prefabricated ( Aircast FoamWalker ) boot . Methods : Surface EMG data were recorded from the gastrocnemius , soleus , and peroneals of 12 normal adults while walking barefoot , in a fiberglass cast with a cast shoe ( cast ) , and while wearing an Aircast FoamWalker ( boot ) . Subjects walked at their self-selected speed for 10 trials in each condition , and the order of barefoot , cast , and boot was r and omly assigned . The data were rectified , integrated across stance phase and normalized to a percent of each subject 's barefoot mean integrated EMG ( iEMG ) value . For each muscle , a linear mixed-effects statistical model ( subject by trial by condition ) was utilized to determine if iEMG activity levels were reduced by immobilization compared to barefoot walking . Results : Activity for all muscles was significantly lower in the boot compared with barefoot ( p < .05 ) . The cast iEMG levels were significantly different from barefoot for the soleus and peroneals ( p < .05 ) . Gastrocnemius activity was significantly decreased in the boot when compared with the cast ( p < .0001 ) . The greater reduction in iEMG levels for the boot indicates that it is superior to a fiberglass cast in reducing gastrocnemius muscle activity during the stance phase of gait . Conclusions : The data show that a prefabricated boot is as effective as a custom applied cast in reducing soleus and peroneal muscle iEMG during stance phase . The boot was more effective in reducing gastrocnemius activity when compared to the cast . Clinical Relevance : This study suggests that a prefabricated boot may be used in place of a custom cast when the goal of treatment is to limit muscle activity of the leg OBJECTIVE To study the effects of foot orthotics on the mean electromyographic amplitude of proximal and distal lower extremity muscle groups during the first 50 % of the stance phase during treadmill running . DESIGN Repeated measures . SETTING Subjects were recruited from the general community . PARTICIPANTS Twelve recreational runners who were symptomatic for lower extremity pain . Clinical and radiographic findings confirmed the presence of structural malalignment of the foot . INTERVENTION Semirigid orthotics were fabricated for each subject , and like footwear provided . MAIN OUTCOME MEASURES Surface electromyogram activity from the tibialis anterior , medial gastrocnemius , vastus medialis , vastus lateralis , and biceps femoris was collected during treadmill running at self-selected speeds for orthotic and nonorthotic conditions . Root mean square values were averaged across 10 cycles , normalized to time and expressed as a percentage of the nonorthotic condition . RESULTS Paired t test results showed statistically significant changes ( p<.05 ) for the biceps femoris ( -11.1 % ) and tibialis anterior ( + 37.5 % ) muscle groups during the orthotic condition . Electromyographic activity in the medial gastrocnemius , vastus medialis , and vastus lateralis with orthotic use was not significantly different from the nonorthotic condition . CONCLUSION Although subjects ' electromyographic responses to orthotic use were highly individualized , the findings of this study may enhance our underst and ing of muscle activity changes associated with positive outcomes from orthotic use The purpose of this study was to determine whether tibialis anterior muscle activity influences the rate of rearfoot motion during walking . Two-dimensional rearfoot motion was recorded from 23 feet . The feet were assigned to one of two experimental groups . Muscle activity was recorded from the tibialis anterior muscle using surface electrodes . The early pronators ( N = 12 ) reached maximal pronation within the first 20 K of the stance phase . The late pronators ( N = 11 ) reached maximal pronation only after 40 % of the stance phase . The results of a C-test showed that there was a significant difference ( P < .05 ) in the time to minimal tibialis anterior muscle activity between the two groups . These results indicate that tibialis anterior muscle activity can influence rearfoot motion during the stance phase of walking . A clinician should consider the muscular system when evaluating and design ing a treatment program for patients with foot-related problems . The results of this study also indicate that static nonweightbearing evaluations alone may not provide an accurate picture of the foot during walking BACKGROUND The Masai barefoot technology is used as a treatment option within the field of physical therapy to treat leg , back or foot problems . No information , however , is available on how Masai barefoot technology changes gait or muscle activity . METHODS Twelve healthy subjects underwent 3D gait analysis with simultaneously collecting surface electromyography data of the leg muscles when walking with regular shoes and with Masai barefoot technology-shoes . Before data collection , subjects were trained in Masai barefoot technology . A within-subjects study - design compared walking with regular shoes and Masai barefoot technology . FINDINGS With Masai barefoot technology , subjects walked slower with smaller steps . Movement pattern at the ankle showed major changes with increased dorsiflexion angle at initial contact followed by a continuous plantarflexion movement until terminal stance phase . With changed kinematics , alterations in the activity of tibialis anterior and gastrocnemius muscles could be observed . Smaller differences in movement and muscle activity were seen at knee and hip level . INTERPRETATION Masai barefoot technology has never been documented in detail concerning changes in movement pattern or muscle activity . This study showed that Masai barefoot technology changes movement patterns , especially at the ankle , and increases muscle activity . It may therefore be a useful training method for strengthening the muscle groups of the lower leg . Knee flexion and electromyographic characteristics around the knee joint are slightly increased and need to be considered in patients with knee problems . Our findings provide critical detailed information on changes compared to walking in regular shoes , but the clinical relevance of those changes remains to be determined OBJECTIVE It is widely accepted that persons with flat or high-arched feet are at increased risk of exercise-associated injury , even though this purported association has not been scientifically evaluated . We evaluate the risk of exercise-associated injury among young men with flat , normal , and high-arched feet . DESIGN A prospect i ve study of 246 US Army Infantry trainees followed up over a rigorous 12-week training program . All subjects were evaluated prior to onset of training . Evaluation included photographs of the right , weight-bearing foot that were digitized and utilized to make several measures of arch height . SETTING An army initial entry training center . SUBJECTS All trainees beginning army training on 2 successive weeks were potential volunteers . There were no criteria for exclusion other than declining to participate ( n = 3 ) . The subjects were healthy , active young men with a mean age of 20.3 years . OUTCOME MEASURE The occurrence of a lower-extremity musculoskeletal injury result ing in a visit to and a diagnosis by an army physician or physician assistant . Treating physicians and physician assistants were blind to participation status and were not study staff members . RESULTS On univariate analysis , there was an association between arch height and risk of injury using several alternative operational definitions of foot type . The 20 % with the flattest feet were at the lowest risk ( reference group ; odds ratio , 1.0 ) , with adjusted odds ratios for any musculoskeletal injury of 3.0 ( P < .05 ) for the middle 60 % group and 6.1 ( P < .05 ) for the highest 20 % group . CONCLUSIONS These findings do not support the hypothesis that low-arched individuals are at increased risk of injury , and they have implication s for runners , exercise enthusiasts , and clinicians . It may be possible to prevent substantial morbidity among active population s by identifying individuals at high risk and advising alternate activities BACKGROUND Some types of foot orthoses have been research ed for their effect on lower limb electromyographic muscle activity during walking . However , foot orthoses with high levels of medial rearfoot wedging ( ' inverted ' foot orthoses ) have not been investigated . METHODS In a cross-sectional study , asymptomatic participants with a pronated foot type ( n=15 ) were each issued with a pair of 0 degrees , 15 degrees and 30 degrees inverted custom-made foot orthoses . After four weeks of habituation to the orthoses , surface electromyography was used to measure the onset and maximum EMG amplitude of tibialis anterior , peroneus longus , medial gastrocnemius and soleus muscles using five conditions [ barefoot , shoe-only , 0 degrees , 15 degrees and 30 degrees inverted foot orthoses conditions ] . FINDINGS A statistically significant increase in tibialis anterior maximum EMG amplitude occurred using the shoe only ( 30 % increase ) , 0 degrees ( 33 % increase ) , 15 degrees ( 38 % increase ) and 30 degrees ( 30 % increase ) inverted orthoses conditions compared to walking barefoot ( P<0.01 ) . Peroneus longus maximum EMG amplitude increased significantly using the 15 degrees inverted orthosis condition compared to walking barefoot ( 21 % increase , P=0.04 ) . INTERPRETATION Footwear and orthoses can significantly alter the maximum EMG amplitude of leg muscles during walking . Foot orthoses appear to increase peroneus longus EMG amplitude compared to footwear alone . However , the level of medial rearfoot posting within an orthosis does not appear to significantly alter maximum EMG amplitude . The individual responses to foot orthoses are highly variable . The changes in EMG amplitude with the use of foot orthoses and shoes may have clinical implication The purpose of this prospect i ve study was to determine whether an association exists between foot structure and the development of musculoskeletal overuse injuries . The study group was a well-defined cohort of 449 trainees at the Naval Special Warfare Training Center in Coronado , California . Before beginning training , measurements were made of ankle motion , subtalar motion , and the static ( st and ing ) and dynamic ( walking ) characteristics of the foot arch . The subjects were tracked prospect ively for injuries throughout training . We identified risk factors that predispose people to lower extremity overuse injuries . These risk factors include dynamic pes planus , pes cavus , restricted ankle dorsiflexion , and increased hindfoot inversion , all of which are subject to intervention and possible correction PURPOSE To provide evidence that lower-extremity muscle activity during running is tuned in response to the loading rate of the impact forces at heel-strike . METHODS Six runners ran two 30-min trials per week for 4 wk . The trials tested two shoes which differed only in the material hardness of the midsole . The shoes were tested in a r and omized sequence . Bipolar surface EMG was recorded from the muscles of the rectus femoris , biceps femoris , medial gastrocnemius , and tibialis anterior . EMG was resolved into time-frequency space using wavelet techniques . EMG was analyzed for the 150 ms time window immediately before heel-strike . RESULTS The intensity of the EMG and the ratio of the EMG intensity between high and low frequency components both showed significant changes between shoes , subjects , and muscles . Additionally , the intensity ratio showed a significant change over the course of each 30-min run . CONCLUSIONS Lower-extremity muscle activity used to tune the muscles for the impact task can be altered by changing the material hardness of the shoe . The changes in the EMG frequency ratio suggest that muscle fiber-type recruitment patterns can also be altered by the choice of midsole material The purpose of this project was to study the EMG pattern of the tibialis anterior muscle in heel-toe running . Specifically , EMG changes in time , intensity and frequency shortly before and after heel-strike were addressed using an EMG-specific non-linearly scaled wavelets analysis . This method allowed extracting the time , intensity and frequency information inherent in the EMG signal at any time . The EMG signals of 40 male subjects were recorded for running barefoot and with shoes . The results confirmed that the pre-heel-strike EMG activities were typically seen at higher EMG frequencies ( 60 - 270Hz ) while the post-heel-strike EMG activities result ed in lower frequency signals ( 10 - 90Hz ) . The timing of the pre-heel-strike EMG activities was not influenced by the used shoe conditions . The timing of the post-heel-strike EMG activities was significantly delayed when wearing shoes . The intensity of the pre-heel-strike muscle activity increased compared to the post-heel-strike one when wearing shoes . One can conclude that the activity of the tibialis anterior adjusts specifically to exterior conditions . The frequency shift between pre- and post heel-strike muscle activity were discussed with respect to activation of different motor units |
11,329 | 24,653,046 | Overall , a lack of validation and a focus upon the physical aspects of symptom management was apparent . | BACKGROUND The increase in the numbers of patients requiring palliative care input prior to death , and a global economic situation where few countries are able to invest further in specialist palliative care services , has meant an increased focus upon ' generalist palliative care provision ' .
The goal of the present review is to ascertain what question naire tools exist to measure the perceived competence of generalists in palliative care provision . | The efficacy of a communication skills training programme was shown through a r and omised trial . Oncologists ( N=160 ) from 34 cancer centres were allocated to written feedback plus course ; course alone ; written feedback alone or control . Each clinician had 6 – 10 interviews with patients videotaped at baseline and 3 months postintervention . Analysis of videotapes revealed improvements in the communication skills of clinicians r and omised to training ( n=80 ) compared with others ( n=80 ) . A 12-month follow-up assessment is reported here . Robust Poisson conditional analyses of counts of changes in communication behaviours revealed no demonstrable attrition in those who had shown improvement previously , including fewer leading questions , appropriate use of focused and open-ended questions and responses to patient cues . Additional skills , not apparent at 3 months , were now evident ; the estimated effect sizes corresponded to 81 % fewer interruptions ( P=0.001 ) and increased summarising of information to 38 % ( P=0.038 ) . However , expressions of empathy ( 54 % , P=0.001 ) declined . The overall results show that 12 – 15 months postintervention , clinicians had integrated key communication skills into clinical practice and were applying others . This is the first RCT to show an enduring effect of communication skills training with transfer into the clinic Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising studies for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding . Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the appraisal process involves a detailed assessment of the patients ( for example , high , medium , or low risk ) , the study interventions ( for example , frequency , degree , and duration ) , and the outcome measurements ( for example , definitions and degree of surveillance ) AIMS To evaluate the effects of a palliative care education programme on the self-reported knowledge and confidence of 72 community nurses . DESIGN a prospect i ve longitudinal postal question naire survey was conducted . FINDINGS seventy-one ( 99 % ) completed a pre-course question naire , 52 ( 72 % ) a question naire at completion of the course , and 37 ( 51 % ) a question naire one year later . Following the programme , more nurses felt that their professional needs were being met well or very well . Confidence in practice showed an increasing trend over time . Desire for education was lower on course completion than at its start . Palliative Care Nursing Quiz scores rose from a pre-course median of 12.5 to 15 at course completion ( P=0.001 ) which was maintained 1 year later . CONCLUSION the education programme was successful in raising st and ards of knowledge , professional development and confidence . Improvement was maintained one year later Prompted by directives from the GMC , ‘ care of the dying ’ is identified as ‘ core curricula ’ for undergraduate medical education . However , there are many technical and interpersonal challenges faced in learning the practice of palliative medicine . Accordingly , the design and delivery of education programmes need to be both carefully considered and evaluated . Using B and ura ’s Social Cognitive Theory as a driver , appropriate methodology for evaluating a novel education programme in palliative medicine was drafted . A pre- and post-survey of an education programme and palliative care placement for fourth year medical undergraduate students from Liverpool University ( n = 216 ) was completed using a composite question naire containing ; i ) Self-efficacy in Palliative Care Scale ( SEPC ) and ii ) Thanatophobia Scale . Both scales have shown reliability and validity within the sample population . Additionally , a r and omly selected Focus Group was conducted to provide qualitative information on the students ’ experience . A total of 139 pre- and post- question naires ( 64 % ) were completed . Analysis identified significant improvements in perceived efficacy ( SEPC Communication t = −16.41 , P < 0.001 ; SEPC Patient Management t = −22.31 , P < 0.001 ; SEPC Multidisciplinary Teamwork t = −15.56 , P < 0.001 ) . Significant improvements in thanatophobia were also recorded ( z = −7.51 , P < 0.001 ) although some interesting anomalies were noted . This study demonstrates that considered and appropriately structured clinical education has been shown to significantly improve students ’ belief in their ability to practice palliative medicine and to improve their attitude towards care . In accordance with the study ’s theoretical driver , it is reasonable to propose that the engaged active learning will have a positive effect on the future care of dying patients We surveyed primary care physicians about their involvement and perceived skills in palliative care . A survey instrument asked how frequently internal medicine and family practice physicians performed 10 palliative care items . Subjects rated their skills in each area . A majority of physicians always or frequently performed all 10 palliative care items , but fewer than 50 % of respondents adequately attended to the spiritual needs and economic problems of patients . Interest in palliative care was associated with an increased frequency in performing palliative care items ( P = 0.036 ) , while training in palliative care was associated with better perceived performance ( P = 0.05 ) . Only 36 % of respondents had received training in palliative care . Internists and family practitioners provide palliative care to patients , but feel their skills are lacking in certain areas . Training may improve care to patients at the end of life This quasiexperimental study examined the effect of an educational program on attitudes toward caring for terminally ill persons and their families . Participants were 115 undergraduate students : intervention group , N = 49 ; control group , N = 66 . Pre and post-intervention measurements were done with the Frommelt Attitude Toward Care of the Dying Scale ( FATCOD , Form B ) . Students in the intervention group participated in a semester-long ( 15-week , 45-hour ) educational program . Demographic variables , including age , gender , religion , major area of study , influence of religious beliefs , profession , previous education , and past or present experience with loss were evaluated . Statistical analyses ( t-test , ANOVA , ANCOVA , and APVs ) indicated a significant positive change in the attitude scores of the intervention group and no significant change in the attitude scores of the control group A r and omly selected sample of 158 South Australian general practitioners ( GPs ) were sent a question naire which assessed opinions and management practice s in the palliative care of terminally ill patients . A total of 117 responses ( 74 % ) were received . Most GPs were at least moderately satisfied with the care they were able to give their terminally ill patients , although a substantial number reported difficulties in pain and other symptom control , dealing with relatives ' emotional distress and attending to patients ' psychosocial needs . There was considerable support for continuing education in these aspects of palliative care . More than half were at least somewhat concerned by opioid side effects and impairment of cognitive function , although opioid dependence was not a concern . Considerable dissatisfaction was expressed with public hospital care for the terminally ill and most felt excluded from decision-making once their patients were admitted . The findings suggest that continuing education is required for GPs and that palliative care should become an integral part of undergraduate education . There is also a need to enhance communication and co-ordination between hospital and community-based services for the terminally ill AIM This paper examines how clinical nurse specialists assessed their competences in relief of symptoms , and explores factors affecting good care routines in palliative care . METHODS A prospect i ve survey among 235 former post-bachelor ( response rate 50.6 % ) students at two university colleges in Norway . RESULTS Correlations between the measured concepts showed a medium to high correlation between all five competences . Use of care routines correlated with all the other factors . The ability to identify lack of care showed significant correlation with one concept : time available for nursing . The results from the regression analysis supported a model with good care routines as a dependent variable ( F=22.59 , df=91 , P<0.001 ) . The independent variables in the model explained almost 57 % of the variance in using care routines . Competences dealing with mouth problems , nausea , anxiety and the use of the Edmonton symptom assessment system ( ESAS ) had a positive effect on care routines . On the other h and , the ability to identify lack of care had a significant negative effect on the use of care routines . CONCLUSIONS The importance of systematic assessment of the palliative patient;s care needs and symptom management are emphasized , and use of the ESAS , and good care routines was affected by post-bachelor competences AIM This paper is a report of part of an evaluation of the impact of a national palliative care education and support programme on the knowledge and confidence of members of district nursing teams . BACKGROUND District nursing teams are the mainstay of ' h and s on ' provision of care at home . In recognition of their central role , the English Department of Health commissioned a national palliative care education programme as post registration education had been limited . METHODS The evaluation , conducted between 2002 and 2004 , had a mixed methods design . In the summative component , 1280 nurses were r and omly selected from eight cancer networks to receive postal question naires 1 year apart , before and after the educational intervention . Changes in scores were calculated and a multiple regression analysis undertaken to identify predictors of improvement in confidence in competence and knowledge . The formative component involved qualitative interviews with a sub- sample of 39 district nurses participating in the programme . FINDINGS Nurses who responded in both years ( 374/32 % ) were included in the analysis . There was a small statistically significant increase in confidence in palliative care competency and knowledge after participation in the educational programmes . Nurses without district nursing qualifications and who had never worked in specialist palliative care had the largest improvements in scores . Qualitative data supported these findings . CONCLUSION The findings suggest that the education programme led to improvements in self-reported district nursing confidence in palliative care competencies and knowledge ; it is likely that the baseline level of palliative care confidence in competency and knowledge has as a result been raised nationally |
11,330 | 17,903,337 | The results in this study indicate behavioural therapy is an effective treatment for depression with outcomes equal to that of the current recommended psychological intervention . | BACKGROUND Depression is a common , disabling condition for which psychological treatments , in particular cognitive behavioural therapies are recommended .
Promising results in recent r and omized trials have renewed interest in behavioural therapy .
This systematic review sought to identify all r and omized trials of behavioural therapy for depression , determine the effect of such interventions and examine any moderators of such effect . | The purpose of this study was to provide an experimental test of the theory of change put forth by A. T. Beck , A. J. Rush , B. F. Shaw , and G. Emery ( 1979 ) to explain the efficacy of cognitive-behavioral therapy ( CT ) for depression . The comparison involved r and omly assigning 150 out patients with major depression to a treatment focused exclusively on the behavioral activation ( BA ) component of CT , a treatment that included both BA and the teaching of skills to modify automatic thoughts ( AT ) , but excluding the components of CT focused on core schema , or the full CT treatment . Four experienced cognitive therapists conducted all treatments . Despite excellent adherence to treatment protocol s by the therapists , a clear bias favoring CT , and the competent performance of CT , there was no evidence that the complete treatment produced better outcomes , at either the termination of acute treatment or the 6-month follow-up , than either component treatment . Furthermore , both BA and AT treatments were just as effective as CT at altering negative thinking as well as dysfunctional attributional styles . Finally , attributional style was highly predictive of both short- and long-term outcomes in the BA condition , but not in the CT condition The brief behavioral activation treatment for depression ( BATD ) is a relatively uncomplicated , time-efficient , and cost-effective method for treating depression . Because of these features , BATD may represent a practical intervention within managed care-driven , inpatient psychiatric hospitals . Based on basic behavioral theory and empirical evidence supporting activation strategies , we design ed a treatment to increase systematic ally exposure to positive activities and thereby help to alleviate depressive affect . This study represents a pilot study that extends research on this treatment into the context of an inpatient psychiatric unit . Results demonstrate effectiveness and superiority of BATD as compared with the st and ard supportive treatment provided within the hospital . A large effect size was demonstrated , despite a limited sample size . The authors discuss the limitations of the study and future directions Antidepressant medication is considered the current st and ard for severe depression , and cognitive therapy is the most widely investigated psychosocial treatment for depression . However , not all patients want to take medication , and cognitive therapy has not demonstrated consistent efficacy across trials . Moreover , dismantling design s have suggested that behavioral components may account for the efficacy of cognitive therapy . The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a r and omized placebo-controlled design in adults with major depressive disorder ( N = 241 ) . In addition , it examined the importance of initial severity as a moderator of treatment outcome . Among more severely depressed patients , behavioral activation was comparable to antidepressant medication , and both significantly outperformed cognitive therapy . The implication s of these findings for the evaluation of current treatment guidelines and dissemination are discussed |
11,331 | 27,173,621 | The present article is aim ed at outlining the current state of knowledge regarding the clinical value of lipoprotein(a ) ( Lp(a ) ) as a marker of cardiovascular disease ( CVD ) risk by summarizing the results of recent clinical studies , meta-analyses and systematic review s. The literature supports the predictive value of Lp(a ) on CVD outcomes , although the effect size is modest .
Lp(a ) would also appear to have an effect on cerebrovascular outcomes , however the effect appears even smaller than that for CVD outcomes . | null | null |
11,332 | 24,798,192 | During stair ascent , knee flexion angle at heel strike and walking velocity were reduced in TKA subjects compared to controls .
Results of other variables were not consistent between studies .
Other results during stair descent were not consistent between studies . | The purpose of this review was to summarize the biomechanical adaptations during stair ambulation that occur after total knee arthroplasty ( TKA ) . | Background Total hip or knee replacement is highly successful when judged by prosthesis-related outcomes . However , some people experience long-term pain . Objectives To review published studies in representative population s with total hip or knee replacement for the treatment of osteoarthritis reporting proportions of people by pain intensity . Data sources MEDLINE and EMBASE data bases search ed to January 2011 with no language restrictions . Citations of key articles in ISI Web of Science and reference lists were checked . Study eligibility criteria , participants and interventions Prospect i ve studies of consecutive , unselected osteoarthritis patients representative of the primary total hip or knee replacement population , with intensities of patient-centred pain measured after 3 months to 5-year follow-up . Study appraisal and synthesis methods Two authors screened titles and abstract s. Data extracted by one author were checked independently against original articles by a second . For each study , the authors summarised the proportions of people with different severities of pain in the operated joint . Results Search es identified 1308 articles of which 115 reported patient-centred pain outcomes . Fourteen articles describing 17 cohorts ( 6 with hip and 11 with knee replacement ) presented appropriate data on pain intensity . The proportion of people with an unfavourable long-term pain outcome in studies ranged from about 7 % to 23 % after hip and 10 % to 34 % after knee replacement . In the best quality studies , an unfavourable pain outcome was reported in 9 % or more of patients after hip and about 20 % of patients after knee replacement . Limitations Other studies reported mean values of pain outcomes . These and routine clinical studies are potential sources of relevant data . Conclusions and implication s of key findings After hip and knee replacement , a significant proportion of people have painful joints . There is an urgent need to improve general awareness of this possibility and to address determinants of good and bad outcomes A gait analysis system was used to evaluate the kinematics of the hip and knee during stair ascending and descending after operation with total knee replacement . Patients with 5 ° varus/valgus alignment or less were selected r and omly to receive either a flat or a concave tibial component with retention of the posterior cruciate ligament . Patients who had more than 5 ° varus/valgus alignment and /or an extension defect of 10 ° or more were selected r and omly to receive the concave or posterior-stabilized tibial component with resection of the posterior cruciate ligament . Twenty patients and 17 controls were studied 1–2 years after the operation . Patients had abnormal kinematics during stair ascending and descending . Both knee extension and flexion were reduced . Hip extension tended to decrease , and decreased hip extension moment was noted . RésuméUn system d’analyse de la marche a été utilisé pour évaluer la cinématique de la hanche et du genou pendant la montée et la descente d’escalier après prothèse totale du genou . Les malades avec 5 ° ou moins de varus/valgus ou moins ont été r and omisés pour recevoir un composant tibial plat ou concave avec conservation du ligament croisé postérieur . Les malades qui avaient plus de 5 ° de varus/valgus et/ou un défaut d’extension de 10 ° ou plus ont été r and omisés pour recevoir un composant tibial concave ou un composant postéro-stabilisé avec résection du ligament croisé postérieur . Vingt et un malades et 17 contrôles ont été étudiés une à deux années après l’opération . Les malades avaient une cinématique anormale pendant la montée et la descente l’escalier . L’extension et flexion du genou étaient plus faibles . L’extension de la hanche avait tendance à diminuer et une augmentation du moment de flexion a été noté A cross-sectional , community-based survey of a r and om sample of 1750 of 242,311 Medicare recipients was performed . The patients were at least sixty-five years old and had had a primary or revision knee replacement ( either unilaterally or bilaterally ) between 1985 and 1989 . Three sample s were surveyed separately : a national sample ( to reflect the United States as a whole ) and sample s from Indiana and the western part of Pennsylvania ( sites chosen for convenience to assess the validity of the findings for the national sample on a regional level ) . Each sample was stratified by race , age , residence ( urban or rural ) , and the year of the procedure . Valid and reliable question naires were used to elicit the participants ' assessment s of pain , physical function , and satisfaction two to seven years after the knee replacement . Of the 1486 patients who were eligible for inclusion in the survey , 1193 ( 80.3 per cent ) responded . The mean age of the respondents was 72.6 years . Eight hundred and forty-nine respondents ( 71.2 per cent ) were white , and 849 ( 71.2 per cent ) were women . The participants reported that they had little or no pain in the knee at the time of the survey , regardless of the age at the time of the knee replacement , the body-mass index , or the length of time since the knee replacement . After adjustment for potential confounding variables , predictors of better physical function after the replacement were an absence of problems with the contralateral knee , primary knee replacement ( rather than revision ) ( Indiana sample only ) , and a lower body-mass index ( Indiana and western Pennsylvania sample s ) . Four hundred and fifteen ( 85.2 per cent ) of the 487 patients in the national sample were satisfied with the result of the knee replacement . In what we believe to be the first community-based study of the outcome of knee replacement , patients reported having significant ( p = 0.0001 ) and persistent relief of pain , improved physical function , and satisfaction with the result two to seven years postoperatively . The findings of the present study suggest that age and obesity do not have a negative impact on patient-relevant outcomes ( pain and physical function ) . Dissemination of these findings has the potential to increase appropriate referrals for knee replacement and thereby reduce the pain and functional disability due to osteoarthrosis of the knee We have developed a 12-item question naire for patients having a total knee replacement ( TKR ) . We made a prospect i ve study of 117 patients before operation and at follow-up six months later , asking them to complete the new question naire and the form SF36 . Some also filled in the Stanford Health Assessment Question naire ( HAQ ) . An orthopaedic surgeon completed the American Knee Society ( AKS ) clinical score . The single score derived from the new question naire had high internal consistency , and its reproducibility , examined by test-retest reliability , was found to be satisfactory . Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ . Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up . We also compared change in scores with the patients ' retrospective judgement of change in their condition . The effect size for the new question naire compared favourably with those for the relevant parts of the SF36 . The change scores for the new knee question naire were significantly greater ( p < 0.0001 ) for patients who reported the most improvement in their condition . The new question naire provides a measure of outcome for TKR that is short , practical , reliable , valid and sensitive to clinical ly important changes over time BACKGROUND Little is known about the effects of total knee replacement surgery on the contributions of individual joint moments to the total support moment . A better underst and ing of these effects may enhance rehabilitation protocol s and determine factors related to long-term surgical outcome . METHOD Twenty-one subjects with total knee replacement and 21 controls performed level walking and stair ascent at two testing periods , pre- and 6 months post-surgery . Variables studied included gait velocity , stride length , knee flexion angle , net joint moments of the hip , knee and ankle , and total support moment . Data were analyzed at the first peak vertical ground reaction force . FINDINGS For level walking , the total support moment , knee extensor moment , and knee flexion angle of total knee replacement patients were less than controls at post-surgery . For stair ascent , the patient group total support moment , ankle plantarflexor moment , and knee flexion angle were less than controls at both testing periods , while knee extensor moment was less than controls at post-surgery . Extensor synergies of the total knee replacement patients revealed less knee and more hip contributions during level walking and larger hip contributions during stair ascent to the total support moment than controls at both testing periods . INTERPRETATION A feature of total knee replacement gait , pre- and post-surgery , is a stiff knee attitude which may serve to protect the quadriceps . The larger hip extensor contribution to the total support moment observed in the patients may compensate for the diminished knee extensor contribution during level walking and stair ascent Objective To assess health-related quality of life ( HRQOL ) in a prospect i ve study with 7 years of follow-up in 49 consecutive patients who underwent a total joint replacement because of osteoarthritis . Methods Generic HRQOL was assessed with the short-form 36 ( SF-36 ) and specific HRQOL with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Results Out of the 39 subjects who have completed the 7 years of follow-up of this study , 22 ( 56.4 % ) underwent a hip replacement surgery and the other 17 ( 43.6 % ) a knee replacement . Six months after surgery , a significant improvement , compared to preoperative scores , was observed in two of the eight dimensions of the SF-36 ( i.e. physical function and pain ) . The same dimensions , pain and physical function , at the same time , 6 months after surgery , measured by the WOMAC , showed a significant improvement as well , but there was no significant change in the stiffness score . From 6 months to the end of follow-up , changes in SF-36 scores showed a significant improvement in physical function ( p = 0.008 ) , role-physical ( p = 0.004 ) and role-emotional ( p = 0.01 ) while all scores of the WOMAC improved ( p < 0.001 for pain , p < 0.001 for stiffness and p < 0.01 for physical function ) . Conclusion The improvements observed in HRQOL at short term after surgery , are at least maintained over a 7-year follow-up period The role of the posterior cruciate ligament ( PCL ) remains controversial in total knee arthroplasty ( TKA ) , with some surgeons who believe in PCL sacrifice and substitution and others who believe in PCL preservation for stability . Manufacturers have developed both cruciate-substituting/posterior stabilized ( PS ) implants typically used when the ligament is sacrificed and cruciate retaining ( CR ) implants design ed for ligament preservation . However , studies demonstrate excellent clinical results with CR implants despite PCL sacrifice . This study sought to determine functional stability differences between PS and CR TKAs following PCL sacrifice . Eighteen ( 9 matched pairs ) subjects with either a PS or CR TKA and sacrificed PCL and a normal contralateral knee were subjected to physical exam and gait analysis ( walking , stair ascent and descent ) using a staircase model , passive reflective arrays and an optoelectric system . No differences were detected between the two groups among any of the measured parameters ( knee flexion angle , knee flexion moment , knee power absorption , pelvic tilt ) . PCL sacrifice in a well-balanced cruciate retaining TKA did not result in instability during stair descent based on gait parameters . The decision to use a posterior stabilized design when faced with an incompetent PCL intraoperatively should be based on factors other than anticipated instability BACKGROUND Currently there is a limited underst and ing of the factors influencing range of motion by comparing patellar resurfacing vs non-resurfacing in total knee arthroplasty during activities of daily living . A recent meta- analysis of patellar replacement confirms better outcome with patella resurfacing ; however , the result can be influenced by many other factors , such as : component design , surgeon experience , and technical aspects of the surgery . This study compares the biomechanics of the knee in patients after total knee arthroplasty with and without patellar resurfacing during stair climbing . METHODS Forty-seven patients with total knee arthroplasty were assessed at the mean follow-up of 24 months . In all of them a posterior stabilised fixed bearing prosthesis ( Optetrak PS , Exactech ) was implanted . Twenty-six patients were treated without patellar resurfacing and 21 with patellar resurfacing . Clinical evaluations were performed using the International Knee Society and the Hospital for Special Surgery scores . Ten patients with patellar resurfacing and 10 patients without patellar resurfacing were also studied with motion analysis during stair climbing ; 10 healthy subjects were studied for statistical comparison . FINDINGS Clinical passive knee flexion , International Knee Society Function and Hospital for Special Surgery scores were significantly higher in the patellar resurfacing group . During stair climbing , active knee joint range of motion during the stance phase was greater in patients with patellar resurfacing . The maximum adduction moment was significantly higher in the group without patellar resurfacing . INTERPRETATION Patients with patellar resurfacing demonstrated better clinical scores , and kinematic and kinetic data while ascending stairs |
11,333 | 30,077,047 | Conclusions Ultrasound‐guided technique for RA access has higher first‐attempt success and lower failure rate compared with palpation alone , with no significant differences in access site hematoma or time to a successful attempt .
These findings support the routine use of US guidance for RA access | Background The radial artery ( RA ) is routinely used for both hemodynamic monitoring and for cardiac catheterization .
Although cannulation of the RA is usually undertaken through manual palpation , ultrasound (US)‐guided access has been advocated as a mean to increase cannulation success rates and to lower RA complications ; however , the published data are mixed .
We sought to evaluate the impact of US‐guided RA access compared with palpation alone on first‐pass success to access RA . | Objective To examine the feasibility of a routine transradial approach ( TRA ) in primary percutaneous coronary intervention ( PPCI ) for acute ST-segment elevation myocardial infa rct ion ( STEMI ) . Design A single-centre observational study with prospect i ve data collection . Setting A high-volume interventional centre in Amsterdam , The Netherl and s. Patients Procedural data were analysed for 2209 consecutive patients presenting with STEMI without cardiogenic shock , between January 2001 and December 2008 . Interventions PPCI routinely performed by the TRA . Main Outcome Measures The primary outcomes of interest were the need for crossover to another vascular access site , the achievement of procedural success and their trends over time . Secondary outcome measures were trends in total procedural duration , fluoroscopy times and use of equipment . Results In a total of 2209 procedures the radial artery was the primary access site , comprising 96.1 % of all procedures performed during the study period . In 84 cases ( 3.8 % ) access site crossover was needed . Crossover rates decreased from 5.9 % in 2001–2 to 1.5 % in 2007–8 ( p=0.001 ) . The procedural success rate was 94.1 % , which remained stable over the years . Despite an increased complexity of PPCI ( more non-left anterior descending infa rct -related arteries , thrombus aspiration and multivessel PPCI ) , total procedural duration decreased from 38 min ( IQR 28–50 ) in 2001–2 to 24 min ( 18–33 ) in 2007–8 , p<0.001 for trend . Conclusions Systematic use of the TRA in PPCI yields low access site crossover , high procedural success rates and excellent procedural performances . It can therefore represent the primary access site in the vast majority of STEMI patients BACKGROUND : Radial arterial cannulation is most commonly done using palpation , but the use of ultrasound has increased the cannulation success rate . This improvement , albeit significant , has not led to a very high success rate especially in trainees . A modified ultrasound technique for vascular cannulation ( dynamic needle tip positioning ) has been described for peripheral venous cannulation . We therefore assessed the success rate of this technique compared to the palpation technique for radial artery cannulation in adult surgical patients . METHODS : We enrolled patients who were having nonemergent operations that required a radial arterial catheter for intraoperative monitoring . Patients were r and omized to either palpation or dynamic needle tip positioning technique . Arterial cannulation was performed by anesthesia residents or faculty members . The primary end point was successful cannulation on the first pass . Secondary end points were overall 5-minute success rate and number of attempts within 5 minutes . RESULTS : Two hundred sixty patients were evaluated . The first-pass success rate was 83 % in the dynamic needle tip positioning technique group ( n = 132 ) and 48 % in the palpation group ( n = 128 ; P < .001 ) ; relative risk was 2.5 ; 95 % confidence interval , 1.7–3.6 . The overall 5-minute success rate was 89 % in the dynamic needle tip positioning technique group compared to 65 % in the palpation group ( P < .001 ) , relative risk was 2.4 ; 95 % confidence interval , 1.2–1.6 . The number of skin puncture attempts was significantly more in the palpation group ( P < .001 ) . The median cannulation times and interquartile ranges were 81.5 ( 61–122 ) seconds in the dynamic needle tip positioning and 76 ( 48–175 ) seconds ( P = .7 ) in the palpation group . CONCLUSIONS : The use of the ultrasound-guided dynamic needle tip positioning technique increased the first and overall success rates compared to palpation in anesthesia residents and faculty members Background This study observed the efficacy of ultrasonic technique with out-of-plane orientation and in-plane guidance in radial artery puncture and cannulation in intensive care unit ( ICU ) shock patients to eluci date the effect of this technique on the security of cannulation . Material / Methods A total of 88 ICU shock patients , r and omized into a palpation ( control ) group and an ultrasound ( experimental ) group , received continuous intravenous sedation and analgesia . The palpation group patients underwent radial artery cannulation using the traditional palpation pulsation approach , and the ultrasound group patients underwent radial artery cannulation under out-of-plane orientation and in-plane guidance using an ultrasonic apparatus . Data were recorded and compared between the 2 groups . Results ( 1 ) The success rate of the first puncture in the ultrasound group and the palpation group was 80 % and 42 % , respectively ( P<0.05 ) . ( 2 ) The cannulation duration in the ultrasound group and the palpation group was 8.77±6.33 s and 28.7±26.33 s , respectively ( P<0.01 ) . ( 3 ) Incidence of hematoma and staxis around stoma in the ultrasound group was 2.5 % and 5 % , respectively , which was significantly lower than that in the palpation group , which was 20 % and 32.5 % , respectively ( P<0.05 ) . ( 4 ) Time to achieve the early goal -directed therapy in the ultrasound group and the palpation group was 306.73±39.98 min and 356.75±40.97 min , respectively ( P<0.01 ) . Conclusions Compared with the traditional method , radial artery cannulation with out-of-plane orientation and in-plane guidance is a quick and secure cannulation method and is appropriate for use in clinics 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 Previous studies have shown ultrasound guidance (USG)for arterial cannulation being advantageous compared to palpation technique , but little is known about its performance by novices . OBJECTIVE This study was to compare the utility of USG radial artery cannulation with palpation technique in terms of success rate , real-time to placement , number of attempts and complications . MATERIAL AND METHOD After IRB approval , a r and omized prospect i ve study was performed November 2009-October 2010 . Ten third-year residents , having performed USG vascular catheterization as yet less than 3 times , were coached on the pork-phantom during a workshop for real time ultrasound-guided vascular access . For the study patients were r and omized to US-guided technique ( US-group ) and palpation ( P-group ) ; ten patients for each resident . RESULTS One hundred adult patients undergoing neurosurgery were enrolled . There were no statistically significant differences between US-group vs. P-group in success rate ( 78 % vs. 82 % ; p = 0.62 ) , time to success ( 60 ( 12.8 , 547.0 ) vs. 52 ( 6.9 , 639.0 ) sec ; p = 0.22 ) , and number of attempts ( 1 ( 1 , 4 ) vs. 1 ( 1 , 3 ) ; p = 0.79 ) . Most common complication was puncture hematoma ( US-group 26 % vs. P-group 24 % ; p = 0.82 ) . Success was defined as no change in catheterization site , performer and technique . CONCLUSION Regarding success rate , attended time , or number of attempts for radial arterial cannulation , we did not find any benefit of ultrasound guidance compared to palpation technique . Our findings were not in accordance to other trials . However , we have to consider operators in our study being in experienced in ultrasound-guided procedures but not in palpation techniques OBJECTIVES Ultrasound guidance for central venous catheterization improves success rates and decreases complications when compared to the l and mark technique . Prior research has demonstrated that arterial and /or posterior vein wall puncture still occurs despite real-time ultrasound guidance . The inability to maintain visualization of the needle tip may contribute to these complications . This study aims to identify whether long-axis or short-axis approaches to ultrasound-guided vascular access afford improved visibility of the needle tip . METHODS A prospect i ve trial was conducted at a level I trauma center with an emergency medicine residency . Medical students and residents placed needles into vascular access tissue phantoms using long-axis and short-axis approaches . Ultrasound images obtained at the time of vessel puncture were then review ed . Primary outcome measures were visibility of the needle tip at the time of puncture and total time to successful puncture of the vessel . RESULTS All subjects were able to successfully obtain simulated blood from the tissue phantom . Mean time to puncture was 14.8 seconds in the long-axis group and 12.4 seconds in the short-axis group ( P = .48 ) . Needle tip visibility at the time of vessel puncture was higher in the long-axis group ( 24/39 , 62 % ) as opposed to the short-axis group ( 9/39 , 23 % ) ( P = .01 ) . CONCLUSIONS In a simulated vascular access model , the long-axis approach to ultrasound-guided vascular access was associated with improved visibility of the needle tip during vessel puncture . This approach may help decrease complications associated with ultrasound-guided central venous catheterization and should be prospect ively evaluated in future studies OBJECTIVES To identify success rates for radial artery cannulation in a pediatric critical care unit using either palpation or ultrasound guidance to cannulate the radial artery . METHODS A prospect i ve r and omized comparative study of critically ill children who required invasive monitoring in a tertiary referral center was conducted . All patients were r and omized by a stratified block of 4 to either ultrasound-guided or traditional palpation radial artery cannulation . The primary outcomes were the first attempt and total success rates . RESULTS Eighty-four children were enrolled , with 43 r and omized to the palpation technique and 41 to the ultrasound-guided technique . Demographic data between the groups were not significantly different . The total success and first attempt rates for the ultrasound-guided group were significantly higher than those for the palpation group ( success ratio , 2.03 ; 95 % confidence interval , 1.13 - 3.64 ; P = .018 ; and success ratio , 4.18 ; 95 % confidence interval , 1.57 - 11.14 ; P = .004 , respectively ) . The median time to success for the ultrasound-guided group was significantly shorter than that for the palpation group ( 3.3 versus 10.4 minutes ; P < .001 ) . Cannulation complications were lower in the ultrasound-guided group than the palpation group ( 12.5 % versus 53.3 % ; P < .001 ) . CONCLUSIONS The ultrasound-guided technique could improve the success rate and allow for faster cannulation of radial artery catheterization in critically ill children Objective : To determine whether ultrasound guidance increases the success rates , decreases the complication rates , and shortens the time to successful radial artery catheterization in infants and small children . Design : R and omized study . Setting : Single university-affiliated hospital . Patients : Infants and children weighing 3–20 kg , undergoing cardiac surgery for congenital heart disease . Intervention : We r and omly assigned the right and left radial arteries of patients undergoing arterial catheterization to ultrasound-guided technique versus the usual palpation technique . Measurements : The primary study endpoints were the rates of successful cannulation at first and within three attempts . The secondary endpoints were time to radial artery identification , number of attempts for successful cannulation , and rate of complications . Main Results : Compared with palpation , ultrasound-guided radial artery catheterization was successful in 76.3 % versus 35.6 % of first attempts and in 94.9 % versus 50.8 % of arteries after three attempts ( both comparisons , p < 0.01 ) . The median time [ interquartile range ] to identification of the arteries ( 18.5 seconds [ 11.25–27.25 ] vs 30 seconds [ 17.75–39.5 ] ) was significantly shorter ( p < 0.01 ) , the number of attempts [ interquartile range ] at successful cannulation ( 1 [ 1–1 ] vs 2 [ 1–2 ] ) was significantly fewer ( p < 0.01 ) , and the proportion of hematomas ( 5.1 % vs 25.4 % ) was significantly lower ( p < 0.01 ) in the ultrasound group than those in the palpation group . Conclusions : In infants and small children , ultrasound-guided radial artery catheterization was more successful and expeditious than the usual palpation technique Background and objective : In small children , the placement of arterial catheters can be technically challenging for even the most experienced anaesthetist . We investigated whether ultrasound imaging would improve the success rate and reduce time dem and and complications of radial artery cannulation . Method : In this prospect i ve r and omized study , we performed radial artery cannulation in 30 small children ( age 40 ± 33 months ) using two different techniques for localization of the vessel . In Group 1 ( n = 15 ) , the traditional palpation method was used , while in Group 2 ( n = 15 ) cannulation was directed by vascular ultrasound imaging . In addition , we used ultrasound to determine the cross‐sectional area of the radial artery with and without dorsiflexion . For statistical analysis , the non‐parametric U‐test for non‐paired data and the Wilcoxon signed rank sum test for paired data were used . Differences were considered significant , when P < 0.05 . Results : Ultrasound‐guided puncture was successful in all children of Group 2 compared to only 12 of 15 ( 80 % ) children in Group 1 . Fewer attempts with the imaging technique were required than with the traditional technique ( 20 vs. 34 , P < 0.05 ) . Dorsiflexion significantly reduced the mean cross‐sectional area of the artery by 19 % . Conclusion : The current pilot study suggests that ultrasound guidance is appropriate for radial artery catheter insertion , sharing many of the benefits of ultrasound‐guided central vein catheter insertion BACKGROUND Arterial cannulation for continuous blood-pressure measurement and frequent arterial-blood sampling commonly are required in critically ill patients . OBJECTIVES To compare ultrasound (US)-guided versus traditional palpation placement of arterial lines for time to placement , number of attempts , sites used , and complications . METHODS This was a prospect i ve , r and omized interventional study at a Level 1 academic urban emergency department with an annual census of 78,000 patients . Patients were r and omized to either palpation or US-guided groups . Inclusion criteria were any adult patient who required an arterial line according to the treating attending . Patients who had previous attempts at an arterial line during the visit , or who could not be r and omized because of time constraints , were excluded . Enrollment was on a convenience basis , during hours worked by research ers over a six-month period . Patients in either group who had three failed attempts were rescued with the other technique for patient comfort . Statistical analysis included Fisher 's exact , Mann-Whitney , and Student 's t-tests . RESULTS Sixty patients were enrolled , with 30 patients r and omized to each group . Patients r and omized to the US group had a shorter time required for arterial line placement ( 107 vs. 314 seconds ; difference , 207 seconds ; p = 0.0004 ) , fewer placement attempts ( 1.2 vs. 2.2 ; difference , 1 ; p = 0.001 ) , and fewer sites required for successful line placement ( 1.1 vs. 1.6 ; difference , 0.5 ; p = 0.001 ) , as compared with the palpation group . CONCLUSIONS In this study , US guidance for arterial cannulation was successful more frequently and it took less time to establish the arterial line as compared with the palpation method BACKGROUND : Currently , short-axis out-of-plane ( SA-OOP ) and long-axis in-plane ( LA-IP ) ultrasound techniques are used to guide radial artery cannulation . In this study , we compared the success rate of a modified SA-OOP technique with that of traditional LA-IP . METHODS : One hundred sixty-four patients who were to undergo liver surgery or splenic resection under general anesthesia were included . Using a sealed envelope method , patients were r and omly divided into 2 groups : the modified SA-OOP or the LA-IP ultrasound guidance approaches . The number of cannula insertion attempts until success was recorded in both groups . The primary end point to compare the groups was the rate of cannula insertion successes on the first attempt . The secondary end points were also recorded and compared : insertion failure rate , inner diameter of the radial artery , depth of artery from the skin , ultrasonic location time , cannulation time , and vascular complications including thrombosis , hematoma , edema , and vasospasm . RESULTS : The cannula insertion success rate on the first attempt was significantly higher in the modified SA-OOP group compared with the LA-IP group ( proportion difference 15.7 % , 95 % confidence interval [ CI ] , 0.6%–30.7 % , P = 0.0158 ) . However , the insertion failure rate was not different between groups ( 95 % CI , −17.7 % to 12.8 % , P = 0.4969 ) . The ultrasonic location time was significantly decreased in the modified SA-OOP group compared with the LA-IP group ( mean difference −9.5 seconds , 95 % CI , −10.6 to −8.5 seconds , P < 0.0001 ) . However , there was no significant difference between groups for cannulation time ( 95 % CI , −0.6 to 7.6 seconds , P = 0.1152 ) , depth of artery ( 95 % CI , −0.07 to 0.57 mm , P = 0.1050 ) , and the diameter of the radial artery ( 95 % CI , −0.30 to 0.03 mm , P = 0.1153 ) . CONCLUSION : The modified SA-OOP technique may improve the success rate of cannula insertion into the radial artery on the first attempt BACKGROUND Radial access is increasingly used for both diagnostic and interventional cardiac procedures . Prospect i ve data comparing ultrasound- versus palpation-guided radial catheterization are largely lacking . METHODS In this prospect i ve , single-center study , a total of 183 consecutive patients scheduled for transradial cardiac catheterization by an experienced interventionalist were assigned 1:1 to either palpation- or ultrasound-guided radial access . Demographic and procedure parameters were prospect ively recorded . RESULTS Baseline demographic and clinical parameters did not differ significantly between the ultrasound group ( n = 92 ) and palpation group ( n = 91 ) . The initial radial catheterization success rate ( 87 % vs 86.8 % ; P=.999 ) and time to access ( 47 seconds [ interquartile range ( IQR ) , 20 - 90 seconds ] versus 31 seconds [ IQR , 20 - 75 seconds ] ; P=.179 ) did not differ between the ultrasound and palpation groups , respectively . Pulse quality ( absent , weak , strong ) was independently associated with access failure in both groups ( P<.001 ) . Obesity was associated with access failure in the palpation group ( P=.005 ) , but not in the ultrasound group ( P=.544 ) . In 3/12 cases ( 25 % ) in the ultrasound group and 2/6 cases ( 33 % ) in the palpation group , the operator was able to establish radial access using the alternative method ( P=.710 ) . If palpation-guided radial access failed , an additional ultrasound-guided attempt before crossover to femoral access was associated with a shorter overall time to access ( 525 seconds [ IQR , 462 - 567 seconds ] versus 744 seconds [ IQR , 722 - 788 seconds ] ; P=.016 ) . CONCLUSIONS Ultrasound-guided radial access seems to provide no substantial additional benefit over palpation-guided access alone . Attempting the alternative guiding methods to establish radial access before crossover to femoral access seems to be a reasonable approach OBJECTIVES This study sought to assess the utility of ultrasound ( US ) guidance for transradial arterial access . BACKGROUND US guidance has been demonstrated to facilitate vascular access , but has not been tested in a multicenter r and omized fashion for transradial cardiac catheterization . METHODS We conducted a prospect i ve multicenter r and omized controlled trial of 698 patients undergoing transradial cardiac catheterization . Patients were r and omized to needle insertion with either palpation or real-time US guidance ( 351 palpation , 347 US ) . Primary endpoints were the number of forward attempts required for access , first-pass success rate , and time to access . RESULTS The number of attempts was reduced with US guidance [ mean : 1.65 ± 1.2 vs. 3.05 ± 3.4 , p < 0.0001 ; median : 1 ( interquartile range [ IQR ] : 1 to 2 ) vs. 2 ( 1 to 3 ) , p < 0.0001 ] and the first-pass success rate improved ( 64.8 % vs. 43.9 % , p < 0.0001 ) . The time to access was reduced ( 88 ± 78 s vs. 108 ± 112 s , p = 0.006 ; median : 64 [ IQR : 45 to 94 ] s vs. 74 [ IQR : 49 to 120 ] s , p = 0.01 ) . Ten patients in the control group required crossover to US guidance after 5 min of failed palpation attempts with 8 of 10 ( 80 % ) having successful sheath insertion with US . The number of difficult access procedures was decreased with US guidance ( 2.4 % vs. 18.6 % for ≥5 attempts , p < 0.001 ; 3.7 % vs. 6.8 % for ≥5min , p = 0.07 ) . No significant differences were observed in the rate of operator-reported spasm , patient pain scores following the procedure , or bleeding complications . CONCLUSIONS Ultrasound guidance improves the success and efficiency of radial artery cannulation in patients presenting for transradial catheterization . ( Radial Artery Access With Ultrasound Trial [ RAUST ] ; NCT01605292 ) Objective To assess the role of a portable ultrasound device in the insertion of radial artery catheters . Design Prospect i ve , r and omized , comparative study . Setting Tertiary university hospital . Patients Elective surgery patients requiring arterial catheter insertion for intraoperative monitoring . Interventions A portable ultrasound device was used to visualize the radial artery at the wrist and to direct arterial catheter insertion . This new technique of arterial catheter insertion was compared with the classic palpation technique . Measurements and Main Results A total of 69 patients requiring an arterial catheter were r and omized to either the ultrasound ( 34 patients ) or palpation technique ( 35 patients ) . The time taken from skin puncture to successful arterial catheter insertion , the time taken per insertion attempt , the number of attempts required , and the number of cannulae used were recorded for each group . The arterial cannula was inserted on the first attempt in 21 ( 62 % ) cases using ultrasound vs. 12 ( 34 % ) cases by palpation ( p = .03 ) . Significantly fewer attempts were required for catheter insertion using ultrasound as compared with palpation ( mean ± sd , 1.6 ± 1.0 vs. 3.1 ± 2.4;p = .003 ) ; however , the time taken for each successful attempt was longer ( 26.1 ± 2.0 vs. 17.3 ± 1.6 secs , p = .001 ) . A trend toward shorter overall time required for catheter insertion was found for the ultrasound group ( 55.5 ± 63.8 vs. 111.5 ± 121.5 secs , p = .17 ) . There were four failures in the ultrasound group and one in the palpation group ( not significant ) . Conclusions Ultrasound is a useful adjunct to arterial catheter insertion and increases the rate of success at first attempt . The technique is easy to learn and may reduce the time taken to insert the catheter We r and omly allocated 749 participants to radial artery cannulation by anaesthetic trainees , guided by Doppler ( 244 ) , palpation ( 256 ) or ultrasound ( 249 ) . Ultrasound increased the rate of cannulation at the first attempt by 14 % ( 95 % CI 5–22 % ) , from 39 % with Doppler or palpation , p = 0.002 for both . There were no differences in the rates of cannulation 5 min after the procedure started : 147/244 ( 60 % ) with Doppler ; 160/256 ( 63 % ) with palpation ; and 171/249 ( 69 % ) with ultrasound , p = 0.13 INTRODUCTION The palpation technique is generally used for radial artery catheterisation , but is associated with a high rate of failure and complications . Dynamic needle tip positioning ( DNTP ) is a new ultrasound-guided technique . We aim ed to compare the traditional palpation technique with DNTP performed by four anaesthesiology residents . METHODS The study was a r and omised , controlled , patient-blinded , crossover study . Fourty patients underwent bilateral radial artery catheterisation using both techniques . The primary endpoint was the first attempt success rate . The secondary endpoints were : 1 ) number of skin perforations , 2 ) number of needle retractions , 3 ) needle manipulation time , 4 ) total time , 5 ) attempts lasting > 180 seconds , 6 ) number of catheters used , 7 ) frequency of aborted attempts or crossovers , and 8) pain scores ( VAS ) . RESULTS The first attempt success rate was significantly higher in the DNTP group compared with the palpation group ( 36/40 vs. 28/40 , p = 0.022).The palpation technique group required a higher number of skin perforations ( 44 vs. 60 , p = 0.016 ) , needle retractions ( p = 0.001 ) and catheters ( 42 vs. 52 , p = 0.011 ) compared with the DNTP group . Neither the total time required for arterial catheterisation , the needle manipulation time nor the VAS scores were significantly different between the groups ( all p>0.407 ) . Aborted attempts were only seen in the palpation group ( 7/40 , p = 0.016 ) . CONCLUSIONS Ultrasound-guided arterial catheterisation using the DNTP technique is superior to the st and ard palpation technique . This study favours the ultrasound-guided DNTP technique as the first choice rather than merely being viewed as a rescue procedure BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management . METHODS We did a r and omised , multicentre , superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infa rct ion who were about to undergo coronary angiography and percutaneous coronary intervention . Patients were r and omly allocated ( 1:1 ) to radial or femoral access with a web-based system . The r and omisation sequence was computer generated , blocked , and stratified by use of ticagrelor or prasugrel , type of acute coronary syndrome ( ST-segment elevation myocardial infa rct ion , troponin positive or negative , non-ST-segment elevation acute coronary syndrome ) , and anticipated use of immediate percutaneous coronary intervention . Outcome assessors were masked to treatment allocation . The 30-day co primary outcomes were major adverse cardiovascular events , defined as death , myocardial infa rct ion , or stroke , and net adverse clinical events , defined as major adverse cardiovascular events or Bleeding Academic Research Consortium ( BARC ) major bleeding unrelated to coronary artery bypass graft surgery . The analysis was by intention to treat . The two-sided α was prespecified at 0·025 . The trial is registered at Clinical Trials.gov , number NCT01433627 . FINDINGS We r and omly assigned 8404 patients with acute coronary syndrome , with or without ST-segment elevation , to radial ( 4197 ) or femoral ( 4207 ) access for coronary angiography and percutaneous coronary intervention . 369 ( 8·8 % ) patients with radial access had major adverse cardiovascular events , compared with 429 ( 10·3 % ) patients with femoral access ( rate ratio [ RR ] 0·85 , 95 % CI 0·74 - 0·99 ; p=0·0307 ) , non-significant at α of 0·025 . 410 ( 9·8 % ) patients with radial access had net adverse clinical events compared with 486 ( 11·7 % ) patients with femoral access ( 0·83 , 95 % CI 0·73 - 0·96 ; p=0·0092 ) . The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery ( 1·6 % vs 2·3 % , RR 0·67 , 95 % CI 0·49 - 0·92 ; p=0·013 ) and all-cause mortality ( 1·6 % vs 2·2 % , RR 0·72 , 95 % CI 0·53 - 0·99 ; p=0·045 ) . INTERPRETATION In patients with acute coronary syndrome undergoing invasive management , radial as compared with femoral access reduces net adverse clinical events , through a reduction in major bleeding and all-cause mortality . FUNDING The Medicines Company and Terumo Purpose The use of ultrasound ( US ) for radial arterial catheterization has been reported to result in faster insertion times with fewer complications when compared with traditional direct palpation ( DP ) . We sought to determine if this applies to expert operators and tested the hypothesis that , among cardiac anesthesiologists , US-guided insertion similarly results in faster insertion times as well as fewer re-directs , attempts , and complications . Methods Following Research Ethics Board Approval , we conducted a r and omized clinical trial in 125 patients scheduled for cardiac surgery at a single tertiary/quaternary care centre . Patients were r and omized to either US- or DP-guided radial artery catheterization by attending cardiac anesthesiologists . The primary endpoint was time to catheter placement . Secondary endpoints included the number of attempts and re-directs as well as the failure rate . Results There were no differences between the DP- ( n = 62 ) vs US-guided ( n = 63 ) groups in median [ interquartile range ] time to placement ( 104 [ 76–212 ] sec vs 104 [ 68–270 ] sec , respectively ; P = 0.66 ) , number of re-directs ( 2 [ 0–6 ] vs 3 [ 1–5 ] , respectively ; P = 0.82 ) , or number of attempts ( 1 [ 1–2 ] vs 1 [ 1–2 ] , respectively ; P = 0.08 ) . The first-attempt success rate was 56.4 % in the DP group and 71.4 % in the US group ( P = 0.10 ) . Failure rate and hematoma rate in the DP group were 21.0 % and 22.6 % , respectively , compared with 12.7 % and 11.1 % in the US group ( P = 0.24 and 0.10 , respectively ) . Conclusions Among experienced cardiac anesthesiologists , the use of US to facilitate radial arterial catheterization did not affect insertion times , the number of re-directs , or the number of attempts when compared with DP . Ultrasound use had no significant effects on the rates of success on first attempt , failure , or hematoma formation . This trial was registered at www . clinical trials.gov : NCT02118441.RésuméObjectifSelon les études , l’utilisation de l’échoguidage ( EG ) pour la canulation de l’artère radiale réduit les temps d’insertion et le nombre de complications par rapport à la palpation directe ( PD ) , qui est la méthode traditionnelle . Notre objectif était de savoir si cette observation s’appliquait aux spécialistes et avons testé l’hypothèse suivante : est-ce que , lorsqu’elle est réalisée par des anesthésiologistes cardiaques , l’insertion avec échoguidage entraîne également une réduction du temps d’insertion , du nombre de tentatives , de changements de direction de la sonde , ou du nombre de complications?MéthodeAprès avoir obtenu le consentement du Comité d’éthique de la recherche , nous avons réalisé une étude clinique r and omisée auprès de 125 patients devant subir une chirurgie cardiaque dans un seul centre de soins tertiaires / quaternaires . Les patients ont été r and omisés à subir une canulation de l’artère radiale par EG ou par PD , réalisée par les anesthésiologistes cardiaques de l’institution . Le critère d’évaluation principal était le temps nécessaire au bon positionnement du cathéter . Les critères d’évaluation secondaires comprenaient le nombre de tentatives d’insertion , de changements de direction de la sonde , ainsi que le taux d’échec . RésultatsAucune différence n’a été observée entre les groupes PD ( n = 62 ) et EG ( n = 63 ) en matière de temps médian [ écart interquartile ] jusqu’au positionnement ( 104 [ 76–212 ] sec vs 104 [ 68–270 ] sec , respectivement ; P = 0,66 ) , du nombre de changements de direction de la sonde ( 2 [ 0–6 ] vs 3 [ 1–5 ] , respectivement ; P = 0,82 ) , ou du nombre de tentatives ( 1 [ 1–2 ] vs 1 [ 1–2 ] , respectivement ; P = 0,08 ) . Le taux de réussite à la première tentative était de 56,4 % dans le groupe PD et de 71,4 % dans le groupe EG ( P = 0,10 ) . Les taux d’échec et d’hématome dans le groupe PD étaient de 21,0 % et 22,6 % , respectivement ( P = 0,24 ) , par rapport à 12,7 % et 11,1 % , respectivement ( P = 0,10 ) , dans le groupe EG . Conclusion Lorsque pratiqué par des anesthésiologistes cardiaques d’expérience , le recours à l’échoguidage pour la canulation de l’artère radiale n’a pas eu d’impact sur le temps d’insertion , ni sur le nombre de tentatives ou de changements de direction de la sonde par rapport à la palpation directe . L’échoguidage n’a pas non plus eu d’effet significatif sur le taux de réussite à la première tentative , d’échec ou de formation d’hématomes . Cette étude a été enregistrée au www . clinical trials.gov : NCT02118441 |
11,334 | 31,093,259 | Results of the meta- analysis suggest that exposure to agrochemicals and working in agriculture increase the risk of CKDnT , but this only reached significance for working in agriculture .
When cross-sectional studies were excluded , agrochemical exposure became significant . | Objectives To evaluate the potential associations between chronic kidney disease of uncertain or non-traditional etiology ( CKDnT ) and agrochemicals , heat stress , heavy metals , and other factors identified in the literature in any region of the world and at any time . | Objectives Experimental studies suggest a relationship between pesticide exposure and renal impairment , but epidemiological evidence is limited . We evaluated the association between exposure to 39 specific pesticides and end-stage renal disease ( ESRD ) incidence in the Agricultural Health Study , a prospect i ve cohort study of licensed pesticide applicators in Iowa and North Carolina . Methods Via linkage to the US Renal Data System , we identified 320 ESRD cases diagnosed between enrolment ( 1993–1997 ) and December 2011 among 55 580 male licensed pesticide applicators . Participants provided information on use of pesticides via self-administered question naires . Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practice s. Cox proportional hazards models , adjusted for age and state , were used to estimate associations between ESRD and : ( 1 ) ordinal categories of intensity-weighted lifetime use of 39 pesticides , ( 2 ) poisoning and high-level pesticide exposures and ( 3 ) pesticide exposure result ing in a medical visit or hospitalisation . Results Positive exposure-response trends were observed for the herbicides alachlor , atrazine , metolachlor , paraquat , and pendimethalin , and the insecticide permethrin . More than one medical visit due to pesticide use ( HR=2.13 ; 95 % CI 1.17 to 3.89 ) and hospitalisation due to pesticide use ( HR=3.05 ; 95 % CI 1.67 to 5.58 ) were significantly associated with ESRD . Conclusions Our findings support an association between ESRD and chronic exposure to specific pesticides , and suggest pesticide exposures result ing in medical visits may increase the risk of ESRD . Clinical trial registration Clinical trials.gov NCT00352924 Background Epidemics of chronic kidney disease ( CKD ) not due to diabetes mellitus ( DM ) or hypertension have been observed among individuals working in hot environments in several areas of the world . Experimental models have documented that recurrent heat stress and water restriction can lead to CKD , and the mechanism may be mediated by hyperosmolarity that activates pathways ( vasopressin , aldose reductase-fructokinase ) that induce renal injury . Here we tested the hypothesis that elevated serum sodium , which reflects serum osmolality , may be an independent risk factor for the development of CKD . Methods This study was a large-scale , single-center , retrospective 5-year cohort study at Center for Preventive Medicine , St. Luke ’s International Hospital , Tokyo , Japan , between 2004 and 2009 . We analyzed 13,201 subjects who underwent annual medical examination of which 12,041 subjects ( age 35 to 85 ) without DM and /or CKD were enrolled . This analysis evaluated age , sex , body mass index , abdominal circumference , hypertension , dyslipidemia , hyperuricemia , fasting glucose , BUN , serum sodium , potassium , chloride and calculated serum osmolarity . Results Elevated serum sodium was an independent risk factor for development of CKD ( OR : 1.03 , 95 % CI , 1.00–1.07 ) after adjusted regression analysis with an 18 percent increased risk for every 5 mmol/L change in serum sodium . Calculated serum osmolarity was also an independent risk factor for CKD ( OR : 1.04 ; 95 % CI , 1.03–1.05 ) as was BUN ( OR : 1.08 ; 95 % CI , 1.06–1.10 ) ( independent of serum creatinine ) . Conclusions Elevated serum sodium and calculated serum osmolarity are independent risk factors for developing CKD . This finding supports the role of limiting salt intake and preventing dehydration to reduce risk of CKD Background Cadmium ( Cd ) , lead ( Pb ) , and mercury ( Hg ) cause toxicological renal effects , but the clinical relevance at low-level exposures in general population s is unclear . The objective of this study is to assess the risk of developing end-stage renal disease in relation to Cd , Pb , and Hg exposure . Methods A total of 118 cases who later in life developed end-stage renal disease , and 378 matched ( sex , age , area , and time of blood sampling ) referents were identified among participants in two population -based prospect i ve cohorts ( 130,000 individuals ) . Cd , Pb , and Hg concentrations were determined in prospect ively collected sample s. Results Erythrocyte lead was associated with an increased risk of developing end-stage renal disease ( mean in cases 76 μg/L ; odds ratio ( OR ) 1.54 for an interquartile range increase , 95 % confidence interval ( CI ) 1.18 - 2.00 ) , while erythrocyte mercury was negatively associated ( 2.4 μg/L ; OR 0.75 for an interquartile range increase , CI 0.56 - 0.99 ) . For erythrocyte cadmium , the OR of developing end-stage renal disease was 1.15 for an interquartile range increase ( CI 0.99 - 1.34 ; mean Ery-Cd among cases : 1.3 μg/L ) . The associations for erythrocyte lead and erythrocyte mercury , but not for erythrocyte cadmium , remained after adjusting for the other two metals , smoking , BMI , diabetes , and hypertension . Gender-specific analyses showed that men carried almost all of the erythrocyte lead and erythrocyte cadmium associated risks . Conclusions Erythrocyte lead is associated with end-stage renal disease but further studies are needed to evaluate causality . Gender-specific analyses suggest potential differences in susceptibility or in exposure biomarker reliability In epidemiologic studies , high arsenic exposure has been associated with adverse kidney disease outcomes . We performed a systematic review of the epidemiologic evidence of the association between arsenic and various kidney disease outcomes . The search period was January 1966 through January 2014 . Twenty-five papers ( comprising 24 studies ) meeting the search criteria were identified and included in this review . In most studies , arsenic exposure was assessed by measurement of urine concentrations or with an ecological indicator . There was a generally positive association between arsenic and albuminuria and proteinuria outcomes . There was mixed evidence of an association between arsenic exposure and chronic kidney disease ( CKD ) , β-2-microglobulin ( β2MG ) , and N-acetyl-β-D-glucosaminidase ( NAG ) outcomes . There was evidence of a positive association between arsenic exposure and kidney disease mortality . Assessment of a small number of studies with three or more categories showed a clear dose-response association between arsenic and prevalent albuminuria and proteinuria , but not with CKD outcomes . Eight studies lacked adjustment for possible confounders , and two had small study population s. The evaluation of the causality of the association between arsenic exposure and kidney disease outcomes is limited by the small number of studies , lack of study quality , and limited prospect i ve evidence . Because of the high prevalence of arsenic exposure worldwide , there is a need for additional well- design ed epidemiologic and mechanistic studies of arsenic and kidney disease outcomes Background The rising prevalence of chronic kidney disease ( CKD ) and subsequent end stage renal failure necessitating renal replacement therapy has profound consequences for affected individuals and health care re sources . This community based study was conducted to identify potential predictors of microalbuminuria in a r and omly selected sample of adults from the North Central Province ( NCP ) of Sri Lanka , where the burden of CKD is pronounced and the underlying cause still unknown . Methods Exposures to possible risk factors were determined in r and omly recruited subjects ( 425 females and 461 males ) from selected areas of the NCP of Sri Lanka using an interviewer administered question naire . Sulphosalicylic acid and the Light Dependent Resister microalbumin gel filtration method was used for initial screening for microalbuminuria and reconfirmed by the Micral strip test . Results Microalbumnuria was detected in 6.1 % of the females and 8.5 % of the males . Smoking ( p < 0.001 ) , alcohol use ( p = 0.003 ) , hypertension ( p < 0.001 ) , diabetes ( p < 0.001 ) , urinary tract infection ( UTI ) ( p = 0.034 ) and consumption of water from wells in the fields ( p = 0.025 ) were associated with microalbuminuria . In the binary logistic regression analysis , hypertension , diabetes mellitus , UTI , drinking well water in the fields , smoking and pesticide spraying were found to be significant predictors of microalbuminuria . Conclusions Hypertension , diabetes mellitus , UTI , and smoking are known risk factors for microalbuminuria . The association between microalbuminuria and consumption of well water suggests an environmental aetiology to CKD in NCP . The causative agent is yet to be identified . Investigations for cadmium as a potential causative agent needs to be initiated BACKGROUND Long-term arsenic exposure is a major global health problem . However , few epidemiologic studies have evaluated the association of arsenic with kidney measures . Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona , Oklahoma , and North and South Dakota . STUDY DESIGN Cross-sectional . SETTING & PARTIPANTS : Strong Heart Study locations in Arizona , Oklahoma , and North and South Dakota . 3,821 American Indian men and women aged 45 - 74 years with urine arsenic and albumin measurements . PREDICTOR Urine arsenic . OUTCOMES Urine albumin-creatinine ratio and albuminuria status . MEASUREMENTS Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic species using inductively coupled plasma mass spectrometry ( ICPMS ) and high-performance liquid chromatography-ICPMS , respectively . Urine albumin was measured by automated nephelometric immunochemistry . RESULTS The prevalence of albuminuria ( albumin-creatinine ratio ≥30 mg/g ) was 30 % . Median value for the sum of inorganic and methylated arsenic species was 9.7 ( IQR , 5.8 - 15.6 ) μg per gram of creatinine . Multivariable-adjusted prevalence ratios of albuminuria ( albumin-creatinine ratio ≥30 mg/g ) comparing the 3 highest to lowest quartiles of the sum of inorganic and methylated arsenic species were 1.16 ( 95 % CI , 1.00 - 1.34 ) , 1.24 ( 95 % CI , 1.07 - 1.43 ) , and 1.55 ( 95 % CI , 1.35 - 1.78 ) , respectively ( P for trend < 0.001 ) . The association between urine arsenic and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria . LIMITATIONS The cross-sectional design can not rule out reverse causation . CONCLUSIONS Increasing urine arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity . Prospect i ve epidemiologic and mechanistic evidence is needed to underst and the role of arsenic as a kidney disease risk factor Background In sub-Saharan Africa , kidney failure has a high morbidity and mortality . Despite this , population -based estimates of prevalence , potential etiologies , and awareness are not available . Methods Between January and June 2014 , we conducted a household survey of r and omly-selected adults in Northern Tanzania . To estimate prevalence we screened for CKD , which was defined as an estimated glomerular filtration rate ≤ 60 ml/min/1.73m2 and /or persistent albuminuria . We also screened for human immunodeficiency virus ( HIV ) , diabetes , hypertension , obesity , and lifestyle practice s including alcohol , tobacco , and traditional medicine use . Awareness was defined as a self-reported disease history and subsequently testing positive . We used population -based age- and gender-weights in estimating prevalence , and we used generalized linear models to explore potential risk factors associated with CKD , including living in an urban environment . Results We enrolled 481 adults from 346 households with a median age of 45 years . The community-based prevalence of CKD was 7.0 % ( 95 % CI 3.8 - 12.3 ) , and awareness was low at 10.5 % ( 4.7 - 22.0 ) . The urban prevalence of CKD was 15.2 % ( 9.6 - 23.3 ) while the rural prevalence was 2.0 % ( 0.5 - 6.9 ) . Half of the cases of CKD ( 49.1 % ) were not associated with any of the measured risk factors of hypertension , diabetes , or HIV . Living in an urban environment had the strongest crude ( 5.40 ; 95 % CI 2.05 - 14.2 ) and adjusted prevalence risk ratio ( 4.80 ; 1.70 - 13.6 ) for CKD , and the majority ( 79 % ) of this increased risk was not explained by demographics , traditional medicine use , socioeconomic status , or co-morbid non-communicable diseases ( NCDs ) . Conclusions We observed a high burden of CKD in Northern Tanzania that was associated with low awareness . Although demographic , lifestyle practice s including traditional medicine use , socioeconomic factors , and NCDs accounted for some of the excess CKD risk observed with urban residence , much of the increased urban prevalence remained unexplained and will further study as demographic shifts reshape sub-Saharan Africa Background Apart from the well-known etiologies , there are still a high proportion of patients with chronic kidney disease of unknown etiology ( CKDu ) , which has rarely been reported on . In this study , we explored the potential associated risk factors for CKDu and identified those that occur in childhood . Methods 700 patients with CKD we were selected r and omly from 4 hospitals in Chengdu and 241 were screened for CKDu . The following clinical information was analyzed : demographic data , life style , personal and family history , nephrotoxic drugs , exposure to poison , allergies , and recurrent respiratory infections in childhood . Results Among 700 CKD patients , 34.43 % ( 241/700 ) were CKDu . Of the 241 patients , there were 67.63 % ( 163/241 ) with at least 1 associated risk factor and 56.44 % ( 92/163 ) with more than 1 . Patients with a personal history of an associated risk factor represented the largest proportion ( 31.95 % , 77/241 ) , while 28.63 % ( 69/241 ) of the CKDu patients had risk factors appearing in childhood . Logistic regression analysis supported the results . Conclusions The study demonstrated that most so-called CKDu patients do have an identifiable etiology , and that several associated risk factors contribute to it . Of all the risk factors , age > 60 years , nephrotoxic drugs , exposure to poison , and alcohol consumption were the independent significant factors for CKDu . Furthermore , many risk factors that caused kidney injury started in childhood Chronic kidney disease ( CKD ) of unknown etiology ( CKDu ) is a serious health issue in Sri Lanka . One-to-one age and sex-matched two sample comparative study was carried out in the Medawachchiya divisional secretariat area of the North Central Province ( NCP ) of Sri Lanka , by r and omly selecting 100 CKDu patients and 100 age and sex-matched subjects from non-CKDu affected families from the same area . An interviewer-administered question naire was used for the collection of data pertaining to occupation , medical history and lifestyle . Data were analyzed using a conditional linear logistic model . Working for > 6 h in the field per day , exposure to sun , drinking water only from well , consumption of <3 L of water per day , and having a history of malaria were found to be having significant ( P < 0.05 ) likelihood toward the development of CKDu . Treatment of water prior to consumption had a significant protective effect against CKDu . Dehydration , history of malaria and drinking untreated well water from are likely contribute to the development of CKD of unknown etiology among the inhabitants of NCP , Sri Lanka There have been major concerns that the nephrotoxicity of commercial formulations of Roundup herbicide is due to the active ingredient glyphosate . We therefore investigated and compared the mechanisms underlining the nephrotoxicity of Roundup herbicide and glyphosate alone in rat . Fifty-six adult male rats r and omized into 7 groups of 8 rats per group were exposed to Roundup formulation and glyphosate alone daily by gavage at 3.6 , 50.4 , and 248.4 mg/kg body weight ( bw ) of glyphosate concentrations for 12 weeks with distilled water administered to the control group . Kidney biomarker ( serum urea and creatinine , plasma cystatin-C , and neutrophil gelatinase-associated lipocalin ) , oxidative stress indices in the kidney tissue , activities of kidney membrane-bound enzymes ( Mg-adenosine triphosphatase [ ATPase ] , Ca-ATPase , Na/K-ATPase , and total ATPase ) , and histopathological changes in the kidney were monitored . Glyphosate concentration in the kidney was quantified by high-performance liquid chromatography with ultraviolet detection . Significant ( P < 0.05 ) alterations in the levels of the kidney biomarker , oxidative stress markers , and membrane-bound enzymes were observed in the rats exposed to Roundup compared to the rats exposed to glyphosate alone . Rats exposed to Roundup accumulated more glyphosate residue in their kidney tissue . Severe histopathological lesions were only seen in the kidneys of rats exposed to Roundup . The nephrotoxicity observed can not be due to the active ingredient in the Roundup formulation , as glyphosate alone has virtually no effect on the renal function of the exposed animals . Therefore , the general cl aim attributing nephrotoxicity of a glyphosate-based herbicide to its active ingredient should be discouraged Background Epidemic levels of CKD of undetermined cause , termed Mesoamerican nephropathy in Central America , have been found in low- and middle-income countries . We investigated the natural history of , and factors associated with , loss of kidney function in a population at high risk for this disease . Methods We conducted a 2-year prospect i ve , longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men ( n=263 ) and a r and om sample of women ( n=87 ) ages 18 - 30 years old without self-reported CKD , diabetes , or hypertension . We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors . Results Among men , we identified three sub population s of eGFR trajectory ( mean baseline eGFR ; mean eGFR change over follow-up ) : 81 % remained stable ( 116 ml/min per 1.73 m2 ; -0.6 ml/min per 1.73 m2 per year ) , 9.5 % experienced rapid decline despite normal baseline function ( 112 ml/min per 1.73 m2 ; -18.2 ml/min per 1.73 m2 per year ) , and 9.5 % had baseline dysfunction ( 58 ml/min per 1.73 m2 ; -3.8 ml/min per 1.73 m2 per year ) . Among women : 96.6 % remained stable ( 121 ml/min per 1.73 m2 ; -0.6 ml/min per 1.73 m2 per year ) , and 3.4 % experienced rapid decline ( 132 ml/min per 1.73 m2 ; -14.6 ml/min per 1.73 m2 per year ; n=3 women ) . Among men , outdoor and agricultural work and lack of shade availability during work breaks , reported at baseline , were associated with rapid decline . Conclusions Although Mesoamerican nephropathy is associated with agricultural work , other factors may also contribute to this disease |
11,335 | 31,349,668 | These results indicate that miRNAs have potential clinical value as prognostic biomarkers in HNC , with miR-21 , 125b , 34c-5p and 18a , in particular , showing great potential as prognostic molecular markers . | Head and Neck Cancer ( HNC ) is the sixth most common type of cancer across the globe , with more than 300,000 deaths each year , globally .
However , there are currently no st and ardised molecular markers that assist in determining HNC prognosis . | BACKGROUND MicroRNAs ( miRNAs ) can be used as prognostic biomarkers in many types of cancer . We aim ed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma . METHODS We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center ( Guangzhou , China ) and 18 specimens of non-cancer nasopharyngitis . Using an 873 probe microarray , we assessed associations between miRNA signatures and clinical outcome in a r and omly selected 156 sample s ( training set ) and vali date d findings in the remaining 156 sample s ( internal validation set ) . We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 sample s from a second r and omisation of the 312 sample s , and vali date d the miRNA signature in 153 sample s from the West China Hospital of Sichuan University in Chengdu , China ( independent set ) . We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival ( DFS ) , distant metastasis-free survival ( DMFS ) , and overall survival . FINDINGS 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues . A signature of five miRNAs , each significantly associated with DFS , was identified in the training set . We calculated a risk score from the signature and classified patients as high risk or low risk . Compared with patients with low-risk scores , patients with high risk scores in the training set had shorter DFS ( hazard ratio [ HR ] 2·73 , 95 % CI 1·46 - 5·11 ; p=0·0019 ) , DMFS ( 3·48 , 1·57 - 7·75 ; p=0·0020 ) , and overall survival ( 2·48 , 1·24 - 4·96 ; p=0·010 ) . We noted equivalent findings in the internal validation set for DFS ( 2·47 , 1·32 - 4·61 ; p=0·0052 ) , DMFS ( 2·28 , 1·09 - 4·80 ; p=0·030 ) , and overall survival ( 2·87 , 1·38 - 5·96 ; p=0·0051 ) and in the independent set for DFS ( 3·16 , 1·65 - 6·04 ; p=0·0011 ) , DMFS ( 2·39 , 1·05 - 5·42 ; p=0·037 ) , and overall survival ( 3·07 , 1·34 - 7·01 ; p=0·0082 ) . The five-miRNA signature was an independent prognostic factor . A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set ( area under receiver operating characteristics 0·68 [ 95 % CI 0·60 - 0·76 ] vs 0·60 [ 0·52 - 0·67 ] ; p=0·013 ) , the internal validation set ( 0·70 [ 0·61 - 0·78 ] vs 0·61 [ 0·54 - 0·68 ] ; p=0·012 ) , and the independent set ( 0·70 [ 0·62 - 0·78 ] vs 0·63 [ 0·56 - 0·69 ] ; p=0·032 ) . INTERPRETATION Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression . FUNDING Science Foundation of Chinese Ministry of Health , National Natural Science Foundation of China , Pearl River Scholar Funded Scheme , Guangdong Key Scientific and Technological Innovation Program , Guangdong Natural Science Foundation , Fundamental Research Funds for the Central Universities BACKGROUND The predictive value of microRNAs ( miRNAs ) in tumour cells and infiltrating immune cells for the efficacy of chemoradiation ( CRTX ) in locally advanced head and neck squamous cell carcinoma ( HNSCC ) was evaluated . METHODS Formalin-fixed , paraffin-embedded tumour material was collected from patients with locally advanced HNSCC treated within the ARO-0401 phase III trial with radiotherapy in combination with either 5-fluorouracil/cisplatin ( CDDP-CRTX ) or 5-fluorouracil/mitomycin C ( MMC-CRTX ) . MiRNA and immune profiles were established in a test cohort of 48 oropharyngeal carcinoma ( OPSCC ) cases by Affymetrix miRNA microarrays and the nanoString PanCancer Immune Panel , respectively . Expression of miRNA c and i date s was measured in 149 HNSCC patients by real-time PCR . Interference of miRNA profiles with CRTX efficacy was determined by Kaplan-Meier and Cox regression analysis . RESULTS Expression levels of five miRNAs ( miR-27b , -130b , -200b , -451 and -532 - 5p ) were significantly associated with overall survival after MMC-CRTX . Six different miRNAs ( miR-125b , -146a , -150 , -155 , -187 and -342 - 5p ) were correlated with overall survival after CDDP-CRTX . Validation by real-time PCR confirmed the predictive value of miR-200b and miR-155 in OPSCC , which was absent in hypopharyngeal carcinomas . MiR-146a was revealed as a prognostic marker for both CRTX regimens . MiR-200b expression was mainly associated with distant metastasis , whereas miR-155 correlated with local recurrence . MiR-155 and miR-146a were identified as surrogate markers for tumour-infiltrating lymphocytes . CONCLUSIONS MiR-200b and miR-155 were established as potential markers for personalised treatment selection of two st and ard regimens of CRTX . The predictive role of miR-155 deserves further investigation , especially within the framework of clinical trials of CRTX/immune checkpoint inhibitor combinations Background : Breast Cancer ( BC ) is the leading cause of deaths in Indian women . Emerging reports reveal alarming evidence of increasing incidence and mortality of BC among young Indian women in addition to the late presentation and poor prognosis . Despite the significant incidence , there is a lack of reliable data re sources and comprehensive epidemiologic studies relating to BC . The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the incidence , prevalence , and mortality of BC in 29 states and seven union territories of India . Methods : Data sources used will be Cochrane Review , MEDLINE , PubMed , Scopus , Science Direct , Web of Science , and international and national cancer registries such as World Health Organization , International Agency for Research on Cancer ( IARC ) , and National Centre for Disease Information and Research (NCDIR)-National Cancer Registry Program initiated by Indian Council of Medical Research . Relevant data will be extracted using a predefined data collection form . A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies . This study protocol was prepared according to the Preferred Reporting Items for Systematic Review s and Meta- Analysis for Protocol s 2015 guidelines . Odds ratios ( ORs ) will be used to measure effect size . The r and om or fixed-effects meta-analyses model will be employed to aggregate the pooled estimates ( ORs ) with 95 % confidence intervals ( CIs ) separately . A forest plot will be produced to assess ORs and 95 % CIs . Publication bias will be assessed using funnel plot , and Egger regression will be applied to test the symmetry of the funnel plot . Ethics and dissemination : This proposed study will be based on published studies and the data from cancer registries . Therefore , human research ethics approval is not required . The results of this study will be published in a peer- review ed journal . PROSPERO registration no : CRD42018084003 Background : The role of miRNA-mediated regulation of RECK in keratinized tumors is unclear . Results : miRNAs express differentially in subtypes of OSCCs , and keratinization-associated miRNAs inversely correlate with RECK in oral cancer cells . Conclusion : miR-7 and miR-21 negatively regulate the tumor suppressor gene RECK . Significance : Keratinization-associated miRNAs may serve as novel targets to reduce tumor aggressiveness . MicroRNAs ( miRNAs ) are small non-coding RNAs that posttranscriptionally regulate gene expression during many biological processes . Recently , the aberrant expressions of miRNAs have become a major focus in cancer research . The purpose of this study was to identify deregulated miRNAs in oral cancer and further focus on specific miRNAs that were related to patient survival . Here , we report that miRNA expression profiling provided more precise information when oral squamous cell carcinomas were subcategorized on the basis of clinicopathological parameters ( tumor primary site , histological subtype , tumor stage , and HPV16 status ) . An innovative radar chart analysis method was developed to depict subcategories of cancers taking into consideration the expression patterns of multiple miRNAs combined with the clinicopathological parameters . Keratinization of tumors and the high expression of miR-21 were the major factors related to the poor prognosis of patients . Interestingly , a majority of the keratinized tumors expressed high levels of miR-21 . Further investigations demonstrated the regulation of the tumor suppressor gene reversion-inducing cysteine-rich protein with kazal motifs ( RECK ) by two keratinization-associated miRNAs , miR-7 and miR-21 . Transfection of miR-7 and miR-21-mimics reduced the expression of RECK through direct miRNA-mediated regulation , and these miRNAs were inversely correlated with RECK in CAL 27 orthotopic xenograft tumors . Furthermore , a similar inverse correlation was demonstrated in CAL 27 cells treated in vitro by different external stimuli such as trypsinization , cell density , and serum concentration . Taken together , our data show that keratinization is associated with poor prognosis of oral cancer patients and keratinization-associated miRNAs mediate deregulation of RECK which may contribute to the aggressiveness of tumors |
11,336 | 27,059,508 | CONCLUSION Excision of benign nonendometriotic ovarian cyst(s ) seems to result in a marked reduction of circulating anti-Müllerian hormone .
It remains to be established whether this reflects a real compromise to ovarian reserve | BACKGROUND Benign nonendometriotic ovarian cysts are very common and often require surgical excision .
However , there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve .
OBJECTIVE The aim of this meta analysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti-Müllerian hormone level . | Objective The aim of this study was to evaluate the surgical impact of benign ovarian mass on ovarian reserve as measured by serum follicle stimulating hormone ( FSH ) , estradiol ( E2 ) and anti-Müllerian hormone ( AMH ) levels , antral follicle count ( AFC ) and ovarian volumes . In addition , the differences in ovarian reserve impairment between endometrioma cystectomy and non-endometrioma cystectomy were investigated . Methods In this prospect i ve study , 22 patients of reproductive age ( range , 18.35 years ) with benign ovarian masses were enrolled to undergo laparoscopic cystectomy . Of whom 12 had endometriomas and 10 had non-endometriomas . On early follicular phase ( day 3 ) of the cycle preceding the operation and three months after the laparoscopic cystectomy , serum levels of FSH , E2 and AMH , AFC and ovarian volumes were measured in all patients . Data were analyzed with Mann-Whitney U-test and Wilcoxon rank test using SPSS ver . 12.0 for statistic analysis . Results Median level of serum AMH was significantly decreased from 5.48 ng/mL ( interquartile range [ IQR ] , 2.80 - 7.47 ) before cystectomy to 2.56 ng/mL ( IQR , 1.74 - 4.32 ) 3 months postoperation ( P<0.05 ) . On the other h and , no significant differences in FSH , E2 , AFC and ovarian volumes were found between the preoperative and three months postoperative levels . In a subgroup analysis of the pathologic type of the ovarian cyst , postoperative serum AMH levels were significantly decreased in the endometrioma group , but not in the non-endometrioma group . Conclusion Serum AMH levels were significantly decreased after laparoscopic cystectomy without any changes of other ovarian reserve tests OBJECTIVE To compare the effects of laparoscopic bipolar electrocoagulation with laparotomic hemostatic suturing during unilateral ovarian cystectomy on the ovarian reserve . METHODS A prospect i ve r and omized trial was conducted on 59 women with unilateral benign ovarian cysts who underwent laparoscopic ovarian cystectomy by a stripping technique ( n = 30 ) or open laparotomy with hemostatic suturing ( n = 29 ) . Serum anti-Müllerian hormone ( AMH ) , antral follicle count ( AFC ) , and ovarian stromal peak systolic velocity ( PSV ) at the 1st , 3rd , and 6th postoperative cycle were used to assess the ovarian reserve . RESULTS Preoperative AMH levels did not differ significantly ( P = 0.18 ) between the laparoscopy and laparotomy groups . In the laparoscopy group , there was a significant decrease in AMH levels , AFC , and PSV at the 3rd and 6th postoperative cycles compared with the 1st postoperative cycle , with an insignificant decrease between the 3rd and 6th cycles . In the laparotomy group , nonsignificant decreases in AMH levels , AFC , and PSV were detected at the 1st , 3rd , and 6th postoperative cycle and between the 3rd and 6th cycles . CONCLUSION Laparoscopic ovarian cystectomy is associated with a significant reduction in ovarian reserve . This is a consequence of damage to the ovarian vascularity and the removal of an increased amount of ovarian tissue STUDY OBJECTIVE To evaluate damage to ovarian reserve following laparoscopic cystectomy of benign ovarian cysts . DESIGN Prospect i ve study ( Canadian Task Force classification II-3 ) . SETTING Tertiary gynecologic endoscopic unit at a university-affiliated hospital . PATIENTS Thirty-one patients who underwent excision of monolateral ( n=25 ) or bilateral ( n=6 ) benign ovarian cysts . INTERVENTIONS Serial transvaginal ultrasound examinations during the first and third postsurgical menstrual cycles . The following ovarian echographic variables were evaluated : antral follicle count , ovarian volume , stromal blood flow , and side of ovulation . Two types of statistical analysis were performed : a paired analysis comparing operated and intact ovaries of the same patient and a prospect i ve analysis comparing ecographic characteristics of the operated gonad at first and second evaluation . MEASUREMENTS AND MAIN RESULTS Antral follicle count and stromal blood flow were not significantly affected by surgery . While ovarian volume was similar in the operated and in the contralateral intact gonad at the first ultrasound evaluation , the volume of the operated ovary was significantly reduced at the second assessment . The median ( interquartile range ) of the percentage of this reduction was 33 % ( 18%-81 % ) . This progressive reduction was confirmed by prospect ively analyzing the operated ovaries . An increased probability of ovulation in the intact gonad was observed at both assessment s. CONCLUSION Laparoscopic excision of ovarian cysts is associated with damage to ovarian reserve , at least immediately after surgery . This effect does not appear to be consequent to an injury to ovarian vascularization OBJECTIVE To evaluate safety and efficacy , in terms of spillage risk and ovarian tissue preservation , of mesial incision for laparoscopic dermoid cystectomy . DESIGN R and omized controlled trial . SETTING University . PATIENT(S ) Sixty-seven women with dermoid cysts . INTERVENTION(S ) Laparoscopic dermoid cystectomy performed by mesial incision ( 33 patients , study group ) or antimesial incision ( 34 patients , control group ) . MAIN OUTCOME MEASURE(S ) Spillage of intracystic content rate , operative times , chemical peritonitis rate , and intraoperative blood loss ( ΔHb ) as primary outcomes . Postoperative ovarian reserve ( ΔFSH levels , basal antral follicle number , mean ovarian diameter , and peak systolic velocity at 3 and 12 months after surgery ) as secondary outcome . RESULT ( S ) Spillage of intracystic content rate and operative time were significantly lower in the study than in the control group . None developed chemical peritonitis . ΔHb was higher in the study group but not significantly . During the follow-up , median FSH values were significantly lower in the study group , with no differences in the E(2 ) levels . Moreover , median basal antral follicle number , median ovarian diameter , and median peak systolic velocity were significantly higher in the study group . CONCLUSION ( S ) Ovarian mesial-side incision appears to be a safe as well as tissue-sparing technique . CLINICAL TRIAL REGISTRATION NUMBER Background To evaluate the impact of the presence of endometrioma and laparoscopic cystectomy on ovarian reserve as assessed by serum anti-Müllerian hormone ( AMH ) level . In addition , factors related to the decline in ovarian reserve were analyzed . Methods From June 2013 to January 2014 , we prospect ively included 40 women with endometriomas as the study group ( group A ) , 36 women with tubal factor infertilities as control group 1 ( group B ) and 22 women with the other benign ovarian cysts as control group 2 ( group C ) . The women with ovarian cysts underwent laparoscopic cystectomy . Serum AMH levels were determined preoperatively and at 1 month after surgery . Results The endometrioma group had lower AMH levels ( 1.53 ± 1.37 ng/ml ) compared with the other benign ovarian cyst group ( 2.20 ± 1.23 ng/ml ) and the tubal factor infertility group ( 2.82 ± 1.74 ng/ml ) . The rate of serum AMH decline 1 month after surgery in the endometrioma group ( 0.62 ± 0.35 ) was larger than the decline in the other benign ovarian cyst group ( 0.32 ± 0.30 ) . The preoperative AMH level showed a significant correlation with patient age ( group A , r = −0.32 ; group B , r = −0.54 ; group C , r = −0.71 ) ; there was a statistically significant correlation between the rate of serum AMH decline and endometrioma diameter as well as with the preoperative serum AMH level . In addition , the rate of serum AMH decline was larger for bilateral endometriomas than for unilateral endometriomas , but there was no similar correlation in the other benign ovarian cyst group . The rate of AMH decline after surgery in the subgroup of > 7 cm was significantly higher than in the subgroup of ≤7 cm . Conclusions Ovarian endometriomas per se may damage ovarian reserve , and cystectomy of endometriomas may cause greater damage to ovarian reserve compared with other benign ovarian cysts . The operation-related damage to the ovarian reserve was positively related to whether the endometriomas were bilateral , as well as cyst size ( especially for cysts > 7 cm ) , but was negatively related to the preoperative serum AMH level . Age was a negative factor that affected the ovarian reserve OBJECTIVE To determine whether the stripping technique by laparoscopy is a tissue-sparing procedure . DESIGN Prospect i ve study . SETTING University hospital . PATIENT(S ) Forty-two women , 21 to 35 years of age , who had a unilateral ovarian cyst ( 26 endometriomas , 7 serous , 6 dermoid , and 3 mucinous cysts ) . INTERVENTION(S ) Laparoscopic excision of ovarian cysts by using the stripping technique . MAIN OUTCOME MEASURE(S ) Histologic analysis of the excised specimens was done to evaluate the presence and nature of ovarian tissue adjacent to the cyst wall . RESULT ( S ) Recognizable ovarian tissue adjacent to the cyst wall was present in 15 of 42 excised specimens ( 36 % ) . A significant difference was present for endometriomas versus non-endometriosis cysts ( ovarian tissue was present in 14 of 26 specimens [ 54 % ] vs. 1 of 16 specimens [ 6 % ] ; P<.005 ) . No specimen showed the normal follicular pattern observed in healthy ovaries . CONCLUSION ( S ) The stripping technique appears to be a tissue-sparing procedure . In 36 % of the cysts , ovarian tissue is excised together with the cyst wall , but this tissue does not show the morphologic characteristics observed in normal ovarian tissue CONTEXT The interindividual variation in the age-related decline of ovarian follicles is wide . Hence , it is important to identify reliable , sensitive , and specific markers to assess the ovarian reserve of the individual woman . OBJECTIVE The aim of this study was to characterize the relation between age and ovarian reserve parameters in a population of healthy women with regular menstrual cycle . DESIGN AND SETTING We conducted a prospect i ve , population -based , cross-sectional study . PARTICIPANTS A total of 366 health care workers aged 21 - 41 years employed at a University Hospital were included . INTERVENTIONS There were no interventions . MAIN OUTCOME MEASURES Serum anti-Müllerian hormone ( AMH ) concentration , antral follicle count ( AFC ) , antral follicle size categories ( small : 2 - 4 mm ; intermediate : 5 - 7 mm ; and large : 8 - 10 mm ) , and ovarian volume were measured . RESULTS Serum AMH level declined by 5.6 % per year ( 95 % confidence interval 3.7 - 7.4 % , P < .001 ) , AFC ( 2 - 10 mm ) declined by 4.4 % per year ( 3.2 - 5.7 % , P < .001 ) , and ovarian volume declined by 1.1 % per year ( 0.2 - 2.0 , P = .002 ) , respectively . The mean proportion of small follicles decreased with age ( P = .04 ) , the proportion of intermediate follicles displayed no significant change with age ( P = .58 ) , and the mean proportion of large follicles increased with age ( P < .001 ) . The prevalence of large follicles increased with decreasing serum AMH concentration [ odds ratio 1.04 per 1 pmol/L ( 1.02 - 1.06 ) , P < .001 , area under the curve 0.66 ] , and with decreasing total AFC [ odds ratio 1.04 per follicle ( 1.02 - 1.05 ) , P < .001 , area under the curve 0.62 ] . CONCLUSION Chronological age was inversely related to serum AMH concentration , total AFC , and ovarian volume . Subclasses of AFC sized 2 - 4 and 5 - 7 mm decreased with increasing age , whereas AFC sized 8 - 10 mm increased with increasing age . Within AFC , a shift toward larger follicles with increasing age was observed . The occurrence of large follicles was more strongly related to biological age in terms of AMH and AFC than chronological age OBJECTIVE To determine whether different methods of hemostasis and pathologic subtypes would lead to significant differences regarding ovarian reserve after laparoscopic ovarian cystectomy . STUDY DESIGN Data were prospect ively collected from 129 patients who underwent laparoscopic ovarian cystectomy with either a hemostatic sealant ( FloSeal or TachoSil ) or bipolar coagulation to achieve hemostasis . Serum anti-Müllerian hormone ( AMH ) levels as measured by enzyme immunoassay . Measurements were made preoperatively and at 3 months postsurgery in each group [ bipolar coagulator group ( n=43 ) , FloSeal group ( n=46 ) , and TachoSil group ( n=40 ) ] . RESULTS Age , BMI , parity , sociodemographic variables , and preoperative AMH levels were similar between the three groups of patients . At 3 months post-surgery , the AMH decline rate was significantly greater in the bipolar coagulation group compared with the two hemostatic sealant groups ( 41.2 % [ IQR , 16.7 - 52.4 ] vs. 15.4 % [ IQR , 5.2 - 41.9 ] , respectively ; P=0.003 ) . However , the AMH decline rates of the two hemostatic sealant groups ( FloSeal and TachoSil ) were not significantly different ( 15.4 % [ IQR , 7.8 - 44.6 ] vs. 15.9 % [ IQR , 0.7 - 41.1 ] , P=0.962 ) . Also , subgroup analysis according to ovarian cyst type revealed no significant differences in the rate of serum AMH decline regardless of the hemostatic method ( bipolar group , P=0.30 ; FloSeal group , P=0.47 , and TachoSil group , P=0.79 ) . CONCLUSION The two hemostatic sealants ( FloSeal and Tachosil ) did not exhibit any significant differences regarding the preservation of ovarian reserve regardless of ovarian cyst type OBJECTIVE To determine whether levels of antimüllerian hormone ( AMH ) in serum vary during the normal menstrual cycle , using the most recently developed immunoassay method . DESIGN Prospect i ve cohort study . SETTING Local community . PATIENT(S ) Women with normal menstrual cycles and between the ages of 18 and 45 years were recruited ( n = 45 ) . Blood sample s were collected on 5 days within each cycle : two in the follicular phase and three after confirmed ovulation . Exclusion criteria were anovulatory cycles , incomplete sample collection , insufficient blood volume , or non-Caucasian ethnicity . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Serum sample s were tested for levels of AMH using a new immunoassay method ( Ansh Labs ) . The effects of body mass index ( BMI ) and smoking on serum AMH levels were considered . RESULT ( S ) Serum AMH levels varied significantly during the menstrual cycle , with the highest levels in the follicular phase . When the analysis was stratified by age , AMH variation during the menstrual cycle was significant only for women older than 30 years . Serum AMH levels were not significantly altered by BMI or smoking . CONCLUSION ( S ) The new AMH immunoassay revealed a follicular phase rise in serum levels , particularly in women over the age of 30 years . This is consistent with other reports finding an interaction of menstrual cycle variation in AMH and chronological age . Nonetheless , the extent of variation is small , and sampling on any day of the menstrual cycle is expected to adequately reflect ovarian reserve . CLINICAL TRIAL REGISTRATION NUMBER NCT01337999 OBJECTIVE To evaluate the ovarian reserve changes after laparoscopic cystectomy , we prospect ively evaluated pre- and postoperative serum anti-Müllerian hormone ( AMH ) level , and ovarian volumes . DESIGN Prospect i ve longitudinal study . SETTING University Hospital . PATIENT(S ) Twenty women with benign ovarian masses participated ; endometrioma [ 13 ] , mature teratoma [ 6 ] , and mucinous cystadenoma [ 1 ] . Seven patients had bilateral ovarian masses . INTERVENTION(S ) All patients had undergone laparoscopic ovarian cystectomy . Serum AMH levels were serially measured : preoperative , 1 week , 1 month , and 3 months after operation . Volumes of total ovary and ovarian mass were measured by 3D ultrasonography before operation . MAIN OUTCOME MEASURE(S ) Postoperative serum AMH level and ovarian volume . RESULT ( S ) Median AMH level was 2.23 ng/mL ( 95 % confidence interval [ CI ] 1.35 - 3.41 ng/mL ) before operation , but reduced to 0.67 ng/mL ( 95 % CI 0.44 - 1.70 ng/mL ) at the first week postoperatively and then increased to 1.14 ng/mL ( 95 % CI 0.79 - 2.36 ng/mL ) in the first month and 1.50 ng/mL ( 95 % CI 0.58 - 3.26 ng/mL ) in the third month . The serum AMH level after 3 months postoperatively was recovered to about 65 % of the preoperative level . The serum AMH level at postoperative 1 week was more decreased in endometrioma compared with nonendometrioma ( 33.9 % vs. 69.2 % of preoperative level ) , and in bilateral group compared with unilateral group ( 16.9 % vs. 62.9 % ) . CONCLUSION ( S ) This study suggests that ovarian reserve could be reduced after laparoscopic cystectomy ; however , it could be restored thereafter up to 3 months postoperative in reproductive women OBJECTIVE To identify the most important factor in predicting ovarian reserve after laparoscopic ovarian cystectomy and to evaluate whether there is any difference in the postoperative decline of ovarian reserve between women with endometrioma and those with other benign ovarian cysts . DESIGN Prospect i ve cohort study . SETTING University hospital . PATIENT(S ) A total of 100 women who had undergone laparoscopic ovarian cystectomy for endometrioma ( n = 68 ) or other benign ovarian cysts ( n = 32 ) . INTERVENTION(S ) Serum antimüllerian hormone ( AMH ) levels measured by enzyme immunoassay preoperatively and at 3 months after surgery . MAIN OUTCOME MEASURE(S ) Rate of AMH decline after surgery and follicle numbers retained in cystectomy specimens . RESULT ( S ) Serum AMH levels were obviously decreased at 3 months after the surgery ( 4.97 ± 2.83 vs. 3.33 ± 2.08 ng/mL , mean ± st and ard deviation ) . Adjusting for several parameters , we could see that bilaterality of the ovarian cyst was the only significant factor in predicting the rate of postoperative decline of AMH levels . The rate of AMH decline did not differ between the endometrioma group and the other benign ovarian cyst group . CONCLUSION ( S ) Bilaterality of the ovarian cyst is the only significant factor in predicting the rate of decline of AMH level after laparoscopic ovarian cystectomy . The rate of decline of AMH levels after surgery was similar between the endometrioma group and the other benign ovarian cyst group OBJECTIVE To investigate the impact of electrocoagulation on ovarian reserve after laparoscopic excision of ovarian cysts and the possible mechanisms . DESIGN A prospect i ve study . SETTING Obstetrics and Gynecology Department of a university hospital . PATIENT(S ) 191 patients with benign ovarian cysts undergoing ovarian cystectomy . INTERVENTION(S ) Laparoscopic ovarian cystectomy using bipolar or ultrasonic scalpel electrocoagulation and laparotomic ovarian cystectomy using sutures after the excision of ovarian cysts . MAIN OUTCOME MEASURE(S ) Follicle-stimulating hormone ( FSH ) assay and transvaginal ultrasound evaluating basal antral follicle number , mean ovarian diameter , and ovarian stromal blood flow velocity at day 3 of menstrual cycles 1 , 3 , 6 , and 12 after surgery . RESULT ( S ) When comparing the bipolar group and ultrasonic scalpel group with the suture group , a statistically significant increase of the mean FSH value was found in bilateral-cyst patients at 1- , 3- , 6- , and 12-month follow-up evaluations and in unilateral-cyst patients at the 1-month follow-up evaluation . Statistically significant decreases of basal antral follicle number and mean ovarian diameter were found during the 3- , 6- , 12-month follow-up evaluations as well as statistically significant decreases of peak systolic velocity at all of the follow-up evaluations . CONCLUSION ( S ) Electrocoagulation after laparoscopic excision of ovarian cysts is associated with a statistically significant reduction in ovarian reserve , which is partly a consequence of the damage to the ovarian vascular system Purpose Aim of the present study is to determine the effects of bipolar electrocoagulation and intracorporeal suture on the ovarian reserve after ovarian cystectomy . Methods Sixty patients aged 18–42 years old and with a persistent adnexal mass were recruited to the study . Patients were r and omized into suture hemostasis group or bipolar hemostasis group . Laparoscopic ovarian cystectomy was performed to all patients . Hemostasis was obtained by bipolar coagulation in 30 patients and by intracorporeal sutures in 30 patients . Serum levels of FSH , LH , estradiol , inhibin B and ultrasonographic measurements ( antral follicle count and ovarian volume ) were analyzed and recorded at day 3 of menstrual cycle , 1 and 3 months after the surgery . Results Basal FSH level measurement at the postoperative third month was significantly increased to 6.96 ± 1.86 mIU/ml ( p < 0.05 ) in the bipolar electrocoagulation group . However , the decreased ovarian volume and antral follicle count was restored at the postoperative third month in the bipolar electrocoagulation group . Preoperative and postoperative FSH , LH , estradiol and inhibin B levels and ultrasonographic measurements were similar in the intracorporeal suture group . Conclusion The unwanted effect of bipolar electrocoagulation on ovarian reserve is probably transient and causes minimal damage to ovary . FSH levels may be slightly elevated . Gentle use of bipolar electrocoagulation or intracorporeal are not found to effect ovarian reserve OBJECTIVES Single-port access ( SPA ) laparoscopic ovarian cystectomy has been reported as a comparable procedure to conventional laparoscopy in terms of operative outcomes . However , whether ovarian function after SPA laparoscopic surgery is similar to conventional laparoscopy is question ed due to the limitations in moving instruments . The aim of this study was to evaluate whether the reduced port number affects the ovarian reserve after laparoscopic ovarian cystectomy . STUDY DESIGN This was a r and omized controlled trial of 87 women with benign ovarian cyst , who attended a university hospital and were scheduled for laparoscopic ovarian cystectomy . Women were r and omized to SPA , two-port access ( TPA ) , or four-port access ( FPA ) laparoscopic groups . The primary outcome was the serum anti-Müllerian hormone ( AMH ) levels : preoperative , 1 week , 1 month and 3 months after the operation . Secondary outcomes were operative outcomes . RESULTS The mean serum AMH levels of preoperative , 1 week , 1 month and 3 months after laparoscopy were 4.4±2.9 , 2.7±2.2 , 2.3±1.9 , and 2.5±1.5ng/mL ( in the SPA group ) , 3.6±2.5 , 2.3±2.2 , 2.6±3.2 , and 2.7±2.6ng/mL ( in the TPA group ) , and 3.9±3.2 , 2.4±2.1 , 2.5±2.0 , and 2.8±2.2ng/mL ( in the FPA group ) , respectively . There was no statistically significant difference in the serial change of AMH levels among the SPA , TPA and FPA groups . CONCLUSIONS The laparoscopic ovarian cystectomy with reduced port number does not affect the serial change of ovarian reserve . The SPA or TPA laparoscopy may be the alternative method to conventional laparoscopy in terms of ovarian reserve To assess the impact of laparoscopic surgery on ovarian reserve , we evaluated pre- and postoperative levels of serum anti-Müllerian hormone ( AMH ) in comparison with basal levels of FSH . The median AMH level was 2.98 ng/mL and 3.92 ng/mL before operation and was significantly reduced to a median level of 2.24 ng/mL and 3.29 ng/mL at 1 month after operation in the endometrioma group ( n = 29 ) and the nonendometrioma group ( n = 21 ) , respectively , whereas postoperative basal FSH levels did not significantly change in comparison with preoperative levels STUDY OBJECTIVE To evaluate the effects of laparoscopic cystectomy of endometrioma and nonendometrioma ovarian cyst on ovarian reserve . DESIGN Prospect i ve follow-up study of patients after laparoscopic ovarian cystectomy ( Canadian Task Force II-2 ) . SETTING Academic hospital . PATIENTS Seventy patients underwent laparoscopic ovarian cystectomy , with bilateral endometrioma ( n = 21 ) , unilateral endometrioma ( n = 29 ) , and unilateral other benign ovarian cyst ( n = 20 ) from February 2011 and May 2012 . The control group ( n = 20 ) comprised patients treated with laparoscopic myomectomy or laparoscopic hydrotubation and fimbrioplasty at the same time period . INTERVENTIONS All laparoscopic operations were applied by suture homeostasis . Ovarian reserve was assessed by serum levels of anti-Müllerian hormone ( AMH ) and follicle-stimulating hormone ( FSH ) and by antral follicle count ( AFC ) , ovarian volume , ovarian stromal pulsatility index , and resistance index on the third day of menstruation preoperatively and in postoperative months 1.6 and 12 . MEASUREMENTS AND MAIN RESULTS FSH levels increased significantly but the AMH and AFC levels declined significantly in the bilateral endometrioma group at 1 month postoperatively compared with preoperative levels ( p < .05 ) but did not differ significantly at 6 and 12 months postoperatively . The ovarian stromal pulsatility and resistance indices in the ipsilateral ovaries decreased significantly in all patients with unilateral ovarian cysts at 6 and 12 months postoperatively compared with preoperative levels ( p < .05 ) , although the mean ipsilateral ovarian volume was significant smaller than the unaffected side . CONCLUSION There was no detectable difference on ovarian reserve marker levels between 4 groups and from baseline values at 6 and 12 months after laparoscopic ovarian cystectomy of endometrioma , although these levels significantly declined in the first month postoperatively STUDY OBJECTIVE This study was conducted to determine the changes in ovarian reserve markers after laparoscopic ovarian cystectomy ( LOC ) . DESIGN Prospect i ve cohort study ( Canadian Task Force classification II-2 ) . SETTING University teaching hospital . PATIENTS Fifty 50 patients who underwent LOC were prospect ively examined to determine the changes in serum markers of ovarian reserve , starting from 1 month before and 3 months after consecutive operations . INTERVENTIONS Changes in serum markers were compared between the following groups : endometrioma cysts ( n = 26 ) versus nonendometrioma cysts ( n = 24 ) , unilateral cystectomy ( n = 38 ) versus bilateral cystectomy ( n = 12 ) , and bilateral endometrioma extirpation ( n = 10 ) versus other cystectomy operations ( n = 40 ) . MEASUREMENTS AND MAIN RESULTS A significant change was noticed between the preoperative and postoperative antimüllerian hormone ( AMH ) levels ( 2.67 ± 2.67 ng/mL vs 1.84 ± 1.72 ng/mL , p < .0001 ) . Serum AMH levels were found to be significantly decreased in endometrioma ( p = .002 ) , nonendometrioma ( p = .019 ) , unilateral cystectomy ( p = .001 ) , bilateral cystectomy ( p = .005 ) , bilateral endometrioma ( p = .011 ) , and cysts other than bilateral endometrioma ( p = .000 ) groups . CONCLUSION The ovarian reserve was found to be diminished after LOC regardless of the presence of endometrioma that could be distinguishable by serum AMH levels |
11,337 | 25,684,602 | The results suggest a lack of evidence to prove that early treatment carries additional benefit over and above that achieved with treatment commencing later ; however , this does not necessarily imply that early treatment is ineffective . | OBJECTIVES To determine whether interceptive orthodontics prior to the age of 11 years is more effective than later treatment in the short- and long-term .
CLINICAL SIGNIFICANCE Interceptive orthodontics is variously recommended for a range of malocclusions both of skeletal and dental aetiology .
The merits of interceptive treatment , however , are often disputed . | INTRODUCTION The aim of this study was to evaluate the effectiveness of early orthodontic treatment with the Twin-block appliance for the treatment of Class II Division 1 malocclusion . This was a multi-center , r and omized , controlled trial with subjects from 14 orthodontic clinics in the United Kingdom . METHODS The study included 174 children aged 8 to 10 years with Class II Division 1 malocclusion ; they were r and omly allocated to receive treatment with a Twin-block appliance or to an initially untreated control group . The subjects were then followed until all orthodontic treatment was completed . Final skeletal pattern , number of attendances , duration of orthodontic treatment , extraction rate , cost of treatment , and the child 's self-concept were considered . RESULTS At the end of the 10-year study , 141 patients either completed treatment or accepted their occlusion . Data analysis showed that there was no differences between those who received early Twin-block treatment and those who had 1 course of treatment in adolescence with respect to skeletal pattern , extraction rate , and self-esteem . Those who had early treatment had more attendances , received treatment for longer times , and incurred more costs than the adolescent treatment group . They also had significantly poorer final dental occlusion . CONCLUSIONS Twin-block treatment when a child is 8 to 9 years old has no advantages over treatment started at an average age of 12.4 years . However , the cost of early treatment to the patient in terms of attendances and length of appliance wear is increased INTRODUCTION Our aim in this prospect i ve r and omized clinical study was to assess the prevalence rate of eruption of palatally displaced canines , diagnosed at an early developmental stage with posteroanterior radiographs and consequently treated by rapid maxillary expansion . METHODS A sample of 60 subjects in the early mixed dentition with palatally displaced canines diagnosed on posteroanterior radiographs was enrolled in the trial . Their age range at the first observation ( T1 ) was 7.6 to 9.6 years , with a prepubertal stage of skeletal maturity ( CS1 or CS2 ) . The 60 subjects were r and omly allocated to the treatment group ( TG , 35 subjects ) or the no-treatment group ( NTG , 25 subjects ) . The TG was treated with a b and ed rapid maxillary exp and er ; after expansion , all patients were retained with the exp and er in place for 6 months . Thereafter , the exp and er was removed , and the patients wore a retention plate at night for a year . The NTG received no treatment . All subjects were reevaluated in the early permanent dentition ( T2 ) ( postpubertal CS4 ) . The number of dropouts was recorded . The main outcome recorded at T2 was successful or unsuccessful eruption of the maxillary permanent canines . The starting forms at T1 for measurements on posteroanterior and panoramic films were compared in the 2 groups with the Mann-Whitney U test ( P < 0.05 ) . The prevalence rates of successful and unsuccessful treatments in the TG were compared with those in NTG with chi-square tests ( P < 0.05 ) . From T1 to T2 , there were 3 dropouts in each group . RESULTS The final sample comprised 32 subjects in the TG and 22 subjects in the NTG . No statistically significant differences were found for any variable at T1 . The prevalence rates of successful eruption of the maxillary canines were 65.7 % ( 21 subjects ) in the TG and 13.6 % ( 3 subjects ) in the NTG . The comparison was statistically significant ( chi-square = 12.4 ; P < 0.001 ) . Subjects with palatally displaced canines in the early mixed dentition do not have transverse deficiency of the maxillary arch . CONCLUSIONS The use of a rapid maxillary exp and er as an early interceptive approach is effective for increasing the rate of eruption of palatally displaced canines INTRODUCTION There are disparities in access to orthodontic treatment for children from low-income families . Systematic programs of limited-care interceptive and preventive orthodontics have been proposed as a solution . The purpose of this r and omized clinical trial was to compare dental outcomes and funding eligibility from a group of Medicaid patients r and omized to receive interceptive orthodontics ( IO ) in the mixed dentition or observation ( OBS ) . METHODS One hundred seventy Medicaid-eligible children were r and omized to receive IO or OBS and followed for 2 years , when complete data were available on 72 and 74 children , respectively . The 2-year changes in the peer assessment rating ( PAR ) were compared using the Student t test . The proportions of children no longer eligible for Medicaid funding as defined by h and icapping labiolingual deviation ( HLD ) scores less than 25 at the 2-year follow-up were compared with the chi-square test . RESULTS The IO patients had significantly greater decreases in the PAR scores--50%-compared with the OBS subjects , -6 % ( P < 0.001 ) . Negative and positive overjet and maxillary alignment were the components most affected by IO ; they decreased by 11.0 , 7.2 , and 3.7 PAR points , respectively ( P < 0.001 ) . Overbite showed little change . At the 2-year follow-up , 80 % of the IO patients ' malocclusions that qualified initially were no longer deemed medically necessary by the HLD index , compared with 6 % in the OBS group ( P < 0.001 ) . CONCLUSIONS IO significantly reduces the severity of malocclusions and moves most from the " medically necessary " category to elective but does not produce finished results for most patients . Overjet and alignment were most readily corrected by interceptive treatment . Deep overbites were the least susceptible to IO correction In a 2-phased , parallel , r and omized trial of early ( preadolescent ) versus later ( adolescent ) treatment for children with severe ( > 7 mm overjet ) Class II malocclusions who initially were developmentally at least a year before their peak pubertal growth , favorable growth changes were observed in about 75 % of those receiving early treatment with either a headgear or a functional appliance . After a second phase of fixed appliance treatment for both the previously treated children and the untreated controls , however , early treatment had little effect on the subsequent treatment outcomes measured as skeletal change , alignment , and occlusion of the teeth , or length and complexity of treatment . The differences created between the treated children and untreated control group by phase 1 treatment before adolescence disappeared when both groups received comprehensive fixed appliance treatment during adolescence . This suggests that 2-phase treatment started before adolescence in the mixed dentition might be no more clinical ly effective than 1-phase treatment started during adolescence in the early permanent dentition . Early treatment also appears to be less efficient , in that it produced no reduction in the average time a child is in fixed appliances during a second stage of treatment , and it did not decrease the proportion of complex treatments involving extraction s or orthognathic surgery INTRODUCTION Many research ers have examined the prevalence of dental injuries in children and adolescents . The purpose of this study was to examine the prevalence and incidence of incisor trauma in subjects who participated in a r and omized clinical trial design ed to investigate early growth modifications in the treatment of Class II malocclusion . METHODS The subjects were r and omized to 3 treatment groups during the initial phase of the study : ( 1 ) headgear or biteplane , ( 2 ) bionator , and ( 3 ) observation ( no treatment ) . All 3 groups underwent phase 2 treatment with fixed appliances . Incisor injury was scored at every data collection point with the Ellis index by a blinded examiner using dental casts , intraoral photos , and panoramic and periapical x-rays . RESULTS Twenty-five percent of the subjects had incisor trauma at the baseline examination , and 28 % experienced new or worsening maxillary incisor injury during the study . No significant differences were found with regard to sex and prevalence of injury at baseline . No differences in incidence of trauma were found between the 3 treatment groups throughout the study ( P = 0.19 ) ; however , boys were more likely to experience maxillary incisor injury ( odds ratio estimate , 2.37 ; 95 % CI , 1.33 , 4.21 ) , and those with an injury at baseline were more likely to experience an additional injury ( odds ratio estimate , 1.81 ; 95 % CI , 1.03 , 3.17 ) . CONCLUSIONS Early orthodontic treatment did not affect the incidence of incisor injury . The majority of the injuries before and during treatment were minor ; therefore , the cost-benefit ratio of orthodontic treatment primarily to prevent incisor trauma is unfavorable OBJECTIVE To investigate the effectiveness of early class III protraction facemask treatment in children under 10 years of age at 3-year follow-up . DESIGN Multicentre r and omized controlled trial . SUBJECTS AND METHODS Seventy-three patients were r and omly allocated , stratified for gender , into early class III protraction facemask group ( PFG ) ( n = 35 ) and a control/no treatment group ( CG ) ( n = 38 ) . OUTCOMES Dentofacial changes were assessed from lateral cephalograms and occlusal changes using the peer assessment rating ( PAR ) . Self-esteem was assessed using the Piers-Harris children 's self-concept scale , and the psychosocial impact of malocclusion with oral aesthetic subjective impact score ( OASIS ) question naire . Temporom and ibular joint ( TMJ ) signs and symptoms were also recorded . The time points for data collection were at registration ( DC1 ) , 15 months later ( DC2 ) and 3 years post- registration ( DC3 ) . RESULTS The following mean skeletal and occlusal changes occurred from the class III starting point to DC3 ( 3-year follow-up ) : SNA , PFG moved forwards + 2·3 ° ( CG forward + 1·6 ° ; P = 0·14 ) ; SNB , PFG moved forwards + 0·8 ° ( CG forward + 1·5 ° , P = 0·26 ) ; ANB , PFG class III base improved + 1·5 ° ( CG stayed about the same at + 0·1 ° ; P = 0·001 ) . This contributed to an overall difference in ANB between PFG and CG of + 1·4 ° in favour of early protraction facemask treatment . The overjet was still improved by + 3·6 mm in the PFG and changed a small amount + 1·1 mm in the CG ( P = 0·001 ) . A 21 % improvement in PAR was shown in the PFG and the CG worsened by 8·4 % ( P = 0·02 ) . There was no increase in self-esteem ( Piers-Harris score ) for PFG compared with the CG ( P = 0·56 ) and no statistically significant difference in the impact of malocclusion ( OASIS ) between groups in terms of the changes from DC1 to DC3 ( P = 0·18 ) . TMJ signs and symptoms were very low at DC1 and DC3 . CONCLUSIONS The favourable effect of early class III protraction facemask treatment undertaken in patients under 10 years of age , is maintained at 3-year follow-up in terms of ANB , overjet and % PAR improvement . The direct protraction treatment effect at SNA is still favourable although not statistically significantly better than the CG . Seventy per cent of patients in PFG had maintained a positive overjet which we have defined as ongoing treatment success . Early protraction facemask treatment does not seem to influence self-esteem or reduce the patient 's personal impact of their malocclusion at 3-year follow-up INTRODUCTION The objective of this 3-arm parallel r and omized clinical trial was to compare the effectiveness of temporary anchorage devices ( TADs ) , Nance button palatal arches , and headgear for anchorage supplementation in the treatment of patients with malocclusions that required maximum anchorage . This trial was conducted between August 2008 and February 2013 in 2 orthodontic departments in the United Kingdom . METHODS The study included 78 patients ( ages , 12 - 18 years ; mean age , 14.2 years ) who needed maximum anchorage . Eligibility criteria included no active caries , exemplary oral hygiene , and maximum anchorage required . OUTCOME The primary outcome was mesial molar movement during the period in which anchorage supplementation was required . The secondary outcomes were duration of anchorage reinforcement , number of treatment visits , number of casual and failed appointments , total treatment time , dento-occlusal change , and patients ' perceptions of the method of anchorage supplementation . R AND OMIZATION Treatment allocation was implemented by contacting via the Internet the r and omization center at the University of Nottingham , Clinical Trials Unit . The r and omization was based on a computer-generated pseudo-r and om code with r and om permuted blocks of r and omly varying size . BLINDING A research assistant who was blinded to the group allocation recorded all data . INTERVENTION The patients were r and omly allocated to receive anchorage supplementation with TADs , a Nance button on a palatal arch , or headgear . They were all treated with maxillary and m and ibular preadjusted edgewise fixed appliances with 0.022-in slot prescription brackets . They were followed until orthodontic treatment was complete . RESULTS Seventy-eight patients were r and omized in a 1:1:1 ratio among the 3 groups . The baseline characteristics were similar in the groups , and they were treated for an average of 27.4 months ( SD , 7.1 months ) ; 71 completed orthodontic treatment . The data were analyzed on a per- protocol basis and showed no differences in the effectiveness of anchorage supplementation between TADs , Nance button palatal arches , and headgear . Compared with headgear , the average mesial movements of the maxillary right molar were 0.62 mm ( -0.32 to 1.55 mm ) with the Nance and -0.58 mm ( -1.53 to 0.36 mm ) with TADs ; the maxillary left molar was moved -0.09 mm ( -1.00 to 0.83 mm ) with the Nance and -0.96 mm ( -1.89 to -0.04 mm ) with the TADs . Peer assessment rating scores were significantly better with the TADs than in the headgear and Nance groups . The patient question naires showed that comfort levels on placement of the TADs and the Nance were similar . Headgear was more troublesome and less popular with the patients . CONCLUSIONS There was no difference in the effectiveness between the 3 groups in terms of anchorage support . There were more problems with the headgear and Nance buttons than with the TADs . The quality of treatment was better with TADs . As a result , TADS might be the preferred method for reinforcing orthodontic anchorage in patients who need maximum anchorage . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00995436 . PROTOCOL The protocol was published on the above site before the trial commencement . FUNDING The British Orthodontic Society Foundation funded the study and American Orthodontics provided all the TADs and associated equipment Objective To determine if the extraction s of lower primary canines are an effective procedure to relieve crowding of the labial segment . Study design r and omized controlled trial . Subject sample 83 cases were collected in clinics in Italy , Germany and Wales . The groups were followed over a 2-year period . Method Subjects were r and omly allocated to a primary canine non- extraction or extraction group . Dental casts of the patients were collected at the start and at the recall period of the trial . The outcome measures recorded were lower incisor crowding , arch length , intermolar width , overbite , overjet , lower clinical crown heights and lower incisor inclinations . Statistics The Mann – Whitney test was used to compare the differences between the extraction and non- extraction groups . Results In both groups , crowding reduced 1.27 mm in the non- extraction group and 6.03 mm in the extraction group . The difference between the 2 groups was 4.76 mm ( P<0.05 ) . The arch perimeter decreased more in the extraction group by 2.73 mm ( P<0.05 ) . As the incisor inclination stayed essentially the same , the loss in arch length was attributed to the molars moving forward . The net gain from extracting deciduous canines was 2.03 mm . Conclusions There was a reduction in lower incisor crowding as a result of lower primary canine extraction . However , arch perimeter decreased more in the extraction group leaving less space for the eruption of the lower secondary canines Both r and omized and nonr and omized studies are integral to orthodontic research and practice because they permit evaluation of relationships between exposures and outcomes , allowing the efficacy , effectiveness , and safety of interventions to be assessed . These design s allow clinical decisions to be informed . Nonr and omized design s include nonr and omized clinical trials , cohort studies , case-control studies , cross-sectional studies , case series , and ecological studies . There is debate surrounding the optimal research design ; however , both r and omized and nonr and omized design s are important to build a broad , informative evidence base . The design s are therefore complementary , with unique advantages and limitations . The applicability of either approach hinges on the clinical question posed , the feasibility of study ing it , and ethical considerations Early treatment for Class II malocclusion is frequently undertaken with the objective of correcting skeletal disproportion by altering the growth pattern . Because the majority of previous studies of growth modification for Class II malocclusion have been based on retrospective record review s , the efficacy of such an approach has not been well established . In this controlled clinical trial , patients in the mixed dentition with overjet > or = 7 mm were r and omly assigned to either early treatment with headgear , or modified bionator , or to observation . All patients were observed for 15 months with no other appliances used during this phase of the trial . The three groups , who were equivalent initially , experienced statistically significant differences ( p < 0.01 ) in skeletal change . There was considerable variation in the pattern of change within all three groups , with about 80 % of the treated children responding favorably . Although patients in both early treatment groups had approximately the same reduction in Class II severity , as reflected by change in the ANB angle , the mechanism of this change was different . The headgear group showed restricted forward movement of the maxilla , and the functional appliance group showed a greater increase in m and ibular length . The permanence of these skeletal changes and their impact on the subsequent treatment remains to be evaluated The aims of this project were to evaluate whether early orthodontic treatment with the Twin-block appliance for the developing Class II Division 1 malocclusion result ed in any psychosocial benefits . This multicenter trial was carried out in the United Kingdom , with 174 children aged 8 to 10 years with Class II Division 1 malocclusions r and omly allocated to receive treatment with Twin-block appliances or to an untreated control group . Data were collected at the start of the study and 15 months later . Results showed that early treatment with Twin-block appliances result ed in an increase in self-concept and a reduction of negative social experiences . The subjects also reported treatment benefits that could be related to improved self-esteem . Further research is needed to determine the extent to which these effects translate into social behavior and experiences INTRODUCTION The objective of this study was to evaluate the long-term effectiveness in a group treated with the FR-2 appliance of Fränkel compared with an untreated Class II control group . METHODS The sample consisted of 30 patients ( 17 boys , 13 girls ) treated exclusively with the FR-2 by Rolf Fränkel . The mean age at the start of treatment was 8 years ( T1 ) , with a posttreatment cephalogram ( T2 ) taken 10 years later . The control group included 20 subjects ( 11 boys , 9 girls ) with untreated Class II malocclusion . Their mean ages at T1 and T2 , and the mean times of observation , matched the treatment group closely . Lateral cephalograms were analyzed with a specific tracing regimen at both T1 and T2 in both groups . The Student t test was used to compare changes between the groups RESULTS The FR-2 group maintained stable correction of the initial Class II malocclusion over the evaluation period . Significant m and ibular and intermaxillary changes and dentoalveolar changes were noted in the treated group , with a 3-mm long-term increase in m and ibular length compared with the untreated Class II controls . CONCLUSIONS This study suggests that correction of a Class II malocclusion with the FR-2 appliance maintains favorable results over the long term with both skeletal and dentoalveolar changes OBJECTIVE To test the null hypothesis that early headgear ( HG ) treatment has no effect on the eruption pattern of the maxillary canines in the early mixed dentition . MATERIAL S AND METHODS Sixty-eight children ( 40 boys and 28 girls ) with a Class II tendency in occlusion and moderate crowding of the dental arches were r and omized into two groups . HG treatment was initiated immediately in the first group . In the second group only minor interceptive procedures were performed during the first follow-up period of 2 years . Orthopantomograms were taken at the baseline , three times at 1-year intervals , and after growth at the age of 16 . Eruption geometry was performed . The space from the maxillary first molar to the lateral incisor was measured on the dental casts . RESULTS The inclination of the maxillary canine in relation to the midline appeared to be significantly more vertically oriented on the right side in the HG group 1 and 2 years after starting the HG therapy ( P = .0098 and P = .0003 , respectively ) . The inclination in relation to the lateral incisors was smaller in the HG group bilaterally after 1 year and 2 years of HG treatment , and on the right side after 3 years of treatment . CONCLUSION The hypothesis is rejected . Early HG treatment significantly affects the inclination of the maxillary canine during eruption . The strongest influence was seen after 2 years of HG use , more prominently in the right-side canine The aim of this study was to determine the long-term effects of early headgear ( HG ) treatment on craniofacial structures . The total study group comprised 68 children ( 40 males and 28 females ) aged 7.6 years ( st and ard deviation 0.3 years ) . The children , who had a Class II tendency in occlusion and moderate crowding , were r and omly divided into two groups of equal size . In the first group , HG treatment was initiated immediately . In the second group , which served as a control group , only minor interceptive procedures were performed during the first follow-up period of 2 years . During the 8 year follow-up , orthodontic therapy , including fixed appliances and possible extraction s , was carried out when necessary . The results showed that the most evident difference between the groups was the wider and longer dental arches in the HG group , which could only partly be explained by the higher rate of extraction s in the control group . For the cephalometric measurements , the most significant difference was in the maxillary plane orientation . The peer assessment rating ( PAR ) score , showing the general outcome of treatment , was at the same level in both groups at follow-up . The deficit of the early HG treatment was the longer mean total treatment time , result ing from the two-phase treatment INTRODUCTION A prospect i ve , controlled cohort study was started in 1998 to investigate the effects of orthodontic treatment in the early mixed dentition with the eruption guidance appliance . METHODS Occlusal changes were recorded in 167 treated children and 104 controls after they had reached the middle mixed-dentition stage . Treatment began when the first deciduous incisor was exfoliated ( T1 ) and ended when all permanent incisors and first molars were fully erupted ( T2 ) . The children 's mean ages were 5.1 years ( SD 0.5 ) at T1 and 8.4 years ( SD 0.5 ) at T2 . RESULTS From T1 to T2 , overjet in the treatment group decreased from 3.1 to 1.9 mm and overbite from 3.2 to 2.1 mm . In the control group , overjet increased from 2.9 to 4.1 mm and overbite from 3.3 to 4.1 mm . At T2 , the differences between the groups were highly significant ( P < .001 ) . At T1 , 18 % of the children in the treatment group and 22 % of the controls had tooth-to-tooth contact between the maxillary and m and ibular incisors . All others had an open bite , or the m and ibular incisors were in contact with the palatal gingiva . At T2 , tooth-to-tooth contact was observed in 99 % of the treated children and 24 % of the controls ( P < .001 ) . Almost half of children in both groups showed incisor crowding at T1 . Good alignment of the incisors was observed in 98 % of the treated children at T2 , whereas maxillary crowding was found in 32 % and m and ibular crowding in 47 % of the controls ( P < .001 ) . At T1 , 41 % of the children in the treatment group and 53 % of the controls had a Class I relationship ; the rest had either a unilateral or a bilateral Class II relationship . At T2 , a Class I relationship was found in 90 % of the treated children and 48 % of the controls ( P < .001 ) . At least 1 occlusal deviation , including overjet > or = 5 mm , overbite > or = 5 mm , open bite , gingival contact of the m and ibular incisors , crowding , or Class II relationship , was observed in 13 % of the treated children , but the deviations were mild , and no child was considered to need treatment . In the control group , 88 % of the children showed at least 1 occlusal deviation ( P < .001 ) . CONCLUSIONS Treatment in the early mixed dentition with the eruption guidance appliance is an effective method to restore normal occlusion and eliminate the need for further orthodontic treatment . Only a few spontaneous corrective changes can be expected without active intervention This study investigated incisor trauma in children with overjets greater than or equal to 7 mm who were enrolled in a clinical trial of 2-phase early orthodontic treatment for Class II malocclusion . In phase 1 , children were r and omly assigned to treatment in the mixed dentition with either modified bionator or combination headgear or to a group in which treatment was delayed until the permanent dentition . All children received comprehensive treatment during phase 2 if necessary . At the start of the trial , 29.1 % of the patients had already had some incisor trauma . This was not significantly related to dental developmental age . During the trial , there was an increase in trauma in all 3 groups , but the magnitude of this increase was not significantly greater in the group for which treatment was delayed until the permanent dentition . This might suggest that orthodontic intervention aim ed at reducing trauma should begin very soon after the eruption of the maxillary incisors . However , the injuries tended to be minor , and the expected cost of treatment related to incisor trauma was small compared with the expected additional cost of a 2-phase orthodontic intervention This study evaluated the effectiveness of early orthodontic treatment with the Twin-block appliance for the developing Class II Division 1 malocclusion . This multicenter trial was carried out in the United Kingdom . A total of 174 children , aged 8 to 10 years old , with Class II Division 1 malocclusion were r and omly allocated to receive treatment with a Twin-block appliance or to an untreated , control group . Data were collected at the start of the study and 15 months later . Results showed that early treatment with Twin-block appliances result ed in reduction of overjet , correction of molar relationships , and reduction in severity of malocclusion . Most of this correction was due to dentoalveolar change , but some was due to favorable skeletal change . Early treatment with the Twin-block appliance is effective in reducing overjet and severity of malocclusion . The small change in the skeletal relationship might not be considered clinical ly significant INTRODUCTION The purpose of this longitudinal r and omized investigation was to determine the long-term changes in the soft-tissue profile during orthodontic treatment when treatment is started with headgear ( HG ) in the early mixed dentition . METHODS The subjects were 68 children ( 28 girls , 40 boys ; mean age , 7.6 years ; SD , 0.3 years ) with a Class II tendency in occlusion and moderate crowding . They were r and omly divided into 2 groups . In the HG group , treatment began immediately . No other appliances were used during the first 2 years . In the control group , only minor interceptive procedures were performed during the first follow-up period of 2 years . During the 8-year follow-up , orthodontic treatment , if needed , comprised fixed appliances and possible extraction s in both groups . Twenty linear and 5 angular soft-tissue measurements were registered from lateral cephalograms taken before treatment and after follow-up-periods of 2 , 4 , and 8 years . RESULTS The major findings were that , at the 8-year follow-up , the soft-tissue chin and the lower lip were significantly thicker , and the mentolabial sulcus was significantly deeper in the HG group than in the control group . In the control group , a larger variation in the upper lip position was found because of more extraction s in this group . CONCLUSIONS Early HG treatment has only a minor effect on the soft-tissue profile . The main effects are on the thickness of the soft-tissue chin and the contour of the lower lip . The differences were not otherwise significant during the long-term follow-up OBJECTIVE To test the applicability and effectiveness of interceptive orthodontics in a community field trial . DESIGN Prospect i ve screening for suitable malocclusions , implementation of treatment and analysis of outcomes 12 months later . SETTING Community dentistry in urban and rural areas of Northern Irel and , 1996 - 98 . SUBJECTS AND METHODS The initial sample consisted of 2002 children ( 1014 boys , 988 girls ) who were screened in routine community dental inspections . One thous and and sixty ( 523 aged 9 years , 537 aged 11 years ) were domiciled in the urban area of greater Belfast and 942 ( 479 aged 9 years , 463 aged 11 years ) in the rural area of Enniskillen and Omagh , Co. Tyrone . INTERVENTIONS Interceptive orthodontic treatment . OUTCOME MEASURES Dental health component of the Index of Orthodontic Treatment Need ( IOTN ) and specially devised local indices of treatment outcomes . RESULTS With the use of an interception gauge , orthodontic screening was included in the community dental inspections without difficulty . Thirty-three per cent of children were in need of interceptive treatment . Only 20 % of those in need both attended for recall and underwent treatment . Compliance was better in the rural area but the need , with particular reference to extraction of carious first molars , was greater in the urban area . The numbers of children in IOTN grade s 4 and 5 fell from 69 % at the beginning of the study to 42 % at the end . The outcome judged by local indices was 94 % in the range of complete success to minimal improvement with only 2 % showing deterioration . CONCLUSIONS One in three children screened in community dental inspections at age 9 and 11 years would benefit from interceptive orthodontics . Parents and children seem reluctant to accept offers of interceptive orthodontics and to having the treatment carried out . Among those complying fully , the interceptive measures are very successful . Not only does community interceptive orthodontics improve the condition being treated but also reduces the need for further treatment INTRODUCTION The purpose of this study was to evaluate the effect of early treatment on the stability of occlusion in patients with Class II malocclusions . The peer assessment rating ( PAR ) index was used to evaluate changes in occlusion after treatment of subjects treated in 1 phase or 2 phases . This study was a prospect i ve , r and omized , controlled clinical trial . METHODS Dental casts were obtained from the participants , who were r and omized into 3 phase-1 early treatment groups : bionator , headgear/bite plane , or observation . Phase 2 consisted of continued treatment of the bionator and the headgear/biteplane subjects and comprehensive treatment of the observation subjects . PAR scores were obtained for 208 subjects at end of treatment ; 173 ( 83 % ) had at least 1 follow-up visit , with a median follow-up time of 5.0 years . PAR scores were calculated for each subject at key treatment and posttreatment time points . Linear mixed-effect models were used to evaluate the impact of phase-1 treatment group , years posttreatment , end of treatment PAR score , and other covariates that could affect stability on the posttreatment PAR score . RESULTS Factors significantly affecting posttreatment PAR scores were PAR score at end of treatment ( P < .0001 ) , years posttreatment ( P = .0064 ) , and PAR score at the start of phase 2 . Although phase-1 treatment was not statistically significant , those with early treatment had lower PAR scores at the start of phase 2 than the observation subjects ( means [ SD ] : bionator 17.5 [ 7.4 ] , headgear/biteplane 15.3 [ 7.0 ] , observation 22.2 [ 8.6 ] , P < .0001 ) . Thus , early treatment had an indirect effect . CONCLUSIONS Factors that affect posttreatment PAR score stability include PAR score at the end of treatment , years posttreatment , and PAR score at the start of phase-2 treatment . The early treatment modalities have limited positive impact on posttreatment stability PAR scores in Class II malocclusion patients due to their effect on PAR scores at the start of phase-2 treatment The purpose of this investigation was to assess the long-term occlusal stability in a group treated early with headgear ( HG ) compared with a control group . The total study group comprised 68 children ( 40 males and 28 females ) aged 7.6 years ( st and ard deviation 0.3 ) , r and omly divided into two groups of equal size . In the first group , HG treatment was initiated immediately , while in the control group only minor interceptive procedures were performed during the follow-up period . Fixed appliance treatment , if needed , including extraction of permanent teeth due to crowding , was undertaken after the completion of early treatment . The records were available from the start of the early treatment and at follow-up after 2 , 4 , 8 , and 13 years . The US-weighted Peer Assessment Rating ( PAR ) Index , grade d according to the severity of malocclusion , was used to evaluate occlusal stability . Little 's Irregularity Index ( LII ) and intercanine distance in the lower arch were measured at all time periods . The Aesthetic Component ( AC ) of the Index of Orthodontic Treatment Need ( IOTN ) scores was used for evaluation of dental aesthetics at the last follow-up . Parametric tests were applied for statistical analyses , except for the evaluation of aesthetics , where a non-parametric test was used . No significant differences were found when long-term stability between the HG and control groups was evaluated at the 13 year follow-up . Lower PAR scores were observed in patients treated without extraction of teeth . A greater irregularity in lower incisor alignment before treatment was found in subjects later treated with extraction s. The findings of this study seem to suggest that treatment timing has only a minor influence on stability INTRODUCTION The purpose of this controlled r and omized clinical trial was to quantify the effects of maxillary protraction with or without palatal expansion . METHODS Forty-six children aged 5 to 10 years were r and omly assigned to 1 of 3 groups : ( 1 ) facemask with palatal expansion , ( 2 ) facemask without palatal expansion , and ( 3 ) observation for 12 months . Cephalometric analysis with traditional cephalometric measurements , an x-y coordinate system , and an occlusal-plane analysis were used . RESULTS Student t tests showed no significant differences ( P < .05 ) between expansion and nonexpansion groups in any measured variable . Comparisons of treated and control subjects showed significant ( P < .01 ) treatment effects beyond normal Class III growth . Analysis of x-y coordinate variables showed the following : 2 mm additional forward displacement of the maxillary complex with counterclockwise rotation , m and ibular clockwise rotation , posterior movement of B-point by an average of 1.5 mm , and forward movement of the maxillary dentition of nearly 1 mm . Analysis of traditional cephalometric measures showed improvements in ANB angle of nearly 4 degrees and Wits appraisal of nearly 4 mm . The occlusal plane analysis showed an apical base change of 4 mm , 1.5 mm forward displacement of the maxillary complex , m and ibular clockwise rotation of 2.5 mm , and forward maxillary molar movement of 1.9 mm . CONCLUSIONS The results of this continuing 5-year clinical trial indicate that early facemask therapy , with or without palatal expansion , is effective to correct skeletal Class III malocclusions INTRODUCTION From an evidence -based point of view , correction of posterior crossbite is not sufficiently evaluated . Thus , the aims of this study were to compare and evaluate the effectiveness of different treatment strategies to correct unilateral posterior crossbite in the mixed dentition by using the r and omized clinical trial methodology with an untreated control group . METHODS Sixty patients participated in the study . All met the following inclusion criteria : mixed dentition , unilateral posterior crossbite , no sucking habits , and no previous orthodontic treatment . The patients were r and omized into 4 groups : quad-helix , expansion plate , composite onlay , and untreated control . The success rates , amounts of maxillary and m and ibular expansion , and treatment times were registered . RESULTS The quad-helix appliance was superior to the expansion plate in success rate and treatment time . Treatment with the expansion plate was unsuccessful in one third of the subjects . Crossbite correction with composite onlay in the mixed dentition was ineffective , and spontaneous correction in the mixed dentition did not occur . CONCLUSIONS If unilateral posterior crossbite is planned to be corrected in the mixed dentition , this study clearly confirmed that treatment with the quad-helix is an appropriate and successful method This study evaluated the effectiveness of two interceptive approaches to palatally displaced canines ( PDC ) , i.e. extraction of the primary canines alone or in association with the use of a cervical-pull headgear . The r and omized prospect i ve design comprised 75 subjects with PDC ( 92 maxillary canines ) who were r and omly assigned to three groups : extraction of the primary canine only ( EG ) , extraction of the primary canine and cervical-pull headgear ( EHG ) , and an untreated control group ( CG ) . Panoramic radiographs were evaluated at the time of initial observation ( T1 ) and after an average period of 18 months ( T2 ) . At T2 , an evaluation of the success of canine eruption was undertaken . Between-group statistical comparisons , Kruskal-Wallis test with Bonferroni correction , were performed on the T1-T2 changes of the diagnostic parameters on panoramic radiographs and the prevalence rates of success in canine eruption . A superimposition study on lateral cephalograms at T1 and T2 was carried out to evaluate the changes in the sagittal position of the upper molars in the three groups . The removal of the primary canine as an isolated measure to intercept palatal displacement of maxillary canines showed a success rate of 65.2 per cent , which was significantly greater than that in the untreated controls ( 36 per cent ) . The additional use of a headgear result ed in successful eruption in 87.5 per cent of the subjects , with a significant improvement in the measurements for intraosseous canine position . The cephalometric superimposition study showed a significant mesial movement of the upper first molars in the CG and EG when compared with the EHG The purpose of this study was to investigate the effects of the maxillary protractor bow appliance ( MPBA ) on dentoalveolar structure and skeletal morphology in patients with Class III malocclusions in different dental stages . The sample consisted of 63 treated and 57 untreated Japanese patients who all had anterior crossbites . The former group was treated with MPBA and included 34 subjects with deciduous dentition ( DT group ) and 29 subjects with early mixed dentition ( MT group ) . In the DT group , MPBA was used over a mean period of 5 months to obtain positive overjet , and , in the MT group , MPBA was used over a mean period of 10 months identically . Analysis of variance with 3 factors ( appliance , treatment stage , sex ) between treated and untreated subjects and unpaired t tests between DT and MT groups were performed from 2 lateral cephalograms before and after treatment to compare the dentofacial changes . The mechanisms of improving anterior crossbite were similar in both groups ; however , the mean skeletal and dentoalveolar changes in the DT group were significantly greater than those in the MT group . The clinical effects of MPBA treatment were greater in the deciduous-dentition group than in the early-mixed-dentition group OBJECTIVE To evaluate the effects of a Class III functional appliance [ the removable m and ibular retractor ( RMR ) ] in the early treatment of skeletal Class III deformities . SET-UP : R and omized controlled trial . SETTING Orthodontic Department , University of Al-Baath Dental School , Hamah , Syria . MATERIAL AND METHODS Sixty-seven skeletal Class III patients were recruited , distributed r and omly into two groups : 1 ) treatment group ( T ) with the RMR : 33 patients ( 17 males and 16 females ) with a mean age of 7.5 ± 1.33 years , 2 ) control group ( C ) : 34 patients ( 15 males and 19 females ) with a mean age of 7.3 ± 1.58 years . Lateral cephalograms were taken at the start of treatment ( T1-T ) or at the start of the observation period ( T1-C ) and after 14.5 ± 0.1 months ( both groups ) . Soft- and hard-tissue changes in both groups were evaluated . RESULTS The main significant findings in the treatment group were 1 ) anterior morphogenetic rotation of the m and ible as a result of upward and forward condylar growth ; 2 ) significant increase in maxillary length ; 3 ) significant increase in maxillary dentoalveolar protrusion ; 4 ) significant decrease in m and ibular dentoalveolar protrusion ; 5 ) significant protrusion of the upper lip ; 6 ) significant retrusion of the lower lip ; and 7 ) significant reduction in nasolabial angle . CONCLUSION The RMR is an effective appliance in the treatment of skeletal Class III patients in the early mixed dentition in the short term The aim of the present study was to determine the effects of early headgear treatment on dental arches and craniofacial morphology in children in the early mixed dentition . The total study group comprised 68 children of both sexes ( 40 boys and 28 girls ) aged 7.6 years [ st and ard deviation ( SD ) 0.3 ] . The children , who had a Class II tendency in occlusion and moderate crowding of the dental arches , were r and omly divided into two groups of equal size , matched according to gender . In the headgear ( HG ) group , treatment was initiated immediately . The mean treatment time was 16 months . In the second group , which served as the control , only interceptive procedures were performed during the follow-up period . The records , which included dental casts and lateral cephalograms , were obtained after follow-up periods of 1 and 2 years . The lengths and the widths of the maxillary and m and ibular dental arches were significantly increased in the HG group after the 2 year follow-up period . The mean increase in lower arch length and width was 2.4 mm ( SD 1.7 ) and 2.2 mm ( SD 1.2 ) , respectively . On average , the space gain in the lower arch was half that of the upper arch . No significant changes were found in the arch dimensions of the control group . Maxillary growth restraint and labial tilting of the incisors were the most significant cephalometric findings in the HG group when compared with the controls . The use of headgear in the early mixed dentition is effective in the treatment of moderate crowding . It is noteworthy that significant space gain in the dimensions of the lower arch can be achieved by headgear application to the upper first molars The aim of this prospect i ve r and omized clinical study was to cephalometrically investigate the dentoalveolar and soft tissue changes produced by a removable appliance with a palatal crib associated with high-pull chin cup therapy in children with an Angle Class I anterior open bite ( AOB ) malocclusion . Thirty children ( 8 males and 22 females ) with an initial mean age of 8.3 years and a mean AOB of 4.1 mm were treated with a removable appliance composed of a palatal crib associated with chin cup therapy for 12 months . A control group of 30 individuals ( 7 males and 23 females ) closely matched for age , initial mean age 8.6 years , gender , and ethnicity with a mean AOB of 4.6 mm was followed without treatment . The measurements ( means and st and ard deviations ) were statistically analysed using a paired t-test . The results showed no significant differences in the level of molar eruption or in lower anterior face height , suggesting that the vertical control expected from the chin cup therapy did not occur . Dentoalveolar changes at the anterior region were evident , with statistically significant extrusion , retrusion , and lingual tipping of the maxillary and m and ibular incisors ( P < or = 0.05 ) . However , these hard tissue changes did not imply soft tissue changes and the variables related to the soft profile were not statistically significantly different between the groups . The dentoalveolar changes at the anterior region of the dental arches were mainly responsible for closure of the AOB in patients treated in the mixed dentition The aim of this study was to determine the hard and soft tissue profile changes in Class III malocclusion subjects following functional regulator III ( FR-3 ) treatment . The material comprised the cephalometric films of 15 patients ( 11 males and four females ; mean ages 10.22 and 10.44 years , respectively ) with a Class III malocclusion and a concave profile treated with the FR-3 , and a control group of 15 subjects ( 11 males and four females ; mean ages 10.39 and 10.27 years , respectively ) with a Class I malocclusion matched for chronological age and observation period with the study group . Fourteen linear and seven angular measurements were measured on the cephalometric films taken before ( T1 ) and after ( T2 ) treatment/observation . The results of the Student 's t-test showed that the treatment group had a concave facial profile when compared with the controls . At the end of treatment , the maxilla and surrounding soft tissues showed significant anterior movement ( P < 0.001 and P < 0.01 , respectively ) , whereas m and ibular growth was restricted . The vertical dimensions increased , the upper incisors proclined , and the lower incisors retroclined significantly ( P < 0.001 ) . The FR-3 appliance produced significant improvements in the hard and soft tissues of Class III subjects with a concave profile Objective To investigate the effectiveness of early class III protraction facemask treatment in children under 10 years of age . Design Multicentre , r and omized controlled trial Setting Eight UK hospital orthodontic units . Subjects and methods Seventy‐three patients were r and omly allocated , stratified for gender , into an early class III protraction facemask group ( PFG ) ( n = 35 ) and a control/no treatment group ( CG ) ( n = 38 ) . Outcomes Dentofacial changes from lateral cephalograms and occlusal changes using the peer assessment rating ( PAR ) . Self‐esteem was assessed using the Piers – Harris children 's self‐concept scale , and the psychosocial impact of malocclusion with an oral aesthetic subjective impact scores ( OASIS ) question naire . Temporom and ibular joint ( TMJ ) signs and symptoms were also recorded . The time points for data collection were at registration ( DC1 ) and 15 months later ( DC2 ) . Results The following mean skeletal and occlusal changes occurred from the class III starting point : SNA , PFG moved forwards 1·4 ° ( CG forward 0·3 ° ; P = 0·018 ) ; SNB , PFG moved backwards −0·7 ° ( CG forward 0·8 ° ; P<0·001 ) ; ANB , PFG class III base improved + 2·1 ° ( CG worsened by −0·5 ° ; P<0·001 ) . This contributed to an overall difference in ANB between PFG and CG of 2·6 ° in favour of early protraction facemask treatment . The overjet improved + 4·4 mm in the PFG and marginally changed + 0·3 mm in the CG ( P<0·001 ) . A 32·2 % improvement in PAR was shown in the PFG and the CG worsened by 8·6 % . There was no increased self‐esteem ( Piers – Harris score ) for treated children compared with controls ( P = 0·22 ) . However , there was a reduced impact of malocclusion ( OASIS score ) for the PFG compared with the CG ( P = 0·003 ) , suggesting treatment result ed in slightly less concern about the tooth appearance . TMJ signs and symptoms were very low at DC1 and DC2 and none were reported during active facemask treatment . Conclusions Early class III orthopaedic treatment , with protraction facemask , in patients under 10 years of age , is skeletally and dentally effective in the short term and does not result in TMJ dysfunction . Seventy per cent of patients had successful treatment , defined as achieving a positive overjet . However , early treatment does not seem to confer a clinical ly significant psychosocial benefit In this study , the clinical effects of two extra-oral orthopaedic appliances were compared cephalometrically . Lateral cephalograms of 60 individuals were used in this investigation . The study group was r and omly divided into three parts as a ) control , b ) m and ibular headgear and c ) chin-cap groups . The subjects of the study group were selected among Class III , low angle or vertically normally growing individuals . The total observation period was one year . Results showed that both appliances were effective skeletally , but there were some differences between them . The results are as follows ; chin-cap therapy led to an inhibition in the development of the upper face and an effective control of the vertical dimension in addition to the posterior positioning of the m and ible . M and ibular headgear inhibited general growth and development of the m and ible and showed an increase in lower anterior face height and also , a significant lower molar distalization was found There is a growing recognition that insufficient attention has been paid to the selection of the outcomes to measure in clinical trials and clinical audit . Outcomes need to be relevant to patients , clinicians , purchasers and policy-makers if the findings of research are to influence practice and future research . In addition , st and ardization of outcomes is needed to combine data from different studies to allow evidence synthesis and to compare data sets . Inconsistent choice of outcome measures means that many meta-analyses are unable to include data from all the relevant studies . For example , the five most accessed Cochrane review s in 2009 , together with the top cited review in that year , all described inconsistencies in the outcomes reported in eligible trials . A call for the st and ardization of outcomes is a regular conclusion of systematic review s. Furthermore , outcome reporting bias , defined as the bias arising from selecting outcomes for publication based on the results , affects many r and omized trials and ‘ is an under-recognized problem that affects the conclusions in a substantial proportion of Cochrane review s ’ . That bias is likely to affect systematic review s more widely as well as affecting individual studies when considered on their own . Similar problems occur with clinical audit , highlighting the importance of establishing national audits that use and report the same outcomes for all participants . All these issues could be addressed with the development and application of agreed st and ardized sets of outcomes that have been termed ‘ core outcome sets ’ . These should be measured and reported , as a minimum , in all relevant clinical trials and national clinical audits for a specific condition . Adopting a core outcome set does not imply that a particular study , review or audit should be restricted to only those outcomes . Rather , the expectation is that , as a minimum , core outcomes will always be collected and reported to allow the results of trials to be compared , contrasted and combined as appropriate . The adoption of core outcomes would have implication s across all areas of research in health and health care , reduce heterogeneity between trials , and lead to research that is more likely to have measured relevant outcomes . Importantly , they would enhance the value of evidence synthesis by reducing the risk of outcome reporting bias and ensuring that all trials contribute usable information . In addition , they will increase the efficiency and value of research . An important rationale for core outcome sets is that outcomes currently reported for trials do not consistently reflect endpoints that are meaningful for patients . Examples exist where trials failed to include all outcomes important to patients and where involvement of patients has identified an outcome that might not have been considered by practitioners on their own . Despite increasing recognition of the importance of incorporating patients ’ opinions , their involvement has been limited . Recent regulatory guidance in the USA requires documented evidence of patient input during the development of instruments to measure patient reported outcomes ( PROs ) . However , measurement of PROs in clinical trials is hampered by the multiplicity and heterogeneity of tools currently available . Many generic , disease and domain-specific instruments have been developed and vali date d , each containing multiple scales and items . As a result , synthesis of PRO data from trials is difficult and review s aim ing to summarize treatment effect according to PROs may fail . There is synergy between the development of core outcome sets for trials and work to select up to seven outcomes that are important to patients for inclusion in Summary of Findings tables in systematic review s. Developed by the GRADE group ( http://www . grade workinggroup.org ) , Cochrane review s have featured such tables since 2008 , and they play a key role in presenting research in guidelines , such as those produced by the World Health Organization ( WHO ) . The development of core outcome sets needs to be accelerated and undertaken in ways that maximize efficiency . The COMET ( Core Outcome Measures in Effectiveness Trials , http://www.comet-initiative.org ) Initiative in the UK brings together research ers interested in the development and application of core outcome sets . These include key participants in a collaboration of research ers in rheumatology who have done the most notable work to date in this area . The COMET Initiative was launched in January 2010 , with a second meeting in July 2011 . Attendees included trialists , systematic review ers , patients , clinicians , journal editors , research funders , policy-makers , people responsible for trials registries and regulators . Data on individual studies , both published and ongoing , are being included in a free , publically available internet-based re source . This will be up date d periodically , to minimize the risk of duplication . Seventy-eight published or ongoing studies have already been entered into the repository . In addition , published review s of outcomes used in clinical trials or studies examining patients ’ views , will be entered INTRODUCTION The long-term stability of posterior crossbite correction in the mixed dentition has not been sufficiently evaluated . Our aim was to compare long-term outcomes in patients with crossbite correction by using matched controls with normal occlusion . METHODS After 35 patients were treated for crossbite with a quad-helix or an expansion plate , we used r and omized controlled trial methodology to follow them for 3 years posttreatment . All had fulfilled our pretreatment criteria : mixed dentition , unilateral posterior crossbite , no sucking habits , and no previous orthodontic treatment . Transverse relationships , maxillary and m and ibular widths , overbite , overjet , arch lengths , and midlines were registered on the study models immediately before and after treatment and at the follow-up 3 years after treatment . The matched control group comprised 20 subjects with normal occlusion and was compared with the first and last registration s for the treated groups . RESULTS At follow-up , changes in the treatment groups were equal and stable . The changes were comparable with the control group . All other changes were minor and had no clinical implication s. The long-term effect of crossbite correction on midline deviation was unpredictable . CONCLUSIONS If crossbite is successfully corrected by the quad-helix appliance or the expansion plate , similar long-term stability is achieved . However , in treated patients , mean maxillary widths never reached those of normal control subjects OBJECTIVES To identify the timing of significant arch dimensional increases during orthodontic alignment involving round and rectangular nickel-titanium ( NiTi ) wires and rectangular stainless steel ( SS ) . A secondary aim was to compare the timing of changes occurring with conventional and self-ligating fixed appliance systems . METHODS In this non- primary publication , additional data from a multicenter r and omised trial initially involving 96 patients , aged 16 years and above , were analysed . The main pre-specified outcome measures were the magnitude and timing of maxillary intercanine , interpremolar , and intermolar dimensions . Each participant underwent alignment with a st and ard Damon ( Ormco , Orange , CA ) wire sequence for a minimum of 34 weeks . Blinding of clinicians and patients was not possible ; however , outcome assessors and data analysts were kept blind to the appliance type during data analysis . RESULTS Complete data were obtained from 71 subjects . Significant arch dimensional changes were observed relatively early in treatment . In particular , changes in maxillary inter-first and second premolar dimensions occurred after alignment with an 0.014 in . NiTi wire ( P<0.05 ) . No statistical differences in transverse dimensions were found between rectangular NiTi and working SS wires for each transverse dimension ( P>0.05 ) . Bracket type had no significant effect on the timing of the transverse dimensional changes . CONCLUSIONS Arch dimensional changes were found to occur relatively early in treatment , irrespective of the appliance type . Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed . CLINICAL SIGNIFICANCE On the basis of this research orthodontic expansion may occur relatively early in treatment . Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed |
11,338 | 29,609,585 | Results Limited evidence provided by a small number of RCTs , and evidence from observational studies of moderate method ological quality , suggest that free-living PA of between one and 21 years ’ duration improves measures of balance in older healthy community-dwelling adults .
Statistical analysis of observational studies found significant effects in favour of more active groups for neuromuscular measures such as gait speed ; functionality using Timed Up and Go , Single Leg Stance , and Activities of Balance Confidence Scale ; flexibility using the forward reach test ; and strength using the isometric knee extension test and ultrasound .
A significant effect was also observed for less active groups on a single sensory measure of balance , the knee joint repositioning test . | Background Poor balance is associated with an increased risk of falling , disability and death in older population s. To better inform policies and help reduce the human and economic cost of falls , this novel review explores the effects of free-living physical activity on balance in older ( 50 years and over ) healthy community-dwelling adults . | Background Diminished control of st and ing balance , traditionally indicated by greater postural sway magnitude and speed , is associated with falls in older adults . Tai Chi ( TC ) is a multisystem intervention that reduces fall risk , yet its impact on sway measures vary considerably . We hypothesized that TC improves the integrated function of multiple control systems influencing balance , quantifiable by the multi-scale “ complexity ” of postural sway fluctuations . Objectives To evaluate both traditional and complexity-based measures of sway to characterize the short- and potential long-term effects of TC training on postural control and the relationships between sway measures and physical function in healthy older adults . Methods A cross-sectional comparison of st and ing postural sway in healthy TC-naïve and TC-expert ( 24.5±12 yrs experience ) adults . TC-naïve participants then completed a 6-month , two-arm , wait-list r and omized clinical trial of TC training . Postural sway was assessed before and after the training during st and ing on a force-plate with eyes-open ( EO ) and eyes-closed ( EC ) . Anterior-posterior ( AP ) and medio-lateral ( ML ) sway speed , magnitude , and complexity ( quantified by multiscale entropy ) were calculated . Single-legged st and ing time and Timed-Up– and -Go tests characterized physical function . Results At baseline , compared to TC-naïve adults ( n = 60 , age 64.5±7.5 yrs ) , TC-experts ( n = 27 , age 62.8±7.5 yrs ) exhibited greater complexity of sway in the AP EC ( P = 0.023 ) , ML EO ( P<0.001 ) , and ML EC ( P<0.001 ) conditions . Traditional measures of sway speed and magnitude were not significantly lower among TC-experts . Intention-to-treat analyses indicated no significant effects of short-term TC training ; however , increases in AP EC and ML EC complexity amongst those r and omized to TC were positively correlated with practice hours ( P = 0.044 , P = 0.018 ) . Long- and short-term TC training were positively associated with physical function . Conclusion Multiscale entropy offers a complementary approach to traditional COP measures for characterizing sway during quiet st and ing , and may be more sensitive to the effects of TC in healthy adults . Trial Registration Clinical Trials.gov Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This work analyses the short-term physiological and neurophysiological effects of a brisk walking programme in ageing , healthy , active men . Twenty-one men 63 to 72 years of age were recruited and separated into 2 groups . One group performed a walking programme ( WP ) ( n = 11 ) and another served as control ( C ) group ( n = 10 ) . The walking programme lasted for twelve weeks and included five sessions per week . Several parameters were assessed before and after the programme for the WP group . The same tests were performed ( separated by twelve weeks ) in group C. During each assessment , the subjects were put through static and dynamic balance tests , spatio-temporal gait analysis , body composition measurements and determination of aerobic capacity and bone mineral density . The statistic analysis showed a significant improvement in dynamic balance performance , especially in lateral sway when the subjects kept their eyes open , an increase of VO(2 ) max and loss of fat mass in the WP group . However , no alterations appeared in spatiotemporal gait characteristics , static balance performance , lean mass or bone mineral density ( total body and hip ) . According to these results , this walking programme may have positive effects on preventing ageing subjects from falling BACKGROUND Taiji ( T'ai Chi ) has been shown to have generally positive effects on functional balance . However , few studies have investigated the mechanisms by which Taiji may improve balance . The goal of this study was to evaluate changes in sensory and biomechanical balance mechanisms as a consequence of a traditional Taiji exercise program for healthy older adults that intentionally emphasized both Taiji forms and Qigong meditation . MATERIAL / METHODS This was a r and omized controlled trial with blind testers . Forty-nine healthy older adults ( mean age 80.4 , SD . 8.6 ) were r and omized to participate in Taiji-Qigong ( TQ ) training ( N=33 ) or a wait-list control group ( WC , N=16 ) . TQ instruction was provided 1 hour/session , 3 sessions a week for six months . Somatosensory , visual , and vestibular ratios of the Sensory Organization Test , and quiet stance Base of Support ( BoS ) and feet opening angle measures were collected prior to instruction ( T0 ) , at two months ( T2 ) , and six months ( T6 ) . RESULTS TQ group vestibular ratio scores ( normalized to T0 ) were + 22 % and + 47 % greater than WC at T2 and T6 , respectively . The TQ group exhibited an increase in quiet stance BoS over time but not feet opening angle , indicating that the increase in BoS was due to the adoption of wider stances . CONCLUSIONS Improved use of vestibular input and wider stances are two mechanisms by which Taiji-Qigong training may improve healthy older adults ' balance . Further study is needed to evaluate other balance mechanisms and the individual and combined effects of different aspects of traditional Taiji practice The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered BACKGROUND Balance disorders increase considerably with age due to a decrease in posture regulation quality , and are accompanied by a higher risk of falling . Conversely , physical activities have been shown to improve the quality of postural control in elderly individuals and decrease the number of falls . The aim of this study was to evaluate the impact of two types of exercise on the visual afferent and on the different parameters of static balance regulation . METHODS Static postural control was evaluated in 44 healthy women aged over 60 years . Among them , 15 regularly practice d proprioceptive physical activities ( Group I ) , 12 regularly practice d bioenergetic physical activities ( Group II ) , and 18 controls walked on a regular basis ( Group III ) . RESULTS Group I participants displayed lower sway path and area values , whereas Group III participants displayed the highest , both in eyes-open and eyes-closed conditions . Group II participants displayed intermediate values , close to those of Group I in the eyes-open condition and those of Group III in the eyes-closed condition . Visual afferent contribution was more pronounced for Group II and III participants than for Group I participants . CONCLUSIONS Proprioceptive exercise appears to have the best impact on balance regulation and precision . Besides , even if bioenergetic activity improves postural control in simple postural tasks , more difficult postural tasks show that this type of activity does not develop a neurosensorial proprioceptive input threshold as well , probably on account of the higher contribution of visual afferent In a well-executed golf swing , golfers must maintain good balance and precise control of posture . Golfing also requires prolonged walking over uneven ground such as a hilly course . Therefore , repeated golf practice may enhance balance control and confidence in the golfers . The objective is to investigate whether older golfers had better balance control and confidence than non-golfing older , healthy adults . This is a cross-sectional study , conducted at a University-based rehabilitation center . Eleven golfers and 12 control subjects ( all male ; mean age : 66.2 ± 6.8 and 71.3 ± 6.6 years , respectively ) were recruited . Two balance control tests were administered : ( 1 ) functional reach test which measured subjects ’ maximum forward distance in st and ing ; ( 2 ) sensory organization test ( SOT ) which examined subjects ’ abilities to use somatosensory , visual , and vestibular inputs to control body sway during stance . The modified Activities-specific Balance Confidence ( ABC ) determined subject ’s balance confidence in daily activities . The golfers were found to achieve significantly longer distance in the functional reach test than controls . They manifested significantly better balance than controls in the visual ratio and vestibular ratio , but not the somatosensory ratio of the SOT . The golfers also reported significantly higher balance confidence score ratios . Furthermore , older adults ’ modified ABC score ratios showed positive correlations with functional reach , visual and vestibular ratios , but not with somatosensory ratio . Golfing is an activity which may enhance both the physical and psychological aspects of balance control . Significant correlations between these measures reveal the importance of the balance control under reduced or conflicting sensory conditions in older adults ’ balance confidence in their daily activities . Since cause- and -effect could not be established in the present cross-sectional study , further prospect i ve intervention design is warranted OBJECTIVES To compare the effects of short-term and long-term Tai Chi training on the sensorimotor and balance performance of able-bodied subjects . DESIGN A nonr and omized cross-sectional controlled trial . SETTING Sport laboratory . PARTICIPANTS Forty-eight healthy subjects , 16 with 3 months of experience in Tai Chi training , 16 with 1 to 3 years of experience in Tai Chi training , and 16 with no experience in Tai Chi training . INTERVENTION Experimental . MAIN OUTCOME MEASURES The reflex contraction latencies ( reaction time ) of medial hamstrings and gastrocnemius after perturbation , the active knee joint angle-repositioning error , and the balance time on a tilt board were measured and analyzed with 1-way analysis of covariance . Significant results were further analyzed with post hoc linear contrasts . RESULTS Long-term Tai Chi practitioners had a significantly faster reflex reaction time in hamstrings ( P<.000 ) and gastrocnemius ( P=.043 ) muscles and a longer balance time on a tilt board ( P<.000 ) than short-term Tai Chi practitioners and nonpractitioners . Both long- and short-term Tai Chi practitioners had significantly less knee joint angle-repositioning error than nonpractitioners ( P=.001 and P=.027 , respectively ) . CONCLUSIONS Tai Chi training of more than 1 year might have the benefits of faster hamstrings and gastrocnemius reflex reaction and improved knee joint position sense ( JPS ) . These changes might be associated with an improved dynamic st and ing balance . Better knee JPS was shown in subjects with 3 months of Tai Chi practice , but this had not led to a significant improvement in balance Background Evidence , mainly from cross-sectional studies , suggests that physical activity is a potentially important modifiable factor associated with physical performance and strength in older age . It is unclear whether the benefits of physical activity accumulate across life or whether there are sensitive periods when physical activity is more influential . Purpose To examine the associations of leisure-time physical activity across adulthood with physical performance and strength in midlife , and to test whether there are cumulative benefits of physical activity . Methods Using data on approximately 2400 men and women from the UK Medical Research Council National Survey of Health and Development , followed up since birth in March 1946 , the associations of physical activity levels during leisure time self-reported prospect ively at ages 36 , 43 , and 53 years with grip strength , st and ing balance , and chair rise times , assessed by nurses at age 53 years ( in 1999 ) , were examined in 2010 . Results There were independent positive effects of physical activity at all three ages on chair rise performance , and at ages 43 and 53 years on st and ing balance performance , even after adjusting for covariates . These results were supported by evidence of cumulative effects found when using structured life course models . Physical activity and grip strength were not associated in women and , in men , only physical activity at age 53 years was associated with grip strength . Conclusions There are cumulative benefits of physical activity across adulthood on physical performance in midlife . Increased activity should be promoted early in adulthood to ensure the maintenance of physical performance in later life OBJECTIVES To assess inter-rater reliability and validity of the Newcastle Ottawa Scale ( NOS ) used for method ological quality assessment of cohort studies included in systematic review s. STUDY DESIGN AND SETTING Two review ers independently applied the NOS to 131 cohort studies included in eight meta-analyses . Inter-rater reliability was calculated using kappa ( κ ) statistics . To assess validity , within each meta- analysis , we generated a ratio of pooled estimates for each quality domain . Using a r and om-effects model , the ratios of odds ratios for each meta- analysis were combined to give an overall estimate of differences in effect estimates . RESULTS Inter-rater reliability varied from substantial for length of follow-up ( κ = 0.68 , 95 % confidence interval [ CI ] = 0.47 , 0.89 ) to poor for selection of the nonexposed cohort and demonstration that the outcome was not present at the outset of the study ( κ = -0.03 , 95 % CI = -0.06 , 0.00 ; κ = -0.06 , 95 % CI = -0.20 , 0.07 ) . Reliability for overall score was fair ( κ = 0.29 , 95 % CI = 0.10 , 0.47 ) . In general , review ers found the tool difficult to use and the decision rules vague even with additional information provided as part of this study . We found no association between individual items or overall score and effect estimates . CONCLUSION Variable agreement and lack of evidence that the NOS can identify studies with biased results underscore the need for revisions and more detailed guidance for systematic review ers using the NOS PURPOSE Our previous studies showed that experienced Tai Chi practitioners had better joint proprioception and balance control during weight shifting . The objective of the present study was to examine whether experienced golfers had attained similar improvement when compared with the Tai Chi practitioners , as well as healthy elderly subjects and young university students . METHODS We compared 12 experienced elderly Tai Chi practitioners , with 11 experienced elderly golfers , 12 healthy elderly subjects , and 12 young university students , who were all males , using : 1 ) passive knee joint repositioning test to assess their joint proprioceptive acuity and 2 ) limits of stability test to assess their ability to voluntarily weight shift within their base of support . RESULTS Both Tai Chi practitioners and golfers had better knee joint proprioceptive acuity than did the elderly control subjects ( P < 0.05 ) . Of special interest is that their performance was similar to that of the young subjects . In the limits of stability test , Tai Chi practitioners and golfers had faster reaction time , leaned further without losing stability , and showed better control of leaning trajectory than did elderly control subjects ( all P < 0.05 ) . The latter two outcome measures were also comparable to those of the young subjects . CONCLUSION These results demonstrate that both experienced Tai Chi practitioners and golfers had improved knee joint proprioception and limits of stability , when compared with those of elderly control subjects similar in age , gender ( male ) , and physical activity level . Such improved outcome measures were comparable to those of young male subjects . These findings suggest that experienced Tai Chi practitioners and golfers had improved joint proprioceptive acuity and dynamic st and ing balance control , despite the known aging effects in these specific sensorimotor functions Background : Optimal patterns of habitual physical activity to ensure healthy aging remain unclear because of measurement limitations ; most investigators have used either subjective question naires , or accelerometer or pedometer measurements limited to a single week , despite evidence of both the limited reliability/validity of question naires and seasonal changes in activity patterns . Objective : This study explored possible associations between indicators of physical fitness ( walking ability , upper- and lower-extremity isometric strength , and static and dynamic balance ) and yearlong pedometer/accelerometer assessment s of the quantity and quality of habitual physical activity in ostensibly healthy older adults . Methods : Subjects were 76 male and 94 female Japanese aged 65–84 years . Each participant wore a pedometer/accelerometer for 1 year ; measurements included the average number of steps taken each day and the duration of activity at an intensity of > 3 metabolic equivalents ( METs ) . Compliance was good , the instrument being removed for intervals of > 3 h on < 5 % of days ; data for such intervals were excluded from analysis . At the year ’s end , traditional laboratory techniques assessed preferred and maximal walking speeds , peak h and grip force , peak knee extension torque , total body sway , and maximal functional reach . Results : After controlling data for age and /or sex , lower-extremity function ( walking speeds and knee extension torque ) showed significant positive relationships with the daily step count and daily duration of activity at > 3 METs , especially in individuals ≥75 years of age . On the other h and , h and grip force and body sway were unrelated to pedometer/accelerometer measurements . Linear and exponential regressions showed positive associations between walking speeds and pedometer/accelerometer scores up to the observed maxima of 13,700 steps/day and 62 min/day at > 3 METs . However , when data were categorized into quartiles , walking speeds were not significantly greater in persons exceeding 7,000–8,000 steps/day and /or 15–20 min/day at > 3 METs . With a few exceptions , subjects meeting these levels of habitual activity had walking speeds above the threshold predicting the development of functional dependence . Conclusion : The present data suggest that fitness is well maintained in elderly people who take > 7,000–8,000 steps/day and /or spend > 15–20 min/day at > 3 METs . Nevertheless , the direction of this association merits exploration by longitudinal prospect i ve studies and /or r and omized controlled trials |
11,339 | 24,283,358 | Topical PUVA and targeted UVB phototherapy are very effective in the treatment of localized psoriasis .
Topical PUVA seems more effective than non-laser targeted UVB phototherapy .
On the other h and , PDT has low efficacy and high percentage of side effects in treating localized psoriasis | Localized phototherapy including topical psoralen plus ultraviolet A ( PUVA ) and targeted ultraviolet B ( UVB ) , and photodynamic therapy ( PDT ) have been increasingly used in the treatment of localized psoriasis .
Yet , there are no systematic review s or meta-analyses that scientifically evaluated the pooled efficacy of these treatments in psoriasis . | We investigated the clinical response of 10 patients with plaque psoriasis to multiple treatments with photodynamic therapy , using topical application of 5-aminolaevulinic acid followed by exposure to broad-b and visible radiation . Treatment was performed up to 3 times per week , with a maximum of 12 treatments , using a light dose of 8 Jcm(-2 ) delivered at a dose-rate of 15 mW cm(-2 ) . Eight patients showed a clinical response . Out of 19 treated sites , 4 cleared , 10 responded but did not clear and 5 showed no improvement . Of the 4 sites that cleared only 1 did so fully , after 7 treatments , 45 days after the start of therapy . Of the 10 sites that responded partially , the greatest reduction in scale , erythema and in duration index occurred after a minimum of 3 and a maximum of 8 treatments . The intensity of 5-aminolaevulinic acid-induced protoporphyrin IX fluorescence , recorded prior to the first treatment , varied between sites on the same patient as well as between patients . There was also a variation in fluorescence intensity recorded from the same site immediately prior to subsequent treatments , although the pretreatment levels generally decreased as the study progressed and then increased as psoriasis relapsed . Biopsies confirmed that fluorescence was localized throughout the epidermis and stratum corneum , but the level was not consistent between sections taken within the same biopsy . We also observed fluorescence at sites distant from the ones that received 5-aminolaevulinic acid , which was not present prior to the start of the treatment programme , but found no evidence of elevated levels of plasma porphyrins . The level of discomfort associated with this therapy increased with increasing values of the calculated photodynamic dose , defined as the product of the initial photosensitizer concentration and the percentage reduction in fluorescence following irradiation . Therefore , although clinical efficacy improved with multiple treatments , unpredictable response and patient discomfort make ALA-PDT unsuitable for the treatment of psoriasis Summary Background The optimum treatment frequency for narrowb and ( TL‐01 ) ultraviolet B ( NB‐UVB ) in psoriasis is not yet known . We have previously found three times weekly to be preferable to five times weekly treatment in our population OBJECTIVE Our purpose was to demonstrate the efficacy of the 308-nm excimer laser for treatment of psoriasis . METHODS This study was a multicenter open trial from 5 dermatology practice s ( one university-based and 4 private practice s ) . Up to 30 patients per center with stable mild to moderate plaque-type psoriasis constituted the study population . Patients received 308-nm ultraviolet B doses to affected areas . The initial dose was based on multiples of a predetermined minimal erythema dose . Subsequent doses were based on the response to treatment . Treatments were scheduled twice weekly for a total of 10 treatments . The main outcome measure was 75 % clearing of the target plaque . Time to clearing was analyzed by Kaplan-Meier methods , accounting for truncated observations . RESULTS One hundred twenty-four patients were enrolled in the study , and 80 completed the entire protocol . The most common reason for exiting from the study was noncompliance . Of the patients who met the protocol requirements of 10 treatments or clearing , 72 % ( 66/92 ) achieved at least 75 % clearing in an average of 6.2 treatments . Eighty-four percent of patients ( 95 % confidence interval [ CI ] , 79%-87 % ) reached improvement of 75 % or better after 10 or fewer treatments . Fifty percent of patients ( 95 % CI , 35%-61 % ) reached improvement of 90 % or better after 10 or fewer treatments . Common side effects included erythema , blisters , hyperpigmentation , and erosions , but they were well tolerated . CONCLUSIONS Monochromatic 308-nm excimer laser treatment appears to be effective and safe for psoriasis . It requires fewer patient visits than conventional phototherapy , and , unlike those treatments , the laser targets only the affected areas of the skin , sparing the surrounding uninvolved skin Targeted broadb and ultraviolet B ( UVB ) phototherapy as well as 308-nm excimer laser have been reported to significantly improve or clear localized psoriatic plaques within 5 to 10 treatments when medium fluences [ i.e. 4 - 6 multiples of minimal erythema doses ( MED ) ] were used . Our study was conducted to determine the effects of different concentrations of topical 8-methoxypsoralen ( 8-MOP ) cream when used in combination with targeted UV phototherapy with regard to number of treatments and cumulative UV doses to clear localized psoriasis . Ten evaluable patients with stable plaque-type psoriasis completed the study . Three different concentrations of 8-MOP creams ( 0.001 % , 0.01 % and 0.1 % ) were applied prior to irradiation with 4 MEDs of targeted narrowb and UVB ( NB-UVB ) , whereas 0.001 % 8-MOP cream was used in conjunction with 5 J/cm(2 ) UVA . All irradiations took place once weekly for 12 weeks . Psoriasis severity index ( PSI ) score was used to evaluate the efficacy of the treatment . With area-under-the-curve analysis , 0.1 % 8-MOP/NB-UVB was superior to other modalities in reducing the PSI scores . The number of treatments and cumulative NB-UVB doses necessary to achieve PSI-95 , a 95 % reduction in the scores , was also lower in the 0.1 % 8-MOP/NB-UVB group , although the differences were not statistically significant . We conclude that topical 8-MOP cream enhances the therapeutic effects of targeted NB-UVB phototherapy without significantly increasing the short-term adverse effects BACKGROUND Ultraviolet radiation has been used for curative purpose s in dermatologic conditions , especially in the last 30 years . OBJECTIVES We analyzed the efficacy of monochromatic excimer light in psoriasis , palmoplantar pustulosis , vitiligo , mycosis fungoides and alopecia areata , and to examine potential new indications . METHODS Two hundred seventy-nine patients with common and persistent skin diseases were enrolled in an open prospect i ve study : 152 patients with stable and localized plaque psoriasis , 47 with palmoplantar psoriasis , 7 with palmoplantar pustulosis , 32 with vitiligo , 11 with prurigo nodularis , 9 with mycosis fungoides stage Ia , 8 with alopecia , 5 with localized scleroderma , 5 with genital lichen sclerosus , and 3 with granuloma annulare . The 308 nm excimer light was used at a power density of 48 mW/cm(2 ) . An average of 12 sessions ( range , 6 - 18 ) , one session per week , was performed and yielded a total dose range of 4 - 12.5 J/cm(2 ) . Clinical response was assessed using photos , biopsies , and specific clinical scores . Patients were monitorized for 6 and 12 months for psoriasis , 12 months for mycosis fungoides , and 4 months for the remaining conditions . RESULTS We observed complete remission in more than 50 % of patients with plaque psoriasis and palmoplantar dermatoses , respectively , complete remission in all patients affected by mycosis fungoides , excellent repigmentation in one third of vitiligo patients , hair regrowth in three patients with alopecia areata , an overall improvement in prurigo nodularis , a partial remission in patients affected by localized scleroderma , and a complete remission in most of the patients with genital lichen sclerosus and granuloma annulare . CONCLUSIONS Our study confirms the use of monochromatic excimer light as a valid choice for the treatment of psoriasis , vitiligo , and mycosis fungoides ; we also observed and report for the first time that monochromatic excimer light produces a therapeutic response in prurigo nodularis , localized scleroderma , genital lichen sclerosus , and granuloma annulare BACKGROUND Psoralen-UVA ( PUVA ) and narrowb and UVB ( 311-nm ) therapy are considered to be first-line phototherapies for patients with moderate to severe psoriasis . To reduce side effects as a result of systemic resorption of psoralens , topical PUVA therapies have been developed and proven to be effective in the treatment of psoriasis . OBJECTIVE We sought to evaluate the combination therapy of narrowb and UVB plus cream PUVA on selected psoriatic plaques compared with narrowb and UVB or cream PUVA alone . METHODS A total of 30 patients ( Psoriasis Area and Severity Index score of 8 - 15 ) were included in the r and omized study . The combination therapy consisting of narrowb and UVB whole-body irradiation followed by cream PUVA therapy for selected psoriatic plaques was evaluated in 10 patients with chronic plaque-stage psoriasis . For comparison , the therapeutic efficacy , number of treatments , and cumulative UV doses until remission ( Psoriasis Area and Severity Index score < 4 ) of cream PUVA therapy or narrowb and UVB alone was determined in 10 patients , respectively . RESULTS Both monotherapies induced clearance of psoriatic lesions in all patients within 5 to 7 weeks . Mean number of treatments for cream PUVA was 24 + /- 5 ; for narrowb and UVB was 21 + /- 3 . The mean cumulative UVA dose was 45.0 + /- 16.3 J/cm(2 ) and the mean cumulative UVB dose was 17.1 + /- 4.1 J/cm(2 ) . Combination therapy result ed in complete clearance of lesions in all patients after 3 to 4 weeks . Mean number of treatment was 14 + /- 2 , mean cumulative UVA dose was 18.7 + /- 4.7 J/cm(2 ) , and mean cumulative UVB dose was 8.2 + /- 3.3 J/cm(2 ) . The number of treatments ( P < .001 , analysis of variance ) , UVA dose ( P < .001 , t test ) , and UVB dose ( P < .001 , t test ) were significantly reduced compared with both monotherapies . CONCLUSIONS Our results indicate that a combination therapy of narrowb and UVB plus cream PUVA appears to have a significantly higher efficacy compared with either monotherapy . The cumulative UV doses were significantly lower in the combination therapy . We conclude that cream PUVA can be used in addition to narrowb and UVB for areas that tend to clear less quickly than the rest of the body Background : Phototherapy is an effective treatment for generalized plaque psoriasis , but is inconvenient and dosimetry is limited by the minimal erythema dose ( MED ) . Objective : This pilot study evaluated the efficacy , safety , and feasibility of excimer laser utilizing a supra-erythemogenic phototherapy strategy ( phototherapy well beyond the MED dose ) to treat generalized psoriasis . Methods : In this 9-month study , 13 patients with psoriasis involving > 10 % but < 30 % body surface area received laser treatment twice weekly for 12 weeks , with 6 months of post-treatment follow-up . The primary endpoint was percentage of patients achieving Psoriasis Area and Severity Index ( PASI ) 75 . Results : Of the 12 patients who completed the treatment phase , 54 % achieved PASI 75 . During the 6-month follow-up period 83 % maintained PASI 50 with no treatment . Limitations : This pilot study had a small sample size . Conclusion : The laser is an effective treatment with a favorable remission rate . With enhanced power in the near future , laser is likely to become more promising for generalized psoriasis Summary Topical photochemotherapy with psoralen and its derivatives 4.5′,8‐trimethylpsoralen ( TMP ) and 8‐methoxypsoralen ( 8‐MOP ) , with UVA irradiation , was evaluated with regard to minimum phototoxic dose , concentration , timing of UVA irradiation and systemic and local side‐effects , in healthy volunteers . Psoralen ( 0.005 % ) in aqueous gel was found to be superior to TMP and 8‐MOP in aqueous gel . No hyperpigmentation was seen after topical PUVA treatment with psoralen in aqueous gel . Patients with plaque‐type psoriasis ( n = 7 ) , palmoplantar psoriasis ( n = 7 ) and hyperkeratotic eczema ( n = 2 ) were treated . Topical PUVA therapy was effective in most psoriasis patients , without the occurrence of local or systemic side‐effects . Moreover , hyperkeratotic eczema patients who did not respond to conventional therapy showed partial remission . These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients , and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema PUVA-bath therapy has proven to avoid many side effects associated with oral 8-methoxypsoralen ( 8-MOP ) treatment . In order to investigate the effectiveness of topical PUVA-bath therapy ( PUVA-soak therapy ) on chronic palmoplantar dermatoses , 30 patients with plaque-type psoriasis , pustular psoriasis , endogenous eczema , dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP . No additional treatment except skin moisturising cream such as unguentum emulsificans aquosum was used during the study period . The single UVA-doses applied ranged from 0.3 to 3.0 J/cm2 ( mean single dose of 1.8 J/cm2 ) , with a mean cumulative dose of 48.6 J/cm2 per patient . Altogether 26 of 30 patients responded well within 8 weeks of treatment with 63 % of all patients showing a complete remission and 23 % showing considerable improvement , as shown by flattening of plaques , decreased scaling and erythema , as well as decreased vesicle and pustule formation . The condition responding best to our therapy was palmoplantar psoriasis followed by atopic eczema . Hyperkeratotic dermatitis displayed the poorest responding rates in this study . Unwanted side effects such as erythema , pain , blistering or patchy hyperpigmentation were not observed in any of the patients . We conclude that PUVA-soak therapy can be highly efficient in the treatment of palmoplantar dermatoses , especially in the management of palmoplantar psoriasis BACKGROUND / PURPOSE The aims of this study were to investigate the clinical and immunohistochemical events of psoriatic plaques during photodynamic therapy ( PDT ) using topical application of 5-aminolaevulinic acid ( ALA ) . METHODS Twelve psoriatic patients were recruited for this study . Four of them dropped out because of pain during treatment . The effect of PDT was evaluated in the remaining eight . One plaque was selected in each patient and treated once weekly with PDT 10 - 30 J/cm(2 ) two to five times . It was evaluated by using the scale , erythema and in duration ( SEI ) index ( maximal score per patient=9 ) . Pain during treatment was assessed by a visual analogue scale ( VAS ) , ranging from 0 to 10 . Skin biopsies were taken before treatment , after two treatments and after completion of treatment , and were evaluated by immunohistochemistry . RESULTS Median SEI scores were significantly reduced from 7 ( range 5 - 9 ) before to 1.5 ( range 0 - 3 ) following treatment ( P<0.0001 ) . The median pain during PDT was 7 . The number of vessels in the subpapillary dermis , identified by antibodies against Factor VIII and endoglin , increased during and /or after treatment in six of eight patients . Before treatment , the epidermal growth factor ( EGF ) receptor was displayed throughout the epidermis , keratin 16 suprabasally , involucrin from the stratum granulosum to the lower spinous layers and filaggrin in stratum granulosum with focal absence . There was a moderate dermal infiltrate of CD4(+ ) cells and a sparse one of CD8(+ ) . Following treatment , the EGF receptor was still displayed throughout the epidermis in seven of eight specimens . Cytokeratin 16 expression decreased markedly . Involucrin was not seen as deep in the spinous layers as before PDT . Filaggrin was expressed throughout the stratum granulosum and often weakly in the upper stratum spinosum . The number of CD4(+ ) and CD8(+ ) dermal cells decreased . CONCLUSION PDT improved psoriasis and induced dermal neovascularization . Although a good clinical response was seen in most of our patients , the high frequency of discomfort during treatment limits the usefulness of ALA-PDT for psoriasis . The mechanism of the neovascularization is unknown . It may be owing to an indirect effect of PDT on the microvasculature and immune system or recovery phenomena Background Excimer laser‐derived 308‐nm ultraviolet ( UV ) B therapy is a new alternative for treating psoriasis by phototherapy . Some studies have been made showing the effectiveness of intralesional phototherapy technology in treating psoriasis . However , there has been no information available so far with regard to the cumulative dosage on a larger group of patients and on therapy optimized treatment strategies Background Topical aminolaevulinic acid‐based photodynamic therapy ( ALA‐PDT ) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis Background : The excimer laser is a new therapeutic option in the treatment of psoriasis vulgaris . Objective : The purpose of this study was to determine the response of psoriasis lesions to the 308-nm excimer laser compared to 311-nm UVB phototherapy . Methods : In this prospect i ve right/left comparative , open , single-blinded trial , selected psoriasis plaques of 16 patients were treated with the excimer laser whereas the rest of the body was treated with UVB narrow-b and phototherapy . A modified PASI score was used to evaluate the results . Results : After 12 treatments , 15 patients were evaluated . In 2 patients no difference between the two body sides was observed . In 9 patients the laser-treated lesions showed better results , whereas in 4 patients the side treated with 311-nm UVB showed more clearing . The mean reduction in PASI score was 5.6 and 4.9 , respectively ( difference not significant ) . Conclusion : The use of the 308-nm xenon chloride excimer laser is an additional effective therapeutic option for the treatment of psoriasis vulgaris Background and objectives The excimer laser delivers high energy monochromatic ultraviolet ( UV ) B at 308 nm . Advantages over conventional UV sources include targeting of lesional skin , reducing cumulative dose and inducing faster clearance . Studies of the pulsed dye laser ( PDL ) in psoriasis report between 57 % and 82 % response rates ; remission may extend to 15 months . To our knowledge , this is the first study assessing both excimer and PDL in psoriasis Three and five times weekly narrow‐b and TL‐01 ( 311–313 nm ) ultraviolet ( UV ) B phototherapy regimens for chronic plaque psoriasis were compared in a r and omized , observer‐blinded , half‐body , within‐patient paired study . Twenty‐one patients [ 13 men , eight women , age range 21–68 years , skin phototypes I ( two patients ) , II ( 14 ) and III ( five ) ] entered the study . Sixteen reached clearance or minimal residual activity ( MRA ) on both sides . Of the other five , three withdrew because they did not reach clearance or MRA on the 5 × weekly side by a maximum of 30 treatments , one when he was satisfied with moderate improvement and one because of repeated failure to attend . Those who completed treatment reached clearance or MRA after a median of 35 days with 5 × weekly treatment compared with 40 days with 3 × weekly treatment ( P = 0.007 ) , but required a median of 23.5 compared with 17 UVB exposures ( P = 0.001 ) and 94 minimal erythema dose multiples ( MEDs ) compared with 64 MEDs ( P = 0.01 ) . Fifteen ( of 16 ) developed at least one episode of well‐demarcated erythema during 5 × weekly treatment compared with just three of 16 treated 3 × weekly ( P < 0.001 ) . There was no significant difference between regimens in duration of remission . For this skin phototype I – III population , the more rapid clearance of psoriasis with 5 × weekly phototherapy is not , for the majority of patients , sufficient to justify the extra exposures and higher UVB dose . We no longer use 5 × weekly phototherapy for psoriasis BACKGROUND Targeted ultraviolet ( UV ) phototherapy is a recent addition to the therapeutic armamentarium for the treatment of localized psoriasis . Topical psoralens enhance the therapeutic effects of UV-based treatment for various dermatoses , but have never been used in conjunction with targeted UVB . PURPOSE To compare the efficacy of targeted narrowb and UVB phototherapy ( NB-UVB ) alone with that of the combination of 0.1 % 8-methoxypsoralen cream and targeted NB-UVB phototherapy ( 8-MOP/NB-UVB ) for the treatment of plaque-type psoriasis . METHODS Two areas within the same lesion of stable psoriasis were r and omized to receive either targeted NB-UVB alone or 8-MOP/NB-UVB . Fluences of UVB delivered were held constant at four minimal erythema doses . The treatments were continued until lesions cleared or 12 treatments . Follow-ups were done until lesional scores returned to 50 % of the baseline values . RESULTS Ten patients completed this study . Four lesions were cleared by 8-MOP/NB-UVB while three were cleared by NB-UVB alone . The improvement in disease activity as reflected by psoriasis severity index score during treatment was statistically significantly better in the combination group ( P=0.005 ) . Mean remission time of lesions which were cleared by 8-MOP/NB-UVB was 8 weeks while that for lesions that were cleared by NB-UVB alone was 4.67 weeks . CONCLUSION We concluded that addition of 0.1 % 8-MOP cream to targeted narrowb and UVB significantly enhances the therapeutic effects of the light treatment without increasing the incidence of adverse effects Nonlaser localized narrowb and ( 290 - 315 nm ) UVB phototherapy was tested in 10 subjects with localized psoriasis . Treatments were given 2 to 3 times weekly . Four patients did not complete the planned 25-treatment course . Of the remaining 6 patients , all reached greater than 90 % clearing of their disease . Localized nonlaser UVB phototherapy is another option for the treatment of localized psoriasis Palmoplantar psoriasis is a chronic disease , which is very resistant to treatment and often leads to severe disabilities . Photochemotherapy employing psoralens combined with UVA irradiation ( PUVA ) is a well-accepted therapy for palmoplantar psoriasis . Its topical application ( bath PUVA ; cream PUVA ) avoids the typical side effects of orally applied psoralens . We compared the efficacy of cream PUVA therapy with monochromatic excimer light therapy , a treatment modality employing 308-nm UVB radiation generated by a new kind of light source . Ten patients with psoriasis of the palms and soles were r and omly assigned to receive cream PUVA on one side and 308-nm UVB on the contralateral side . Based on the psoriasis area and severity index ( PASI ) score , clinical assessment was carried out before and 5 weeks after the beginning of the study . At the end of the treatment period both test groups showed a remarkable PASI score reduction ( 308-nm UVB , 63.57 % ; cream PUVA , 64.64 % ) . No relevant adverse effects were observed , except for mild irritation in a few patients . After a 12-week follow-up , a relapse of the disease was only observed in one patient . Thus , mono-chromatic excimer light cleared palmoplantar psoriasis as rapidly as cream PUVA . In contrast to cream PUVA , monochromatic excimer light therapy is not associated with prior drug application . This might lead to a lower incidence of adverse reactions and better compliance . Therefore , monochromatic excimer light therapy seems to be a useful new therapeutic option for palmoplantar psoriasis Topical psoralen plus UV‐A irradiation ( topical PUVA ) was re‐evaluated with regard to the timing of UV‐A exposure . Symmetrical lesions of fifteen patients with psoriasis were treated with topical PUVA . One side was exposed to UV‐A 2 h after topical application of 1 % 8‐methoxypsoralen ( 2‐h interval therapy ) , while the other side was exposed to the same doye of UV‐A within 5 min of the topical application ( non‐interval therapy ) . Both regimens were effective . The non‐interval therapy was preferred in one ease , the 2‐hour interval was preferred in three cases , and there was no clear difference in the other eleven cases . There was less tendency to burning with the non‐interval therapy , and our study suggests that this is a useful regimen in the out‐patient treatment of psoriasis |
11,340 | 28,283,002 | Despite heterogeneity of foot complications and geographic variations , the search methodology revealed substantial costs and further healthcare burden for people with diabetes .
Amputations due to suboptimally treated foot infections contribute to the already high rates of hospitalizations and readmissions .
Moreover , the findings suggest that the cost of amputation in the US is generally higher compared to the cost in European countries . | INTRODUCTION Diabetes mellitus is a chronic disease with high prevalence worldwide and a range of serious related complications .
Amongst them , diabetic foot is one of the most disabling , posing a substantial health and economic burden on patients and healthcare systems .
Areas covered : According to projections , the expected lower limb morbidity is about to increase - in this light the present review aim ed at identifying cost-of-illness studies on the management and treatment of conditions related to the diabetic foot , in an aim to provide a body of evidence for an increasing health care burden .
Expert commentary : Recent literature review surfaced a plethora of cost studies . | Aims /hypothesisThe aim of the present study was to investigate re source utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in re source utilisation between individuals with or without peripheral arterial disease ( PAD ) and /or infection . Methods Data on re source utilisation were collected prospect ively in a European multicentre study . Data on 1,088 patients were available for the analysis of re source use , and data on 821 patients were included in the costing analysis . Costs were calculated for each patient by multiplying the country-specific direct and indirect unit costs by the number of re sources used from inclusion into the study up to a defined endpoint . Country-specific costs were converted into purchasing power st and ards . Results Re source use and costs varied between outcome groups and between disease severity groups . The highest costs per patient were for hospitalisation , antibiotics , amputations and other surgery . All types of re source utilisation and costs increased with the severity of disease . The total cost per patient was more than four times higher for patients with infection and PAD at inclusion than for patients in the least severe group , who had neither . Conclusions /interpretationImportant differences in re source use and costs were found between different patient groups . The costs are highest for individuals with both peripheral arterial disease and infection , and these are mainly related to substantial costs for hospitalisation . In view of the magnitude of the costs associated with in-hospital stay , reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease OBJECTIVE Determine the cost-effectiveness of extracellular matrix ( ECM ) relative to human fibroblast-derived dermal substitute ( HFDS ) on diabetic foot ulcer ( DFU ) wound closure . METHOD Outcomes data were obtained from a 12-week , r and omised , clinical trial of adults aged 18 years or older diagnosed with type 1 or type 2 diabetes with a DFU . Patients were treated with either ECM or HFDS treatment . A two-state Markov model ( healed and unhealed ) with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of closed-wound weeks and the expected DFU cost per patient . Results were recorded over 12 weeks to estimate the number of closed-wound weeks per treatment and the average cost to achieve epithelialisation ( primary outcome ) . The perspective of the analysis was that of the payer , specifically the Centers for Medicare and Medicaid Services . No cost discounting was performed because of the short duration of the study . RESULTS The study consisted of 26 patients , with 13 in each group . In the ECM group , 10 wounds closed ( 77 % ) , with an average closure time of 36 days ; 11 wounds closed in the HFDS group ( 85 % ) , with an average closure time of 41 days . There was no significant difference between these results ( p=0.73 ) . Over 12 weeks , the expected cost per DFU was $ 2522 ( £ 1634 ) for ECM and $ 3889 ( £ 2524 ) for HFDS . Patients treated with HFDS incurred total treatment costs that were approximately 54 % higher than those treated with ECM . Sensitivity analyses revealed that the total cost of care for two applications of HFDS was more costly than eight applications of ECM by approximately $ 500 ( £ 325 ) . CONCLUSION In patients with DFU , ECM yielded similar clinical outcomes to HFDS but at a lower cost . Health-care providers should consider ECM as a cost-saving alternative to HFDS . DECLARATION OF INTEREST A.M. Gilligan , and C.R. Waycaster , are employees of Smith & Nephew Inc .. This study was funded by Smith & Nephew Inc .. A.L. L and sman , reports no conflicts of interest BACKGROUND Despite significant advances , the treatment of diabetic foot ulcers ( DFUs ) remains a major therapeutic challenge for clinicians , surgeons , and other health care professionals . There is an urgent need for new strategies with clinical ly effective interventions to treat DFUs to reduce the burden of care in an efficient and cost-effective way . OBJECTIVE This r and omized trial evaluated and compared the clinical effectiveness , tolerability , and costs of clostridial collagenase ointment ( CCO ) debridement to that of debridement using saline moistened gauze ( SMG ) and selective sharp debridement for the treatment of DFUs . METHODS R and omized , controlled , parallel group , multicenter , open-label , 12-week study of 48 patients with neuropathic DFUs r and omized to 4 weeks of treatment with either CCO or SMG after baseline surgical debridement . The primary end point was the condition of the ulcer bed at the end of treatment as measured using a st and ardized wound assessment tool . Secondary end points were the percentage of reduction in wound area and therapeutic response rates . Adverse events were monitored for the tolerability analysis . In addition , a comparative cost-effectiveness analysis was performed from the perspective of the Centers for Medicare and Medicaid Services as a payer . RESULTS Both the CCO and SMG groups had significantly improved wound assessment scores after 4 weeks of treatment ( CCO , -2.5 , P = 0.007 ; SMG , -3.4 , P = 0.006 ) . Only CCO treatment result ed in a statistically significant decrease from baseline in the mean wound area at the end of treatment ( P = 0.0164 ) and at the end of follow-up ( P = 0.012 ) . In addition , the CCO group exhibited a significantly better response rate at the end of follow-up compared with the SMG group ( 0.92 vs 0.75 , P < 0.05 ) . Reported adverse events were similar between the 2 treatment groups . None of the reported adverse events were considered to be related to treatment . The economic analysis indicated that the direct mean costs per responder in the physician office setting of care were $ 832 versus $ 1042 for the CCO group versus the SMG group , whereas the direct mean costs per responder in the hospital outpatient department setting were $ 1607 versus $ 1980 . CONCLUSIONS CCO treatment provides equivalent debridement of DFUs similar to SMG while fostering better progress toward healing as measured by decreasing wound area over time and improved response rates at the end of follow-up . In addition , CCO yields a more favorable cost-effectiveness ratio in both the physician office and hospital outpatient department setting s of care . Clinical Trials.gov identifier : NCT01056198 OBJECTIVE To estimate the annual , per-patient incremental burden of diabetic foot ulcers ( DFUs ) . RESEARCH DESIGN AND METHODS DFU patients and non-DFU patients with diabetes ( controls ) were selected using two deidentified data bases : ages 65 + years from a 5 % r and om sample of Medicare beneficiaries ( St and ard Analytical Files , January 2007–December 2010 ) and ages 18–64 years from a privately insured population ( OptumInsight , January 2007–September 2011 ) . Demographics , comorbidities , re source use , and costs from the payer perspective incurred during the 12 months prior to a DFU episode were identified . DFU patients were matched to controls with similar pre-DFU characteristics using a propensity score methodology . Per-patient incremental clinical outcomes ( e.g. , amputation and medical re source utilization ) and health care costs ( 2012 U.S. dollars ) during the 12-month follow-up period were measured among the matched cohorts . RESULTS Data for 27,878 matched pairs of Medicare and 4,536 matched pairs of privately insured patients were analyzed . During the 12-month follow-up period , DFU patients had more days hospitalized ( + 138.2 % Medicare , + 173.5 % private ) , days requiring home health care ( + 85.4 % Medicare , + 230.0 % private ) , emergency department visits ( + 40.6 % Medicare , + 109.0 % private ) , and outpatient/physician office visits ( + 35.1 % Medicare , + 42.5 % private ) than matched controls . Among matched patients , 3.8 % of Medicare and 5.0 % of privately insured DFU patients received lower limb amputations . Increased utilization result ed in DFU patients having $ 11,710 in incremental annual health care costs for Medicare , and $ 16,883 for private insurance , compared with matched controls . Privately insured matched DFU patients incurred excess work-loss costs of $ 3,259 . CONCLUSIONS These findings document that DFU imposes substantial burden on public and private payers , ranging from $ 9–13 billion in addition to the costs associated with diabetes itself OBJECTIVE ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications . The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers . METHOD eighteen diabetic patients with ischaemic , non-healing lower-extremity ulcers were recruited in a double-blind study . Patients were r and omly assigned either to receive 100 % oxygen ( treatment group ) or air ( control group ) , at 2.4 atmospheres of absolute pressure for 90 min daily ( total of 30 treatments ) . RESULTS healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group . The median decrease of the wound areas in the treatment group was 100 % and in the control group was 52 % ( p=0.027 ) . Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen , there was a potential saving in the total cost of treatment for each patient during the study . CONCLUSION hyperbaric oxygen enhanced the healing of ischaemic , non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible This prospect i ve observational study was carried out to assess the annual preventive and curative treatment costs for diabetic foot problems . Measures of re source use over the 1-year study period were taken for 151 patients whose lesions covered the entire Wagner classification . Treatment was provided under the current protocol s of a multidisciplinary team . The 1993 market prices for health services were used to convert units of health service utilization to expenditures by the social insurance system and the patients . The severity of the foot problems determined the medical cost . Preventive care ( 47 cases ) , represented an average cost per case of US$ 880 ( 1 US$ 1993=BEF 30.65 ) . Curative care ( 120 cases ) , including diagnostic tests , wound dressings , antibiotic therapy , revascularization and off loading techniques result ed in a mean cost of US$ 5227 per ulcer . Care for the 16 most severe wounds and amputations involved hospitalization and surgery at a mean cost per ulcer of US$ 31716 . The most important cost contributers were hospitalizations ( 72 % ) , drugs ( 11 % ) and diagnostic examinations ( 4 % ) . Preventive treatment for diabetic foot problems can represent a significant saving for the social insurance system as well as for the patients Abstract Objective : To calculate costs for the management of deep foot infections and to identify the most important factors related to treatment costs . Design : Costs for in-hospital care , surgery , investigations , antibacterials , visits to the foot-care team , orthopaedic appliances and topical treatment were calculated retrospectively from diagnosis until healing or death . Multiple regression analysis was used to identify factors that independently affect costs . Setting : A multidisciplinary foot-care team . Patients : 220 prospect ively followed patients with diabetes mellitus and deep foot infections who were referred to the team from 1986 to 1995 . Main Outcome Measures and Results : Total cost for healing without amputation was Swedish kronor (SEK)136 600 per patient , while the corresponding cost for healing with minor amputation was SEK260 000 and with major amputation was SEK234 500 . All costs were quoted in SEK at 1997 price levels ( £ 1 sterling and $ US1 equalled approximately SEK12.50 and SEK7.64 , respectively ) . The cost of antibacterials was 4%of total costs . The cost of topical treatment was 51 % of total costs and related to wound healing time . Number of weeks between diagnosis of deep foot infection and healing , and number of surgical procedures were variables that explained 95 % of costs in the multiple regression analysis . It was not possible to find any parameters present at diagnosis that could contribute to an explanation of total treatment costs . Conclusions : Topical treatment accounted for the largest proportion of total costs and the most important cost driving factors were wound healing duration and repeated surgery . Costs of antibacterials should not be used as an argument in the choice between early amputation and conservative treatment Diabetic foot ulcers ( DFUs ) are a leading cause of morbidity and hospitalisation among patients with diabetes . We analysed cl aims data for Medicare part B diabetic foot ulcer patients treated with Negative Pressure Wound Therapy at home ( N = 1135 ) and diabetic foot ulcer patients from a published meta- analysis of r and omised controlled wet-to-moist therapy . The expected costs of care for the two treatments were also compared . A significantly greater proportion of wounds treated with NPWT achieved a successful treatment endpoint compared with wet-to-moist therapy at both 12 weeks ( 39.5 % versus 23.9 % ; P < 0.001 ) and 20 weeks ( 46.3 % versus 32.8 % ; P < 0.001 ) . NPWT-treated patients reached a successful wound treatment endpoint more rapidly , and the benefit was apparent in all wound sizes . Expected 20-week treatment costs for NPWT were similar to those for wet-to-moist therapy if one nursing visit per day for the latter is assumed but 42 % less if two nursing visits per day are made . Thus , NPWT may improve the proportion of DFUs that attain a successful wound treatment endpoint and decrease re source utilisation by a given health care system compared with st and ard wet-to-moist therapy OBJECTIVES The objective of this study was to develop a model capable of assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower extremity ulcers with becaplermin gel ( Regranex ) plus good wound care ( GWC ) relative to treating them with GWC alone . METHODS A Markov simulation model was developed that includes six health states : Uninfected Ulcer , Infected Ulcer , Gangrene , Healed Ulcer , Healed Ulcer-History of Amputation , and Deceased . To predict clinical outcomes , information was taken from a specially design ed prospect i ve 9-month follow-up study of 183 neuropathic patients in the US treated with GWC . Cost of treatment data were taken primarily from a study of a cohort of 314 patients in Sweden . The efficacy of becaplermin was assumed equal to that achieved in a pooled analysis of four r and omized clinical trials . A model application provides expected clinical outcomes for a cohort of patients . Annual treatment costs per patient were estimated using treatment practice and unit prices from Sweden . RESULTS Due to a higher rate of healing and a shorter average healing time , treatment with becaplermin gel was predicted to increase the average number of months spent in the healed state over the first year following development of an ulcer by 24 % relative to GWC alone . In addition , the corresponding number of amputations was 9 % lower for the becaplermin-treated cohort . The average expected cost of $ 12,078 US for an individual treated with GWC alone declines to $ 11,708 US for one treated with becaplermin , in spite of $ 1262 becaplermin costs . Expenses related to topical treatment and inpatient care account for 83 % of the re sources conserved . CONCLUSIONS Our results suggest that in Sweden treatment with becaplermin in conjunction with GWC consumes fewer re sources and generates better outcomes than treatment with GWC alone for diabetic neuropathic ulcers . In light of the high and increasing incidence of such ulcers , the potential savings in costs and suffering may be important . Results are difficult to extrapolate internationally because they are strongly related to country-specific treatment practice s and price levels BACKGROUND To evaluate re source utilization and direct economic costs of care for patients treated with negative-pressure wound therapy ( NPWT ) , using the Vacuum-Assisted Closure ( V.A.C. ) system , compared to st and ard moist wound therapy ( MWT ) . METHODS A total of 162 diabetic patients with post-amputation wounds ( up to the trans-metatarsal level ) entered a 16-week , r and omized clinical trial . Patients r and omized to V.A.C. ( n = 77 ) received therapy with dressing changes every 48 hours . Control patients ( n = 85 ) received st and ard MWT . Re source utilization , procedures , and direct costs were calculated and analyzed in this post hoc retrospective study . RESULTS There was no difference between groups for in-patient hospital stay ( number of admissions or length of stay ) . More surgical procedures ( including debridement ) were required in the MWT group ( 120 vs 43 NPWT , P < .001 ) . The average number of dressing changes performed per patient was 118.0 ( range 12 - 226 ) for MWT versus 41 ( 6 - 140 ) for NPWT ( P = .0001 ) . The MWT group had 11 ( range 0 - 106 ) outpatient treatment visits during the study versus 4 ( range 0 - 47 ) in the NPWT group ( P < .05 ) . The average direct cost per patient treated for 8 weeks or longer ( independent of clinical outcome ) was $ 27,270 and $ 36,096 in the NPWT and MWT groups , respectively . The average total cost to achieve healing was $ 25,954 for patients treated with NPWT ( n = 43 ) compared with $ 38,806 for the MWT group ( n = 33 ) . CONCLUSION Treatment of diabetic patients with post amputation wounds using NPWT result ed in lower re source utilization and a greater proportion of patients obtaining wound healing at a lower overall cost of care when compared to MWT INTRODUCTION In Denmark , approximately 300,000 patients have a diabetes mellitus diagnosis . Recently published guidelines emphasise that health-care professionals who are in direct contact with citizens should be aware of the importance of prevention and early detection of diabetic foot ulcers . The objective of this study was to evaluate the mortality , length of hospital stay and economic impact on health care in patients with acute diabetic foot ulcers who were hospitalised in the Department of Orthopaedic Surgery , Aalborg University Hospital , Denmark . METHODS This was a prospect i ve cohort study including all patients admitted with a diagnosis of acute foot ulcer to the Department of Orthopaedic Surgery , Aalborg , Denmark , from September 2011 to February 2012 . RESULTS A total of 48 patients were referred for surgical treatment of a diabetic foot ulcer . The average age on admission was 64 years ( 35 - 87 years ) . The median length of hospital stay was 17 days ( 3 - 150 days ) , and 14 patients were readmitted within the first year . Within the first year of enrolment , 13 patients died , corresponding to a 36 % mortality rate . Based on the Danish Diagnosis-Related Groups rates , the median cost associated with a case in the study population was 133,867 DKK . CONCLUSION Patients referred for surgical revision of diabetic foot ulcers are often severely ill , and the condition is associated with a high one-year mortality rate . Furthermore , the cost of these cases is considerable . Preventive interventions , early diagnosis and treatment and multidisciplinary interventions – before and during hospitalisation – should be implemented . FUNDING not relevant . TRIAL REGISTRATION The Danish Data Protection Agency ( J. No. 2008 - 58 - 0028 ) approved the study OBJECTIVE To determine whether staged management of foot ulcers reduces health care costs and utilization . DESIGN Nonr and omized retrospective study using data from 1998 - 1999 in the Louisiana public hospital system . SETTING Louisiana public hospital system . PARTICIPANTS Forty-five patients with diabetes foot ulcer who received staged management foot care and 169 patients with diabetes foot ulcer who received st and ard foot care . INTERVENTIONS Staged management of foot ulcers consisting of devices to offload pressure ; self-care education ; and , after healing , custom-fabricated orthoses and footwear , and monitored progressive ambulation . MAIN OUTCOME MEASURES One-year levels of the number of foot-related inpatient hospitalizations , number of amputation-related hospitalizations , total number of foot-related inpatient days , total charges for foot-related inpatient hospitalizations , all-cause outpatient visits , total charges for all-cause outpatient visits , and combined outpatient and foot-related inpatient charges . RESULTS Over the 12-month study period , the staged management group had a lower foot-related hospitalization rate than did the comparison group ( .09 admissions per person vs.50 admissions per person , P=.0002 ) ; lower foot-related inpatient days ( .91d per person vs 3.97d per person , P=.0289 ) ; lower foot-related inpatient charges ( $ 1321 per person vs $ 5411 per person , P=.0151 ) ; fewer amputation-related hospitalizations ( .04 per person vs.19 per person , P=.0351 ) ; fewer emergency department visits ( .60 visits per person vs 1.22 visits per person , P=.0043 ) ; lower emergency department charges ( $ 104 per person vs $ 208 per person , P=.0057 ) ; and lower total charges ( $ 4776 per person vs $ 9402 per person , P=.0141 ) . The staged management group had a higher number of outpatient visits ( 24.91 per person vs 8.04 per person , P<.0001 ) and higher outpatient charges ( $ 2169 per person vs $ 1471 per person , P<.0001 ) . CONCLUSIONS A staged management diabetes foot program significantly reduced emergency department and hospital utilization and charges in a statewide public hospital system |
11,341 | 28,219,330 | Other differences in outcomes among antifungals were not statistically significant .
From the rank probability plot , caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality , whereas micafungin tended to be superior for treatment response .
The results were stable after excluding RCTs with high risk of bias , whereas micafungin had the lowest fungal infection-related mortality .
Conclusions Our results highlighted the necessity of empiric antifungal treatment and indicates that echinoc and ins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response . | Background The most optimal antifungal agent for empiric treatment of invasive fungal diseases ( IFDs ) in febrile neutropenia is controversial .
Our objective was evaluate the relative efficacy of antifungals for all-cause mortality , fungal infection-related mortality and treatment response in this population . | Abstract Objective : To evaluate the cost-effectiveness of caspofungin versus liposomal amphotericin B ( L-AmB ) for empirical antifungal therapy in patients with persistent fever and neutropenia in Sweden . Methods : With a decision-analytic model , the expected direct costs , life-years lost and quality adjusted life-years lost were estimated for an average patient in Sweden . Efficacy/tolerability data were obtained from analysis of a r and omized , double-blind multinational trial . Life expectancy , medical re source use and unit costs data were gathered from the literature and expert opinion . Probabilistic sensitivity analysis was used to evaluate the impact of uncertainty in data on outcomes . Results : The direct cost with caspofungin amounted to 233,851 SEK ( 95 % uncertainty interval 225,091–242,210 ) and with L-AmB to 271,921 SEK ( 262,935–281,363 ) , a difference of 38,070 SEK ( 31,745–44,811 ) favouring caspofungin . Treatment with caspofungin result ed in 0.25 ( 0.01–0.55 ) quality -adjusted life-years ( QALYs ) saved in comparison to L-AmB. Given the uncertainty in the estimates there is a > 95 % probability that caspofungin is economically dominant over L-AmB , i.e. cost-saving and QALY-saving . Conclusion : Given the underlying assumptions and data used , caspofungin is expected to be cost-effective with at least comparable outcomes compared to L-AmB for the empirical treatment of patients with suspected fungal infections in Sweden Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data , we performed a prospect i ve , r and omized , controlled trial that evaluated 110 neutropenic children with persistent fever . Those at high risk for invasive fungal infections ( IFI ) received caspofungin ( Arm C ) or liposomal amphotericinB ( Arm B ) ; those with a lower risk were r and omized to receive Arm B , C , or no antifungal treatment ( Arm A ) . Complete response to empirical antifungal therapy was achieved in 90/104 patients ( 86·5 % ) : 48/56 at high risk ( 85·7 % ) [ 88·0 % in Arm B ; 83·9 % in Arm C ( P = 0·72 ) ] , and 42/48 at low risk ( 87·5 % ) [ 87·5 % in control Arm A , 80·0 % Arm B , 94·1 % Arm C ; ( P = 0·41 ) ] . None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response . IFI was diagnosed in nine patients ( 8·2 % , 95 % confidence interval , 3·8–15·0 ) . This r and omized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged < 18 years and defined with low risk of IFI . Higher risk patients , including those with relapsed cancer , appear to be the target for empirical antifungal therapy during protracted febrile neutropenia In 2005 , several groups , including the European Group for Blood and Marrow Transplantation , the European Organization for Treatment and Research of Cancer , the European Leukemia Net and the Immunocompromised Host Society created the European Conference on Infections in Leukemia ( ECIL ) . The main goal of ECIL is to elaborate guidelines , or recommendations , for the management of infections in leukemia and stem cell transplant patients . The first sets of ECIL slides about the management of invasive fungal disease were made available on the web in 2006 and the papers were published in 2007 . The third meeting of the group ( ECIL 3 ) was held in September 2009 and the group up date d its previous recommendations . The goal of this paper is to summarize the new proposals from ECIL 3 , based on the results of studies published after the ECIL 2 meeting : ( 1 ) the prophylactic recommendations for hematopoietic stem cell transplant recipients were formulated differently , by splitting the neutropenic and the GVHD phases and taking into account recent data on voriconazole ; ( 2 ) micafungin was introduced as an alternative drug for empirical antifungal therapy ; ( 3 ) although several studies were published on preemptive antifungal approaches in neutropenic patients , the group decided not to propose any recommendation , as the only r and omized study comparing an empirical versus a preemptive approach showed a significant excess of fungal disease in the preemptive group OBJECTIVE To evaluate the cost-effectiveness of caspofungin versus liposomal amphotericin B as empiric antifungal treatment in patients with neutropenic fever in Italy . METHODS The cost-effectiveness of caspofungin versus liposomal amphotericin B was evaluated using a decision-tree model . Patients were stratified by presence or absence of baseline infection . Model outcomes included success in terms of resolution of fever , resolution of baseline infection , absence of breakthrough infection , survival , and quality -adjusted life years ( QALYs ) saved . Discontinuation because of nephrotoxicity or other adverse events were included in the model . Efficacy and safety data were based on a r and omized , double-blind , multinational trial of caspofungin compared to liposomal amphotericin B ( Walsh 2004 ) . Information on life expectancy , quality of life , medical re source consumption , and costs was obtained from the literature . RESULTS The caspofungin estimated total treatment cost amounted to 8351 euros ( 95 % uncertainty interval 7801 euros-8903 euros ) , which is 3470 euros ( 2575 euros-4382 euros ) less than with liposomal amphotericin B. Treatment with caspofungin result ed in 0.25 ( -0.11 ; 0.59 ) QALYs saved in comparison to treatment with liposomal amphotericin B. Probabilistic sensitivity analysis demonstrated a 93 % probability that caspofungin was economically dominant , i.e. , cost and QALY saving , and a probability of more than 99 % that the costs per QALY saved were below 20,000 euros , a commonly accepted threshold for cost-effectiveness . Additional analyses with alternative doses of liposomal amphotericin B confirmed these findings . CONCLUSION Given the underlying assumptions , our economic evaluation demonstrated that caspofungin is cost-effective compared to liposomal amphotericin B in empiric antifungal treatment of patients with neutropenic fever in Italy Micafungin , a clinical ly important echinoc and in antifungal drug , needs to be investigated as empirical therapy in febrile neutropenia in comparison with azole compounds . A prospect i ve r and omized study was conducted to compare clinical outcomes between micafungin and intravenous itraconazole as an empirical therapy for febrile neutropenia in hematological malignancies . The antifungal drug ( micafungin 100 mg or itraconazole 200 mg IV once daily ) was given for high fever that was sustained despite the administration of appropriate antibiotics . Treatment success was determined by composite end points based on breakthrough invasive fungal infection ( IFI ) , survival , premature discontinuation , defervescence , and treatment of baseline fungal infection . Duration of fever , hospital stay , and overall survival ( OS ) were studied . A total of 153 patients were r and omized to receive micafungin or itraconazole . The overall success rate was 7.1 % point higher in the micafungin group ( 64.4 vs. 57.3 % , p = 0.404 ) , satisfying the statistical criteria for the non-inferiority of micafungin . The duration of fever and hospital stay were significantly shorter in the micafungin group ( 6 vs. 7 days , p = 0.014 ; 22 vs. 27 days , p = 0.033 , respectively ) . Grade 3 adverse events including hyperbilirubinemia ( 2 vs. 7 ) , elevation of transaminase levels ( 2 vs. 4 ) , electrolyte imbalance ( 1 vs. 2 ) , atrial fibrillation ( 1 vs. 0 ) , and anaphylaxis ( 1 vs. 0 ) occurred in 7 and 13 patients in the micafungin ( 10.4 % ) and itraconazole ( 18.8 % ) groups , respectively . Micafungin , when compared with itraconazole , had favorably comparable success rate and toxicity profiles on febrile neutropenia in patients with hematological malignancies . In addition , it showed superior effect on shortening the hospital stay BACKGROUND Patients with neutropenia and persistent fever are often treated empirically with amphotericin B or liposomal amphotericin B to prevent invasive fungal infections . Antifungal triazoles offer a potentially safer and effective alternative . METHODS In a r and omized , international , multicenter trial , we compared voriconazole , a new second-generation triazole , with liposomal amphotericin B for empirical antifungal therapy . RESULTS A total of 837 patients ( 415 assigned to voriconazole and 422 to liposomal amphotericin B ) were evaluated for success of treatment . The overall success rates were 26.0 percent with voriconazole and 30.6 percent with liposomal amphotericin B ( 95 percent confidence interval for the difference , -10.6 to 1.6 percentage points ) ; these rates were independent of the administration of antifungal prophylaxis or the use of colony-stimulating factors . There were fewer documented breakthrough fungal infections in patients treated with voriconazole than in those treated with liposomal amphotericin B ( 8 [ 1.9 percent ] vs. 21 [ 5.0 percent ] , P=0.02 ) . The voriconazole group had fewer cases of severe infusion-related reactions ( P<0.01 ) and of nephrotoxicity ( P<0.001 ) . The incidence of hepatotoxicity was similar in the two groups . Patients receiving voriconazole had more episodes of transient visual changes than those receiving liposomal amphotericin B ( 22 percent vs. 1 percent , P<0.001 ) and more hallucinations ( 4.3 percent vs. 0.5 percent , P<0.001 ) . Parenteral voriconazole was changed to the oral formulation in 22 percent of the voriconazole group , with a reduction in the mean duration of hospitalization by one day in all patients ( P=0.17 ) but by two days in patients at high risk ( P=0.03 ) . CONCLUSIONS Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever BACKGROUND With use of data from the Prospect i ve Antifungal Therapy ( PATH ) Alliance registry , we performed this multicenter , prospect i ve , observational study to assess the epidemiologic characters and outcomes of invasive fungal infection ( IFI ) in hematopoietic stem cell transplant ( HSCT ) recipients . METHODS Sixteen medical centers from North America reported data on adult HSCT recipients with proven or probable IFI during the period July 2004 through September 2007 . The distribution of IFIs and rates of survival at 6 and 12 weeks after diagnosis were studied . We used logistic regression models to determine risk factors associated with 6-week mortality for allogeneic HSCT recipients with invasive aspergillosis ( IA ) . RESULTS Two hundred thirty-four adult HSCT recipients with a total of 250 IFIs were included in this study . IA ( 59.2 % ) was the most frequent IFI , followed by invasive c and idiasis ( 24.8 % ) , zygomycosis ( 7.2 % ) , and IFI due to other molds ( 6.8 % ) . Voriconazole was the most frequently administered agent ( 68.4 % ) ; amphotericin B deoxycholate was administered to a few patients ( 2.1 % ) . Ninety-three ( 46.7 % ) of 199 HSCT recipients with known outcome had died by week 12 . The 6-week survival rate was significantly greater for patients with IA than for those with invasive c and idiasis and for those with IFI due to the Zygomycetes or other molds ( P < .07 ) . The 6-week mortality rate for HSCT recipients with IA was 21.5 % . At 6 weeks , there was a trend toward a worse outcome among allogeneic HSCT recipients with IA who received myeloablative conditioning ( P = .07 ) ; absence of mechanical ventilation or/ and hemodialysis ( P = .01 ) were associated with improved survival . CONCLUSIONS IA remains the most commonly identified IFI among HSCT recipients , but rates of survival in persons with IA appear to have improved , compared with previously reported data . Invasive c and idiasis and IFI due to molds other than Aspergillus species remain a significant problem in HSCT recipients The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospect i ve , r and omized , double-blind study . The proportion of patients who developed significant drug-related adverse event(s ) ( defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation ) was compared in 120 patients [ caspofungin 50 mg , or 50 mg following a 70-mg loading dose on Day 1 ( hereinafter , 70/50 mg ) group : 60 patients ; micafungin 150 mg : 60 patients ] . The overall response rate was primarily evaluated in the per- protocol set ( PPS ) population . The proportion of patients who developed significant drug-related adverse events was 5.0 % ( 3/60 ) in the caspofungin group and 10.0 % ( 6/60 ) in the micafungin group [ 95 % confidence interval ( CI ) for the difference : −15.9 % , 5.2 % ] . The favorable overall response in the PPS population for patients with esophageal c and idiasis , invasive c and idiasis , and chronic pulmonary aspergillosis including aspergilloma was 100.0 % ( 6/6 ) , 100.0 % ( 3/3 ) , and 46.7 % ( 14/30 ) in the caspofungin group , and 83.3 % ( 5/6 ) , 100.0 % ( 1/1 ) , and 42.4 % ( 14/33 ) in the micafungin group , respectively . In Japanese patients with C and ida or Aspergillus infections , there was no statistical difference in the safety between caspofungin and micafungin . Consistent with other data on these two agents , the efficacy of caspofungin and micafungin was similar Prolonged neutropenia is a major risk factor for invasive fungal infection ( 1 - 6 ) . The incidence among neutropenic patients with cancer who are receiving intensive cytotoxic therapy ranges from 2 % to 47 % , depending on other concomitant risk factors ( 7 ) . Mortality rates range from 35 % to 90 % ( 8) . Fever may be the only clinical sign of infection , and definitive diagnosis is often problematic . Empirical therapy with amphotericin B deoxycholate reduces the relative risk for documented infection by 50 % to 80 % and overall mortality rates by 23 % to 45 % ( 1 , 2 , 9 , 10 ) . This practice is now st and ard in neutropenic patients with cancer who have persistent fever that does not respond to 3 to 7 days of treatment with broad-spectrum antibiotics ( 11 ) . Rates of clinical response to empirical amphotericin B of 43 % to 72 % have been reported in neutropenic patients ( 1 - 6 ) . However , treatment is associated with significant dose-limiting toxicity in approximately 35 % to 82 % of patients ( 1 - 14 ) . Consequently , less toxic alternatives have been investigated , including lipid formulations of amphotericin B and fluconazole ( 3 - 6 , 13 - 15 ) . Although lipid-based formulations have an efficacy similar to that of conventional amphotericin B , infusion-related side effects and nephrotoxicity remain a concern . Their high cost also prohibits routine use in most hospitals ( 4 - 6 ) . Fluconazole is limited by its lack of activity against Aspergillus species and some non-albicans C and ida species . In addition , recent reports reveal an increasing prevalence of resistance among C and ida species after long-term fluconazole treatment ( 16 , 17 ) . In contrast , the broad-spectrum triazole itraconazole combines improved safety with activity against Aspergillus and C and ida species , including many fluconazole-resistant C and ida species ( 18 , 19 ) . Itraconazole is now available as an intravenous formulation and an oral solution , which is readily absorbed in neutropenic patients ( 20 - 22 ) . Itraconazole may therefore be an alternative to amphotericin B for empirical therapy in persistently febrile neutropenic patients with suspected systemic fungal infection . We conducted an international , multicenter , r and omized trial to compare the safety and efficacy of itraconazole and amphotericin B as empirical antifungal therapy in these high-risk patients . Methods Study Design This open , multicenter , r and omized , controlled clinical trial was performed at 60 oncology centers in 10 countries between March 1996 and December 1997 . Patients were r and omly assigned in a 1:1 ratio to receive itraconazole or amphotericin B by using a central ized computer . A contract research organization , ID2 ( Brussels , Belgium ) , performed central r and omization on a per center basis and ensured that participants were stratified by presence of signs and symptoms attributable to deep fungal infection and underlying disease . At each center , balancing ensured that each treatment was allocated to an equal number of participants . The study was powered to demonstrate equivalency between treatments . The protocol was review ed and approved by review boards and ethics committees of each participating institution . Written informed consent was obtained from participants before enrollment . Patient Enrollment and Stratification Patients 18 years of age or older who were hospitalized for treatment of hematologic cancer with intensive myelosuppressive cytotoxic therapy , with or without autologous hematopoietic stem-cell support , were eligible . Other eligibility criteria were 1 ) an absolute neutrophil count of 0.5 109 cells/L or less with an expected duration of 7 or more days and 2 ) body temperature greater than 38 C that was unrelated to blood product transfusions or medications and that persisted despite 3 or more days of treatment with parenteral broad-spectrum antibiotics . Patients were excluded if they had previously been enrolled in the trial ; had been treated with other investigational drugs ; or were receiving medications known to interact with itraconazole , including terfenadine , astemizole , midazolam , triazolam , cisapride , phenytoin , isoniazid , phenobarbital , and rifampicin . Other exclusion criteria were proven invasive fungal infection ( positive histology or culture from a normally sterile body fluid , except urine ) , resident signs of an invasive fungal infection ( highly suggestive chest radiograph or computed tomogram ) during previous neutropenic episodes , a bacterial or viral infectious cause of fever at trial entry , and receipt of an allogeneic hematopoietic stem-cell transplant . Patients with severe liver dysfunction ( aminotransferase levels 5 times the upper limit of normal and total bilirubin level 50 mmol/L ) , renal failure ( calculated creatinine clearance < 0.5 mL/s ) , or HIV seropositivity were excluded . Prophylactic antibacterial and antiviral therapy was permitted during the study , but prophylaxis with systemic antifungal drugs was discontinued at study entry . Patients were stratified according to receipt or nonreceipt of an autologous hematopoietic stem-cell transplant and by the absence or presence of 1 or more signs and symptoms potentially attributable to invasive fungal infections ( cough , dyspnea , chest pain , increased respiratory rate , headaches , and confusion ) . The four strata of signs ( yes or no ) and transplantation status ( yes or no ) were evenly distributed across the study groups ( Table 1 ) . Table 1 . Baseline Demographic Characteristics of Patients Administration of Study Medication Intravenous itraconazole ( Sporanox IV , Janssen Pharmaceutica , Beerse , Belgium ) , 200 mg , was administered by infusion as a 40 % hydroxypropyl -- cyclodextrin solution in water every 12 hours for the first 48 hours , followed by 200 mg daily from days 3 to 14 . From day 15 , oral itraconazole solution ( Sporanox Oral Solution , Janssen Pharmaceutica ) , 400 mg/d , replaced intravenous itraconazole . However , if patients were able to tolerate oral medication , oral itraconazole could replace intravenous itraconazole as early as day 7 . Amphotericin B deoxycholate ( Fungizone , Bristol-Myers Squibb , Princeton , New Jersey ) in 5 % dextrose in water was infused intravenously over 4 to 6 hours at a daily dose of 0.7 to 1.0 mg/kg of body weight for up to 28 days . Infusion-related toxicities were treated with hydrocortisone , antihistamines , or antipyretics at the investigators ' discretion . Participants received therapy until defervescence and recovery from neutropenia ( absolute neutrophil count > 0.5 109 cells/L on 2 successive days ) . Pharmacokinetic Evaluation of Itraconazole To determine plasma levels of itraconazole and its active metabolite , hydroxyitraconazole , venous blood was sample d before administration of itraconazole on days 0 , 3 ( before the fifth infusion ) , and 8 ( before intravenous or , where applicable , oral administration ) and on days 15 , 22 , and 28 ( during oral treatment ) . Each 10-mL sample was drawn from the arm opposite the administration site , or from a central intravenous line , into heparinized tubes and was separated by centrifugation ( 1000 g for 10 minutes ) . The lines were flushed before and after administration of the study drug to reduce the chance that residual drug remained in the tubing . Plasma sample s were stored at 20 C until assay by using high-performance liquid chromatography . Patients who had received previous itraconazole prophylaxis before the study were excluded from pharmacokinetic analysis . Evaluation Criteria and Definitions The primary efficacy measurement was a favorable response at the end of treatment . Patients were evaluable for response if they had received study medication for 3 or more days . A favorable treatment response was defined as a patient who became afebrile ( daily oral peak temperature < 38 C ) and recovered from neutropenia ( absolute neutrophil count > 0.5 109 cells/L on 2 successive days ) . Patients who became afebrile but were still neutropenic were considered nonresponders , unless they had received study medication for 10 days or longer and remained afebrile for 3 consecutive days after treatment discontinuation . Failure of treatment was defined as the presence of any of the following conditions : documented breakthrough invasive fungal infection , death from any cause after 3 days of treatment with study drug , failure to defervesce by the time of marrow recovery or by day 28 , persistent fever requiring a change in therapy , or treatment discontinuation due to intolerance . Patients who received the study drug for fewer than 3 days or in whom a viral , bacterial , or fungal cause of persistent fever was identified at study entry were considered nonevaluable . Nonevaluable patients who received at least one dose of study medication were included in the safety analysis . The response rate in the intention-to-treat analysis was defined as the number of responders divided by the total number of patients ( those who responded , those who had treatment failure , and nonevaluable patients ) . An additional outcome analysis was performed by using the composite end points described by Walsh and colleagues ( 5 ) , in which treatment success was defined as survival for 7 days after start of treatment , defervescence during neutropenia , absence of breakthrough invasive fungal infection during drug administration or within 7 days of study completion , and no premature withdrawal of study medication because of intolerance or lack of efficacy . Subgroup Analysis Further planned analyses were performed in patient subgroups for the primary efficacy end point ( defervescence and recovery from neutropenia ) according to the following criteria : fever of less than 5 days ' or 5 or more days ' duration before study entry , duration of neutropenia since study initiation of less than 7 days or 7 or more days , and receipt of antifungal prophylaxis before enrollment . Monitoring of Adverse Events All patients receiving study medication were evaluated for safety . Adverse events were monitored prospect ively . Nephrotoxicity was defined as a OBJECTIVES In cases of hematological malignancy , patients with persistent fever and neutropenia receive antifungal empirical therapy to prevent and treat invasive fungal infections . The clinical efficacy and safety of micafungin and voriconazole were compared . METHODS In this r and omized , cooperative group , open-label trial , we assessed and compared the efficacy and safety of micafungin and voriconazole as an empirical antifungal therapy in febrile neutropenic patients with hematological malignancy . Patients were classified according to invasive fungal infection risk . RESULTS There were no significant differences in clinical efficacy between the two treatments , evaluated based on ( i ) successful treatment of baseline fungal infection ( no evaluation ) , ( ii ) absence of breakthrough fungal infection ( P = 0.106 ) , ( iii ) survival for ≥7 days after study completion ( P = 0.335 ) , ( iv ) premature study discontinuation due to poor efficacy ( P = 0.424 ) , and ( v ) resolution of fever during neutropenia ( P = 0.756 ) . Discontinuation due to drug-related adverse events ( grade s 3 - 4 ) occurred less frequently in the micafungin group ( P = 0.005 ) . CONCLUSIONS The clinical efficacy did not differ between micafungin and voriconazole . Micafungin was generally better tolerated than voriconazole when given as an empirical antifungal therapy in patients with persistent fever and neutropenia ABSTRACT The combination of liposomal amphotericin B ( LAMB ) and caspofungin ( CAS ) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis . Little is known , however , about the safety and pharmacokinetics of the combination in patients at high risk for these infections . The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified , r and omized , multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients ( aHSCT ) with granulocytopenia and refractory fever . The patients received either CAS ( 50 mg/day ; day 1 , 70 mg ) , LAMB ( 3 mg/kg of body weight/day ) , or the combination of both ( CASLAMB ) until defervescence and granulocyte recovery . Safety , development of invasive fungal infections , and survival were assessed through day 14 after the end of therapy . Pharmacokinetic sampling and analysis were performed on days 1 and 4 . All three regimens were well tolerated . Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18 , 2/20 , and 0/17 patients r and omized to CAS , LAMB , and CASLAMB , respectively . Adverse events not leading to study drug discontinuation were frequent but similar across cohorts , except for a higher frequency of hypokalemia with CASLAMB ( P < 0.05 ) . Drug exposures were similar for patients receiving combination therapy and those r and omized to monotherapy . There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy . CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics , lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses Amphotericin B , despite its intrinsic servere toxicity , is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy . The aim of this study was to show whether fluconazole was as effective as , and less toxic than , amphotericin , with no effort made to compare the antifungal activity of the two drugs . A group of 112 persistently febrile ( > 38 degrees C ) and granulocytopenic ( < 1000 cells/mm3 ) cancer patients , not receiving any absorbable antifungal antibiotic for prophylaxis , with a mean age of 27 years ( range 1 - 73 years ) , undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy , were r and omised to receive either fluconazole ( 6 mg/kg/day up to 400 mg/day ) or amphotericin B ( 0.8 mg/kg/day ) as empirical antifungal treatment . Patients were required to have normal chest X-rays at r and omisation , no previous history of aspergillosis and negative surveillance cultures for Aspergillus . The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients ( 75 % ) in the fluconazole group and in 37 of 56 ( 66 % ) in the amphotericin B group ( P = 0.4 ) . Duration of therapy was 6 days ( 95 % CI = 4 - 8 days ) in both groups . Death occurred in 3 patients ( 5 % ) in the fluconazole and in 2 ( 4 % ) in the amphotericin B group . No fungal death was documented in either group . Adverse events developed in 18 of 56 patients ( 32 % ) in the fluconazole group and in 46 of 56 ( 82 % ) in the amphotericin B group ( P < 0.001 ) . In the amphotericin B group , 5 patients had treatment discontinued because of toxicity , versus none in the fluconazole group , a difference which approached statistical significance ( P = 0.06 ) . This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B , in pragmatical terms and for this specific indication . However , numbers are too small to allow definitive conclusions about efficacy , and the use of fluconazole for this indication remains experimental . Future studies should try to identify patients more at risk of fungal infections , with the aim of individualising antifungal approaches BACKGROUND Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections . Caspofungin , a member of the new echinoc and in class of compounds , may be an effective alternative that is better tolerated than amphotericin B. METHODS In this r and omized , double-blind , multinational trial , we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy . At study entry , patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis . A successful outcome was defined as the fulfillment of all components of a five-part composite end point . RESULTS Efficacy was evaluated in 1095 patients ( 556 receiving caspofungin and 539 receiving liposomal amphotericin B ) . After adjustment for strata , the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B ( 95.2 percent confidence interval for the difference , -5.6 to 6.0 percent ) , fulfilling statistical criteria for the noninferiority of caspofungin . Among patients with baseline fungal infections , a higher proportion of those treated with caspofungin had a successful outcome ( 51.9 percent vs. 25.9 percent , P=0.04 ) . The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group ( 92.6 percent vs. 89.2 percent , P=0.05 ) . Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group ( 10.3 percent vs. 14.5 percent , P=0.03 ) . The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups . Fewer patients who received caspofungin sustained a nephrotoxic effect ( 2.6 percent vs. 11.5 percent , P<0.001 ) , an infusion-related event ( 35.1 percent vs. 51.6 percent , P<0.001 ) , or a drug-related adverse event or discontinued therapy because of drug-related adverse events . CONCLUSIONS Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia Background : Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a st and ard of care . However , little is known about the role of echinoc and ins and liposomal amphotericin B ( L-AmB ) for empiric antifungal therapy in pediatric patients . Methods : Patients between the ages of 2 to 17 years with persistent fever and neutropenia were r and omly assigned to receive caspofungin ( 70 mg/m2 loading dose on day 1 , then 50 mg/m2 daily [ maximum 70 mg/d ] ) or l-AmB ( 3 mg/kg daily ) in a 2:1 ratio . Evaluation of safety was the primary objective of the study . Efficacy was also evaluated , with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint . Suspected invasive fungal infections were evaluated by an independent , treatment-blinded adjudication committee . Results : Eighty-two patients received study therapy ( caspofungin 56 , l-AmB 26 ) , and 81 were evaluated for efficacy ( caspofungin 56 ; l-AmB 25 ) . Outcomes for safety and efficacy endpoints were similar for both study arms . Adverse drug-related event rates [ 95 % confidence interval ] were similar between the caspofungin and l-AmB groups ( clinical 48.2 % [ 34.7–62.0 ] versus 46.2 % [ 26.6–66.6 ] ; laboratory 10.7 % [ 4.0–21.9 ] versus 19.2 % [ 6.6–39.4 ] ) . Serious drug-related adverse events occurred in 1 ( 1.8 % ) of caspofungin-treated patients and 3 ( 11.5 % ) of l-AmB-treated patients . Overall success rates [ 95 % CI ] were 46.4 % [ 33.4–59.5 ] for caspofungin and 32.0 % [ 13.7–50.3 ] for l-AmB. Conclusions : Caspofungin and l-AmB were comparable in tolerability , safety , and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients Safety , tolerability and efficacy of itraconazole and amphotericin B ( AMB ) were compared for empirical antifungal treatment of febrile neutropenic cancer patients . Patients and Methods : In an open , r and omised study , 162 patients with at least 72 h of antimicrobial treatment received either intravenous followed by oral itraconazole suspension or intravenous AMB for a maximum of 28 days . Permanent discontinuation of study medication due to any adverse event was the primary safety parameter . Efficacy parameters included response and success rate for both treatment groups . Results : Significantly fewer itraconazole patients discontinued treatment due to any adverse event ( 22.2 vs. 56.8 % AMB ; p < 0.0001 ) . The main reason for discontinuation was a rise in serum creatinine ( 1.2 % itraconazole vs. 23.5 % AMB ) . Renal toxicity was significantly higher and more drug-related adverse events occurred in the AMB group . Intention-to-treat ( ITT ) analysis showed favourable efficacy for itraconazole : response and success rate were both significantly higher than for AMB ( 61.7 vs. 42 % and 70.4 vs. 49.3 % , both p < 0.0001 ) . Treatment failure was markedly reduced in itraconazole patients ( 25.9 vs. 43.2 % ) , largely due to the better tolerability . Conclusions : Itraconazole was tolerated significantly better than conventional AMB and also showed advantages regarding efficacy . This study confirms the role of itraconazole as a useful and safe agent in empirical antifungal therapy of febrile neutropenic cancer patients Background : The aim of the study was to compare the efficacy of empirical antifungals in combination with broad spectrum antibiotics with that of antibiotics alone in high risk febrile neutropenic cancer patients not responding to initial antibacterial therapy . Patients and Methods : A prospect i ve , r and omized controlled trial was conducted at 22 cancer centers in Germany . Patients with fever of unknown origin were r and omized to either piperacillin ( Pip ) plus an aminoglycoside ( AMG ) ( arm A ) or a third generation cephalosporin ( Ceph ) plus AMG ( arm B ) . Patients not responding after 4–6 days were r and omized to either imipenem ( Imi ) plus glycopeptide ( GLP ) ( arm C ) , or Imi/GLP plus amphotericin B deoxycholate ( AmB ) plus 5-flucytosine ( 5-FC ) ( arm D ) , or Imi/GLP plus fluconazole ( Fluco ) ( arm E ) . A successful outcome was defined as resolution of fever . Results : In arm A , 192 of 373 patients ( 51.5 % ) responded as compared to 176 of 344 patients ( 51.2 % ) in arm B. The response rates of 155 patients r and omized for further empirical treatment were 55.6 % , 77.8 % and 62.5 % in arm C , D and E , respectively . The difference between arm C and D was of borderline statistical significance ( p = 0.06 ) after correction for multiple testing . Conclusion : In neutropenic cancer patients with persistent fever the combination of antibiotics with AmB/5-FC is superior to salvage antibacterial therapy alone . There is no difference in efficacy between Pip and third generation Ceph given as initial empirical therapy in combination with an AMG One hundred and thirty‐four adults and 204 children were r and omized in two prospect i ve , parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d ( c‐AMB ) , liposomal amphotericin B 1 mg/kg/d ( L‐AMB1 ) or liposomal amphotericin B 3 mg/kg/d ( L‐AMB3 ) . Patients were entered if they had a pyrexia of unknown origin ( PUO ) defined as temperature of 38 ° C or more , not responding to 96 h of systemic broad‐spectrum antibiotic treatment , and neutropenia ( < 0.5 × 109/l ) . The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed , with success defined as resolution of fever for 3 consecutive days ( < 38 ° C ) without the development of any new fungal infection . Clinical and laboratory parameters were collected for safety analysis . In both the paediatric and adult population s , L‐AMB treated patients had a 2–6‐fold decrease in the incidence ( P 0.01 ) of test‐drug‐related side‐effects , compared to c‐AMB . Severe trial‐drug‐related side‐effects were seen in 1 % of L‐AMB treated patients , in contrast to 12 % of patients on c‐AMB ( P < 0.01 ) . Nephrotoxicity , in the patient subset not receiving concomitant nephrotoxic agents , defined as a doubling from the patients baseline serum creatinine level , was not observed in the L‐AMB1 arm whereas the incidence was 3 % in patients on L‐AMB3 and 23 % in those on c‐AMB ( P < 0.01 ) . Moreover , time to develop nephrotoxicity was longer in both L‐AMB arms than c‐AMB ( P < 0.01 ) . Severe hypokalaemia was observed less frequently in both L‐AMB arms ( P < 0.01 ) Invasive fungal infections from febrile neutropenia are associated with significant cost and mortality . The mainstay of treatment has been liposomal amphotericin B , however , echinoc and ins and azoles have shown promise as alternative treatments . Data on clinical efficacy exist , however , data incorporating pharmacoeconomic considerations are required in Turkey . The aim of this study was to investigate the cost effectiveness of caspofungin vs. voriconazole in empiric treatment of febrile neutropenia in Turkey . A decision analytic model was utilised , built upon two r and omised-controlled trials and supplemented with expert panel input from clinicians in Turkey . A five-point composite outcome measure was utilised and sensitivity analyses were performed to demonstrate the robustness of the model . The base case scenario result ed in caspofungin being preferred by TL2,533 , TL29,256 and TL2,536 per patient treated , successfully treated patient and patient survival , respectively ( approx . USD1414 , 16 328 and 1415 ) ; sensitivity analyses did not change the outcome . Monte Carlo simulation highlighted a 78.8 % chance of favouring caspofungin . The result was moderately sensitive to treatment duration and acquisition cost of the antifungal agents compared . This is the first pharmacoeconomic study comparing caspofungin to voriconazole within Turkey , result ing in an advantage towards caspofungin . The study will aid in formulary decision-making based on the clinical and economic consequences of each agent in the Turkish health care setting BACKGROUND In patients with persistent fever and netropenia , amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections . Despite this treatment , there are chances of breakthrough fungal infections and drug is also toxic . MATERIAL S AND METHODS A multicentric , r and omized , controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy . RESULTS The average body weight of patients was 26.4 ± 14.8 ( n=22 ) , 32.9 ± 19.4 ( n=23 ) and 37.9 ± 20.0 ( n=20 ) kg in 1 mg , 3 mg Fungisome ( liposomal amphotericin B ) and 1 mg/kg/day conventional amphotericin B group , respectively . The mean age was 16.2 ± 13.4 , 16.0 ± 10.9 and 22.7 ± 16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group , respectively . The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17 ± 9.8 , 16.2 ± 8.3 , and 14.7 ± 10.7 days , respectively . The time to resolve fever was 13.3 ± 10.2 , 10.9 ± 7.1 , 10.1 ± 6.7 days , and for absolute neutrophil count ( ANC ) to be above 500 cells per microliter , it took 13.4 ± 9.6 , 10.6 ± 7.6 and 7.3 ± 3.4 days , respectively . Liposomal formulations were well-tolerated compared to conventional amphotericin B. CONCLUSIONS This small r and omized study showed that the indigenous liposomal formulation Fungisome appears to be equally efficacious and safer than conventional amphotericin B. Also , the lower dose Fungisome ( 1 mg/kg/day ) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome ( 3 mg/kg/day ) . Treatment cost would be a major factor for limiting use of higher dose of Fungisome In two major clinical trials , voriconazole and caspofungin were recommended as alternatives to liposomal amphotericin B for empirical use in febrile neutropenia . This study investigated the health economic impact of using voriconazole vs. caspofungin in patients with febrile neutropenia . A decision analytic model was developed to measure downstream consequences of empirical antifungal therapy . Clinical outcomes measured were success , breakthrough infection , persistent base-line infection , persistent fever , premature discontinuation and death . Treatment transition probabilities and patterns were directly derived from data in two relevant r and omised controlled trials . Re source use was estimated using an expert clinical panel . Cost inputs were obtained from latest Australian sources . The analysis adopted the perspective of the Australian hospital system . The use of caspofungin led to a lower expected mean cost per patient than voriconazole ( AU$40,558 vs. AU$41,356 ) , with a net cost saving of AU$798 ( 1.9 % ) per patient . Results were most sensitive to the duration of therapy and the alternative therapy used post-discontinuation . In uncertainty analysis , the cost associated with caspofungin is less than that with voriconazole in 65.5 % of cases . This is the first economic evaluation of voriconazole vs. caspofungin for empirical therapy . Caspofungin appears to have a higher probability of having cost-savings than voriconazole for empirical therapy . The difference between the two medications does not seem to be statistically significant however |
11,342 | 27,820,461 | RESULTS The construct of caregiver burden is not st and ardized , and many terms are used to describe burden . | OBJECTIVE The overall objective of this review is to quantitatively measure the psychometric properties and the feasibility of caregiver burden screening tools .
The more specific objectives were to determine the reliability , validity as well as feasibility of tools that are used to screen for caregiver burden and strain .
The Zarit Burden Interview ( ZBI ) , in particular the 22-item version , has been examined the most throughout the literature .
In addition to its sound psychometric properties , the ZBI has been widely used across language s and cultures . | Background and Purpose — A large proportion of disabled stroke survivors live at home and are supported by informal caregivers . Identification of determinants of caregiver burden will help to target caregiver interventions . Methods — Data on patient , caregiver , and health and social support characteristics were collected prospect ively over 1 year in 232 stroke survivors in a r and omized trial of caregiver training . The contribution of these variables to caregiver burden score ( CBS ) and quality of life ( QOL ) measures at 3 months and 1 year was analyzed using regression models . Results — Stroke patients had a mean age of 74±11 years , and 120 ( 52 % ) were men . The mean age of caregivers was 65.7±12.5 years , 149 ( 64 % ) were females , and 116 ( 50 % ) had received caregiver training . The mean CBS was 48±13 and 38±11 ( score range of bad to good 88 to 22 ) and QOL score was 75±16 and 75±15 ( score range of bad to good 0 to 100 ) at 3 months and 1 year , respectively . CBS and QOL correlated with each other and with patient ( age , dependency , and mood ) , caregiver ( age , gender , mood , and training ) , and support ( social services and family networks ) variables . Of these , only patient and caregiver emotional status , caregiver age and gender , and participation in caregiver training were independent predictors of either outcome at 3 months . Patient dependency and family support were additional independent predictors at 1 year . Social services support predicted institutionalization but not caregiver outcomes . Conclusion — Advancing age and anxiety in patients and caregivers , high dependency , and poor family support identify caregivers at risk of adverse outcomes , which may be reduced by caregiver training OBJECTIVE The objective of this study was to evaluate the strengths and weaknesses of a group support program and a home visiting program for family caregivers of stroke patients . It also examined the best fit between intervention variant and family caregiver and patient characteristics . van den Heuvel 's previous effect study showed positive effects of the same intervention program , but unlike our present study differences between the two support variants could not be measured . METHODS Of 257 family caregivers who were included and r and omly assigned to an intervention variant or a control group , 127 family caregivers completed the intervention in either the group program or the home visiting program . RESULTS Evaluation data showed that both intervention variants had been helpful and feasible , but home visit participants missed peer contact and follow-up contacts were missed in both intervention programs . In comparison to the home visiting program , the group program participants showed more benefit especially with respect to informational and emotional components . Caregivers ' preference for type of intervention revealed that both types of intervention had its supporters . Those that preferred the group program could be clearly characterised : they were burdened , lived with a more psychologically h and icapped relative , were using active coping strategies more frequently or lived in a region which is considered to be more sociable . CONCLUSION The present study adds extensively to van den Heuvel 's effect study with respect to discriminative aspects of group and home intervention programs and their respective benefits for specific family caregiver groups . PRACTICE IMPLICATION S In order to suitably match an intervention type with specific caregiver characteristics the intervention provider should utilize caregiver self- selection or undertake professional screening of caregiver burden . Telephone contacts should be offered in addition to the interventions BACKGROUND : Few studies have examined the factors associated with depression in informal caregivers of HIV-infected persons . OBJECTIVE : To investigate the relationship between depression and caregiver burden among informal caregivers of HIV-infected individuals . DESIGN : Cross-sectional study using baseline data from an ongoing r and omized trial of a supportive telephone intervention . PARTICIPANTS : One hundred seventy-six dyads of HIV patients and their informal caregiver . MEASUREMENTS : Depression was defined as a Beck Depression Inventory > 10 . A Caregiver Strain Index > 6 identified informal caregivers with a high caregiver burden . We used logistic regression to identify characteristics that were associated with depression in the informal caregiver . RESULTS : Informal caregivers were 42 years old ( SD , 13 ) , 53 % female , 59 % nonwhite , and 30 % had education beyond high school . Forty-seven percent of informal caregivers were the patient ’s partner , 18 % a friend , and 35 % a family member . Twenty-seven percent of informal caregivers had a high caregiver burden , and 50 % were depressed . We found significantly greater odds of informal caregiver depression with high caregiver burden ( OR , 6.08 ; 95 % CI , 2.40 to 15.4 ) , informal caregiver medical comorbidity besides HIV ( OR , 2.32 ; 95 % CI , 1.09 to 4.92 ) , spending all day together ( OR , 3.92 ; 95 % CI , 1.59 to 9.69 ) , having to help others besides the HIV patient ( OR , 2.55 ; 95 % CI , 1.14 to 5.74 ) , and duration of the HIV patient ’s diagnosis ( OR , 1.01 per month ; 95 % CI , 1.00 to 1.01 ) . CONCLUSIONS : High caregiver burden was strongly associated with depression among HIV-infected individuals ’ informal caregivers , who themselves had difficult life circumstances . Informal caregivers of HIV patients may be in need of both mental health services and assistance in caregiving Purpose : To evaluate the feasibility and effectiveness of early supported discharge ( ESD ) following acute stroke . Method : An ESD scheme was compared to conventional rehabilitation in a r and omized controlled trial . All patients admitted with acute stroke were considered for inclusion . Eighty-eight ( 20.2 % ) were found to be eligible and 82 were r and omized either to early supported discharge ( n=42 ) or conventional rehabilitation ( n=40 ) . The primary outcome measure was the Nottingham Extended Activities of Daily Living Scale . The General Health Question naire , the Montgomery Aasberg Depression Rating Scale , mortality , placement and patient and carer satisfaction served as secondary outcome measures . Results : Median length of stay was reduced from 31 days in the conventional hospital rehabilitation group to 22 days in the early supported discharge group ( p=0.09 ) . No differences were found regarding primary outcome . The General Health Question naire score showed a significant difference in favour of the early supported discharge group at three months ( 19.5/24 , p = 0.02 ) , but not at six . At six months , the proportion of patients being dead or in institution showed a trend of being higher in the conventional rehabilitation group ( OR 3.8 , 95 % CI 0.8 - 23 ) . Conclusions : Early supported discharge after stroke is feasible and it is possible that it has benefits compared with conventional rehabilitation Family caregivers , the “ second victims ” or hidden patients in dementia care , are at risk for social isolation , stress , depression , and mortality . Telephone-based support ( telesupport groups ) represents a practical , low-burden , low-cost source of emotional support . The present study evaluated the feasibility and effectiveness of professionally led telephone-based support groups for female family caregivers of community-dwelling dementia patients . Recruited through various community sources , 103 female caregivers were r and omized to the telesupport group treatment or a control condition . Effects on caregiver burden , depression , and personal gains were evaluated at 6 months , the main end point . Older care-givers ( ≥65 ) in telesupport reported lower depression than control group caregivers did The present research describes the association between objective and subjective caregiver burden experienced by families and friends of individuals with chronic mental illness . Although there has been a significant quantity of research conducted about burden and mental illness , the findings have been equivocal because of varying definitions of burden and varying sampling procedures . The present research utilizes a st and ardized interview instrument for caregivers . Caregivers were named by a stratified r and om sample of clients who have been certified as severely mentally disabled and have received publicly-funded community mental health services in the state of Ohio during the 1990 fiscal year . Data were collected by the first author and a research assistant during telephone interviews between August 1991 and May 1992 . One hundred and eighty-nine caregivers were interviewed . Findings showed that the majority of caregivers are female , white , and aged 50 years or more . Parents comprise the largest group of caregivers and slightly more than one third of clients live with the caregiver . The relationship between caregiver and client is generally described as positive ; however , the interviews were conducted during a period when the clients ' symptomatology was more under control than previously in the relationship . Caregivers state that the clients need help much more often than they ask for it in all categories of possible help . Considering caregiver burden in relation to caregiver behaviors , time management is a somewhat frequent problem that is very troublesome to the caregiver . Considering client behaviors in relation to caregiver burden , embarrassing behaviors are most troublesome and occur with moderate frequency . The surprise element of these behaviors seems to be the most problematic Purpose : This paper explores the perceived health and reported level of strain in the primary carers of severely brain injured individuals , 15 - 18 months after discharge from inpatient rehabilitation . Method : Seventy carers took part in a prospect i ve descriptive study utilizing a semistructured interview and st and ardized measures including the SF36 , The Carer Strain Index and the Relative Question naire . Functional consequences for the injured person were also assessed . Results : The SF36 demonstrated a trend towards lower perceived health for carers than that reported in the general population . Neither perceived health status nor level of strain differed significantly according to the type of injury sustained ( haemorrhagic or traumatic ) nor initial severity of injury . Factors that contributed to carers having worse health status included the injured person 's level of disability and interpersonal factors such as the nature of the relationship , with spouses having lower perceived health status than parents . Conclusions : Irrespective of cause of injury , generalised health consequences result for the carers of those with disabling consequences of brain injury . Factors independent of the injured individual themselves ( such as the nature of the relationship to the carer ) need to be taken into consideration when exploring wellbeing of carers and planning services This investigation evaluates the moderating influence of social support on the negative effects of stress for family caregivers and vali date s the Perceived Stress Scale as a st and ard of measurement . Seventy-five family caregivers to older adults with heart failure were interviewed in their homes about perceived stress , depressive symptoms , and social support after hospital discharge . The Perceived Stress Scale demonstrated internal consistency . Social support did not moderate the effects of stress on depressive symptoms . Lack of a significant association between salivary cortisol and the Perceived Stress Scale did not support testing of construct validity . Stress levels , however , frequently vary due to caregiving dem and s and additional influencing factors ABSTRACT Objective : Despite response variability , cholinesterase inhibitors are recommended in mild to moderate Alzheimer 's disease . Dose titration is common ; however r and omized controlled trials ( RCTs ) have mainly investigated fixed-dose regimens . We examined practice patterns and outcomes of 6 ± 1.5-month rivastigmine therapy . Methods : Prospect i ve , pharmacoepidemiologic , naturalistic study of 175 evaluable patients with mild to moderate Alzheimer 's disease ( + 151 caregivers ) from 52 centers in Belgium on 6 ± 1.5 month ( titrated ) rivastigmine treatment . Main outcome measures : Measured at baseline ( enrollment ) and follow-up ( 6 ± 1.5 months ) . For patients : Mini-Mental State Exam ( MMSE ) , Activities of Daily Living ( ADL ) , Neuropsychiatric Inventory ( NPI ) , Global Deterioration Scale ( GDS ) scores ; treatment response ( improvement , maintenance , or decline less than normative slope ) . For caregivers : hours/week spent caring ; Zarit Caregiver Burden Scale ( ZCBS ) , 12‐item version of General Health Question naire ( GHQ‐12 ) , Instrumental Activities of Daily Living ( IADL ) scores . Results : Patients ’ MMSE and NPI scores ( p < 0.001 ) improved from baseline to follow-up , but not ADL and GDS scores . Treatment response was 89.1 % of patients for MMSE ( including 60.6 % with improvement ) and 77.7 % for NPI ( including 57.1 % with improvement ) . Quadratic curves were fitted for the average daily dose and the MMSE and NPI scores ; with a trend towards average daily dose of 6.0 ± 3.0 mg/day . Caregivers ’ ZCBS ( p = 0.036 ) and GHQ‐12 ( p = 0.029 ) scores improved , but not IADL scores and time spent caring . Conclusions : Patients ’ MMSE and ADL scores confirmed the meta-analyses of rivastigmine efficacy trials , while NPI scores exceeded efficacy results . Proportionately more patients responded to ( titrated ) treatment than in fixed-dose RCTs . Caregivers reported less burden ( similar to meta- analysis ) and better general health over the study period . Where efficacy and effectiveness results diverge , the benefit is in ‘ real-world ’ effectiveness . Large sample , multi-country replications , less sensitive to censoring secondary to missing data and powered to permit advanced modeling , as well as RCTs with adaptive design s to accommo date titration , are needed . The profile of patients most likely to benefit from treatment or most vulnerable to treatment outcome must be studied , as must the impact of physician- and center-related variables on outcomes Objective : To assess the effectiveness of community-based rehabilitation for stroke patients who were not admitted to hospital in South London . Design : R and omized controlled trial . Setting : Patients ' homes in South London . Subjects : Stroke patients not admitted to hospital after a stroke . Intervention : Rehabilitation at home by rehabilitation team for up to three months or usual care . Main outcome measures : The primary outcome measure was the Barthel score . Secondary measures included the Motricity Index , Rivermead ADL , Hospital Anxiety and Depression score and Nottingham Health Profile . Results : Forty-three patients who remained at home were r and omized to rehabilitation team ( 23 ) or ‘ usual ’ care ( 20 ) . The mean number of physiotherapy sessions was three ( range 1–14 ) for the rehabilitation team group and two for the usual care group . Patients ( with a deficit ) in the rehabilitation arm of the trial were more likely to receive occupational , physical and speech therapy than those in the control arm ( p = 0.03 , 0.01 and 0.008 , respectively ) . For those patients actually receiving therapy , there was no evidence that the amount received differed between the groups . However , the number of patients in each of these comparisons was very small . The outcome for patients in the rehabilitation team arm of the trial was nonsignificantly higher ( 0.05 < p < 0.2 ) than for those in the control arm for the areas of Nottingham Health Profile , anxiety , depression , caregiver strain and the proportion of patients living at home . Based on the data observed here , a trial with approximately 150 patients in each arm would be needed to have adequate power to detect a 33 % difference between intervention and control groups in these outcomes . Conclusion : Community therapy support for patients not admitted to hospital is feasible but to determine whether it is cost- or clinical ly effective would require trials of adequate size BACKGROUND Care for elderly persons with disabilities is usually characterized by fragmentation , often leading to more intrusive and expensive forms of care such as hospitalization and institutionalization . There has been increasing interest in the ability of integrated models to improve health , satisfaction , and service utilization outcomes . METHODS A program of integrated care for vulnerable community-dwelling elderly persons ( SIPA [ French acronym for System of Integrated Care for Older Persons ] ) was compared to usual care with a r and omized control trial . SIPA offered community-based care with local agencies responsible for the full range and coordination of community and institutional ( acute and long-term ) health and social services . Primary outcomes were utilization and public costs of institutional and community care . Secondary outcomes included health status , satisfaction with care , caregiver burden , and out-of-pocket expenses . RESULTS Accessibility was increased for health and social home care with increased intensification of home health care . There was a 50 % reduction in hospital alternate level inpatient stays ( " bed blockers " ) but no significant differences in utilization and costs of emergency department , hospital acute inpatient , and nursing home stays . For all study participants , average community costs per person were C dollar 3390 higher in the SIPA group but institutional costs were C dollar 3770 lower with , as hypothesized , no difference in total overall costs per person in the two groups . Satisfaction was increased for SIPA caregivers with no increase in caregiver burden or out-of-pocket costs . As expected , there was no difference in health outcomes . CONCLUSIONS Integrated systems appear to be feasible and have the potential to reduce hospital and nursing home utilization without increasing costs Objective : To establish the feasibility and method of evaluation of an early supported hospital discharge policy for patients with acute stroke . Design : A r and omized controlled trial comparing an early supported discharge service to conventional care . Setting : Three acute hospitals in Newcastle upon Tyne . Subjects : Ninety-two eligible patients with acute stroke admitted between 1 February 1995 and 31 January 1996 . Main outcome measures : Placement , length of stay , readmission rates , mortality , functional ability ( Nottingham Extended Activities of Daily Living ( ADL ) Scale ) , h and icap ( Oxford H and icap Scale ) , global health status ( Dartmouth Coop Function Charts ) and carer stress ( General Health Question naire 30 item ) . Results : The median length of stay for patients r and omized to early supported discharge was 13 days compared to 22 days in the conventional care group ( p = 0.02 ) . The median Barthel ADL Index at seven days post stroke of patients r and omized to early supported discharge was 15 , and 13 for those r and omized to conventional care ( NS ) . At three months post stroke the median Nottingham EADL score of patients r and omized to early supported discharge was 10 compared to 7 for those who received conventional care ( NS ) . There were no statistically significant differences in the global health status of patients or carer stress . Conclusion : An early supported discharge service following acute stroke with individualized rehabilitation in the community is feasible and can be evaluated by a r and omized controlled trial but a larger multicentre trial is needed before such a service is widely adopted OBJECTIVES to identify the impact of behavior disturbances on subjective burden of caregivers in demented patients attending day care services . METHODS subjects were 379 primary caregivers of r and omly sample d demented patients living at home , who attended geriatric day care programs . The caregiver burden of the mobile and non-mobile demented patients were measured using the Zarit Caregiver Burden Interview ( ZBI ) . The Mini-Mental State Examination ( MMSE ) and the Personal Self-Maintenance Scale ( PSMS ) were used to assess the patients ' condition . The Troublesome Behavior Scale ( TBS ) , originally developed in Japan , was used to assess the frequency of behavior disturbances exhibited by patients . RESULTS the caregivers of the mobile demented patients reported greater caregiver burden compared to those of the non-mobile demented patients . The frequency of behavior disturbance was significantly higher in the mobile patients than the non-mobile patients . For the mobile patient caregivers , w and ering , interfering , aggression and repetition were the predictors of caregiver burden . For the non-mobile patient caregivers , ' repeating same questions and /or clinging ' was the only predictor of caregiver burden . CONCLUSION the caregivers of the mobile demented patients reported higher burden due to the patients ' behavior disturbance compared to those of the non-mobile patients . These findings indicate a need for further development of interventions to prevent behavior disturbances that are especially burdensome for caregivers Despite a rapid increase in disabled elderly in Japan , the burden of the caregiver has not been properly assessed due to a lack of objective measurements . Our study was aim ed at adapting and validating the Zarit Caregiver Burden Interview ( ZBI ) in Japan , which is one of the most widely used measurements for caregivers ' burden in the United States . Sixty-six caregivers answered the self-administered question naire , involving the Japanese version of the ZBI and questions regarding their caregiving situation . Our study demonstrated that the Japanese version of the ZBI had equally as high reliability and validity as the original version . The Japanese ZBI had a high test-retest reliability ( r = 0.76 ) and internal consistency ( Cronbach 's alpha = 0.93 ) . The total score of the ZBI was highly correlated with the caregivers ' score of the Center for Epidemiologic Studies Depression Scale ( CES-D ) score ( r = 0.50 ) , as well as a single global rating of burden ( r = 0.71 ) . It was also shown that demographic distribution of the score of the Japanese version had a similar trend to that of the original version . Caregivers who looked after patients with behavioral disturbances were found to have a significantly higher ZBI score than those who looked after patients without behavioral disturbances , which is consistent with previous findings . It is concluded that the Japanese version of the ZBI can be used to measure feelings of burden of caregivers in the Japanese population and can be used for cross-cultural comparison Abstract Objective : To assess the clinical effectiveness of an early discharge policy for patients with stroke by using a community based rehabilitation team . Design : R and omised controlled trial to compare conventional care with an early discharge policy . Setting : Two teaching hospitals in inner London . Subjects : 331 medically stable patients with stroke ( mean age 71 ) who lived alone and were able to transfer independently or who lived with a resident carer and were able to transfer with help . Interventions : 167 patients received specialist community rehabilitation for up to 3 months after r and omisation . 164 patients continued with conventional hospital and community care . Main outcome measures : Barthel score at 12 months . Secondary outcomes measured impairment with motoricity index , minimental state examination , and Frenchay aphasia screening test ; disability with the Rivermead activity of daily living scales , hospital anxiety and depression scale , and 5 m walk ; h and icap with the Nottingham health profile ; carer stress with caregiver strain index and patient and carer satisfaction . The main process measure was length of stay after r and omisation . Results : One year after r and omisation no significant differences in clinical outcomes were found apart from increased satisfaction with hospital care in the community therapy group . Length of stay after r and omisation in the community therapy group was significantly reduced ( 12 v 18 days ; P<0.0001 ) . Patients with impairments were more likely to receive treatment in the community therapy group . Conclusions : Early discharge with specialist community rehabilitation after stroke is feasible , as clinical ly effective as conventional care , and acceptable to patients . Considerable reductions in use of hospital beds are achievable . Key messages Early discharge from hospital after stroke with specialist rehabilitation at home is feasible without an increase in readmission rates or stress to carers This r and omised controlled trial shows this method to be as effective as conventional care when assessed with a range of measures of impairment , disability , h and icap , carer stress , and patient and carer satisfaction at 1 year Significant reductions in bed usage can be achieved by the provision of a community rehabilitation team with no significant increase in rehabilitation 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 BACKGROUND Many studies have assessed the impact of caregivers ' work activities on the caregiver . There is growing concern about the ever-increasing problems , both physical and physiological , faced by health care workers who provide care for the ill and incapacitated . AIM The aim of the study was to examine what , if any , differences exist between male and female caregivers . This study primarily focused on caregivers who were taking care of a family member . METHOD Three hundred and eighty-eight caregivers ( 280 females and 108 males ) were recruited from 16 r and omly selected home-care agencies in Southern Taiwan . The participants completed the Chinese Health Question naire-12 and the Self-Rated Health Scale . They also completed question naires drawn up specifically for the purpose of this study . RESULTS Compared to the male caregivers , the female caregivers more often reported they suffered from symptoms of lack of well being , a decrease in psychosocial health and overall self-rated health . CONCLUSION The results reiterate the importance of considering gender differentiation in the caregiving role . Major differences were found in the extent to which negative health consequences were experienced by the male and female caregivers . The results suggest that caregivers , especially female caregivers , urgently require adequate professional health care assistance in order to reduce the negative physical and physiological effects of caregiving on the health caregiver Most care received by cancer patients is provided in the community by informal or unpaid caregivers . The unrelenting care dem and s can lead to physical , emotional , social , and financial reactions ; furthermore , studies indicate that the effects of caregiving may endure after the patient 's death . A need therefore exists for instruments measuring both caregiving and post-caregiving reactions . Among available instruments , the Caregiver Reaction Assessment ( CRA ) is a multidimensional , 5-factor measure design ed to assess the negative and positive aspects of caregiving . The current study examined the psychometric properties and factor structure of responses to a modified Hebrew version of the CRA aim ed at measuring caregiving and post-care-giving reactions . Although the scale was modified , it was assumed that , similar to the original CRA , a 5-factor structure would be supported by means of confirmatory factor analysis . A total of 236 bereaved primary caregivers of cancer patients from central and southern regions of Israel were recruited over a period of 18 months . As hypothesized , results provide support for a 5-factor structure of responses to this modified version of the CRA . The concurrent validity of responses to the scale was also supported . Replication of the findings with r and omly derived and larger sample sizes is needed AIM This paper reports on a study to establish the profile of need for psychosocial family interventions and to examine the concurrent validity of the Relatives ' Cardinal Needs Schedule with an Asian population of carers in Engl and , UK . BACKGROUND Although psychosocial interventions for schizophrenia have a strong evidence base , little is known of the needs of Asian families . A cardinal need is indicative of the existence of a problem causing the carer a strain for which the carer is willing to co-operate if help is offered and for which systematic help has not been provided in the last 12 months . METHODS The Relatives ' Cardinal Needs Schedule was used to assess needs in a small r and omly selected sample of Asian carers in one English locality and to compare the results with independent measures of patient symptoms and carer distress . RESULTS Feedback from carers indicated that the Relatives ' Cardinal Needs Schedule was culturally acceptable and appropriate to their needs . There was evidence for the validity of the assessment in that there were large and statistically significant associations between the number of needs detected by the Relatives ' Cardinal Needs Schedule and independent measures of both carer distress ( as measured by the 28 item General Health Question naire ) and patient symptom severity ( as reliably assessed from case notes ) . CONCLUSION The Relatives ' Cardinal Needs Schedule may prove useful for nurses and service managers in establishing the need for psychosocial family interventions amongst Asian families in the United Kingdom OBJECTIVE To assess the impact on burden reported by caregivers of patients with mild to moderate Alzheimer 's disease ( AD ) who were treated with metrifonate during a r and omized double blind clinical trial . DESIGN R and omized clinical trial , with a 2-week screening period and a 26-week double blind , placebo controlled , treatment phase . Caregivers were assessed at baseline , at 12 weeks , and at end of trial . SETTING Caregivers were interviewed at clinics as part of the assessment of the patients . PARTICIPANTS Six hundred and three caregivers of AD patients who were enrolled in the MALT trial ; 591 ( 98 % ) provided data suitable for analysis at baseline , and 546 ( 91 % ) provided data allowing for inclusion in the analysis of change scores . MEASUREMENTS The Caregiver Burden Assessment consisted of the Screen for Caregiver Burden , including both subjective ( SCB-subj ) and objective ( SCB-obj ) scores ; the cognitive subscale of Poulshock and Deimling ( PD ) ; an abridged version of the Relatives Stress Scale ( aRSS ) ; assessment s of time spent in providing care , including the Caregiver Activity Time Scale ( CATS ) ; and demographic and background variables on both the patient and caregiver . RESULTS Treatment of mild to moderate AD patients with metrifonate for a duration of 26 weeks significantly reduced the psychological burden of care to the caregivers , as measured by the SCB-subj , the PD , and the aRSS . There were no statistically significant differences on the measures assessing the time spent in caregiving , except for the caregiver 's subjective impression of the change in time spent providing care during the trial . When comparing individual dose groups , most of the measures of burden showed the largest benefits in burden for the 60/80 mg group , followed by the 40/50 mg group , and then the placebo group . However , there was no statistically significant dose effect . CONCLUSIONS This study provides the first evidence from a r and omized clinical trial of any acetylcholinesterase inhibitor used in the treatment of AD demonstrating a positive impact on the patient 's caregiver as well as benefits to the patient . These results were shown consistently across several measurement scales and were observed after six months of treatment . These findings reinforce the clinical significance of research that has shown that metrifonate has beneficial impacts on the cognitive , behavioral , and functional abilities of AD patients . Because caregiver burden is a leading factor in the decision for institutional care placement , the ability to favorably impact that burden through pharmacological treatment of the patient is important Objective : To investigate the factor structure and concurrent validity of the Caregiver Appraisal Scale ( CAS ) in a sample of caregivers of adults with traumatic brain injury ( TBI ) . Design : Prospect i ve cohort study . Setting : Two sites : ( 1 ) Outpatient clinics associated with a comprehensive inpatient brain injury rehabilitation program and ( 2 ) a comprehensive residential postacute rehabilitation program in the Southern United States . Participants : One hundred forty-nine caregivers of adults with TBI enrolled in the TBI Model Systems Project and 92 caregivers of adults with TBI admitted to a residential postacute rehabilitation program . Most caregivers were women and either parents or spouses of the injured person . Main Outcome Measures : Caregiver Appraisal Scale ( CAS ) ; Subjective Burden Scale ( SBS ) ; Objective Burden Scale ( OBS ) ; General Health Question naire ( GHQ ) . Results : Principal components analysis with varimax rotation yielded four factors : perceived burden ( PB ) , caregiver relationship satisfaction ( CRS ) , caregiving ideology ( CI ) , and caregiving mastery ( CM ) , which were found to be fairly stable across treatment setting s. Adequate concurrent validity was demonstrated for the perceived burden factor , and adequate internal consistency was found for three of four scales . Conclusions : Preliminary support for the use of the CAS in caregivers of adults with TBI was obtained . However , further scale development , particularly for the CM factor , will likely improve the stability and usefulness of this instrument |
11,343 | 25,519,688 | Despite collating more event data than previous systematic review s of r and omised controlled trials , there is insufficient power to confirm clinical ly important effects of dietary advice and salt substitution on cardiovascular mortality in normotensive or hypertensive population s. Our estimates of the clinical benefits from advice to reduce dietary salt are imprecise , but are larger than would be predicted from the small blood pressure reductions achieved .
Our findings do not support individual dietary advice as a means of restricting salt intake . | BACKGROUND This is an up date of a Cochrane review that was first published in 2011 of the effects of reducing dietary salt intake , through advice to reduce salt intake or low-sodium salt substitution , on mortality and cardiovascular events .
To assess the long-term effects of advice and salt substitution , aim ed at reducing dietary salt , on mortality and cardiovascular morbidity.2 .
To investigate whether a reduction in blood pressure is an explanatory factor in the effect of such dietary interventions on mortality and cardiovascular outcomes . | Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery . In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output . In the present study , we measured the effect of long-term severe sodium restriction on vasopressin ( AVP ) and oxytocin ( OT ) levels during normal pregnancy and after delivery . Fifty-nine healthy nulliparous women were r and omized either for a low sodium diet ( 20 mmol sodium daily ) or for a normal diet from week 12 of pregnancy onwards . Circulating plasma levels and urinary excretion of AVP and OT , their neurophysins ( Np-AVP and Np-OT ) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery . After completion of the study , women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables . After r and omization , a reduction in urinary sodium excretion of , on average , 40 - 82 % was found . In general , no effect of sodium restriction could be demonstrated on the various parameters ( 0.53 < P < 0.98 ) with the exception of a significantly lower 24-h urinary AVP excretion by non-smokers with sodium restriction compared with non-smokers having a normal diet ( P = 0.018 ) . For all parameters , clear changes were found in the course of pregnancy and puerperium ( P < 0.0001 to P < 0.005 ) . Platelet-bound AVP decreased and Np-OT increased during pregnancy . After birth , free plasma AVP , platelet-bound AVP , OT , osmolality , sodium and potassium increased , while Np-AVP and Np-OT decreased . Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones , pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels . Long-term severe sodium restriction diminishes urinary AVP excretion in ( non-smoking ) pregnant women , without changing circulating levels of AVP and OT , despite the known reduction in circulating volume . The reduced circulating ( platelet-bound ) AVP levels during pregnancy , whether or not in combination with severe sodium restriction , support the absence of significant non-osmotic stimulation of AVP during pregnancy 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 Background Decreasing salt consumption can prevent cardiovascular diseases ( CVD ) . Practically , it is difficult to promote people ’s awareness of daily salt intake and to change their eating habits in terms of reducing salt intake for better cardiovascular health . Health education programs visualizing daily dietary salt content and intake may promote lifestyle changes in patients at high risk of cardiovascular diseases . Methods / Design This is a cluster r and omized trial . A total of 800 high-CVD-risk patients attending diabetes and hypertension clinics at health centers in Muang District , Chiang Rai province , Thail and , will be studied with informed consent . A health center recruiting 100 participants is a cluster , the unit of r and omization . Eight clusters will be r and omized into intervention and control arms and followed up for 1 year . Within the intervention clusters the following will be undertaken : ( 1 ) salt content in the daily diet will be measured and shown to study participants ; ( 2 ) 24-hour salt intake will be estimated in overnight-collected urine and the results shown to the participants ; ( 3 ) a dietician will assist small group health education classes in cooking meals with less salt . The primary outcome is blood pressure change at the 1-year follow-up . Secondary outcomes at the 1-year follow-up are estimated 24-hoursalt intake , incidence of CVD events and CVD death . The intention-to-treat analysis will be followed . Blood pressure and estimated 24-hour salt intake will be compared between intervention and control groups at the cluster and individual level at the 1-year follow-up . Clinical CVD events and deaths will be analyzed by time-event analysis . Retinal blood vessel calibers of CVD-risk patients will be assessed cross-sectionally . Behavioral change to reduce salt intake and the influencing factors will be determined by structured equation model ( SEM ) . Multilevel regression analyses will be applied . Finally , the cost effectiveness of the intervention will be analyzed . Discussion This study is unique as it will recruit the individuals most vulnerable to CVD morbidity and mortality by applying the general Framingham CVD risk scoring system . Dietary salt reduction will be applied as a prioritized , community level intervention for the prevention of CVD in a developing country . Trial registration IS RCT 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 The Hypertension Prevention Trial ( HPT ) was a r and omized , controlled , multicenter ( four clinics , four re source centers ) trial design ed to test the feasibility of achieving and sustaining dietary changes in the intake of calories , sodium , and potassium and to assess the effect of those changes on blood pressure in a normotensive population . The trial involved 841 men and women ( plus a test cohort of 78 ) who , at the first baseline ( BL ) examination , were in the age range of 25 - 49 years and had diastolic blood pressure ( DBP ) greater than or equal to 76 but less than 100 mm Hg ( average of two readings ) , and at the examination prior to r and omization ( BL 2 ) had DBP greater than or equal to 78 but less than 90 mm Hg ( also averaged ) . Participants were r and omly assigned to a control treatment group ( no dietary counseling ) or to one of four dietary treatment groups involving counseling design ed to reduce calorie intake , reduce sodium intake , reduce sodium and calorie intake , and reduce sodium and increase potassium intake . Dietary counseling was provided primarily in group setting s and was aim ed at changing participants ' shopping , cooking , and eating habits related to a design ated treatment assignment . The effect of dietary counseling was measured through changes in urinary excretion of sodium and potassium , changes in body weight , and changes in reported food intake based on 24-hour food records . Blood pressure changes during the 3-year course of followup were based on measurements taken at 6-month intervals from enrollment using a r and om-zero sphygmomanometer . This chapter provides a general description of the design and methods of the HPT and the underlying rationale for decisions affecting the design BACKGROUND The beneficial effects of potassium-enriched salt on blood pressure have been reported in a few short-term trials . The long-term effects of potassium-enriched salt on cardiovascular mortality have not been carefully studied . OBJECTIVE The objective was to examine the effects of potassium-enriched salt on cardiovascular disease ( CVD ) mortality and medical expenditures in elderly veterans . DESIGN Five kitchens of a veteran retirement home were r and omized into 2 groups ( experimental or control ) and veterans assigned to those kitchens were given either potassium-enriched salt ( experimental group ) or regular salt ( control group ) for approximately 31 mo . Information on death , health insurance cl aims , and date s that veterans moved in or out of the home was gathered . RESULTS Altogether , 1981 veterans , 768 in the experimental [ x ( + /-SD ) age : 74.8 + /- 7.1 y ] and 1213 in the control ( age : 74.9 + /- 6.7 y ) groups , were included in the analysis . The experimental group had better CVD survivorship than did the control group . The incidence of CVD-related deaths was 13.1 per 1000 persons ( 27 deaths in 2057 person-years ) and 20.5 per 1000 ( 66 deaths in 3218 person-years ) for the experimental and control groups , respectively . A significant reduction in CVD mortality ( age-adjusted hazard ratio : 0.59 ; 95 % CI : 0.37 , 0.95 ) was observed in the experimental group . Persons in the experimental group lived 0.3 - 0.90 y longer and spent significantly less ( approximately US Dollars 426/y ) in inpatient care for CVD than did the control group , after control for age and previous hospitalization expenditures . CONCLUSIONS This study showed a long-term beneficial effect on CVD mortality and medical expenditure associated with a switch from regular salt to potassium-enriched salt in a group of elderly veterans . The effect was likely due to a major increase in potassium and a moderate reduction in sodium intakes The Hypertension Prevention Trial ( HPT ) was a r and omized unmasked multicenter trial design ed to address questions concerning the feasibility and efficacy of dietary intervention in the primary prevention of hypertension . Participants in the diet treatments were given counseling to achieve and sustain changes in calorie , sodium , and /or potassium intake . Diet composition , sodium and potassium excretion , and body weight were assessed for all participants at 6-mo intervals over 3 y. This paper provides information about extent and possible sources of bias in the dietary assessment methodology used in the HPT . Estimates of nutrient intake were derived from food records , urinalysis , and measurement of body weight . Reported potassium intake increased and sodium intake declined to a greater degree during the study than did potassium and sodium excretion . Our results indicate that repeated assessment s of diet , which depend upon participant recording , may not accurately represent usual diet in a dietary trial BACKGROUND Despite the reported benefits , weight loss is not always advised for older adults because some observational studies have associated weight loss with increased mortality . However , the distinction between intentional and unintentional weight loss is difficult to make in an observational context , so the effect of intentional weight loss on mortality may be clarified in the setting of a r and omized controlled trial . OBJECTIVE The objective was to determine the effect of intentional weight loss on all-cause mortality by using follow-up data from a r and omized trial completed in 1995 that included a weight-loss arm . DESIGN The Trial of Nonpharmacologic Intervention in the Elderly ( TONE ) used a 2 × 2 factorial design to determine the effect of dietary weight loss , sodium restriction , or both on blood pressure control in 585 overweight or obese older adults being treated for hypertension ( mean ± SD age : 66 ± 4 y ; 53 % female ) . All-cause mortality was ascertained by using the Social Security Index and National Death Index through 2006 . RESULTS The mortality rate of those who were r and omly assigned to the weight-loss intervention ( n = 291 ; mean weight loss : 4.4 kg ) did not differ significantly from that of those who were not r and omly assigned to this group ( n = 294 ; mean weight loss : 0.8 kg ) . The adjusted HR was 0.82 ( 95 % CI : 0.55 , 1.22 ) . CONCLUSIONS Intentional dietary weight loss was not significantly associated with increased all-cause mortality over 12 y of follow-up in older overweight or obese adults . Additional studies are needed to confirm and extend our findings to older age groups . This trial is registered at clinical trials.gov as NCT00000535 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 grams/day , most have found an inverse association of intake with outcome ; in subjects with average intakes greater than 4.5 grams/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 to 6.0 grams/day are associated with increased cardiovascular risk . This robust body of evidence does not support universal reduction of sodium intake BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals Background — Recent studies have raised the possibility of adverse effects of low sodium , particularly < 2300 mg/d , on cardiovascular disease ; however , these paradoxical findings might have result ed from suboptimal measurement of sodium and potential biases related to indication or reverse causation . Methods and Results — Phases 1 and 2 of the Trials of Hypertension Prevention ( TOHP ) collected multiple 24-hour urine specimens among prehypertensive individuals . During extended posttrial surveillance , 193 cardiovascular events or cardiovascular disease deaths occurred among 2275 participants not in a sodium reduction intervention with 10 ( TOHP II ) or 15 ( TOHP I ) years of posttrial follow-up . Median sodium excretion was 3630 mg/d , with 1.4 % of the participants having intake < 1500 mg/d and 10 % < 2300 mg/d , consistent with national levels . Compared with those with sodium excretion of 3600 to < 4800 mg/d , risk for those with sodium < 2300 mg/d was 32 % lower after multivariable adjustment ( hazard ratio , 0.68 ; 95 % confidence interval , 0.34–1.37 ; P for trend=0.13 ) . There was a linear 17 % increase in risk per 1000 mg/d increase in sodium ( P=0.05 ) . Spline curves supported a linear association of sodium with cardiovascular events , which continued to decrease from 3600 to 2300 and 1500 mg/d , although the data were sparse at the lowest levels . Controlling for creatinine levels had little effect on these results . Conclusions — Results from the TOHP studies , which overcome the major method ological challenges of prior studies , are consistent with overall health benefits of reducing sodium intake to the 1500 to 2300 mg/d range in the majority of the population , in agreement with current dietary guidelines Phase II of the Trials of Hypertension Prevention is a multicenter , r and omized , controlled trial design ed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure . The 2 x 2 factorial study design includes weight loss alone , restricted sodium intake alone , the combination of weight loss and sodium restriction , and a control group . Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months , which exceeded the sample size goal of 2250 . Among r and omized participants , 21 % were minorities and 34 % were women . Overall , direct mail generated the most r and omized participants ( 73 % ) , followed by community screening ( 12 % ) and media advertisement ( 11 % ) . Referrals from community health care providers yielded few participants . Prescreening improved overall efficiency and reduced costs . Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger , single , male , smokers , and less educated Background — Despite compelling evidence for sodium ’s adverse effects on blood pressure , it remains uncertain whether excess sodium intake is a risk factor for coronary heart disease ( CHD ) in the overall population and in potentially more susceptible subgroups . Methods and Results — We prospect ively followed 7543 adults aged 28 to 75 years and free of cardiovascular and kidney disease in 1997/1998 of the Prevention of Renal and Vascular End-stage Disease ( PREVEND ) study . Sodium excretion was measured in two 24-hour urine collection s at baseline . Potential susceptibility factors were blood pressure and plasma N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) . Median 24-hour sodium excretion was 137 mmol ( Q1–Q3 , 106–171 mmol ) . During a median follow-up of 10.5 ( Q1–Q3 : 9.9–10.8 ) years , 452 CHD events occurred . In the entire cohort , there was no association between each 1-g/d ( 43 mmol/24 h ) increment in sodium excretion and CHD risk ( adjusted hazard ratio , 1.07 ; 95 % confidence interval , 0.98–1.18 ; P=0.15 ) . However , the association of sodium excretion with CHD risk tended to be modified by mean arterial pressure ( Pinteraction=0.08 ) and was modified by NT-proBNP ( Pinteraction=0.002 ) . When stratified , each 1-g/d increment in sodium excretion was associated with an increased risk for CHD in subjects with hypertension ( adjusted hazard ratio , 1.14 ; 95 % confidence interval , 1.01–1.28 ; n=2363 ) and in subjects with NT-proBNP concentrations above the sex-specific median ( adjusted hazard ratio , 1.16 ; 95 % confidence interval , 1.03–1.30 ; n=3771 ) . Conclusions — Overall , there was no association between sodium excretion and risk of CHD . The association between sodium excretion and CHD risk was modified by NT-proBNP . Higher sodium excretion was associated with an increased CHD risk among subjects with increased NT-proBNP concentrations or with hypertension 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 OBJECTIVE Many guidelines recommend that patients with type 2 diabetes should aim to reduce their intake of salt . However , the precise relationship between dietary salt intake and mortality in patients with type 2 diabetes has not been previously explored . RESEARCH DESIGN AND METHODS Six hundred and thirty-eight patients attending a single diabetes clinic were followed in a prospect i ve cohort study . Baseline sodium excretion was estimated from 24-h urinary collection s ( 24hUNa ) . The predictors of all-cause and cardiovascular mortality were determined by Cox regression and competing risk modeling , respectively . RESULTS The mean baseline 24hUNa was 184 ± 73 mmol/24 h , which remained consistent throughout the follow-up ( intraindividual coefficient of variation [ CV ] 23 ± 11 % ) . Over a median of 9.9 years , there were 175 deaths , 75 ( 43 % ) of which were secondary to cardiovascular events . All-cause mortality was inversely associated with 24hUNa , after adjusting for other baseline risk factors ( P < 0.001 ) . For every 100 mmol rise in 24hUNa , all-cause mortality was 28 % lower ( 95 % CI 6–45 % , P = 0.02 ) . After adjusting for the competing risk of noncardiovascular death and other predictors , 24hUNa was also significantly associated with cardiovascular mortality ( sub-hazard ratio 0.65 [ 95 % CI 0.44–0.95 ] ; P = 0.03 ) . CONCLUSIONS In patients with type 2 diabetes , lower 24-h urinary sodium excretion was paradoxically associated with increased all-cause and cardiovascular mortality . Interventional studies are necessary to determine if dietary salt has a causative role in determining adverse outcomes in patients with type 2 diabetes and the appropriateness of guidelines advocating salt restriction in this setting The angiotensinogen gene has been linked to essential hypertension and increased blood pressure . A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels . To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction , 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus . Participants had diastolic blood pressures between 83 and 89 mm Hg and were r and omized in a 2x2 factorial design to sodium reduction , weight loss , combined intervention , or usual care groups . Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension ( 44.6 % ) compared with those with the GG genotype ( 31.5 % ) , with a relative risk of 1.4 ( 95 % confidence interval [ 0.87 , 2.34 ] , test for trend across all 3 genotypes , P=0.10 ) . In contrast , the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype ( relative risk=0.57 [ 0.34 , 0.98 ] versus usual care ) but not for persons with the GG genotype ( relative risk=1.2 [ 0.79 , 1.81 ] , test for trend P=0.02 ) . Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes ( P=0.01 ) , with greater net blood pressure reduction in those with the AA genotype ( -2.2 mm Hg ) than those with the GG genotype ( + 1.1 mm Hg ) . A similar trend across the 3 genotypes for net systolic blood pressure reduction ( -2.7 for AA versus -0.2 mm Hg for GG ) was not significant ( P=0.17 ) . Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction . We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension Objective Dietary sodium and potassium consumption is associated with blood pressure levels . The objective of this study was to define a practical and low-cost method for the control of blood pressure by modification of these dietary cations in rural Chinese . Methods This study was a double-blind , r and omized , controlled trial design ed to establish the long-term effects of a reduced-sodium , high-potassium salt substitute ( 65 % sodium chloride , 25 % potassium chloride , 10 % magnesium sulphate ) compared to normal salt ( 100 % sodium chloride ) on blood pressure among high-risk individuals . Following a 4-week run-in period on salt substitute , participants were r and omly assigned to replace their household salt with either the study salt substitute or normal salt for a 12-month period . Results The mean age of the 608 r and omized participants was 60 years and 56 % of them were female . Sixty-four percent had a history of vascular disease and 61 % were taking one or more blood pressure-lowering drugs at entry . Mean baseline blood pressure was 159/93 mmHg ( SD 26/14 ) . The mean overall difference in systolic blood pressure between r and omized groups was 3.7 mmHg ( 95 % confidence interval 1.6–5.9 , P < 0.001 ) . There was strong evidence that the magnitude of this reduction increased over time ( P = 0.001 ) with the maximum net reduction of 5.4 mmHg ( 2.3–8.5 ) achieved at 12 months . There were no detectable effects on diastolic blood pressure . Conclusion Salt substitution produced a substantial and sustained systolic blood pressure reduction in this population , and should be actively promoted as a low-cost alternate or adjunct to drug therapy for people consuming significant quantities of salt 31 patients with a diastolic blood-pressure between 95 and 109 mm Hg have been treated for two years with a regimen involving a moderate restriction of salt in the diet . The results are compared with those in a control group and in a drug-treated group . Salt restriction has reduced the diastolic blood-pressure by 7.3+/-1.6 mm Hg , a result similar to that in patients treated with antihypertensive drugs . In the untreated group the diastolic blood-pressure rose by 1.8+/-1.1 mm Hg . Most patients did not achieve the desired amount of salt restriction and a stricter adherence to the diet might have caused further falls in blood-pressure . Excessive salt intake is probably a major cause of the epidemic of hypertension in " civilised " countries and a reduction in salt intake may help to control the epidemic . In persons with a diastolic blood-pressure between 90 and 105 mm Hg salt restriction should be tried before drugs PURPOSE To study the consequences of a diet with usual salt quantity ( non salt-restricted ) on hospital treatment of congestive heart failure ( CHF ) , in behalf of a better food intake . METHODS Thirty-two patients admitted to compensation of class III or IV CHF , r and omly allowed to group I ( 2 g salt per day diet ) or II ( 10 g salt ) . Hypertensive , renal failure or restrictive syndrome cases were excluded . Oral medication and water intake were st and ardized ; furosemide dosage was adjusted on a daly basis , allowing the study of this drug 's requirements in each group . Compensation of CHF was defined as a return to classes I or II without edema . RESULTS Group I included 14 and group II 18 patients . There was no significant difference between groups respective to the time needed for compensation of CHF ( 7.5 x 6.6 days , mean ) percentual weight loss ( 12.2 x 10.0 % ) , cumulative furosemide dosage ( 568 x 599 mg ) , mean daily furosemide dosage per kilogram of lean weight ( 1.43 x 1.58 mg/kg/day ) , and to 24-hour urinary excretion of sodium ( 241 x 254 mEq ) and potassium ( 38.8 x 53.9 mEq ) . Small elevations of blood urea and potassium were an uniform trend . There was no significant alteration of plasmatic sodium . Food intake was adequate . There was one death for each group , from causes not directly related to CHF . CONCLUSION Dietary salt intake did not adversely influence in-hospital compensation of severe CHF in studied group . In selected cases , adoption of a more liberal diet in this aspect may allow the patient a better ingestion of food Background / objectives : To examine whether dietary interventions promote intakes of fruit , vegetable , fish and lower salt intake were effective in preventing cognitive decline in older people . Dietary factors have been associated with cognitive function in older people . Subjects/ methods : A total of 429 non-demented subjects in 14 old age hostels , with an average age of 83 years , were r and omly assigned by hostel to have either regular group dietary counselling and menu changes or advice on hostel menu only . Food and salt intakes were estimated at regular intervals by 24-h recall or food record and fasting urinary sodium , respectively . The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale score . Secondary clinical outcomes were mini mental state examination , category fluency test , body weight , blood pressures and health-related quality of life . Results : At baseline , the intervention group had more men and lower fish intake . When compared with control group , the intervention group had significantly less decline in intakes of fruit and fish . At month 33 % , 22.2 % and 27.2 % of intervention and control group subjects had cognitive decline , respectively ( Unadjusted P=0.285 , χ2 test ) . There were no significant group changes in secondary clinical outcomes . On subgroup analysis , fewer cognitively normal subjects in intervention group had cognitive decline at month 24 ( adjusted P=0.065 ) . Conclusions : Dietary interventions in older people were effective in maintaining fruit and fish intake , but this did not lead to a significant reduction in cognitive decline Objective To examine the effectiveness of the st and ard policy in the Netherl and s to prescribe a sodium restricted diet to prevent or to treat mild pregnancy‐induced hypertension OBJECTIVE To compare the effectiveness of different approaches to participant enrollment in a behavior modification trial . DESIGN Concurrent , prospect i ve evaluation performed in context of recruitment for a r and omized , controlled trial . SETTING Four study centers located in Baltimore , Maryl and , Memphis , Tennessee New Brunswick , New Jersey , and Winston-Salem , North Carolina . PARTICIPANTS Men and women aged 60 to 80 years who were being treated with a prescription medication for control of hypertension . MAIN OUTCOME MEASURES Visit counts and percent yields were assessed at each stage of the screening and r and omization process . Logistic regression was used to contrast the r and omization yields for different recruitment strategies and to explore the impact of sociodemographic characteristics and geographic location on recruitment yields . RESULTS The overall r and omization yields from a prescreen contact and a first screening visit to enrollment in the trial were 11 % and 31 % , respectively . R and omization yields varied significantly by participant age , education , and marital status . CONCLUSIONS Our results demonstrate the feasibility of recruitment for trials of nonpharmacologic interventions in older people and suggest that mass mailing and mass media advertising campaigns provide an effective means of enrolling in such studies participants with a broad range of personal characteristics AIM To determine the effect on blood pressure from brisk walking with or without salt restriction in a community based sample of treated hypertensives . METHODS The intervention was undertaken in a community setting with a factorial r and omised controlled trial and blinded assessment of blood pressure . One hundred and eighty one healthy adult volunteers with a sedentary lifestyle and on pharmacological therapy for hypertension briskly walked for 40 minutes three times per week with or without salt restriction . Systolic and diastolic blood pressure were assessed at three and six months . RESULTS Of the original 208 participants 181 ( 87 % ) completed the study . significant reductions of up to 7 mm Hg were found in systolic blood pressure at 3 months for brisk walking alone ( p = 0.04 ) and salt restriction alone ( p = 0.03 ) but not for the combined intervention ( p = 0.17 ) . No significant change was found for diastolic blood pressure . There was no significant change in blood pressure at 6 months . CONCLUSIONS Simple advice on exercise and sodium restriction in a community setting can significantly lower systolic blood pressure at least for 3 months . The combination of the two interventions was less effective than each therapy alone Phase II of the Trials of Hypertension Prevention ( TOHP ) is a multicenter , r and omized trial sponsored by the National Heart , Lung , and Blood Institute design ed to test whether weight loss alone , sodium reduction alone , or the combination of weight loss and sodium reduction will decrease diastolic ( DBP ) and systolic blood pressure ( SBP ) as well as the incidence of hypertension ( DBP > or = 90 mm Hg , SBP > or = 140 mm Hg , and /or use of antihypertensive medications ) in subjects with high-normal DBP ( 83 to 89 mm Hg ) and SBP less than 140 mm Hg at entry . These interventions were chosen for longer-term testing with end points including hypertension prevention as well as blood pressure ( BP ) change based on their demonstrated short-term efficacy in reducing BP in phase I of TOHP . The phase II study population is comprised of 2382 participants ( 1566 men and 816 women ) who are 110 to 165 % of desirable body weight , allocated at r and om to the four treatment arms using a 2 x 2 factorial design . The trial has 80 % power to detect an overall treatment effect on DBP of 1.2 mm Hg for weight loss or sodium reduction and a difference of 1.6 mm Hg between the combined intervention and placebo groups . BP observers are blinded to participant treatment assignments . Participants will be followed for 3 to 4 years . This trial may have important public policy implication s concerning the ability of life-style modifications to reduce BP and prevent the development of hypertension over the long term , thereby avoiding the need for drug therapy which while effective is costly and may have side effects 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 Fifth Report of the Joint National Committee on Detection , Evaluation , and Treatment of High Blood Pressure recommends that attempts to discontinue antihypertensive drug therapy be considered after blood pressure ( BP ) has been controlled for 1 year . However , discontinuation of drug therapy could unmask underlying conditions and precipitate clinical cardiovascular events . The Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) was a clinical trial of the efficacy of weight loss and /or sodium reduction in controlling BP after withdrawal of drug therapy in patients with a BP < 145/85 mm Hg on 1 antihypertensive medication . Of 975 participants , 886 entered the drug withdrawal phase of the trial and 774 were successfully withdrawn from their medications . Thirty-three events ( stroke , transient ischemic attack , myocardial infa rct ion , arrhythmia , congestive heart failure , angina , other ) occurred between r and omization and the onset of drug withdrawal ( median time 3.6 months ) , 57 events occurred either during or after drug withdrawal ( 14.0 months ) , and 36 events occurred after resumption of antihypertensive therapy ( 15.9 months ) . Event rates per 100 person-years were 5.5 , 5.5 , and 6.8 for the 3 time periods ( p=0.84 ) in the nonoverweight group and 7.2 , 5.2 , and 5.6 ( p=0.08 ) in the overweight group . The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressure > or = 150/90 mm Hg at withdrawal , providing that good BP control can be maintained with nonpharmacologic therapy Phase I of the Trials of Hypertension Prevention was design ed to test the effectiveness and safety of three life-style ( weight loss , sodium restriction , and stress management ) and four nutrition supplement ( calcium , magnesium , potassium , and fish oil ) interventions in reducing diastolic blood pressure ( DBP ) in persons with a high-normal blood pressure . A total of 2182 persons with a DBP between 80 and 89 mm Hg met the eligibility criteria for participation in phase I and were r and omized to one of the active intervention or control treatment groups . Most were white ( 82 % ) , male ( 70 % ) , married ( 76 % ) , nonsmoking ( 88 % ) , college graduate ( 53 % ) , full-time employees ( 91 % ) . The average blood pressure prior to entry into the trial was 124.9 mm Hg systolic and 83.8 mm Hg diastolic . A variety of baseline observations , including sociodemographic characteristics , personal and family medical history , health habits , diet , and biologic measurements , were documented before r and omization and compared among the seven active intervention and control groups . As might be expected in a r and omized trial of this sample size , the distribution of measured baseline characteristics was virtually identical in the treated and control groups . Based on this finding and the knowledge that r and omization procedures were implemented without deviation from the phase I protocol , it is probable that unknown potential confounders were also equally distributed at entry into the study . Given the achievement of high rates of follow-up , subsequent differences in blood pressure are unlikely to have been due to baseline differences between the active treatment and control groups , and can probably be attributed to effects of the active interventions The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure ( BP ) . However , data to support such recommendations in older persons are virtually nonexistent . The Trials of Nonpharmacologic Intervention in the Elderly ( TONE ) is a r and omized , controlled trial that will test whether weight loss or a reduced sodium ( Na ) intake or both can maintain satisfactory BP control , without unacceptable side effects , after withdrawal of antihypertensive drug therapy . Medication-treated hypertensives ( aged 60 to 80 years ) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are r and omly assigned to one of four groups : ( 1 ) weight loss alone , ( 2 ) reduced Na intake alone , ( 3 ) combined weight loss and reduced Na intake , or ( 4 ) usual life-style ( control group ) . Overweight participants are r and omized to one of these four groups , while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group . The interventions , tailored to the needs of older persons , use behavioral approaches to accomplish intervention-specific goals ( weight loss > or = 10 lb , daily Na intake < or = 80 mEqa ) . Three months after the start of intervention , antihypertensive drug therapy is withdrawn . The primary trial end point is a BP of 150/90 mm Hg or higher , resumption of antihypertensive drug therapy , or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up . It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy 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 CONTEXT Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly , but there is a paucity of evidence from r and omized controlled trials in support of this recommendation . OBJECTIVE To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension . DESIGN R and omized controlled trial . PARTICIPANTS A total of 975 [ corrected ] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication . SETTING Four academic health centers . INTERVENTION The 585 obese participants were r and omized to reduced sodium intake , weight loss , both , or usual care , and the 390 nonobese participants were r and omized to reduced sodium intake or usual care . Withdrawal of antihypertensive medication was attempted after 3 months of intervention . MAIN OUTCOME MEASURE Diagnosis of high blood pressure at 1 or more follow-up visits , or treatment with antihypertensive medication , or a cardiovascular event during follow-up ( range , 15 - 36 months ; median , 29 months ) . RESULTS The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake ( relative hazard ratio , 0.69 ; 95 % confidence interval [ CI ] , 0.59 - 0.81 ; P<.001 ) and , in obese participants , among those assigned vs not assigned to weight loss ( relative hazard ratio , 0.70 ; 95 % CI , 0.57 - 0.87 ; P<.001 ) . Relative to usual care , hazard ratios among the obese participants were 0.60 ( 95 % CI , 0.45 - 0.80 ; P<.001 ) for reduced sodium intake alone , 0.64 ( 95 % CI , 0.49 - 0.85 ; P=.002 ) for weight loss alone , and 0.47 ( 95 % CI , 0.35 - 0.64 ; P<.001 ) for reduced sodium intake and weight loss combined . The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups . CONCLUSION Reduced sodium intake and weight loss constitute a feasible , effective , and safe nonpharmacologic therapy of hypertension in older persons Identifying effective , nonpharmacologic means of preventing or significantly delaying the onset of hypertension would be a major advance in the primary prevention of cardiovascular disease . In the first phase of the Trials of Hypertension Prevention ( TOHP I ) , adults with high-normal diastolic blood pressure were r and omly assigned to one of seven nonpharmacologic interventions . Only weight loss and reduction of dietary sodium proved to be effective strategies for reducing blood pressure . The second phase of TOHP ( TOHP II ) will test the effectiveness of weight loss , reduction of dietary sodium , and their combination of lowering blood pressure and preventing the onset of hypertension over a 3- to 4-year follow-up period . This article describes the three interventions used in TOHP II , methods used to maintain continued participation in this long-term trial , and protocol enhancements design ed to maximize intervention effectiveness The Hypertension Prevention Trial ( HPT ) was a multicenter r and omized trial design ed to assess the effects of long-term dietary changes on blood pressure in a normotensive population ( diastolic blood pressure greater than or equal to 78 but less than 90 mm Hg ) for a period of 3 years . The dietary treatments were reduction of sodium intake , increase of potassium intake , and decrease of energy intake . Estimates of changes in food intake were made by comparing 24-hour food records of the treatment and control participants . The participants in the treatment groups reported sodium intakes that were 30 % to 40 % lower than those of the controls . The restriction was achieved mainly by reducing intake of salt , meats , and grain products . Meats and grain products were still a major source of total sodium intake after treatment ( 41 % to 47 % ) , perhaps because of continued use of processed foods . Potassium intake was reported to be 16 % to 25 % higher in the treatment groups than in the controls , the increase achieved largely through increased consumption of fruits , with a lesser contribution from vegetables . Participants with higher initial body weights reported smaller increases in fruit and vegetable consumption than participants of normal weight , perhaps because of concerns about weight gain . Energy intake in the weight loss groups was 8 % to 11 % less than that of the controls . Men reported success in restricting calories from meats , dairy products , fats , beverages , and sugars . Women were less successful in restricting calories from most food groups . ( ABSTRACT TRUNCATED AT 250 WORDS 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 BACKGROUND Diuretics have been accepted as first-line treatment in refractory congestive heart failure ( CHF ) , but a lack of response to them is a frequent event . A r and omized , single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution ( HSS ) infusion in the treatment of refractory New York Heart Association ( NYHA ) class IV CHF and a normosodic diet during follow-up . Material s and Methods One hundred seven patients ( 39 women and 68 men , age range 65 - 90 years ) with refractory CHF ( NYHA class IV ) of different etiologies , who were unresponsive to high oral doses of furosemide , angiotensin-converting enzyme inhibitors , digitalis , and nitrates , were enrolled . Inclusion criteria included an ejection fraction ( EF ) < 35 % , serum creatinine level < 2 mg/dL , blood urea nitrogen level < or = 60 mg/dL , reduced urinary volume , and low natriuresis . The patients were r and omized in 2 groups ( single-blind ) . Patients in group 1 ( 20 women and 33 men ) received an intravenous ( IV ) infusion of furosemide ( 500 - 1000 mg ) plus HSS ( 150 mL of 1.4%-4.6 % NACl ) twice a day in 30 minutes . Patients in group 2 ( 19 women and 35 men ) received an IV bolus of furosemide ( 500 - 1000 mg ) twice a day , without HSS , during a period lasting 6 to 12 days . Both groups received IV KCl ( 20 - 40 mEq ) to prevent hypokalemia . At study entry , all patients underwent a physical examination and measurement of body weight ( BW ) , blood pressure ( BP ) , and heart rate ( HR ) , an evaluation of signs of CHF , and measurement of control levels of serum Na , K , Cl , bicarbonate , albumin , uric acid , creatinine , urea , and glycemia daily during hospitalization , and measurements of the daily output of urine for Na , K , and Cl . A chest radiograph , electrocardiogram , and echocardiogram were obtained at study entry , during hospitalization , and at the time of discharge from the hospital . During the treatment and after discharge , the daily dietary Na intake was 120 mmol in group 1 versus 80 mmol in group 2 , with a fluid intake of 1000 mL daily in both groups . An assessment of BW and 24-hour urinary volume , serum , and urinary laboratory parameters were performed daily until patients reached a compensated state , when IV furosemide was replaced with oral administration ( 250 - 500 mg/d ) . After discharge from the hospital , patients were observed as out patients weekly for the first 3 months and , subsequently , once a month . RESULTS The groups were similar in age , sex , EF , risk factors , treatment , and etiology of CHF . All patients showed a clinical improvement . Ten patients in both groups had hyponatremia at entry . A significant increase in daily diuresis and natriuresis was observed in both groups , but it was more significant in the group receiving HSS ( P < .05 ) . The serum Na level increased in group 1 and decreased in group 2 ( P < .05 ) . The serum K level was decreased in both groups ( P < .05 ) . BW was reduced in both groups ( P < .05 ) . Group 2 had an increase in serum creatinine level . Serum uric acid levels increased in both groups . BP values decreased and HR was corrected to normal values in both groups . In the follow-up period ( 31 + /- 14 months ) , 25 patients from group 1 were readmitted to the hospital for heart failure . In group 2 , 43 patients were readmitted to the hospital at a higher class than at discharge . Twenty-four patients in group 1 died during follow-up , versus 47 patients in group 2 ( P < .001 ) . CONCLUSION This treatment is effective and well tolerated , improves the quality of life through the relief of signs and symptoms of congestion , and may delay more aggressive treatments . The effects were also beneficial in a long period for mortality reduction ( 55 % vs 13 % survival rate ) and for clinical improvement The Hypertension Prevention Trial ( HPT ) was a multicenter , r and omized trial testing calorie control , sodium restriction , and potassium increases in the prevention of hypertension in 841 men and women . Thirty four variables that were potentially related to changes in urine sodium , urine potassium , and weight were examined individually and together across 3 years of treatment and maintenance sessions . Univariate and multivariate analysis did not reveal a consistent pattern of variables associated with successful attainment of treatment goals or failure to do so . Baseline levels of urine sodium , urine potassium , and weight were the variables most consistently associated with compliance . Household composition , such as number of people living in the house or marital status and control over selection and preparation of foods , was associated with compliance in sodium reduction treatments . Number of complaints about the diets were positively associated with noncompliance . Attendance at treatment sessions was generally associated with compliance especially for weight loss . Practical implication s of these results are discussed The aim of this study was to assess the effectivity of dietary measures in the treatment of hypertension . Therefore , a single-blind r and omised clinical trial was carried out in elderly persons with recently diagnosed hypertension . Patients were recruited from a general practice ( 6555 persons ) during visits or after written invitation or invitation by phone . New hypertensive patients ( with measurements taken on three different occasions > 159 mm Hg systolic and /or > 94 mm Hg diastolic ) , aged 60–80 years , without target-organ damage , dementia , diabetes mellitus or malignant disease entered a 3-month intervention programme of either intensive dietary counselling , receiving a sodium-reduced ( < 100 mmol/24h ) , potassium-enriched ( > 75 mmol/24h ) , and weight-reducing diet ( BMI < 25 ) , or only 25 mg chlorthalidone a day . forty-two newly diagnosed hypertensive subjects met the inclusion criteria . two dropped out from the chlorthalidone group , one with side effects and another after a myocardial infa rct ion . although blood pressure ( bp ) in the diet group decreased less than in the drug group , of the patients in the diet group 45 % fell back to a normal systolic and 50 % to a normal diastolic bp ( drug treatment group , systolic 75 % and diastolic 85 % ) . in contrast with the diet group , lipid spectrum and blood glucose concentration in the diuretic group , however , deteriorated slightly . the dietary intervention was effective in elderly patients with a systolic or diastolic bp in the range of 160–180 and 95–100 mm hg , respectively . reduction in weight should be the primary aim . it is argued that sodium reduction can be achieved better by collective measures . in patients with a bp of more than 180 mm hg systolic or 100 mm hg diastolic , dietary advice and drug treatment should be combined Phase II of the Trials of Hypertension Prevention ( TOHP II ) is a multicenter , controlled clinical trial design ed to test whether weight loss , a reduced sodium intake , or a combination of weight loss and a reduced sodium intake will lower blood pressure ( BP ) and prevent the occurrence of hypertension . The study population consists of middle-aged , moderately overweight individuals with a diastolic BP between 83 and 89 mm Hg . Of the 2382 r and omized participants , 816 ( 34 % ) are female and 494 ( 21 % ) are from a racial or ethnic minority background . At baseline , mean dietary intakes of sodium , based on measurements of 24-hour urinary excretion , were 199 mmol/d in men and 154 mmol/d in women . The average body mass index was 30.9 kg/m2 . Across the four r and omized groups , there was no substantial imbalance in the distribution of baseline variables ; however , the mean age in the four groups was slightly but significantly different ( range : 43.2 to 44.2 years , P = 0.02 ) . A comparison of baseline characteristics of TOHP II participants with those of participants in three other primary prevention trials reveals a high level of mean dietary sodium intake in each study . Data reported in this article indicate that any subsequent differences in BP among the r and omized groups are unlikely to result from maldistribution of known confounding variables at baseline . Finally , because of the high prevalence of overweight and excessive sodium intake in the United States , results from TOHP II should be broadly applicable to the general population OBJECTIVE To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure . DESIGN R and omized control multicenter trials . SETTING Volunteers recruited from the community , treated and followed up at special clinics . PARTICIPANTS Of 16,821 screenees , 2182 men and women , aged 30 through 54 years , with diastolic blood pressure from 80 through 89 mm Hg were selected . Of these , 50 did not return for follow-up blood pressure measurements . INTERVENTIONS Three life-style change groups ( weight reduction , sodium reduction , and stress management ) were each compared with unmasked nonintervention controls over 18 months . Four nutritional supplement groups ( calcium , magnesium , potassium , and fish oil ) were each compared singly , in double-blind fashion , with placebo controls over 6 months . MAIN OUTCOME MEASURES Primary : change in diastolic blood pressure from baseline to final follow-up , measured by blinded observers . Secondary : changes in systolic blood pressure and intervention compliance measures . RESULTS Weight reduction intervention produced weight loss of 3.9 kg ( P less than .01 ) , diastolic blood pressure change of -2.3 mm Hg ( P less than .01 ) , and systolic blood pressure change of -2.9 mm Hg ( P less than .01 ) . Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h ( P less than .01 ) , diastolic blood pressure by 0.9 mm Hg ( P less than .05 ) , and systolic blood pressure by 1.7 mm Hg ( P less than .01 ) . Despite good compliance , neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly ( P greater than .05 ) . CONCLUSIONS Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons . Sodium reduction is also effective . The long-term effects of weight reduction and sodium reduction , alone and in combination , require further evaluation Assigned participants in the Hypertension Prevention Trial to one of four diets for a period of 3 years : ( a ) weight loss , ( b ) reduced sodium , ( c ) weight loss plus reduced sodium , and ( d ) reduced sodium plus increased potassium . At 6-month intervals , they reported problems they were having adhering to their diets . Problem attributions were coded along the dimensions of internality , stability , and controllability and were categorized as intrapersonal or extrapersonal . Attributions were found to differ by type of diet and sex of participant . Participants assigned to weight-loss groups were significantly more likely than those assigned to non-weight-loss groups to blame themselves for their problems with adherence , making characterological as opposed to external or situational attributions . Men perceived problems to be more controllable than women . Attributions did not predict weight loss , change in urinary sodium , or change in potassium excretion CONTEXT Extrapolations from observational studies and short-term intervention trials suggest that population -wide moderation of salt intake might reduce cardiovascular events . OBJECTIVE To assess whether 24-hour urinary sodium excretion predicts blood pressure ( BP ) and health outcomes . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve population study , involving 3681 participants without cardiovascular disease ( CVD ) who are members of families that were r and omly enrolled in the Flemish Study on Genes , Environment , and Health Outcomes ( 1985 - 2004 ) or in the European Project on Genes in Hypertension ( 1999 - 2001 ) . Of 3681 participants without CVD , 2096 were normotensive at baseline and 1499 had BP and sodium excretion measured at baseline and last follow-up ( 2005 - 2008 ) . MAIN OUTCOME MEASURES Incidence of mortality and morbidity and association between changes in BP and sodium excretion . Multivariable-adjusted hazard ratios ( HRs ) express the risk in tertiles of sodium excretion relative to average risk in the whole study population . RESULTS Among 3681 participants followed up for a median 7.9 years , CVD deaths decreased across increasing tertiles of 24-hour sodium excretion , from 50 deaths in the low ( mean , 107 mmol ) , 24 in the medium ( mean , 168 mmol ) , and 10 in the high excretion group ( mean , 260 mmol ; P < .001 ) , result ing in respective death rates of 4.1 % ( 95 % confidence interval [ CI ] , 3.5%-4.7 % ) , 1.9 % ( 95 % CI , 1.5%-2.3 % ) , and 0.8 % ( 95 % CI , 0.5%-1.1 % ) . In multivariable-adjusted analyses , this inverse association retained significance ( P = .02 ) : the HR in the low tertile was 1.56 ( 95 % CI , 1.02 - 2.36 ; P = .04 ) . Baseline sodium excretion predicted neither total mortality ( P = .10 ) nor fatal combined with nonfatal CVD events ( P = .55 ) . Among 2096 participants followed up for 6.5 years , the risk of hypertension did not increase across increasing tertiles ( P = .93 ) . Incident hypertension was 187 ( 27.0 % ; HR , 1.00 ; 95 % CI , 0.87 - 1.16 ) in the low , 190 ( 26.6 % ; HR , 1.02 ; 95 % CI , 0.89 - 1.16 ) in the medium , and 175 ( 25.4 % ; HR , 0.98 ; 95 % CI , 0.86 - 1.12 ) in the high sodium excretion group . In 1499 participants followed up for 6.1 years , systolic blood pressure increased by 0.37 mm Hg per year ( P < .001 ) , whereas sodium excretion did not change ( -0.45 mmol per year , P = .15 ) . However , in multivariable-adjusted analyses , a 100-mmol increase in sodium excretion was associated with 1.71 mm Hg increase in systolic blood pressure ( P.<001 ) but no change in diastolic BP . CONCLUSIONS In this population -based cohort , systolic blood pressure , but not diastolic pressure , changes over time aligned with change in sodium excretion , but this association did not translate into a higher risk of hypertension or CVD complications . Lower sodium excretion was associated with higher CVD mortality BACKGROUND The aim of the trial was to evaluate the effectiveness of a program of cooperation between physician and pharmacist to reduce cardiovascular risk factors in patients with mild to moderate hypertension by promoting better blood pressure ( BP ) control , appropriate changes in antihypertensive medications , and beneficial changes in lifestyle . METHODS The 132 subjects in this r and omized , controlled trial were in the age range of 40 - 79 years . The inclusion criteria were : systolic BP ( SBP ) ranging from 140 - 179 mm Hg and /or diastolic BP ( DBP ) ranging from 90 - 99 mm Hg and treatment-naive ( untreated for hypertension ) ; or on a regimen of medication for hypertension . Of these 132 subjects , 124 ( 94 % ) were already receiving treatment with antihypertensive medications . Equal numbers of subjects were r and omly assigned to one of two groups : a physician-pharmacist intervention group ( n = 66 ) and a control group ( n = 66 ) . RESULTS The 6-month follow-up rate was 97 % in both groups . At 6 months , the mean decrease in SBP/DBP , as measured at home in the morning , was 2.9/3.3 mm Hg in the intervention group relative to baseline ( P = 0.02 and P < 0.0001 for SBP and DBP , respectively ) . The mean decrease in home morning SBP in the intervention group was not significantly greater than in the control group . However , the DBP decline was significantly greater in the intervention than control groups , which showed a mean decrease of 2.8 mm Hg ( confidence interval : -5.5 to -0.1 ; P = 0.04 ) . The percentage of patients in whom control of home morning BP was achieved was 53 % in the intervention group and 47 % in the control group ( P = 0.40 ) . A higher percentage of patients in the intervention group , relative to the control group , were able to reduce the use of antihypertensive medications ( 31 vs. 8 % , P < 0.0001 ) , and fewer patients in this group required additional medications or increases in dosage relative to the controls ( 11 vs. 28 % , P = 0.03 ) . Patients of the intervention group were more likely to show reduction in body mass index and sodium intake and to stop smoking , as compared with the control group . CONCLUSIONS A program of cooperation between physician and pharmacist was successful in reducing cardiovascular risk factors in patients with mild to moderate hypertension by promoting better blood pressure ( BP ) control , appropriate changes in antihypertensive medications , and beneficial changes in lifestyle |
11,344 | 16,707,073 | However , the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries . | OBJECTIVES To assess the effectiveness and cost-effectiveness of HealOzone ( CurOzone USA Inc. , Ontario , Canada ) for the management of pit and fissure caries , and root caries .
The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface , the use of a remineralising solution immediately after application of ozone and the supply of a ' patient kit ' , which consists of toothpaste , oral rinse and oral spray all containing fluoride . | Abstract s on this page have been chosen and edited by Dr Trevor Watts Abstract Failure rates were higher for glass ionomer ( GIC ) , but caries progression was more likely on tooth surfaces adjacent to amalgam ( AM ) restorations The purpose of this study was to evaluate the efficacy of non-invasive methods of treatment for active incipent occlusal caries . Anamnesis , professional prophylaxis , and visual inspection were used to classify 250 Brazilian pre-school-children . First permanent decayed molars ( n=98 ) from thirty-one subjects ( 6 years+ 6 months ) were selected and divided into three groups . Group 1 : fissure sealants with resin-modified glass ionomer - Vitremer ( n=29 ) ; Group 2 : fluoride varnish -Duraphat ( n=36 ) and control group : tooth brushing and 0.2 percent NaF weekly mouthwashes ( n=33 ) . Four clinical evaluations were carried out over three , six , nine , and twelve months . Caries activity and progression were observed through clinical and radiographic evaluation . The results were analyzed by Fisher = s Exact test . After twelve months , the results showed 100 percent of arrestment of caries activity for Group 1 , 83.3 percent for group 2 , and 72.7 percent for control group . At the same time , the results showed 0 percent of caries progression for group 1 , 5.5 percent for Group 2 , and 6.1 percent for control group . Group 1 showed a better inactivation property than the other groups ( p<0.05 ) . There were no statistically significant differences in caries progression among these groups ( p>0.05 ) . It was concluded that this non-invasive methods were able to arrest the progression of occlusal caries , but fissure sealant showed better results in controlling caries activity There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion , with respect to caries efficacy . This r and omized , double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm , 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control . A population of 5439 elementary schoolchildren , aged 6 - 15 years , was recruited from an urban central Ohio area with a low fluoride content water supply ( < 0.3 ppm ) . Subjects were examined by visual-tactile and radiographic examination at baseline and after 1 , 2 , and 3 years of using the sodium fluoride dentifrices . Subjects were stratified according to gender , age and baseline DMFS scores derived from the visual-tactile baseline examination and r and omly assigned to one of four treatment groups : 0.243 % sodium fluoride ( 1100 ppm fluoride ion ) , 0.376 % sodium fluoride ( 1700 ppm fluoride ion ) , 0.486 % sodium fluoride ( 2200 ppm fluoride ion ) , and 0.619 % sodium fluoride ( 2800 ppm fluoride ion ) . All products were formulated with the same fluoride compatible silica abrasive . Results after 1 year provided evidence of a positive sodium fluoride dose response . Compared to the 1100 ppm fluoride treatment group , the 1700 ppm fluoride treatment group had an 11.0 % reduction in DMFS that was not statistically significant , while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant ( P<0.05 ) reductions of 18.6 % and 20.4 % , respectively . The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types , but were most pronounced for occlusal surfaces . Results at years 2 and 3 were confounded by a concurrent fluoride rinse program , which involved portions of the study population . While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3 , the difference observed between treatments were substantially less and failed to reach statistical significance ( P<0.05 ) . Collectively , the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment . This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1 The aim of this study was to compare the longevity and cariostatic effects of everyday conventional glass-ionomer and amalgam restorations in primary teeth . The material s consisted of 515 Ketac-Fil glass-ionomer restorations and 543 Dispersalloy amalgam restorations prepared in 666 children , from 3 to 13 years of age , by 14 dentists within the Danish Public Dental Health Service in the municipalities of Vaerlose and Hillerød . The restorations , of which 79 % were of the Class II type , were in contact with 593 unrestored surfaces in adjacent primary and permanent teeth . After 3 years , 6 % of the patients had dropped out of the study , and 33 % of the teeth were exfoliated with the restoration in situ . A further 37 % of the glass-ionomer and 18 % of the amalgam restorations were recorded as failed ( p < 0.001 ) . The frequency of failures was highest for Class II glass-ionomer restorations , which showed a 50 % median survival time of only 34½ months , because of many fractures , while the 75 % survival time for Class II amalgam restorations just exceeded the actual 36 months ( p < 0.001 ) . Caries progression was most often recorded in surfaces adjacent to amalgam restorations , and 21 % of these surfaces needed restorative treatment vs. 12 % of the surfaces adjacent to glass-ionomer restorations ( p < 0.01 ) . The three-year results indicated that conventional glass ionomer is not an appropriate alternative to amalgam for all types of restorations in primary teeth . In particular , the short longevity of Class II glass-ionomer restorations could not be compensated for by the reduced caries progression and need for restorative therapy of adjacent surfaces OBJECTIVE To examine the effect of reported toothbrushing frequency and method of rinsing after brushing on caries experience and increment . METHODS Data are presented from 2621 adolescents ( mean age 12.5 years at outset ) participating in a 3-year double-blind caries clinical trial . At baseline , examiners question ed each participant about their toothbrushing habits , and at subsequent examinations , this information was obtained using a self-administered computer-based question naire . Participants used a fluoride-containing dentifrice throughout and clinical examinations were conducted using a mirror , CPITN probe and fibre-optic transillumination . RESULTS The reported brushing frequency increased throughout the trial . Caries experience at baseline was inversely related to toothbrushing frequency with mean DMFS=9.66 , 8.12 and 7.63 respectively for < 1/day , 1/day and > 1/day brushers ( P<0.001 ) . Mean 3-year DMFS increments of 8.90 , 6.63 and 5.48 ( P<0.01 ) were observed in those reporting to brush < 1/day , 1/day or > 1/day , on not less than two of the three clinical examinations during the trial . Caries increment was also significantly related to the cl aim ed method used to rinse post-brushing . Overall frequency of brushing and rinsing method accounted for over 50 % of the explained variance in the ANOVA model used to analyse the DMFS increments . CONCLUSIONS Stated toothbrushing frequency and rinsing method after brushing were found to be strongly correlated with caries experience and caries increment . These factors should be reflected in the design of oral health education material and taken into account in the design and analysis of caries clinical trials Abstract Restorations made of a combination of resin modified glass ionomer cement ( RMGIC ) and composite resin ( CR ) – open s and wich fillings – have been recommended for use in proximal boxes of molar cavities . The aim of this study was to compare the clinical behaviour over time of RMGIC/CR s and wich restorations versus CR restorations in Class II molar cavities . During a period of 2 years , a total of 220 restorations were placed in 118 patients by one operator ( VV ) . A r and om block allocation was used to allocate cavities to one of the two restorative techniques . Bitewing radiographs and photographs were taken at baseline and at annual recall appointments . At present , a total of 210 restorations have been evaluated after 1 year and 141 restorations after 2 years . All restorations were evaluated using a modification of USPHS criteria . A total of three RMGIC/CR and two CR restorations ( 2.8 % ) were rated as failures caused by endodontic complications or major fractures . Twenty-eight teeth were reported to have postoperative sensitivity at the baseline evaluation 1 week following placement . Nine RMGIC/CR ( 8.5 % ) and four CR ( 4.9 % ) restorations with minor fractures were rated Charlie but were still acceptable . Bitewing radiographs revealed progression of carious lesions in proximal surfaces of originally intact or restored teeth adjacent to five ( 5.9 % ) RMGIC/CR restorations and eight ( 10.9 % ) CR restorations . No statistically significant differences between the two types of restoration were observed with respect to marginal adaptation , discoloration and caries progression . However , a higher number of large CR fillings exhibited postoperative sensitivity at baseline compared to moderate CR or extensive and moderate RMGIC/CR restorations BACKGROUND The biofilm that forms and remains on tooth surfaces is the main etiological factor in caries and periodontal disease . Prevention of caries and periodontal disease must be based on means that counteract this bacterial plaque . OBJECTIVE To monitor the incidence of tooth loss , caries and attachment loss during a 30-year period in a group of adults who maintained a carefully managed plaque control program . In addition , a comparison was made regarding the oral health status of individuals who , in 1972 and 2002 , were 51 - 65 years old . MATERIAL AND METHODS In 1971 and 1972 , more than 550 subjects were recruited . Three hundred and seventy-five subjects formed a test group and 180 a control group . After 6 years of monitoring , the control group was discontinued but the participants in the test group was maintained in the preventive program and was finally re-examined after 30 years . The following variables were studied at Baseline and after 3 , 6 , 15 and 30 years : plaque , caries , probing pocket depth , probing attachment level and CPITN . Each patient was given a detailed case presentation and education in self-diagnosis . Once every 2 months during the first 2 years , once every 3 - 12 months during years 3 - 30 , the participants received , on an individual need basis , additional education in self-diagnosis and self-care focused on proper plaque control measures , including the use of toothbrushes and interdental cleaning devices ( brush , dental tape , toothpick ) . The prophylactic sessions that were h and led by a dental hygienist also included ( i ) plaque disclosure and ( ii ) professional mechanical tooth cleaning including the use of a fluoride-containing dentifrice/paste . RESULTS Few teeth were lost during the 30 years of maintenance ; 0.4 - 1.8 in different age cohorts . The main reason for tooth loss was root fracture ; only 21 teeth were lost because of progressive periodontitis or caries . The mean number of new caries lesions was 1.2 , 1.7 and 2.1 in the three groups . About 80 % of the lesions were classified as recurrent caries . Most sites , buccal sites being the exception , exhibited no sign of attachment loss . Further , on approximal surfaces there was some gain of attachment between 1972 and 2002 in all age groups . CONCLUSION The present study reported on the 30-year outcome of preventive dental treatment in a group of carefully monitored subjects who on a regular basis were encouraged , but also enjoyed and recognized the benefit of , maintaining a high st and ard of oral hygiene . The incidence of caries and periodontal disease as well as tooth mortality in this subject sample was very small . Since all preventive and treatment efforts during the 30 years were delivered in one private dental office , caution must be exercised when comparisons are made with longitudinal studies that present oral disease data from r and omly selected subject sample PURPOSE To assess the effect of ozone on the microbial flora and clinical severity of primary root caries . METHODS 26 patients with 70 primary root carious lesions ( PRCLs ) were entered . Each PRCL was classified in terms of color , cavitation , size , hardness , distance from the gingival margin and severity . Overlying plaque was then removed and each lesion dried . A biopsy was taken from half of each PRCL using a sterile excavator . Subsequently , the remaining lesions were exposed to ozone gas for a period of either 10 seconds ( n = 35 ) or 20 seconds ( n = 35 ) and a further biopsy was taken . RESULTS Using a paired Student t-test , a significant ( P < 0.001 ) difference ( mean + /- SE ) in total micro-organisms was observed in the ozone-treated sample s after either a 10 seconds ( log10 4.35 + /- 0.49 ) or 20 seconds ( log10 0.46 + /- 0.26 ) ozone application compared with the control sample s ( log10 7.00 + /- 0.24 ) and ( log10 6.00 + /- 0.21 ) respectively . Using Pearson 's correlation tests , there were significant correlations for the reduction in total micro-organisms after 10 seconds of ozone application with cavitation , size , distance from gingival margin and severity of PRCLs ( P < 0.05 ) . In conclusion , ozone application either for 10 or 20 seconds dramatically reduced most of the micro-organisms in PRCLs without any side effects recorded at recall intervals between 3 and 5.5 months . Out of the 65 PRCLs review ed , 33 lesions had become hard , 27 lesions reversed to severity index 1 from severity index 2 , and five lesions remained the same following ozone application for a period of either 10 or 20 seconds Changes in restorative techniques and the development of newer restorative material s have allowed for the use of more conservative cavity preparations . This 10-year study evaluated bonded and sealed composite restorations placed directly over frank cavitated lesions extending into dentin vs. sealed conservative amalgam restorations and conventional unsealed amalgam restorations . The results indicate that both types of sealed restorations exhibited superior clinical performance and longevity compared with unsealed amalgam restorations . Also , the bonded and sealed composite restorations placed over the frank cavitated lesions arrested the clinical progress of these lesions for 10 years |
11,345 | 10,390,305 | Different studies addressing the cost-effectiveness of screening asymptomatic carotid stenosis result ed in strikingly divergent conclusions , from being cost-effective to being detrimental . | BACKGROUND AND PURPOSE This work was undertaken to review research addressing the cost-effectiveness of stroke-related diagnostic , preventive , or therapeutic interventions .
Many stroke evaluation and treatment policies may result in benefits to health that are considered worth their cost . | This study used data from a multinational phase III r and omized , double-blind , vehicle-controlled trial to evaluate the cost-effectiveness of tirilazad mesylate ( Freedox ) in the treatment of aneurysmal subarachnoid hemorrhage . In men , therapy with 6 mg/kg per day of tirilazad mesylate was associated with significantly increased survival , increased cost of care , and ratios of cost per death averted that compare favorably with the ratios of other life and death interventions . In women , it appeared to have no effects on costs or survival . Further clinical studies may provide additional information about the cost-effectiveness of this intervention PURPOSE The purpose of this study was to determine the cost-effectiveness of carotid endarterectomy for treating asymptomatic patients with > or = 60 % internal carotid stenosis , based on outcomes reported in the Asymptomatic Carotid Atherosclerosis Study ( ACAS ) . METHODS A cost-effectiveness analysis was performed using a Markov decision model in which the probabilities for base-case analysis ( average age , 67 years ; 66 % male ; perioperative stroke plus death rate , 2.3 % ; ipsilateral stroke rate during medical management , 2.3 % per year ) were based on ACAS . The model assumed that patients who had TIAs or minor strokes during medical management crossed over to surgical treatment , and used the NASCET data to model the outcome of these now-symptomatic patients . Average cost of surgery ( $ 8500 ) , major stroke ( $ 34,000 plus $ 18,000 per year ) , and other costs were based on local cost determinations plus a review of the published literature . Cost-effectiveness was calculated as the incremental cost of surgery per quality -adjusted life year ( QALY ) saved when compared with medical treatment , discounting at 5 % per year . Sensitivity analysis was performed to determine the impact of key variables on cost-effectiveness . RESULTS In the base-case analysis , surgical treatment improved quality -adjusted life expectancy from 7.87 to 8.12 QALYs , at an incremental lifetime cost of $ 2041 . This yielded an incremental cost-effectiveness ratio of $ 8,000 per QALY saved by surgical compared with medical treatment . The high cost of care after major stroke during medical management largely offset the initial cost of endarterectomy in the surgical group . Furthermore , 26 % of medically managed patients eventually underwent endarterectomy because of symptom development , which also decreased the cost differential . Sensitivity analysis demonstrated that the relative cost of surgical treatment increased substantially with increasing age , increasing perioperative stroke rate , and decreasing stroke rate during medical management . CONCLUSION For the typical asymptomatic patient in ACAS with > or = 60 % carotid stenosis , our results indicate that carotid endarterectomy is cost-effective when compared with other commonly accepted health care practice s. Surgery does not appear cost-effective in very elderly patients , in setting s where the operative stroke risk is high , or in patients with very low stroke risk without surgery Cost-effectiveness analyses of stroke management are hampered by paucity of economic data . We made an up date of the direct and indirect costs of stroke in Sweden ( population , 8.5 million ) . Methods Direct costs ( ie , the costs for hospital and outpatient care and social services ) were estimated on the basis of two prospect i ve population -based studies of stroke and of two nationwide cross-sectional inventories of bed-days and diagnoses . Indirect costs ( ie , the costs for loss of productivity and early retirement ) were based on official statistics . Results The direct annual costs of care for stroke patients in 1991 equaled 7836 million Swedish krona ( SKr ) ( $ 1306 million in US dollars ) , and the indirect costs , 2430 million SKr ( $ 405 million ) . The cost of stroke care was 1208 SKr ( $ 201 ) per inhabitant in Sweden . The expected direct costs per patient from first stroke to death were 440 000 SKr ( $ 73 333 ) . When prestroke costs for other diseases and advanced age were subtracted , the sum was reduced to 180 000 SKr ( $ 30 000 ) . Conclusions Costs for hospital and outpatient care and social services accounted for 76 % of Swedish stroke costs and for 24 % of costs for loss of production and early retirement . Only 41 % of direct costs were stroke-related Stroke occurs in more than 500 000 persons annually and is the leading cause of long-term illness and the third leading cause of death in the United States [ 1 ] . The debilitating nature of a new-onset stroke is compounded by a high risk for subsequent neurologic and cardiac events [ 2 - 4 ] . The annual cost of stroke in the United States , including the indirect costs of lost productivity , has been estimated to be $ 15 billion to $ 30 billion [ 5 ] . Cardiovascular sources of emboli may account for 15 % to 45 % of all strokes [ 6 ] . Transesophageal echocardiography has allowed placement of a higher-frequency ultrasonic transducer closer to cardiac structures , thereby producing images with better resolution than those produced by transthoracic echocardiography . Transesophageal echocardiography has substantially improved the identification of thrombi in the left atrium and left atrial appendage . When surgical inspection is used as the gold st and ard , the sensitivity and specificity of transesophageal echocardiography have been shown to exceed 99 % [ 7 ] . Transesophageal echocardiography has also improved detection of patent foramen ovale , atrial septal defects , atrial septal aneurysms , spontaneous echocardiographic contrast in the left atrium [ 8 - 14 ] , and protruding atheromata in the ascending aorta and aortic arch [ 15 , 16 ] . Recent studies [ 16 , 17 ] showed that patients with cardiovascular sources of emboli have a worse prognosis than do patients without cardiovascular sources of emboli . Identification of potential sources of emboli is an important step in reducing recurrent strokes and future expenditures . Anticoagulation has repeatedly been shown to be beneficial in subgroups of patients at risk for stroke [ 18 ] . The extent of the benefit of anticoagulation in patients who have had stroke and who have documented or possible thrombi on transesophageal echocardiography is currently unknown and must be weighed against the increased risk for intracranial hemorrhage in such patients . The indications for cardiovascular imaging in patients who have had stroke are inconsistent [ 19 ] . Performance of cardiovascular imaging varies among physicians : Some physicians routinely order echocardiography , some use echocardiography in accordance with the patient 's clinical history , and some rarely order cardiac imaging studies in patients who have had stroke . Concern about the cost of echocardiography may influence practice patterns . To evaluate the benefits , risks , and costs of different diagnostic approaches , we performed a cost-effectiveness analysis of common cardiovascular imaging strategies used in patients who have had stroke . Methods Design A Markov decision analysis [ 20 ] was done by using a commercially available computer program ( Decision-Maker 7.0 , Pratt Medical Group , Boston , Massachusetts ) to evaluate nine diagnostic strategies in a hypothetical cohort of 65-year-old patients in normal sinus rhythm with new-onset stroke ( Figure 1 ) . ( See the Glossary for definitions of terms . ) The treat-none and treat-all strategies did not include imaging . In the all-transthoracic , all-transesophageal , and all-sequential strategies , imaging was done in all patients . In the selective-transthoracic , selective-esophageal , and selective-sequential-1 strategies , imaging was done only in patients who had a history of cardiac problems ( left ventricular dysfunction or valvular disease ) . The selective-sequential-2 strategy used a sequential approach in patients with a history of cardiac problems and used transesophageal echocardiography in patients with no such history . Figure 1 . Nine possible diagnostic strategies for patients with stroke . The cohort consisted of patients with four types of underlying pathologic condition : thrombi in the left atrium , other potential cardiac sources of emboli , aortic plaque only , and no identifiable cardiovascular source of emboli ( Figure 2 ) . Identification of the underlying condition depended on the imaging strategy used ( Figure 1 ) . For example , the all-transesophageal strategy identified all potential sources of emboli , the all-transthoracic strategy identified only some of the sources , and the treat-none strategy identified none of the sources . Anticoagulation was started on the basis of the results of the imaging studies . For the imaging strategies included in the base-case analysis , only patients with thrombus received anticoagulants ; other patients received aspirin . Figure 2 . Health states for the Markov model . The cohort was then followed through monthly cycles for events , including recurrent cerebrovascular accident , intracranial hemorrhage , gastrointestinal bleeding , and death ( Figure 2 ) . Event and mortality rates were calculated on the basis of the underlying condition and treatment . Costs and outcomes for each health state were summed over the cycles . Patients in the cohort were followed over a lifetime horizon to provide the most relevant analysis from a societal perspective . Major Clinical Assumptions Several assumptions were necessary to implement the Markov model . First , patients had no obvious clinical cause of stroke ( that is , no evidence of periprocedural stroke , recent myocardial infa rct ion , prosthetic valve , known endocarditis , and so on ) . Second , patients were not receiving anticoagulants or antiplatelet agents at the time of stroke . Third , the subtype of ischemic stroke ( such as lacunar or cortical ) was independent of the underlying condition . Fourth , transesophageal echocardiography did not cause enough discomfort to decrease quality of life . Fifth , given the same underlying condition , the risk for recurrent stroke was independent of the history of cardiac disease ( angina , valvular disease , and so on ) . Sixth , only the first major complication after stroke was considered in the analysis ( for example , patients could not have both recurrent stroke and intracranial hemorrhage ) . Finally , new-onset and recurrent strokes were assumed to have similar relative effects on quality of life and on risk for death . Results of Diagnostic Imaging and Occurrence of Subsequent Events We performed a systematic review of the literature to gather the best available evidence about the prevalence of various cardiovascular sources of emboli in patients who have had stroke . A MEDLINE search from 1990 to 1995 was done by using cerebrovascular accident and transesophageal echocardiography as keywords ( before 1990 , transesophageal echocardiography was not a keyword ) . References from papers identified in the MEDLINE search were used to find relevant studies published before 1990 . Studies were chosen if they reported the prevalence of potential cardiovascular sources of emboli identified by transesophageal echocardiography in a defined cohort of patients who had had stroke [ 8 - 1417 , 21 , 22 ] ( Table 1 and Table 4 ) . Studies were distinguished with respect to four characteristics : patient selection ( all patients who had had stroke rather than only patients referred for echocardiography ) , performance of intracardiac contrast studies , blinding of image readers to clinical history , and use of multiple readers . Only single-plane and biplane probes were used in the studies . Thrombi in the left atrium or left atrial appendage were more often identified in studies with selected patients , but other cardiac sources of emboli were identified at similar rates in selected and nonselected patients . Major findings on transesophageal echocardiography did not significantly differ among the studies with regard to use of echocardiographic contrast , blinded readers , or multiple readers . In the papers in which it was mentioned , positive cardiac history was generally defined as atrial fibrillation ( patients with atrial fibrillation were excluded from our cohort ) , decreased left ventricular function , or valvular disease known at the time of transthoracic or transesophageal echocardiography . Rates of identification of aortic plaques varied widely , in part because of poor st and ardization of diagnostic criteria . Because no group of studies was clearly superior in design and conduct , base-case imaging results were obtained from the mean of the results weighted by the number of participants in each study . Table 1 . Systematic Review of the Literature on Transesophageal Echocardiography after Stroke , 1989 - 1995 Table 4 . Table 1 . Continued Secondary event rates and mortality rates ( including the rate of death from nonvascular causes ) were determined by using the best available estimates in the literature ( Table 2 ) [ 1 - 418 , 23 - 30 ] . The estimated relative risk reduction for recurrent stroke ( that is , efficacy ) with anticoagulation ranged from 0 % [ 23 ] to 84 % [ 24 ] . Meta-analyses of studies of patients with atrial fibrillation estimated the efficacy of anticoagulation to be 60 % to 67 % and the efficacy of aspirin to be 33 % compared with that of no therapy [ 18 , 25 ] . Ezekowitz and colleagues [ 26 ] estimated a relative risk reduction of 40 % for anticoagulation in patients with a history of atrial fibrillation and stroke , a patient population that may be similar to our patients who had stroke and documented thrombus in the left atrium or left atrial appendage . We chose a relative risk reduction of 33 % for anticoagulation compared with aspirin and used a wide range ( 17 % to 67 % ) for sensitivity analysis . Table 2 . Input Variables Prospect i ve information on the incidence of intracranial hemorrhage with anticoagulation after a stroke is also scarce . In a previous decision analysis , Eckman and colleagues [ 27 ] estimated the annual incidence of major bleeding to be 4.5 % with anticoagulation . In a case series , L and efeld and Goldman [ 28 ] found that one third of all major bleeding episodes with anticoagulation were intracranial hemorrhage . Thus , we used a 1.5 % annual incidence of anticoagulant-related hemorrhagic stroke . This estimate closely reflects that found in prospect i ve studies of patients with atrial fibrillation that showed an overall incidence of about 1 % per year , with higher Tissue plasminogen activator ( tPA ) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset . The costs associated with this new treatment will be a factor in determining the extent of its utilization . Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients . A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients . One-way and multiway sensitivity analyses ( using Monte Carlo simulation ) were performed to estimate the overall uncertainty of the model results . In the NINDS rt-PA Stroke Trial , the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients ( 10.9 versus 12.4 days ; p = 0.02 ) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home ( 48 % versus 36%;p = 0.002 ) . The Markov model estimated an increase in hospitalization costs of $ 1.7 million and a decrease in rehabilitation costs of $ 1.4 million and nursing home cost of $ 4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities . Multiway sensitivity analysis revealed a greater than 90 % probability of cost savings . The estimated impact on long-term health outcomes was 564 ( 3 to 850 ) quality -adjusted life-years saved over 30 years of the model per 1,000 patients . Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system 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 BACKGROUND The management of unruptured intracranial aneurysms requires knowledge of the natural history of these lesions and the risks of repairing them . METHODS A total of 2621 patients at 53 participating centers in the United States , Canada , and Europe were enrolled in the study , which had retrospective and prospect i ve components . In the retrospective component , we assessed the natural history of unruptured intracranial aneurysms in 1449 patients with 1937 unruptured intracranial aneurysms ; 727 of the patients had no history of subarachnoid hemorrhage from a different aneurysm ( group 1 ) , and 722 had a history of subarachnoid hemorrhage from a different aneurysm that had been repaired successfully ( group 2 ) . In the prospect i ve component , we assessed treatment-related morbidity and mortality in 1172 patients with newly diagnosed unruptured intracranial aneurysms . RESULTS In group 1 , the cumulative rate of rupture of aneurysms that were less than 10 mm in diameter at diagnosis was less than 0.05 percent per year , and in group 2 , the rate was approximately 11 times as high ( 0.5 percent per year ) . The rupture rate of aneurysms that were 10 mm or more in diameter was less than 1 percent per year in both groups , but in group 1 , the rate was 6 percent the first year for giant aneurysms ( > or = 25 mm in diameter ) . The size and location of the aneurysm were independent predictors of rupture . The overall rate of surgery-related morbidity and mortality was 17.5 percent in group 1 and 13.6 percent in group 2 at 30 days and was 15.7 percent and 13.1 percent , respectively , at 1 year . Age independently predicted surgical outcome . CONCLUSIONS The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2 . The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter OBJECTIVE To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation ( NVAF ) with or without additional stroke risk factors ( a prior stroke or transient ischemic attack , diabetes , hypertension , or heart disease ) . DESIGN Decision and cost-effectiveness analyses . The probabilities for stroke , hemorrhage , and death were obtained from published r and omized controlled trials . The quality -of-life estimates were obtained by interviewing 74 patients with atrial fibrillation . Costs were estimated from literature review , phone survey , and Medicare reimbursement . PATIENTS In the base case , the patients were 65 years of age and good c and i date s for warfarin therapy . INTERVENTIONS Treatment with warfarin , aspirin , or no therapy in the decision analytic model . MAIN OUTCOME MEASURES Quality -adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy . RESULTS For patients with NVAF and additional risk factors for stroke , warfarin therapy led to a greater quality -adjusted survival and to cost savings . For patients with NVAF and one additional risk factor , warfarin therapy cost $ 8000 per quality -adjusted life-year saved . For 65-year-old patients with NVAF alone , warfarin cost about $ 370,000 per quality -adjusted life-year saved , as compared with aspirin therapy . However , for 75-year-old patients with NVAF alone , prescribing warfarin cost $ 110,000 per quality -adjusted life-year saved . For patients who were not prescribed warfarin , aspirin was preferred to no therapy on the basis of both quality -adjusted survival and cost in all patients , regardless of the number of risk factors present . CONCLUSIONS Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke . In 65-year-old patients with NVAF but no other risk factors for stroke , prescribing warfarin instead of aspirin would affect quality -adjusted survival minimally but increase costs significantly We report the results of the Ticlopidine Aspirin Stroke Study , a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride ( 500 mg daily ) with those of aspirin ( 1300 mg daily ) on the risk of stroke or death . The medications were r and omly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia . Follow-up lasted for two to six years . The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin -- a 12 percent risk reduction ( 95 percent confidence interval , -2 to 26 percent ) with ticlopidine ( P = 0.048 for cumulative Kaplan-Meier estimates ) . The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin -- a 21 percent risk reduction ( 95 percent confidence interval , 4 to 38 percent ) with ticlopidine ( P = 0.024 for cumulative Kaplan-Meier estimates ) . Ticlopidine was more effective than aspirin in both sexes . The adverse effects of aspirin included diarrhea ( 10 percent ) , rash ( 5.5 percent ) , peptic ulceration ( 3 percent ) , gastritis ( 2 percent ) , and gastrointestinal bleeding ( 1 percent ) . With ticlopidine , diarrhea ( 20 percent ) , skin rash ( 14 percent ) , and severe but reversible neutropenia ( less than 1 percent ) were noted . The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin ( P less than 0.01 ) . The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups . We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population , although the risks of side effects were greater Carotid endarterectomy ( CEA ) reduces the risk of stroke in symptomatic patients with high- grade carotid stenosis . In this study , we evaluated the long-term , societal cost-benefit ratio of endarterectomy using a decision analysis model . We review ed the results of 150 CEAs performed at an academic center and established a Markov model comparing cohorts of patients who experienced transient ischemic attacks and then underwent observation , aspirin therapy , or CEA . The cost-effectiveness of CEA was estimated using perioperative complication rates from our review and from the North American Symptomatic Carotid Endarterectomy Trial . Stroke and mortality rates were estimated from the literature . Cost estimates were based on medicare reimbursement data . Among the 150 CEAs review ed , complications included major stroke ( 0.67 % ) , minor stroke ( 1.33 % ) , myocardial infa rct ion ( 1.33 % ) , pulmonary edema ( 0.67 % ) , and wound hematoma ( 3.33 % ) . There were no deaths or intracerebral hemorrhages . Using complication rates from our review , CEA produced cost savings of $ 5730.62 over the cost of observation and $ 3264.66 over the cost of aspirin treatment . CEA extended the average quality -adjusted life expectancy 15.8 months over that of observation and 13.2 months over that of aspirin . Substituting the North American Symptomatic Carotid Endarterectomy Trial results , CEA yielded savings of $ 2997.50 over the cost of observation and $ 531.54 over the cost of aspirin . Quality -adjusted life expectancy was extended 13.8 months compared with observation and 11.2 months compared with aspirin therapy . This analysis demonstrates that when performed with low perioperative morbidity and mortality rates , CEA is a highly cost-effective therapy for symptomatic carotid stenosis and results in substantial societal cost and life savings R and omized trials have found that carotid endarterectomy can reduce rates of stroke in patients who have carotid stenoses greater than 70 % and mild neurologic symptoms , such as transient ischemic attack , amaurosis partialis fugax lasting less than 24 hours , or nondisabling stroke with symptoms lasting more than 24 hours [ 1 , 2 ] . However , several r and omized trials of carotid endarterectomy [ 3 - 5 ] done in asymptomatic persons found that surgery reduced neither the incidence of stroke nor mortality rates . These findings led to the consensus that routine screening to identify carotid stenosis in asymptomatic persons was not indicated . The results of the Asymptomatic Carotid Atherosclerosis Study ( ACAS ) challenge this view . This r and omized , controlled trial of carotid endarterectomy in asymptomatic patients with stenosis of the internal carotid artery of 60 % or more found that surgery done under carefully controlled conditions could decrease the risk for future strokes . During the 5-year study period , surgically treated patients had a 53 % reduction in the risk for ipsilateral strokes and a 20 % reduction in the risk for any strokes ( ipsilateral and contralateral ) or death [ 6 ] . Do these results mean that all patients with asymptomatic carotid stenosis should have carotid surgery ? If so , should screening for asymptomatic carotid stenosis be implemented on a wide scale ? To address these questions , we determined whether a screening program design ed to identify persons with asymptomatic carotid stenosis would be a cost-effective strategy for stroke prevention . Methods Decision Model We used st and ard cost-effectiveness analysis methods [ 7 , 8 ] to evaluate a screening program that would identify high- grade carotid stenosis in a cohort of 65-year-old men who did not have such neurologic symptoms of carotid disease as transient ischemic attack , reversible ischemic neurologic deficit , amaurosis fugax , or previous stroke . Our decision tree compared screening for carotid disease done using duplex Doppler ultrasonography with no screening . If significant carotid stenosis ( 60 % ) was found on ultrasonography , disease would be confirmed by angiography . Patients who have angiography bear a risk for a major complication , such as stroke ; we assumed that patients who had stroke or another major complication during the evaluation were no longer c and i date s for surgery . If angiography had a positive outcome and was uneventful , carotid endarterectomy would be done . A patient having carotid endarterectomy could have several outcomes . First , the operation could be uncomplicated and technically successful . Second , death could result from surgery . Third , a nonfatal stroke could occur . Fourth , the operation could be technically successful but could result in a nonfatal myocardial infa rct ion . Transient complications of surgery were not explicitly modeled ; Figure 1 shows a schematic of the decision model . Figure 1 . Decision tree schematic showing options and outcomes of screening compared with no screening for carotid stenosis . Data software , version 2.5 for Macintosh ( Tree-Age Software , Inc. , Boston , Massachusetts ) , was used to build the decision tree and to do model calculations for initial 5-year analyses . Programming for extended time horizon modeling was done with Excel , version 4.0 ( Microsoft Corp. , Redmond , Washington ) . Assumptions Our evaluation included direct medical costs ; indirect societal costs , such as loss of work , were omitted . Our baseline case considered screening in a cohort of 65-year-old men . Men were chosen because they have higher rates of stroke and carotid disease than women do [ 9 ] and because about two thirds of the persons in ACAS were male . We modeled for a 65-year-old person because 65 years was the approximate mean age of patients in ACAS and because risk for stroke increases rapidly between 60 and 70 years of age [ 9 ] . Because of this increase , screening was expected to have the greatest benefit when applied to 65-year-old men : If screening was not cost-effective for this group it could not be cost-effective for any group . As did ACAS , we defined carotid stenosis as an occlusion of 60 % or more of at least one carotid vessel . Outcomes of stroke ( of varying levels of severity ) , deaths , and lasting complications of angiography and endarterectomy were the health state outcomes of interest . Myocardial infa rct ion due to endarterectomy was also included as an outcome . Transient ischemic attacks were not included as outcome measures because they are by definition transient and by themselves affect neither mortality nor quality of life . No empirical data exist on the efficacy of endarterectomy more than 5 years after surgery . Because surgery imposes short-term risks and costs while offering the promise of future benefit , we evaluated the cost-effectiveness of screening under the assumption that surgery has prolonged benefits . To do this , we used extended time-horizon modeling , in which the time horizon was the lifetime of the cohort . Beyond the 5 years studied by ACAS , age-specific mortality is modeled correctly and reasonable assumptions about disease-specific ( in this case , stroke-specific ) mortality and morbidity are made [ 10 ] . We assumed that the reduction in the rate of stroke conferred by surgery would diminish gradually over time , and we used an exponential hazard function to model this decline . For the baseline case , we assumed that 10 years after surgery , the survivors of endarterectomy who had not had stroke would have the same rate of stroke as a person without stroke who did not have surgery . Using this assumption , our model determined that the survival curves would equalize at year 30 ( and therefore the survival advantage conferred by surgery would disappear ) . We then did a sensitivity analysis that modeled for rates of stroke equalizing at years 20 and 30 ( the lifetime of the entire cohort ) . In our model , duplex ultrasonography was chosen as the screening method because it is considered to be one of the best methods for detecting carotid occlusive disease , because it is well tolerated and safe , and because its use is accepted practice for the initial evaluation of carotid stenosis . The sensitivity and specificity ranges for duplex ultrasonography are approximately 81 % to 90 % and 82 % to 95 % , respectively [ 11 , 12 ] . Conventional carotid angiography is considered to be the reference diagnostic test for the evaluation of carotid artery disease . In current clinical practice , it is recommended that angiography be done before carotid endarterectomy [ 11 ] . Although ACAS reported that angiography had a complication rate of 1.2 % , large series [ 13 , 14 ] have shown rates of 0.45 % to 1.3 % for transient neurologic complications , 0.1 % for permanent neurologic deficits , and 0 % to 0.1 % for death . Patients with carotid ischemic disease , however , can have an increased risk for complications [ 14 ] . Magnetic resonance angiography is rapidly gaining acceptance as a method for the diagnosis of extracranial vascular disease , but most clinicians do not consider it sufficient to substitute for contrast angiography in evaluation before endarterectomy . Recent series show that , compared with conventional angiography , magnetic resonance angiography has a sensitivity of 84 % to 92 % and a specificity of 76 % to 81 % [ 15 - 17 ] . The Glasgow Neurologic Outcome Scale was used in ACAS to define stroke severity [ 18 ] . Our model classified strokes as either major ( Glasgow score of 2 to 4 ) or minor ( Glasgow score of 1 ) , consistent with the categories of stroke used in ACAS . We assumed that the distribution of strokes in the major and minor categories was the same as that in ACAS . To capture differences in cost of stroke care , major strokes were further design ated as severe or moderate . We defined severe stroke as the presence of permanent neurologic deficits leading to institutionalized care . This encompassed Glasgow scores 3 and 4 , which are respectively described as severe disability with lack of independence and persistent vegetative state . Although follow-up care is also required after a moderate stroke , the costs of this care are much less than those of severe stroke . Moderate stroke ( Glasgow score of 2 ) corresponds to moderate disability but with functional independence [ 18 ] . Gresham and associates [ 19 ] found that approximately 15 % of clinical ly relevant strokes led to institutionalization . Therefore , 15 % of strokes were considered to be severe . Data from ACAS showed that 53 % of strokes were mild . The remaining 32 % were considered to be moderate . This distribution was used to determine costs of stroke care and the future likelihood of death . Markov modeling [ 20 , 21 ] was used to estimate annual transitions to different health states . On the basis of the presence or absence of stenosis and whether the patient had had surgery , persons were assigned probabilities of remaining in good health or moving into the stroke or death states ; once in a stroke state , a person could remain in the same state or proceed to a more severe stroke state or to death [ 6 , 9 , 22 , 23 ] . In the following discussion of specific Markov states for the rightmost branches of our decision tree , the states are ordered from mildest to most severe . Patients are distributed among three possible Markov states for major complications of angiography : minor stroke , major stroke , and death . The rule of thumb is that each year , patients in each group have a transition probability of staying in the same state or moving to a more severe health state but can not move to a less severe state . For example , patients with minor strokes can remain within the minor stroke state or move into the major stroke state or the death state . Patients with major strokes can stay in the major stroke state or move into the death state . Once in the death state , patients remain there . If sufficient time should pass , everyone will be in the death state . Patients having endarterectomy will be distributed over the well , minor CLINICAL SCENARIO You recall from the first of our 2 articles 1 concerning economic analysis of clinical practice that your chief of medicine has asked you to review relevant economic evidence from the literature and report to the hospital 's pharmacy and therapeutics committee , which is trying to decide on formulary guidelines for the use of streptokinase and tissuetype plasminogen activator ( t-PA ) in the treatment of acute myocardial infa rct ion ( AMI ) . Your literature search identified 2 recent key cost-effectiveness studies : an analysis of economic data collected prospect ively as part of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries ( GUSTO ) trial 2 of streptokinase vs t-PA by Mark et al , 3 and a decision-analytic model by Kalish et al. 4 In the first article of this 2-part series we showed you how to evaluate the validity of the different economic appraisal study methods . In this article , we |
11,346 | 30,824,865 | These symptom-based subtypes were associated with differences in biomarker profiles and functional connectivity , but results have not sufficiently been replicated .
Although the review ed work provides many leads for future research , the method ological differences across studies and lack of replication preclude definitive conclusions about the existence of clinical ly useful and generalizable biological subtypes | Research into major depressive disorder ( MDD ) is complicated by population heterogeneity , which has motivated the search for more homogeneous subtypes through data -driven computational methods to identify patterns in data .
In addition , data on biological differences could play an important role in identifying clinical ly useful subtypes .
This systematic review aim ed to summarize evidence for biological subtypes of MDD from data -driven studies . | BACKGROUND Depression is one of the most disabling diseases , and causes a significant burden both to the individual and to society . WHO data suggests that depression causes 6 % of the burden of all diseases in Europe in terms of disability adjusted life years ( DALYs ) . Yet , the knowledge of the economic impact of depression has been relatively little research ed in Europe . AIMS OF THE STUDY The present study aims at estimating the total cost of depression in Europe based on published epidemiologic and economic evidence . METHODS A model was developed to combine epidemiological and economic data on depression in Europe to estimate the cost . The model was populated with data collected from extensive literature review s of the epidemiology and economic burden of depression in Europe . The cost data was calculated as annual cost per patient , and epidemiologic data was reported as 12-month prevalence estimates . National and international statistics for the model were retrieved from the OECD and Eurostat data bases . The aggregated annual cost estimates were presented in Euro for 2004 . RESULTS In 28 countries with a population of 466 million , at least 21 million were affected by depression . The total annual cost of depression in Europe was estimated at Euro 118 billion in 2004 , which corresponds to a cost of Euro 253 per inhabitant . Direct costs alone totalled dollar 42 billion , comprised of outpatient care ( Euro 22 billion ) , drug cost ( Euro 9 billion ) and hospitalization ( Euro 10 billion ) . Indirect costs due to morbidity and mortality were estimated at Euro 76 billion . This makes depression the most costly brain disorder in Europe , accounting for 33 % of the total cost . The cost of depression corresponds to 1 % of the total economy of Europe ( GDP ) . DISCUSSION Our cost results are in good agreement with previous research findings . The cost estimates in the present study are based on model simulations for countries where no data was available . The predictability of our model is limited to the accuracy of the input data employed . As there is no earlier cost-of-illness study conducted on depression in Europe , it is , however , difficult to evaluate the validity of our results for individual countries and thus further research is needed . CONCLUSION The cost of depression poses a significant economic burden to European society . The simulation model employed shows good predictability of the cost of depression in Europe and is a novel approach to estimate the cost-of-illness in Europe . IMPLICATION S FOR HEALTH CARE PROVISION AND POLICIES : Health and social care policy and commissioning must be evidence -based . The empirical results from this study confirm previous findings , that depression is a major concern to the economic welfare in Europe which has consequences to both healthcare providers and policy makers . One important way to stop this explosion in cost is through increased research efforts in the field . Moreover , better detection , prevention , treatment and patient management are imperatives to reduce the burden of depression and its costs . Mental healthcare policies and better access to healthcare for mentally ill are other challenges to improve for Europe . IMPLICATION S FOR FURTHER RESEARCH This study has identified several research gaps which are of interest for future research . In order to better underst and the impact of depression to European society long-term prospect i ve epidemiology and cost-of-illness studies are needed . In particular data is lacking for Central European countries . On the basis of our findings , further economic evaluations of treatments for depression are necessary in order to ensure a cost-effective use of European healthcare budgets Identifying data -driven subtypes of major depressive disorder ( MDD ) is an important topic of psychiatric research . Currently , MDD subtypes are based on clinical ly defined depression symptom patterns . Although a few data -driven attempts have been made to identify more homogenous subgroups within MDD , other studies have not focused on using human genetic data for MDD subtyping . Here we used a computational strategy to identify MDD subtypes based on single-nucleotide polymorphism genotyping data from MDD cases and controls using Hamming distance and cluster analysis . We examined a cohort of Mexican-American participants from Los Angeles , including MDD patients ( n=203 ) and healthy controls ( n=196 ) . The results in cluster trees indicate that a significant latent subtype exists in the Mexican-American MDD group . The individuals in this hidden subtype have increased common genetic substrates related to major depression and they also have more anxiety and less middle insomnia , depersonalization and derealisation , and paranoid symptoms . Advances in this line of research to vali date this strategy in other patient groups of different ethnicities will have the potential to eventually be translated to clinical practice , with the tantalising possibility that in the future it may be possible to refine MDD diagnosis based on genetic data Background Due to a lack of evidence , there is no consistent age of onset to define early onset ( EO ) versus later onset ( LO ) major depressive disorder ( MDD ) . Fractional anisotropy ( FA ) , derived from diffusion tensor imaging ( DTI ) , has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry , abnormalities of which might facilitate the delineation of EO versus LO MDD . Method In this study , 61 pairs of untreated , non-elderly , first-episode MDD patients and healthy controls ( HCs ) aged 18–45 years old received DTI scans . The voxel-based analysis method ( VBM ) , classification analysis , using the Statistical Package for the Social Sciences ( SPSS ) , and regression analyses were used to determine abnormal FA clusters and their correlations with age of onset and clinical symptoms . Results Classification analysis suggested in the best model that there were two subgroups of MDD patients , delineated by an age of onset of 30 years old , by which MDD patients could be divided into EO ( 18–29 years old ) and LO ( 30–45 years old ) groups . LO MDD was characterized by decreased FA , especially in the white matter ( WM ) of the fronto-occipital fasciculus and posterior limb of internal capsule , with a negative correlation with the severity of depressive symptoms ; in marked contrast , EO MDD showed increased FA , especially in the WM of the corpus callosum , corticospinal midbrain and inferior fronto-occipital fasciculus , while FA of the WM near the midbrain had a positive correlation with the severity of depressive symptoms . Conclusion Specific abnormalities of the brain circuitry in EO vs. LO MDD were delineated by an age of onset of 30 years old , as demonstrated by distinct abnormal FA clusters with opposite correlations with clinical symptoms . This DTI study supported the evidence of an exact age for the delineation of MDD , which could have broad multidisciplinary importance . Trial Registration Clinical Trials.gov This paper describes the application of prospect i ve longitudinal data from an epidemiological sample of young adults to define subtypes of major depression . Depression was classified on a spectrum from subthreshold manifestation of symptoms and duration at one end , to cases with recurrent episodes of depression meeting duration criteria for major depressive episodes at the other . There was a direct relationship between the severity of depression over the longitudinal course and both duration and recurrence of depressive episodes . The subgroup of depression with recurrence of both brief and longer duration episodes could be discriminated on most of the indicators of validity including symptoms , impairment , family history , and suicide attempts . In light of the young age of this cohort , the strong history of suicide attempts and other complications of depression among the subjects with recurrent depression was striking . These findings underscore the importance of employing course as a classification criterion of depression , and the inclusion of subthreshold episodes of depression in the characterization of course |
11,347 | 21,833,947 | Neuromuscular training alone appears effective in the short term but whether this advantage would persist on longer-term follow-up is not known .
While there is insufficient evidence to support any one surgical intervention over another surgical intervention for chronic ankle instability , it is likely that there are limitations to the use of dynamic tenodesis .
After surgical reconstruction , early functional rehabilitation appears to be superior to six weeks immobilisation in restoring early function | BACKGROUND Chronic lateral ankle instability occurs in 10 % to 20 % of people after an acute ankle sprain .
Initial treatment is conservative but if this fails and ligament laxity is present , surgical intervention is considered .
OBJECTIVES To compare different treatments , conservative or surgical , for chronic lateral ankle instability . | To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Functional outcome , stability at radiographic investigation and ankle joint torque after anatomical reconstruction of the lateral ankle ligaments were evaluated in patients with early postoperative mobilization versus those with cast immobilization . Thirty patients with chronic lateral ligament instability of the ankle underwent anatomical reconstruction of the ligaments . Postoperatively the patients were r and omly allocated to two groups : Group A ( n=15 ) were immobilized in a below-knee plaster for 6 weeks and Group B ( n=15 ) underwent early controlled range of motion training using an Air-Cast ankle brace . The functional results were evaluated using a scoring scale and objective results using st and ardized stress radiographs . Also eccentric and concentric muscle torque at 60 degrees/s was measured in plantar flexion and dorsiflexion , respectively . The functional results were satisfactory in 12/15 ankles in Group A and 14/15 in Group B ( n.s . ) . All the patients with satisfactory results regained normal range of motion . Patients with unsatisfactory results had either residual pain or recurrent instability . In Group B , the strength measurements revealed significantly higher peak torque values after three months in plantar flexion at 60 degrees/s . Six months postoperatively , the torque values did not differ significantly between the groups . Also , there was no group difference in the laxity of the ankle joint , including both anterior talar translation test and talar tilt test , at the two-year follow-up . One patient had a superficial wound infection . We conclude that after the reconstruction of chronic lateral ligament instability of the ankle the functional and stability results were equally good with early postoperative mobilization and 6-week immobilization . However , using early mobilization plantar flexion strength was regained earlier than with cast immobilization , without any risk of short- or medium-term complications , such as increased ankle laxity . We recommend early mobilization after anatomical reconstruction of the lateral ankle ligaments To study the efficacy of an injury prevention program in a r and omized trial , 12 teams ( 180 players ) in a male senior soccer division were followed up for 6 months . The 12 teams were allocated at r and om to two groups of six teams , one being given a prophylactic program and the other serving as control . The program was based on previous studies of injury mechanisms . It comprised ( 1 ) correction of training , ( 2 ) provision of optimum equipment ; ( 3 ) prophylactic ankle taping ; ( 4 ) controlled rehabilitation ; ( 5 ) exclusion of players with grave knee instability ; ( 6 ) information about the impor tance of disciplined play and the increased risk of injury at training camps ; and ( 7 ) correction and supervision by doctor(s ) and physiotherapist(s ) . The injuries in the test teams were 75 % fewer than in the controls . The most common types of soccer injuries , sprains and strains to ankles and knees , were all significantly reduced . It is concluded that the pro posed prophylactic program , including close supervi sion and correction by doctors and physiotherapists , significantly reduces soccer injuries Abstract We compared sport-specific skills in 23 athletes with functionally unstable ankle joints to those of 18 healthy volunteers by performing a Japan test as well as a specially design ed single-leg jumping test . For external stabilization of the ankle , an Aircast brace , a Ligafix Air brace , a Malleoloc brace and a tape b and age were applied . For the Japan test in the group with uninjured ankle joints , the best results were obtained when wearing the Aircast brace , followed by tape b and age , Ligafix brace and no stabilizing device in descending order . The worst results were presented by the group with the Malleoloc brace . However , there were no significant differences among these devices . In the group with functionally unstable ankle joints , the best score was achieved with the tape b and age , followed by the Ligafix brace , Malleoloc brace and Aircast brace . The unstabilized group showed significantly worse results compared with all other groups . In the single-leg jumping test , the stabilizing devices had no negative influence on the jumping capability in the uninjured ankle joints . Additionally , there was no significant difference among the orthoses . Volunteers with unstable ankle joints experienced a significant improvement of jumping performance with most of the devices . The best results were achieved with the Aircast brace , followed by the Malleoloc brace , Ligafix brace and tape b and age . However , there was no significant difference among these orthoses . While the reaction time of the volunteers was the same for all test situations , the time for dynamically stabilizing the ankle joint appeared to be significantly worse in those ankle joints without a brace . For athletic activities , which are dominated by movement patterns comparable to the Japan test as well as the jumping test used , these stabilizing devices seem to have no negative effect on sport-specific capabilities STUDY DESIGN R and omized controlled trial with pretraining , posttraining , and follow-up repeated measures . OBJECTIVE To determine the effectiveness of a 4-week elastic resistance exercise program on balance in subjects with and without a history of sprained ankles . BACKGROUND Several research ers have suggested that improving balance may help alleviate the symptoms of functional ankle instability and reduce the rate of recurrent ankle sprains . METHODS AND MEASURES Forty subjects ( 20 males , 20 females ; 20 subjects with chronic ankle instability [ CAI ] , 20 healthy ) participated in the study . Ten subjects ( 5 males , 5 females ) from each CAI and healthy group were r and omly assigned to either the exercise or control group , result ing in a total of 4 groups . Total travel distance of the center of pressure , monitored using a force platform , was measured before training , after 4 weeks of training , and at a 4-week follow-up . RESULTS There were no interactions between gender , ankle sprain history , or training groups . Balance significantly improved in subjects with and without a history of ankle sprains following 4 weeks of elastic resistance exercises . Mean improvement in balance for the exercise group following training , reflected through a decrease in total travel distance , was -11.1 cm ( 95 % confidence interval : -14.0 to -8.2 cm ) . These improvements in balance were retained 4 weeks after training . CONCLUSIONS Balance was improved after 4 weeks of elastic resistance exercise in subjects with and without a history of lateral ankle sprains . Balance improvements persisted 4 weeks following the treatment cessation Objective : To examine the effects of a four-week balance training programme on ankle kinematics during walking and jogging in those with chronic ankle instability . A secondary objective was to evaluate the effect of balance training on the mechanical properties of the lateral ligaments in those with chronic ankle instability . Design : R and omized controlled trial . Setting : Laboratory . Subjects/ patients : Twenty-nine participants ( 12 males , 17 females ) with self-reported chronic ankle instability were r and omly assigned to a balance training group or a control group . Intervention : Four weeks of supervised rehabilitation that emphasized dynamic balance stabilization in single-limb stance . The control group received no intervention . Main outcome measures : Kinematic measures of rearfoot inversion/eversion , shank rotation , and the coupling relationship between these two segments throughout the gait cycle during walking and jogging on a treadmill . Instrumented ankle arthrometer measures were taken to assess anterior drawer and inversion talar tilt laxity and stiffness . Results : No significant alterations in the inversion/eversion or shank rotation kinematics were found during walking and jogging after balance training . There was , however , a significant decrease in the shank/rearfoot coupling variability during walking as measured by deviation phase after balance training ( balance training posttest : 13.1 ° ± 6.2 ° , balance training pretest : 16.2 ° ± 3.3 ° , P = 0.03 ) , indicating improved shank/rearfoot coupling stability . The control group did not significantly change . ( posttest : 16.30 ° ± 4.4 ° , pretest : 18.6 ° ± 7.1 ° , P40.05 ) There were no significant changes in laxity measures for either group . Conclusions : Balance training significantly altered the relationship between shank rotation and rearfoot inversion/eversion in those with chronic ankle instability Background Ankle sprains are common injuries that often lead to functional ankle instability ( FAI ) , which is a pathology defined by sensations of instability at the ankle and recurrent ankle sprain injury . Poor postural stability has been associated with FAI , and sports medicine clinicians rehabilitate balance deficits to prevent ankle sprains . Subsensory electrical noise known as stochastic resonance ( SR ) stimulation has been used in conjunction with coordination training to improve dynamic postural instabilities associated with FAI . However , unlike static postural deficits , dynamic impairments have not been indicative of ankle sprain injury . Therefore , the purpose of this study was to examine the effects of coordination training with or without SR stimulation on static postural stability . Improving postural instabilities associated with FAI has implication s for increasing ankle joint stability and decreasing recurrent ankle sprains . Methods This study was conducted in a research laboratory . Thirty subjects with FAI were r and omly assigned to either a : 1 ) conventional coordination training group ( CCT ) ; 2 ) SR stimulation coordination training group ( SCT ) ; or 3 ) control group . Training groups performed coordination exercises for six weeks . The SCT group received SR stimulation during training , while the CCT group only performed coordination training . Single leg postural stability was measured after the completion of balance training . Static postural stability was quantified on a force plate using anterior/posterior ( A/P ) and medial/lateral ( M/L ) center-of-pressure velocity ( COPvel ) , M/L COP st and ard deviation ( COPsd ) , M/L COP maximum excursion ( COPmax ) , and COP area ( COParea ) . Results Treatment effects comparing posttest to pretest COP measures were highest for the SCT group . At posttest , the SCT group had reduced A/P COPvel ( 2.3 ± 0.4 cm/s vs. 2.7 ± 0.6 cm/s ) , M/L COPvel ( 2.6 ± 0.5 cm/s vs. 2.9 ± 0.5 cm/s ) , M/L COPsd ( 0.63 ± 0.12 cm vs. 0.73 ± 0.11 cm ) , M/L COPmax ( 1.76 ± 0.25 cm vs. 1.98 ± 0.25 cm ) , and COParea ( 0.13 ± 0.03 cm2 vs. 0.16 ± 0.04 cm2 ) than the pooled means of the CCT and control groups ( P < 0.05 ) . Conclusion Reduced values in COP measures indicated postural stability improvements . Thus , six weeks of coordination training with SR stimulation enhanced postural stability . Future research should examine the use of SR stimulation for decreasing recurrent ankle sprain injury in physically active individuals with FAI STUDY DESIGN Within-group repeated measures . OBJECTIVES To determine the effect of a semi-rigid prophylactic ankle stabilizer ( PAS ) on performance of subjects with post-acute , unilateral ankle sprains who have mechanically stable ankles , but are functionally impaired . BACKGROUND Most studies on PAS performance to date are limited to subjects with noninjured , nonimpaired ankles . No research has been reported to determine the effect PASs have on performance in subjects who have a mechanically stable , nonacute ankle sprain with functional impairment . METHODS AND MEASURES Twenty-five subjects ( 8 men and 17 women ; average height = 168.91 + /- 33.02 cm , average weight = 61.10 + /- 29.5 kg , and average age = 16.2 + /- 6 years ) met the qualification criteria of the study . Subjects had unilateral grade I or II lateral ankle sprains of 3 to 4 weeks duration and were cleared medically to return to activities of daily living . Each subject 's injured ankle was mechanically stable as determined by physical exam but was functionally impaired as determined by instability during the modified Rhomberg test . Separate 2 x 2 ANOVAs with repeated measures on brace condition ( Aircast SportStirrup and nonbraced control ) and test session ( test session 1 and test session 2 ) were completed to assess the effect of ankle stabilization on 2 dependent variables ( 36.58-m shuttle-run and vertical-jump ) . RESULTS Shuttle-run time was significantly faster for the braced condition ( mean = 9.43 + /- .72 seconds ) than for the nonbraced control ( mean = 9.57 + /- .75 seconds ) , regardless of test session . Shuttle-run time was significantly faster for test session 2 ( mean = 9.43 + /- .79 seconds ) than for test session 1 ( mean = 9.57 + /- .68 seconds ) , regardless of brace condition . No significant main or interaction effects occurred for vertical-jump . CONCLUSIONS Use of a semi-rigid PAS significantly increased shuttle-run but not vertical-jump performance . This effect was immediate and did not require PAS acclimation 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 Early range of motion training after ligament reconstruction of the ankle ligaments for chronic ankle joint instability was evaluated . Forty patients were operated on with anatomic reconstruction of the lateral ankle ligaments , i.e. shortening , imbrication and reinsertion . The patients were r and omized postoperatively between two groups : ( 1 ) immobilization for 6 weeks in a plaster cast and ( 2 ) early range of motion training , in a Walker-Boot . Both groups underwent an identical rehabilitation program . with peroneal strengthening and co-ordination training after 6 weeks . The functional results were evaluated using a scoring scale and the mechanical stability with st and ardized stress radiographs . The minimum follow-up was 2 years . The functional results were satisfactory in 16 ( 80 % ) of the patients in group I , and 19 ( 95 % ) in group II . The mean values of anterior talar translation and talar tilt were not significantly different between the groups preoperatively nor at follow-up . The mean time period for sick leave was significantly shorter for group II , 6.5±1.6 weeks compared with 8.5±1.8 weeks for group I. The mean time period for return to sports activity was significantly shorter for group II , 9.5±2.2 weeks , compared with 12.5±2.6 weeks for group I. Early range of motion training is recommended after ligament reconstruction of the ankle , as it will enable earlier return to sports activities , shorter sick leave and preserved mechanical stability Injury to the lateral ligaments of the ankle is one of the most common sports-related injuries . Although these injures generally resolve with non-operative treatment reconstruction of the lateral ligaments of the ankle is occasionally necessary . We report the surgical technique and result of reconstruction of the anterior talo-fibular ligament using a semi-tendinosis free graft in 26 patients with an average follow-up of 24 months . 81 % of patients reported complete resolution or substantial improvement in instability , swelling and sharp pain . Episodes of functional instability persisted in five patients post operatively . No significant differences were noted between the operated and contra-lateral non-operated ankle in range of motion or uniaxial balance assessment . Kin-Com testing of hamstring strength showed no differences between sides . Short term results suggest that this ligament reconstruction provides good results without sacrifice of peroneal function and has minimal donor site morbidity 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 A study was undertaken to evaluate the effect of a semi rigid ankle orthosis ( Sport-Stirrup ) on the incidence of ankle sprains in soccer players during 1 playing season . Senior soccer players were divided into 2 groups : play ers with previous ankle sprains ( N = 258 ) and players without such history ( N = 246 ) . The players in these groups were each r and omly allocated to either a semi rigid orthosis or a control group at the start of the playing season . All subsequent injuries during the season and the total number of playing hours were documented . There was a significant reduction in the incidence of ankle sprains ( injuries/1 000 playing hours ) by ankles in the orthosis group with previous sprains ( 0.14 ) com pared with the nonbraced group with previous sprains ( 0.86 ) . The incidence of ankle sprains was significantly higher in the nonbraced group with previous sprains ( 0.86 ) compared with the nonbraced group without pre vious sprains ( 0.46 ) . Thus , in this study , a semirigid or thosis significantly reduced the incidence of recurrent ankle sprains in soccer players with previous history of ankle sprains 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 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 PURPOSE Recurrence of ankle sprains is common among athletes . Although ankle taping reduces the risk of injury , the mechanism underlying its effectiveness remains unclear . Anecdotal reports suggest a role of the belief among athletes that taping will protect them from injury . That is , taping may have a placebo effect . The purpose of the present study was to determine whether there was a placebo effect with ankle taping in individuals with ankle instability . METHODS Thirty participants with ankle instability completed a hopping test and a modified star excursion balance test under three conditions : ( i ) real tape , ( ii ) placebo tape , and ( iii ) control ( no tape ) . Participants were blinded to the purpose of the study and were informed that the study aim ed to compare two methods of ankle taping referred to as mechanical ( real ) and proprioceptive ( placebo ) . The order of testing the three conditions and the two functional tests was r and omized . RESULTS There was no significant difference in performance among the three conditions for the hopping test ( P = 0.865 ) or the modified star excursion balance test ( P = 0.491 ) . However , a secondary exploratory analysis revealed that participants ' perceptions of stability , confidence , and reassurance increased with both real and placebo ankle taping when performing the functional tasks . CONCLUSION The role of the placebo effect of ankle taping in individuals with ankle instability remains unclear . Clinicians should , therefore , continue to use ankle-taping techniques of known efficacy . They should , however , focus on maximizing patients ' beliefs in the efficacy of ankle taping , because its application reassured participants and improved their perceived stability and confidence . The effect of ankle taping on participants ' perceptions may contribute to its effectiveness in preventing injury The present study investigated the effects of two different surgical procedures for the treatment of chronic ankle instability . Ten patients treated with an anatomic reconstruction using a periosteal flap were compared with a second group that received an Evans tenodesis . All patients were evaluated before and after surgery with clinical and radiographic examinations as well as dynamic pedobarography . Patient satisfaction and radiographic and functional results were comparable in both groups and revealed a good restoration of joint stability and gait symmetry . Our results indicate that both methods of ankle ligament reconstruction achieve a comparable clinical and functional outcome within 1 year after surgery OBJECTIVE To examine the effects of ankle-strengthening exercises on joint position sense and strength development in subjects with functionally unstable ankles . DESIGN AND SETTING Subjects were r and omly assigned to a training or control group . The training group participated in a 6-week strength-training protocol using rubber tubing 3 times a week throughout the training period . The control group did not participate in the strength-training protocol . SUBJECTS Twenty healthy college students ( 10 females , 10 males , age = 20.6 + /- 2.23 years ; ht = 176.40 + /- 7.14 cm ; wt = 74.18 + /- 10.17 kg ) with a history of functional ankle instability volunteered to participate in this study . MEASUREMENTS We pretested and posttested dorsiflexor and evertor isometric strength with a h and held dynamometer and collected joint position sense ( JPS ) data at 20 degrees for inversion and plantar flexion and at 10 degrees for eversion and dorsiflexion . RESULTS Statistical tests for strength and JPS revealed significant group-by-time interactions for dorsiflexion strength , eversion strength , inversion JPS , and plantar flexion JPS . Simple main-effects testing revealed improvements in training group strength and JPS at posttesting . There were no significant effects for eversion JPS , but the group main effect for dorsiflexion JPS was significant , with the experimental group having better scores than the control group . CONCLUSIONS Ankle-strengthening exercises improved strength , inversion JPS , dorsiflexion JPS , and plantar flexion JPS in subjects with functionally unstable ankles 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 OBJECTIVE The purpose of this study was to determine the efficacy of adjusting the ankle in the treatment of subacute and chronic grade I and grade II ankle inversion sprains . DESIGN A single-blind , comparative , controlled pilot study . SETTING Technikon Natal Chiropractic Day Clinic . PARTICIPANTS Thirty patients with subacute and chronic grade I and grade II ankle inversion sprains . Patients were recruited from the public ; they responded to advertisements placed in newspapers and on notice boards around the campus and local sports clubs . INTERVENTION Each of the 15 patients in the treatment group received the ankle mortise separation adjustment . Each of the 15 patients in the placebo group received 5 minutes of detuned ultrasound treatment . Each participant received a maximum of 8 treatment sessions spread over a period of 4 weeks . MAIN OUTCOME MEASURE Patients were evaluated at the first treatment , at the final treatment , and at a 1-month follow-up consultation . Subjective scores were obtained by means of the short-form McGill Pain Question naire and the Numerical Pain Rating Scale 101 . Objective measurements were obtained from goniometer readings measuring ankle dorsiflexion range of motion and algometer readings measuring pain threshold over the ankle lateral ligaments . A functional evaluation of ankle function was also used . RESULTS Although both groups showed improvement , statistically significant differences in favor of the adjustment group were noted with respect to reduction in pain , increased ankle range of motion , and ankle function . CONCLUSIONS This study appears to indicate that the mortise separation adjustment may be superior to detuned ultrasound therapy in the management of subacute and chronic grade I and grade II inversion ankle sprains 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 Physiotherapists frequently use manipulative therapy techniques to treat dysfunction and pain result ing from ankle sprain . This study investigated whether a Mulligan 's mobilization with movement ( MWM ) technique improves talocrural dorsiflexion , a major impairment following ankle sprain , and relieves pain in subacute population s. Fourteen subjects with subacute grade II lateral ankle sprains served as their own control in a repeated measures , double-blind r and omized controlled trial that measured the initial effects of the MWM treatment on weight bearing dorsiflexion and pressure and thermal pain threshold . The subacute ankle sprain group studied displayed deficits in dorsiflexion and local pressure pain threshold in the symptomatic ankle . Significant improvements in dorsiflexion occurred initially post-MWM ( F(2,26 ) = 7.82 , P = 0.002 ) , but no significant changes in pressure or thermal pain threshold were observed after the treatment condition . Results indicate that the MWM treatment for ankle dorsiflexion has a mechanical rather than hypoalgesic effect in subacute ankle sprains . The mechanism by which this occurs requires investigation if we are to better underst and the role of manipulative therapy in ankle sprain management Eighty-six patients with acute ( < 24 h ) grade II or III lateral ligament ruptures were r and omized into two different non-surgical treatment groups . The main difference in treatment protocol s between the two groups was during the first week after injury . Group I ( n = 46 ) was to receive functional treatment using specially design ed compression pads , elevation of the injured foot ( 24 h ) , repeated elastic wrapping ( compression b and age followed by ankle tape ) , early full weight-bearing and proprioceptive range-of-motion training . Group II ( n = 40 ) was to receive conventional treatment with an elastic b and age , partial weight bearing and crutches until the pain subsided . One week after the injury , patients from both groups were given identical rehabilitation instructions . No early surgery was performed . The mean follow-up period was 18 months . The functional results were satisfactory in 91 % of the patients in group I and in 87 % of the patients in group II ( NS ) . Five patients had been operated on due to recurrent instability , two in group I and three in group II ( NS ) . The mean sick leave was significantly shorter in group I ; 5.6 + /- 4.2 days compared with 10.2 + /- 6.8 days in group II . Return to sports activities was also significantly earlier in group I , 9.6 + /- 4.8 days compared with 19.2 + /- 9.5 days in group II . In this study , non-surgical treatment of acute grade II and III ligament injuries of the ankle produced satisfactory results in the majority of patients . Early functional treatment result ed in shorter sick leave and facilitated an earlier return to sports , but it did not influence the final results This r and omized clinical study was design ed to pro spectively determine the efficacy of a semirigid ankle stabilizer in reducing the frequency and severity of acute ankle injuries in basketball . Athletic shoe , playing surface , athlete-exposure , ankle injury history , and brace assignment were either statistically or experimen tally controlled . Participants in the study were 1601 United States Military Academy cadets with no prepar ticipation , clinical , functional , or radiographic evidence of ankle instability . Subjects experienced a total of 13,430 athlete-exposures in the 1990 and 1991 intra mural basketball seasons . Ankle injury was defined as acute trauma to the ankle ligaments that result ed in an athlete 's inability to participate in basketball 1 day after the injury . Use of ankle stabilizers significantly reduced the frequency of ankle injuries . Reduction in ankle in juries , however , depended on the nature of injury ( fewer contact injuries occurred among those who wore braces ) . Injury severity was not statistically reduced , and wearing the ankle stabilizer did not affect the fre quency of knee injuries . Attitude toward ankle stabilizer use improved as use of the stabilizer increased 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 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 PURPOSE The purpose of this r and omized controlled trial was to determine the effect of a 4-wk balance training program on static and dynamic postural control and self-reported functional outcomes in those with chronic ankle instability ( CAI ) . METHODS Thirty-one young adults with self-reported CAI were r and omly assigned to an intervention group ( six males and 10 females ) or a control group ( six males and nine females ) . The intervention consisted of a 4-wk supervised balance training program that emphasized dynamic stabilization in single-limb stance . Main outcome measures included the following : self-reported disability on the Foot and Ankle Disability Index ( FADI ) and the FADI Sport scales ; summary center of pressure ( COP ) excursion measures including area of a 95 % confidence ellipse , velocity , range , and SD ; time-to-boundary ( TTB ) measures of postural control in single-limb stance including the absolute minimum TTB , mean of TTB minima , and SD of TTB minima in the anteroposterior and mediolateral directions with eyes open and closed ; and reach distance in the anterior , posteromedial , and posterolateral directions of the Star Excursion Balance Test ( SEBT ) . RESULTS The balance training group had significant improvements in the FADI and the FADI Sport scores , in the magnitude and the variability of TTB measures with eyes closed , and in reach distances with the posteromedial and the posterolateral directions of the SEBT . Only one of the summary COP-based measures significantly changed after balance training . CONCLUSIONS Four weeks of balance training significantly improved self-reported function , static postural control as detected by TTB measures , and dynamic postural control as assessed with the SEBT . TTB measures were more sensitive at detecting improvements in static postural control compared with summary COP-based measures Previous studies concerning ruptures of the lateral ligaments of the ankle dealt with acute first ruptures . There are a few articles about chronic instability of the ankle but no prospect i ve investigations have been reported concerning the treatment of recurrent ruptures . Good results were obtained following after non-operative treatment of acute ruptures of the fibular ligaments of the ankle joint . This prospect ively r and omized study was commenced to test whether recidivations of the rupture of the lateral ligaments can also be treated non-operatively or if they are in need of operative repair . The second question to be answered was whether these injuries should be treated differently depending on the treatment of the first rupture . From December 1986 to November 1989 , 109 patients with a recidivation of a rupture of the ankle joint lateral ligaments were included in this prospect i ve trial at the Department of Trauma Surgery , Hannover Medical School . They were divided into two groups depending on the therapy used to treat the first injury : The relapse was classified as a second-stage-rupture in cases where treatment of the first ligament rupture did not involve an operation and as a rerupture if the initial rupture was surgically repaired . Half of each group was treated r and omly either with surgical ligament repair or without . A total of 100 patients ( 92 % ) at an average age of 24 years ( 11 to 49 years ) was seen for follow-up examination one year after the relapse : The follow-up included the patient 's subjective assessment , a clinical examination , and stress radiography . A 70 point score was used for evaluation of the total result . Two wound infections requiring reoperation were observed in the operative treatment groups . The follow-up examination revealed better results in both operative treatment groups ( A and C ) , which was statistically significant ( P < 0.05 ) . Patients with a second-stage-rupture showed a significantly higher ( P < 0.001 ) stability by stress radiography after surgical treatment ( group A ) in contrast to non-operative treatment ( group B ) . In addition , the subjective and clinical results indicated a tendency towards better results which were not statistically significant ( P < 0.09 and P < 0.07 ) . In cases of rerupture the patient 's subjective assessment revealed significantly more ( P < 0.05 ) complaints after non-operative treatment ( group D ) . Clinical results were comparable , and radiologic assessment showed a tendency towards higher joint stability after surgical treatment ( group C ) , although it was not statistically significant ( P < 0.07 ) . Based on the results presented , the authors recommend the surgical repair of ankle joint ligaments in cases of second-stage- or rerupture Background : A search of the literature shows that the effect of surgery on ankle proprioception has been hardly investigated . Objective : To examine the effect of anatomical reconstruction of the anterolateral capsuloligamentous complex on ankle joint position sense . Methods : A prospect i ve study using the “ slope box ” test . Ten consecutive patients were included in the study , and 10 healthy athletes represented the control group . Results : Similar test-retest reliability rates ( overall reliability 0.92 ; p = 0.0013 ) were obtained to those of the original design ers of the method . There were no significant differences with respect to side dominance ( p = 0.9216 ) . Investigation of the characteristics of mean absolute estimate errors showed that the controls tested became error prone in the range of slope altitudes 7.5–25 ° in every direction , compared with the range 0–5 ° ( range of p values 0.00003–0.00072 ) . The results of the intervention group showed that , for the two main directions of interest ( anterior and lateral ) , preoperative differences in mean absolute estimate errors between injured ( anterior 3.91 ( 2.81 ) ° ; lateral 4.06 ( 2.85 ) ° ) and healthy ( anterior 2.94 ( 2.21 ) ° , lateral 3.19 ( 2.64 ) ° ) sides ( anterior , p = 0.0124 ; lateral , p = 0.0250 ) had disappeared ( postoperative differences : anterior , p = 0.6906 ; lateral , p = 0.4491 ) . The afflicted ankle had improved significantly after surgery in both important directions ( anterior , p<0.0001 ; lateral , p = 0.0023 ) . Conclusions : The study shows that differences in joint position sense between healthy and injured ankles disappeared as the result of surgery . Preoperative data show that proprioceptive malfunction is a cause of functional instability . If treatment is by means of surgery , the retensioning of the original anterolateral structures is inevitable , even if other grafting or surgical techniques are used We prospect ively and r and omly compared the out comes of the Chrisman-Snook and modified-Broström procedures for chronic lateral ankle instability in 40 patients . Both operations provided good or excellent stability in more than 80 % of the patients . However , the modified-Broström procedure result ed in higher Sefton scores than the Chrisman-Snook procedure . In addi tion , a statistically significant greater proportion of complications occurred in patients treated with the Chrisman-Snook procedure Many techniques have been described in acute and chronic lateral ligament insufficiency in the ankle . At present , the Bostrom-Gould and Chrisman-Snook procedures and their variations remain the " gold st and ard " . Recent assessment of important etiologic factors has shed some light on the relationship between the original injury or injuries and the subsequent development of the varus tibiotalar joint with or without secondary osteoarthritis . The development of Taylor Spatial Frame may well revolutionize its management . In the meantime , further consideration should be given to well- design ed and evaluated r and omized controlled trials , improved underst and ing of the biomechanics , and function of the ligaments , for example , proprioceptive function and their healing . Newer and less invasive arthroscopic and percutaneous techniques are being developed Functional ankle instability , orthoses , and passive resistive torque tolerated have not been research ed . The purpose of the study was to evaluate the passive resistance torque exerted by a flexible and semirigid orthosis for individuals with chronic instability . Twenty-two subjects were evaluated on the passive ankle resistance unit during unbraced , flexible , and semirigid brace conditions . Data from the final three trials for each condition were analyzed using a multiple analysis of variance with repeated measures for resistive torque and inversion range of motion . The semirigid and flexible braces tolerated significantly greater torque forces and less inversion range than the unbraced condition ( P < 0.000 ) . External orthotic support , in particular that of a semirigid orthosis , may be beneficial toward reducing injury or be an effective prophylactic for the healthy population Kakihana W , Torii S , Akai M , Nakazawa K , Fukano M ; Naito K : Effect of a lateral wedge on joint moments during gait in subjects with recurrent ankle sprain . Am J Phys Med Rehabil 2005;84:858 - 864 . This study assessed the biomechanic effects of wearing a lateral wedge on the subtalar joint moment during gait in athletes with and without an unstable lateral ankle . A crossover design was applied whereby 50 collegiate males walked with two different wedges : a 0 ° control wedge and a 6 ° lateral wedge . We investigated frontal plane angles and moments at the subtalar joint and the knee joint , as well as ground reaction forces and center of pressure excursion . Moments were derived using a three-dimensional inverse dynamics model of the lower extremity . The 6 ° lateral wedge significantly increased the subtalar joint valgus moment ( P < 0.001 ) and reduced the knee joint varus moment ( P < 0.001 ) when compared with no wedge . The differences between wedge conditions were associated with a laterally shifted location of the center of pressure during stance phase . However , there were diverse , sometimes reversed effects with the wedge among the athletes with an unstable lateral ankle . These results indicate that biomechanical indications and limitations of lateral wedges in unstable lateral ankles should be analyzed in more detail , possibly leading to new guidelines for the use of such foot orthoses In a prospect i ve study , 82 patients with 89 chronic lateral unstable ankles were r and omly allocated to either static ( Group S ) or dynamic ( Group D ) reconstruction . For static reconstruction a procedure involving the distal part of the peroneus brevis tendon was used . The bore holes in the lateral malleolus were placed at the insertions of the original ligaments . For dynamic reconstruction the anterior one-half of the peroneus brevis tendon was used . On muscular contraction the split tendon will slide through a bore canal in the lateral malleolus . Theoretically , both procedures can stabilize the ankle and subtalar joint . Fifty-six patients were assigned to static reconstruction and , because of thin tendons , only 26 were assigned to dynamic reconstruction . Thirty-three cases had increased subtalar mobility . All patients had st and ardized clinical and roentgenographic examinations preoperatively and at nine and 25 months postoperatively . At the 25-month follow-up examinations the clinical results were best in Group S. The number of reinjuries was highest in Group D , and two patients had given up sports . The inversion movement was most restricted in Group S but without functional importance . A significant reduction of talar tilting and anterorotational talar displacement was seen in both groups but was most pronounced in Group S. Also , postural balance improved in both groups . Complications in Group S were venous thrombosis in two patients , dysesthesia in the cicatrix in two , hyposensibility of the lateral foot edge in one , and calcification at one bore hole in one patient . Complications in Group D were hyposensibility and dysesthesia in the cicatrix in one patient . The static procedure is recommended for reconstruction of chronically unstable ankles , especially if associated with increased subtalar mobility BACKGROUND Functional ankle instability is defined as the subjective sensation of giving way or feeling joint instability after repeated episodes of ankle sprain . The purpose of this study was to examine the effects of 12-week biomechanical ankle platform system training on static postural stability and ankle reposition sense in subjects with unilateral functional ankle instability . METHODS Twelve university students ( 4 females and 8 males ) with unilateral functional ankle instability volunteered as subjects . The active and passive reposition senses were assessed using an isokinetic dynamometer . The mean radius of the center of pressure excursion was recorded during single-leg st and ing with a force platform . A 12-week training program and a progression test for controlling the platform in certain directions and advancing to next training level was given to each subject . Repeated- measures 2-way analyses of variance were conducted to determine differences in postural stability and ankle proprioception between each limb before and after the training period . FINDINGS The mean radius of center of pressure on unilateral st and ing and the absolute error from pre-selected ankle angle in the functional ankle instability limb were significantly reduced after 12 weeks of training . INTERPRETATION These improvements in postural stability appear to reflect improved neuromuscular ability along with enhanced functional joint stability , as ankle proprioception also demonstrated the same positive improvements after training OBJECTIVE The aim of the present investigation was to test the stability of 10 different ankle braces under passive and rapidly induced loading conditions in a population suffering from chronic ankle instability in order to provide objective information to choose or recommend an appropriate model for specific needs . In addition , the relationship between passive and rapidly induced testing of the stabilizing effect against inversion was evaluated to identify if passive support characteristics of braces are reflected under rapidly induced conditions . DESIGN An experimental in vivo study with a repeated- measures design was used . BACKGROUND Ankle braces are commonly used for treatment , rehabilitation , and prevention of ankle injuries . A variety of products exists but there is few information available to assist clinicians , physiotherapists and coaches as well as consumers in choosing a brace on a basis of objective information . Furthermore , there is a lack of studies that provide data for both passively and rapidly induced movement of the ankle joint when using different ankle braces . METHODS Twenty-four subjects with chronic ankle instability participated in the project . Passive ankle range of motion measurements were performed in a custom-built fixture and simulated inversion sprains were elicited on a tilting platform . RESULTS The tested braces restrict range of motion significantly compared to the no-brace condition for both the passively and rapidly induced inversion and marked differences between braces were revealed . A close relationship between passive and rapidly induced test results for inversion was found . CONCLUSIONS Passive as well as rapidly induced stability tests provide a basis of objective information to describe the characteristics of different ankle braces . Combined results of passive and rapidly induced inversion as well as correlation between results demonstrate that passive support characteristics of braces are reflected under rapidly induced conditions but the amount of restriction is reduced . Therefore , caution should be taken when recommending braces for applications under dynamic circumstances only on the basis of passive support characteristics . RELEVANCE A basis of information regarding the stability characteristics of different ankle braces under passive and rapidly induced conditions will help the clinician and consumer in choosing the most appropriate brace model for specific use . The results also provide more insights into factors that influence stability characteristics of ankle braces Two anatomic reconstructions for correction of chronic lateral ankle joint instability were compared . In a pro spective , r and omized study , 60 patients were allocated to one of two treatment groups : reconstruction of the ligaments as described by Karlsson et al. ( Group I ) or with the modification of the Broström procedure as described by Gould et al. ( Group II ) . The functional results were evaluated with a scoring scale , and the mechanical stability with st and ardized stress radio graphs . The minimum follow-up period was 2 years . The functional results were satisfactory in 27 of 30 ( 90 % ) patients in Group I and 25 of 30 ( 83 % ) in Group II . There was no significant difference between the groups regarding mechanical stability . The mean an terior talar translation in Group I was 7.1 mm ( range , 4 to 10 ) at followup , compared with 6.7 mm ( range , 3 to 9 ) in Group II . The corresponding values for talar tilt were 4.9 ° ( range , 0 ° to 8 ° ) in Group I and 4.4 ° ( range , 0 ° to 8 ° ) in Group II . The duration of operation time was significantly longer in Group II and surgical complica tions were more frequent , probably due to the more extensive surgical exposure . This study showed that the majority of patients with chronic ankle instability can be successfully treated with anatomic reconstruc tion of the lateral ankle ligaments . Mechanical stability was restored with both methods STUDY DESIGN A double-blind r and omized crossover experimental study with repeated measures , including a no-treatment control condition . OBJECTIVE To evaluate the initial effect of 2 mobilization with movement ( MWM ) treatment techniques performed in weight bearing and non-weight bearing on posterior talar glide and talocrural dorsiflexion in individuals with recurrent lateral ankle sprain . BACKGROUND MWM treatment techniques are commonly used in the treatment of musculoskeletal pain , such as lateral ankle sprain . Recent evidence indicates that a lack of posterior talar glide and weight-bearing ankle dorsiflexion are common physical impairments in individuals with recurrent ankle sprains . MWM of the ankle joint involves the application of a combined posterior talar glide mobilization and active dorsiflexion movement . The recurrent ankle sprain injury and the MWM treatment techniques for the ankle seemingly provide an appropriate model to further evaluate the effects and mechanism(s ) of action of the MWM treatment techniques in a way that they have not been tested to date . METHODS Sixteen subjects ( mean + /- SD age , 19.8 + /- 2.3 years ) with a history of recurrent lateral ankle sprain and deficits in posterior talar glide ( 71 % ) and weight-bearing dorsiflexion ( 34 % ) were studied . A within-subjects study design was used to evaluate the effect of 2 independent variables : treatment conditions ( weight-bearing MWM , non-weight-bearing MWM , and a no-treatment control group ) and time ( pretreatment and posttreatment ) on the dependent variables of posterior talar glide and weight-bearing dorsiflexion . RESULTS Both the weight-bearing and non-weight-bearing MWM treatment techniques significantly improved posterior talar glide by 55 % and 50 % of the preapplication deficit between affected and unaffected sides , respectively , which was significantly greater than that of the control group ( P<.001 ) . The weight-bearing and non-weight-bearing MWM treatment techniques improved weight-bearing dorsiflexion by 26 % ( P<.017 ) , compared to 9 % for the control condition . The change in posterior talar glide , expressed as a proportion of pretreatment deficit , was correlated to the change in weight-bearing dorsiflexion ( r = .88 , P<.001 ) , but only after the weight-bearing MWM technique . CONCLUSION This preliminary study demonstrated an initial ameliorative effect of MWM treatment techniques on posterior talar glide and dorsiflexion range of motion in individuals with recurrent lateral ankle sprain . These results suggest that this technique should be considered in rehabilitation programs following lateral ankle sprain . This study provides justification for follow-up research of the long-term effects of MWM on lateral ankle sprain and proposes further work be conducted on the posterior talar glide test The authors analyze the r and omized use of three ankle arthrodesis techniques . Indications for this procedure , which are pain , instability , deformity and articular degeneration , are common to the three groups . In group I the Gatellier-Adams technique was used by transfibular approach . In group II the Kenneth-Johnson technique was adopted , using Cal and ruccio external fixator . The same surgical procedure was adopted in group III , using crossed canulated screws as fixation device . The specific advantages and disadvantages of each method are discussed . The criteria for evaluation of the results are the final roentgenographic position of the foot and the achievement of union . The critical analysis conclude that the major indications for group I technique are cases of " in situ " arthrodesis , for group II infected cases and for group III cases with severe malalignment 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 OBJECTIVE To test whether a rigid or a flexible ankle orthosis affects postural sway in single-limb stance as quantified by stabilometry . DESIGN Crossover trial . SETTING University laboratory . PARTICIPANTS Twenty-two athletes with functional ankle instability ( consecutive sample of patients with recurrent ankle sprains but without mechanical instability ) and 22 healthy athletes ( control group of volunteers matched to age , height , weight , physical activity ) . INTERVENTIONS Stabilometry in single-limb stance on a force platform . Participants were tested on each leg with and without a rigid or a flexible ankle orthosis . The order of test conditions was r and omized . MAIN OUTCOME MEASURES Sway velocities , sway pattern , and sway area as calculated from center of pressure movements . The two groups were compared by Mann-Whitney test , and the different orthoses within each group were compared by Wilcoxon test , paired sample s ( type I error 5 % , Bonferroni adjustment ) . RESULTS In athletes with functional ankle instability , both a rigid and a flexible ankle orthosis significantly reduced mediolateral sway velocity . A flexible ankle orthosis also changed sway pattern significantly , by reducing the percentage of linear movements of less than 5 degrees per .01 sec. CONCLUSIONS In athletes with functional ankle instability , ankle orthoses reduce mediolateral sway velocity , possibly because of improved mediolateral proprioception |
11,348 | 29,764,272 | The results indicated that elevated S100B levels might be associated with mood episodes in affective disorders . | BACKGROUND S100B is a calcium-binding protein located in glial cells ; it is regarded as a potential biomarker in affective disorders .
AIM To review the literature investigating the role of S100B in patients with affective disorders . | S100B is a protein which exerts both detrimental and neurotrophic effects , depending on its concentration in brain tissue . An increase of S100B in micromolar concentrations is observed in traumatic brain conditions and is associated with poor outcome . Micromolar levels of extracellular S100B in vitro may have deleterious effects . However , in nanomolar concentrations S100B has multiple neurotrophic effects in vitro may in vivo be regarded as a hallmark of neuroprotective efforts . This pilot study addresses the hypothesis that S100B serum concentrations may be of predictive validity for the response to antidepressant treatment in patients with major depression . S100B plasma levels were determined in 25 patients with major depression and 25 matched healthy controls using an immunofluorimetric s and wich assay . S100B plasma levels were significantly higher in major depressive patients than in healthy controls and positively correlated with treatment response after 4 weeks of treatment . In a linear regression model , a significant predictive effect was found only for S100B and severity of depressive symptoms upon admission . These results suggest that neuroprotective functions of S100B counterbalance neurodegenerative mechanisms that are involved in the pathophysiology of major depression and in the response to antidepressant treatment Background Acute management of traumatic brain injury ( TBI ) , in particular mild TBI , focuses on the detection of the 5–7 % who may be harboring potentially life-threatening intracranial hemorrhage ( IH ) using CT scanning . Guidelines intending to reduce unnecessary head CT scans using available clinical variables to detect those at high IH risk have shown varying results . Recently , the Sc and inavian Neurotrauma Committee ( SNC ) derived a new set of high-IH risk variables for adults with TBI using an evidence -based literature review . Unlike previous guidelines , the SNC guideline incorporates serum values of the brain protein S100B with clinical variables . Methods We performed a nested cohort study of adults with mild TBI presenting to six emergency departments in New York and Pennsylvania within 6 h of injury . Patients were managed according to existing guidelines for CT selection . All patients underwent head CT scanning and serum S100B measurement , as well as prospect i ve collection of clinical variables , as a requirement of the parent study . Using the SNC guidelines , S100B values and clinical variables were applied to these subjects , classifying each into one of five pre-defined severity categories , as well as predicting the need for head CT scanning to identify IH . This classification was then compared to actual head CT results to determine guideline sensitivity and specificity . Results In total , 662 adults ( mean age 42 years , range 18–96 ; 258 females , 549 Caucasians ) were available for analysis ; 36 ( 5 % ) had IH on head CT scan . The SNC guidelines had a sensitivity of 97 % ( 95 % CI , 84–100 % ) and a specificity of 34 % ( 95 % CI , 30–37 % ) for the detection of IH on head CT . Application of the SNC guidelines would have result ed in a CT reduction of 32 % ( 211/662 patients ) . One patient with low-risk mild TBI and a S100B level under 0.10 μg/L had a traumatic CT abnormality and would have been discharged with strict adherence to the guidelines . However , this patient did not need any intervention for the injury and had a good outcome . Conclusion Using the SNC guideline could save approximately one third of CT scans in a pre-selected cohort of mild TBI patients with little or no impact on patient outcome Rationale S100B is an astrocytic , calcium-binding protein which in nanomolar concentrations has neuroprotective and regenerating effects on neurons and glial cells . Increased levels have been shown to be positively correlated with therapeutic response in major depression . Event-related potentials ( ERP ) have been reported to be impaired in depressed patients . Objectives The aim of our study was to assess the relationship between S100B and visually evoked ERP in depression . Methods ERP and S100B serum concentration were studied in 18 patients with major depression , before and after 4 weeks of antidepressant treatment . Results The S100B concentration in patients was increased at intake and after 4 weeks of treatment compared to healthy controls . Initially increased P3-latency normalized and P2-latency significantly decreased after 4 weeks of treatment , although only in patients with clearly elevated initial S100B levels ( mean plus 2 SD of the healthy controls ) . Conclusion The neuroregenerative activity of moderately increased S100B levels in major depression might be a factor contributing to a decrease of prolonged ERP parameters in major depression during antidepressant treatment Disturbances in the serotonergic system are considered to be implicated in the pathophysiology of depressive disorders . The possible role of the neurotrophic factor S100 beta , which is suspected to regulate regeneration of serotonergic synapses , has not been investigated in depressive disorders . The S100 beta concentration in the cerebrospinal fluid was measured in 11 patients with the current diagnosis of mild or moderate depressive episodes ( DSM-IV ) and in 11 matched control patients . Using the t test for paired sample s , the presence of a depressive episode was significantly associated with an elevation of the cerebrospinal fluid concentration of S100 beta ( t = 2.6 , d.f . = 10 , p = 0.024 ) . Replications of this finding in severely depressed patients are necessary to confirm the association between neurotrophic factor S100 beta and depressive disorders |
11,349 | 22,624,862 | In view of their high overall prevalence and significant morphologic variability , 3D radiographic imaging prior to sinus floor augmentation may help to reduce complication rates in the presence of maxillary sinus septa | AIM To gain further insights and resolve conflicting results in the literature regarding prevalence , predominant location and morphologic variability of maxillary sinus septa . | BACKGROUND The lateral window approach to maxillary sinus augmentation is a well-accepted treatment option in implant dentistry . The most frequent complication reported with traditional techniques has been the perforation of the Schneiderian membrane , with perforation rates ranging from 11 % to 56 % . The purpose of this retrospective , consecutive case series from two private practice s was to report on the rate of Schneiderian membrane perforations and arterial lacerations when a piezoelectric surgical unit was used in conjunction with h and instrumentation to perform lateral window sinus elevations . METHODS Clinical data ( Schneiderian membrane perforation , Underwood septa , and laceration of the lateral arterial blood supply to the maxillary sinus ) were obtained retrospectively from two private practice s and pooled for analysis . The information was collated after an exhaustive chart review . Fifty-six consecutively treated lateral window sinus lifts were performed on 50 partially or completely edentate patients . RESULTS Zero perforations of the Schneiderian membrane occurred during the piezoelectric preparation of the lateral antrostomies , whereas two perforations were noted during subsequent membrane elevations using h and instrumentation . In both instances , membrane perforations were associated with sinus septa . The overall sinus perforation rate was 3.6 % . Arterial branches of the posterior superior alveolar artery were encountered in 35 cases , and there were zero instances of arterial laceration . CONCLUSIONS This retrospective case series from clinical private practice s confirmed that a lateral window approach to sinus elevation incorporating piezoelectric technology in conjunction with h and instrumentation was an effective means to achieve sinus elevation while minimizing the potential for intraoperative complications . Further prospect i ve and r and omized controlled studies are warranted to qualify these observations Elevation of the sinus floor allows the correct number and length of oral implants to be placed . The sinus membrane is dissected blindly , usually by a crestal approach , but several internal configurations of the maxillary sinus or intrasinus septa can cause problems . We studied 150 sinuses from 40 male cadavers , and 35 r and omised male patients by anatomical dissection and computed tomography . Forty-six subjects ( 61 % ) had no bony septa or had septa less than 4 mm . Twenty-nine ( 39 % ) had bony septa of which seven were incomplete , one had a complete bony septum in each maxillary sinus , and 20 had symmetrical bony septa . We present the results of a study of bony intramaxillary sinus septa and the potential problems they can cause during elevation of the sinus floor PURPOSE The purpose of this study was to compare Unilab Surgibone ( USB ) ( Mississauga , Ontario , Canada ) , a bone xenograft ( bovine ) , with platelet-rich plasma ( PRP ) and USB without PRP to augment the human maxillary sinus in preparation to receive dental implants . PATIENTS AND METHODS Patients who had bilateral pneumatized maxillary sinuses were included . Sinuses on one side were augmented with the USB-PRP combination and formed the study group , whereas the opposite-side sinuses were augmented with USB alone and served as controls . Bone biopsy specimens were taken during implant placement at 6.8 ± 0.9 months after maxillary sinus floor augmentation . Resonance frequency analysis measurements were performed at implant placement ( first control ) and before the prosthetic stage ( second control ) , at 6.5 ± 0.7 months after implant surgery . RESULTS There were 10 patients ( 7 men and 3 women ; mean age , 53.7 ± 0.8 years ) . Integration between new bone and residual grafts was histologically observed in all sample s. The volumes of soft tissue were 59.9 % ± 7.5 % and 57.8 % ± 4.4 % in the control and study groups , respectively ; residual graft , 21.9 % ± 6.6 % and 23.6 % ± 5.9 % , respectively ; new bone , 15.8 % ± 4.8 % and 16.0 % ± 3.8 % , respectively ; and trabecular bone , 64.7 % ± 22.5 % and 69.1 % ± 18.6 % , respectively . A positive correlation was found between new bone volume and trabecular bone volume ( P = .0001 ) . The mean Implant Stability Quotient ( ISQ ) values were 71.7 ± 4.9 and 70.3 ± 5.7 in the control and study groups , respectively , at first control and 75.4 ± 6.4 and 74.4 ± 6.4 , respectively , at second control . The mean ISQ values at second control in both groups were significantly higher than at first control ( P = .043 and P = .028 , respectively ) . No statistically significant differences were observed between groups ( P > .05 ) . CONCLUSION The combination of USB and PRP does not have any effect on new bone formation and implant stabilization |
11,350 | 27,128,779 | RESULTS The majority of studies support the feasibility/acceptance of telemedicine for use in primary care , although it varies significantly by demographic variables , such as gender , age , and socioeconomic status , and telemedicine has often been found more acceptable by patients than healthcare providers .
Outcomes data are limited but overall suggest that telemedicine interventions are generally at least as effective as traditional care .
Cost analyses vary , but telemedicine in primary care is increasingly demonstrated to be cost-effective .
CONCLUSIONS Telemedicine has significant potential to address many of the challenges facing primary care in today 's healthcare environment . | INTRODUCTION This article presents the scientific evidence for the merits of telemedicine interventions in primary care .
Although there is no uniform and consistent definition of primary care , most agree that it occupies a central role in the healthcare system as first contact for patients seeking care , as well as gatekeeper and coordinator of care .
It enables and supports patient-centered care , the medical home , managed care , accountable care , and population health .
Increasing concerns about sustainability and the anticipated shortages of primary care physicians have sparked interest in exploring the potential of telemedicine in addressing many of the challenges facing primary care in the United States and the world . | Purpose of the study : to examine the costs and cost-effectiveness of ‘ second-generation ’ telecare , in addition to st and ard support and care that could include ‘ first-generation ’ forms of telecare , compared with st and ard support and care that could include ‘ first-generation ’ forms of telecare . Design and methods : a pragmatic cluster-r and omised controlled trial with nested economic evaluation . A total of 2,600 people with social care needs participated in a trial of community-based telecare in three English local authority areas . In the Whole Systems Demonstrator Telecare Question naire Study , 550 participants were r and omised to intervention and 639 to control . Participants who were offered the telecare intervention received a package of equipment and monitoring services for 12 months , additional to their st and ard health and social care services . The control group received usual health and social care . Primary outcome measure : incremental cost per quality -adjusted life year ( QALY ) gained . The analyses took a health and social care perspective . Results : cost per additional QALY was £ 297,000 . Cost-effectiveness acceptability curves indicated that the probability of cost-effectiveness at a willingness-to-pay of £ 30,000 per QALY gained was only 16 % . Sensitivity analyses combining variations in equipment price and support cost parameters yielded a cost-effectiveness ratio of £ 161,000 per QALY . Implication s : while QALY gain in the intervention group was similar to that for controls , social and health services costs were higher . Second-generation telecare did not appear to be a cost-effective addition to usual care , assuming a commonly accepted willingness to pay for QALYs . Trial registration number : IS RCT N 43002091 INTRODUCTION We wanted to examine how Danes use the Internet for health-related purpose s. How much are the existing possibilities used ? Who are the users ? What are the consequences of this use ? MATERIAL S AND METHODS In October 2005 - -as part of a large EU supported study --a telephone survey was carried out among 1000 r and omly selected Danes between the age of 15 and 80 . RESULTS 60 % of the Danish population use the Internet to seek health-related information . The Internet is especially used for health purpose s by people with a high education , by women , by people with poor health and by people with children . Every fourth Dane experiences feelings of reassurance or relief after having read about illness on the Internet and this number is 3 times higher than the number of people that experience concern and anxiety . 3 % state that they have changed their medication after having read information on the Internet and this is done without prior contact to their doctor . 8 % of Danes have at some point consulted their doctor over the Internet , and if given the opportunity , 58 % would read their own patient record online . CONCLUSIONS For many Danes it is common practice to use the Internet for health-related purpose s. However , the position of the general practitioner as the primary source of health-related information is not threatened . Danes use the Internet as a supplement to their doctor and many -- especially women -- use the Internet information in their dialogue with their doctor . Danes increasingly seek solutions to enable them to get online contact with the different players in the health care sector BACKGROUND Pediatric subspecialists are often separated from the children who need them by distance , time , or socioeconomic factors . The Electronic Children 's Hospital of the Pacific is an Internet-based store- and -forward pediatric consultation system established to overcome these barriers . OBJECTIVE To characterize the use of the Electronic Children 's Hospital of the Pacific and its impact on access to specialty care , the quality of the care provided , and cost savings . DESIGN Prospect i ve trial . SETTING Twenty-two military treatment facilities in the Pacific . PARTICIPANTS Primary care providers , pediatric consultants , and 5 review ers . MAIN OUTCOME MEASURES Consult response time , physician panel review , and evacuation cost avoidance . RESULTS There were 267 cases from 16 sites . The mean + /- SD response time by a consultant was 32 + /- 8 hours . The panel review deemed that the initial diagnosis was changed or modified in 15 % ( 39/267 ) of the cases , the diagnostic plan was changed or modified in 21 % ( 57/267 ) , and the treatment plan was changed or modified in 24 % ( 64/267 ) ( P < .01 for all ) . Routine air evacuations to a tertiary care medical center were avoided in 32 cases ( 12 % ) , with an estimated cost savings of $ 185 408 . CONCLUSIONS The Electronic Children 's Hospital of the Pacific improved the quality of patient care by providing expeditious specialty consultation . Significant cost avoidance in this military pediatric population was documented . Store- and -forward Internet-based teleconsultation is an effective means of providing pediatric subspecialty consultation to a population of underserved children Background Missed appointments are known to interfere with appropriate care and to misspend medical and administrative re sources . The aim of this study was to test the effectiveness of a sequential intervention reminding patients of their upcoming appointment and to identify the profile of patients missing their appointments . Methods We conducted a r and omised controlled study in an urban primary care clinic at the Geneva University Hospitals serving a majority of vulnerable patients . All patients booked in a primary care or HIV clinic at the Geneva University Hospitals were sent a reminder 48 hrs prior to their appointment according to the following sequential intervention : 1 . Phone call ( fixed or mobile ) reminder ; 2 . If no phone response : a Short Message Service ( SMS ) reminder ; 3 . If no available mobile phone number : a postal reminder . The rate of missed appointment , the cost of the intervention , and the profile of patients missing their appointment were recorded . Results 2123 patients were included : 1052 in the intervention group , 1071 in the control group . Only 61.7 % patients had a mobile phone recorded at the clinic . The sequential intervention significantly reduced the rate of missed appointments : 11.4 % ( n = 122 ) in the control group and 7.8 % ( n = 82 ) in the intervention group ( p < 0.005 ) , and allowed to reallocate 28 % of cancelled appointments . It also proved to be cost effective in providing a total net benefit of 1846 . - EUR/3 months . A satisfaction survey conducted with 241 patients showed that 93 % of them were not bothered by the reminders and 78 % considered them to be useful . By multivariate analysis , the following characteristics were significant predictors of missed appointments : younger age ( OR per additional decade 0.82 ; CI 0.71 - 0.94 ) , male gender ( OR 1.72 ; CI 1.18 - 2.50 ) , follow-up appointment > 1year ( OR 2.2 ; CI : 1.15 - 4.2 ) , substance abuse ( 2.09 , CI 1.21 - 3.61 ) , and being an asylum seeker ( OR 2.73 : CI 1.22 - 6.09 ) . Conclusion A practical reminder system can significantly increase patient attendance at medical outpatient clinics . An intervention focused on specific patient characteristics could further increase the effectiveness of appointment reminders IMPORTANCE Hospital readmissions are common and costly , and no single intervention or bundle of interventions has reliably reduced readmissions . Virtual wards , which use elements of hospital care in the community , have the potential to reduce readmissions , but have not yet been rigorously evaluated . OBJECTIVE To determine whether a virtual ward-a model of care that uses some of the systems of a hospital ward to provide interprofessional care for community-dwelling patients -can reduce the risk of readmission in patients at high risk of readmission or death when being discharged from hospital . DESIGN , SETTING , AND PATIENTS High-risk adult hospital discharge patients in Toronto were r and omly assigned to either the virtual ward or usual care . A total of 1923 patients were r and omized during the course of the study : 960 to the usual care group and 963 to the virtual ward group . The first patient was enrolled on June 29 , 2010 , and follow-up was completed on June 2 , 2014 . INTERVENTIONS Patients assigned to the virtual ward received care coordination plus direct care provision ( via a combination of telephone , home visits , or clinic visits ) from an interprofessional team for several weeks after hospital discharge . The interprofessional team met daily at a central site to design and implement individualized management plans . Patients assigned to usual care typically received a typed , structured discharge summary , prescription for new medications if indicated , counseling from the resident physician , arrangements for home care as needed , and recommendations , appointments , or both for follow-up care with physicians as indicated . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of hospital readmission or death within 30 days of discharge . Secondary outcomes included nursing home admission and emergency department visits , each of the components of the primary outcome at 30 days , as well as each of the outcomes ( including the composite primary outcome ) at 90 days , 6 months , and 1 year . RESULTS There were no statistically significant between-group differences in the primary or secondary outcomes at 30 or 90 days , 6 months , or 1 year . The primary outcome occurred in 203 of 959 ( 21.2 % ) of the virtual ward patients and 235 of 956 ( 24.6 % ) of the usual care patients ( absolute difference , 3.4 % ; 95 % CI , -0.3 % to 7.2 % ; P = .09 ) . There were no statistically significant interactions to indicate that the virtual ward model of care was more or less effective in any of the prespecified subgroups . CONCLUSIONS AND RELEVANCE In a diverse group of high-risk patients being discharged from the hospital , we found no statistically significant effect of a virtual ward model of care on readmissions or death at either 30 days or 90 days , 6 months , or 1 year after hospital discharge . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01108172 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 Background Telephone or text-message reminders have been shown to significantly reduce the rate of missed appointments in different medical setting s. Since text-messaging is less re source -dem and ing , we tested the hypothesis that text-message reminders would be as effective as telephone reminders in an academic primary care clinic . Methods A r and omized controlled non-inferiority trial was conducted in the academic primary care division of the Geneva University Hospitals between November 2010 and April 2011 . Patients registered for an appointment at the clinic , and for whom a cell phone number was available , were r and omly selected to receive a text-message or a telephone call reminder 24 hours before the planned appointment . Patients were included each time they had an appointment . The main outcome was the rate of unexplained missed appointments . Appointments were not missed if they were cancelled or re-scheduled before or independently from the intervention . We defined non-inferiority as a difference below 2 % in the rate of missed appointments and powered the study accordingly . A satisfaction survey was conducted among a r and om sample of 900 patients ( response rate 41 % ) . Results 6450 patients were included , 3285 in the text-message group and 3165 in the telephone group . The rate of missed appointments was similar in the text-message group ( 11.7 % , 95 % CI : 10.6 - 12.8 ) and in the telephone group ( 10.2 % , 95 % CI : 9.2 - 11.3 p = 0.07 ) . However , only text message reminders were cost-effective . No patient reported any disturbance by any type of reminder in the satisfaction survey . Three quarters of surveyed patients recommended its regular implementation in the clinic . Conclusions Text-message reminders are equivalent to telephone reminders in reducing the proportion of missed appointments in an academic primary care clinic and are more cost-effective . Both types of reminders are well accepted by patients BACKGROUND Improvement in quality of life ( QOL ) is a long term goal of drug treatment . Although some brief interventions have been found to reduce illicit drug use , no trial among adult risky ( moderate non-dependent ) drug users has tested effects on health-related quality of life . METHODS A single-blind r and omized controlled trial of patients enrolled from February 2011 to November 2012 was conducted in waiting rooms of five federally qualified health centers . 413 adult primary care patients were identified as risky drug users using the WHO-ASSIST and 334 ( 81 % response ; 171 intervention , 163 control ) consented to participate in the trial . Three-month follow-ups were completed by 261 patients ( 78 % ) . Intervention patients received the QUIT intervention of brief clinician advice and up to two drug-use health telephone sessions . The control group received usual care and information on cancer screening . Outcomes were three-month changes in the Short Form Health Survey ( SF-12 ) mental health component summary score ( MCS ) and physical health component summary score ( PCS ) . RESULTS The average treatment effect ( ATE ) was non-significant for MCS ( 0.2 points , p-value=0.87 ) and marginally significant for PCS ( 1.7 points , p-value=0.08 ) . The average treatment effect on the treated ( ATT ) was 0.1 ( p-value=0.93 ) for MCS and 1.9 ( p-value=0.056 ) for PCS . The effect on PCS was stronger at higher ( above median ) baseline number of drug use days : ATE=2.7 , p-value=0.04 ; ATT=3.21 , p-value=0.02 . CONCLUSIONS The trial found a marginally significant effect on improvement in PCS , and significant and stronger effect on the SF-12 physical component among patients with greater frequency of initial drug use Despite the common use of electronic communication in other aspects of everyday life , its use between patients and health care providers has been slow to diffuse . Possible explanations are security issues and lack of payment mechanisms . This study investigated how patients value secure electronic access to their general practitioner ( GP ) . One hundred and ninety-nine patients were asked an open-ended willingness-to-pay ( WTP ) question as part of a r and omised controlled trial . We compared the WTP values between two groups of respondents ; one group had had the opportunity to communicate electronically with their GP for a year and the other group had not . Fifty-two percent of the total sample was willing to pay for electronic GP contact . The group of patients with access revealed a significantly lower WTP than the group without such access . Possible explanations are that the system had fewer benefits than expected , a presence of hypothetical bias or simply a preference for face-to-face encounters Background : Automated home monitoring systems have been used to coordinate care to improve patient outcomes and reduce rehospitalizations , but with little formal study of efficacy . The Geisinger Monitoring Program ( GMP ) interactive voice response protocol is a post-hospital discharge telemonitoring system used as an adjunct to existing case management in a primary care Medicare population to reduce emergency department visits and hospital readmissions . Objectives : To determine if use of GMP reduced 30-day hospital readmission rates among case-managed patients . Research Design : A pre-post parallel quasi-experimental study . Methods : A total of 875 Medicare patients who were enrolled in the combined case-management and GMP program were compared with 2420 matched control patients who were only case managed . Cl aims data were used to document an acute care admission followed by a readmission within 30 days in the preintervention and postintervention periods ( ie , before and during 2009 ) . Regression modeling was used to estimate the within-patient effect of the intervention on readmission rates . Results : The use of GMP with case management was associated with a 44 % reduction in 30-day readmissions in the study cohort ( 95 % confidence interval , 23%−60 % , P=0.0004 ) , when using the control group to control for secular trends . Similar estimates were obtained when using different propensity score adjustment methods or different approaches to h and ling dropout observations . Conclusions : Investing in automated monitoring systems may reduce hospital readmission rates among primary care case-managed patients . Evidence from this quasi-experimental study demonstrates that the combination of telemonitoring and case management , as compared with case management alone , may significantly reduce readmissions in a Medicare Advantage population OBJECTIVE Communication failures account for many adverse drug events ( ADEs ) in adult primary care . Improving patient-physician communication may improve medication safety . Accordingly , the goal of this study was to learn whether electronic medication safety messages directed to patients can improve communication about medications and identify ADEs . DESIGN We studied adult patients enrolled in a patient Internet portal at three primary care practice s affiliated with a teaching hospital . MedCheck , a medication safety application , sent patients a secure electronic message 10 days after they received a new or changed prescription . MedCheck asked if the patient had filled the prescription or experienced medication-related problems , and then forwarded the patient 's response to their primary care physician . MEASUREMENTS We selected a stratified r and om sample of 267 subjects from 1821 patients who received and opened a MedCheck message from April 2001 to June 2002 . We review ed subjects ' medical records for three months following their first MedCheck message . We analyzed patient and clinician response rates and times , examined patient-clinician communication about medications , and identified ADEs . RESULTS Patients opened 79 % of MedCheck messages and responded to 12 % ; 77 % responded within 1 day . Patients often identified problems filling their prescriptions ( 48 % ) , problems with drug effectiveness ( 12 % ) , and medication symptoms ( 10 % ) . Clinicians responded to 68 % of patients ' messages ; 93 % answered within 1 week . Clinicians often supplied or requested information ( 19 % ) , or made multiple recommendations ( 15 % ) . Patients experienced 21 total ADEs ; they reported 17 electronically . CONCLUSION Patients and physicians responded promptly to patient-directed electronic medication messages , identifying and addressing medication-related problems including ADEs BACKGROUND Non-attendance is common in primary care and previous studies have reported that reminders were useful in reducing broken appointments . OBJECTIVE To determine the effectiveness of a text messaging reminder in improving attendance in primary care . DESIGN Multicentre three-arm r and omized controlled trial . SETTING Seven primary care clinics in Malaysia . Participants . Patients ( or their caregivers ) who required follow-up at the clinics between 48 hours and 3 months from the recruitment date . Interventions . Two intervention arms consisted of text messaging and mobile phone reminders 24 - 48 hours prior to scheduled appointments . Control group did not receive any intervention . Outcome measures . Attendance rates and costs of interventions . RESULTS A total of 993 participants were eligible for analysis . Attendance rates of control , text messaging and mobile phone reminder groups were 48.1 , 59.0 and 59.6 % , respectively . The attendance rate of the text messaging reminder group was significantly higher compared with that of the control group ( odds ratio 1.59 , 95 % confidence interval 1.17 to 2.17 , P = 0.005 ) . There was no statistically significant difference in attendance rates between text messaging and mobile phone reminder groups . The cost of text messaging reminder ( RM 0.45 per attendance ) was lower than mobile phone reminder ( RM 0.82 per attendance ) . CONCLUSIONS Text messaging reminder system was effective in improving attendance rate in primary care . It was more cost-effective compared with the mobile phone reminder BACKGROUND Non-attendance results in administrative problems and disruption in patient care . Several interventions have been used to reduce non-attendance , with varying degree of success . A relatively new intervention , text messaging , has been shown to be as effective as telephone reminders in reducing non-attendance . However , no study has looked specifically at using text messaging reminders to reduce non-attendance in chronic disease care . AIM To determine if text messaging would be effective in reducing non-attendance in patients on long-term followup , compared with telephone reminders and no reminder . DESIGN OF STUDY A r and omised controlled trial with three arms : text messaging reminder , telephone reminder , and control . SETTING Two primary care clinics in Malaysia . METHOD A total of 931 subjects who had been on at least 6 months of follow-up were r and omised into the three groups . Demographic variables were recorded at the first visit . In the intervention arms , a reminder was sent 24–48 hours prior to the appointment . Non-attendance rate was documented at the second visit . Non-attenders were defined as those who did not attend , attended early , or attended late without rescheduling their appointment . Attenders were defined as participants who had turned up for their scheduled appointment and those who had changed or cancelled their appointment with notification . RESULTS The non-attendance rates in the text messaging group ( odds ratio [ OR ] = 0.62 , 95 % confidence interval [ CI ] = 0.41 to 0.93 , P = 0.020 ) and the telephone reminder group ( OR = 0.53 , 95 % CI = 0.35 to 0.81 ) , P = 0.003 ) were significantly lower than the control group . The absolute non-attendance rate for telephone reminders was lower by 2 % compared to the text messaging group . This difference was not found to be statistically significant ( P = 0.505 ) . CONCLUSION Text messaging was found to be as effective as telephone reminder in reducing non-attendance in patients who required long-term follow-up for their chronic illnesses in this study . It could be used as an alternative to conventional reminder systems The aim of the present study was make chronic cough guidelines more practical and user friendly by developing an internet-based interactive diagnostic question naire for chronic cough . A prospect i ve cohort study of chronic cough sufferers was conducted in the UK , following European Respiratory Society guidelines for the diagnosis and management of chronic cough . Depending on the response to 16 specific questions , the medical condition responsible for the patient 's chronic cough was ascertained according to a predetermined diagnostic algorithm design ed to differentiate the three common causes of chronic cough . Appropriate advice and treatment recommendations were then provided . 8,546 adults with chronic cough completed the Cough Clinic diagnostic question naire . 46.1 % were suggested to have reflux , 38.7 % asthma and 15.2 % rhinitis . Participants found the website easy to use ( 94 % ) , the advice helpful ( 73 % ) and that it helped them to communicate with their general practitioner better ( 60 % ) , and 62 % reported taking the recommended treatment . The Cough Clinic , an internet-based diagnostic site for chronic cough , had a large uptake by chronic cough sufferers in the UK . Almost half were diagnosed as having reflux as the probable cause of their chronic cough . Internet diagnosis by expert algorithm provides a novel mechanism for patients to access guideline -recommended therapies and enhances dialogue between patients and physicians Objectives To identify barriers to deployment of four articulated Integrated Care Services supported by Information Technologies in three European sites . The four services covered the entire spectrum of severity of illness . The project targeted chronic patients with obstructive pulmonary disease , cardiac failure and /or type II diabetes mellitus . Setting One health care sector in Spain ( Barcelona ) ( n = 11.382 ) ; six municipalities in Norway ( Trondheim ) ( n = 450 ) ; and one hospital in Greece ( Athens ) ( n = 388 ) . Method The four services were : ( i ) Home-based long-term maintenance of rehabilitation effects ( n = 337 ) ; ( ii ) Enhanced Care for frail patients , n = 1340 ) ; ( iii ) Home Hospitalization and Early Discharge ( n = 2404 ) ; and Support for remote diagnosis ( forced spirometry testing ) in primary care ( Support ) ( n = 8139 ) . Both r and omized controlled trials and pragmatic study design s were combined . Two technological approaches were compared . The Model for Assessment of Telemedicine applications was adopted . Results The project demonstrated : ( i ) Sustainability of training effects over time in chronic patients with obstructive pulmonary disease ( p < 0.01 ) ; ( ii ) Enhanced care and fewer hospitalizations in chronic respiratory patients ( p < 0.05 ) ; ( iii ) Reduced in-hospital days for all types of patients ( p < 0.001 ) in Home Hospitalization/Early Discharge ; and ( iv ) Increased quality of testing ( p < 0.01 ) for patients with respiratory symptoms in Support , with marked differences among sites . Conclusions The four integrated care services showed high potential to enhance health outcomes with cost-containment . Change management , technological approach and legal issues were major factors modulating the success of the deployment . The project generated a business plan to foster service sustainability and health innovation . Deployment strategies require site-specific adaptations OBJECTIVE To investigate whether an electronic prescribing and integrated drug information system was more likely to be used by primary care physicians for patients of low socioeconomic ( SES ) patients . METHODS Prospect i ve 9 months follow-up study was conducted in Montreal , Canada from March to November 2003 . The study included 28 primary care physicians and their 4096 respective patients with provincial drug insurance . Utilization rate was defined as the number of times the electronic medication history ( EMH ) and electronic prescribing system ( E-rx ) were accessed divided by the total number of medical visits made by those patients . System audit trails ( utilization ) , provincial health insurance data bases ( visits ) were used to measure system utilization rate . For each patient neighborhood-based measures of household income , derived from Statistics Canada , were used to measure socioeconomic status . RESULTS The EMH was used 14.5 times per 100 visits . In comparison to high SES patients , there was a significant 70 % increase ( RR : 1.70 ; 95%CI : 1.15 - 2.47 ) in the EMH utilization for low SES patients . The electronic prescribing system was used 38.5 times per 100 visits and did not vary by patient SES . The EMH utilization rate for low SES patients with multiple emergency room ( ER ) visits was 2.4 times higher than for high SES patients with < 1 ER visit ( RR : 2.38 ; 95%CI : 1.36 - 4.14 ) . The utilization rate for low SES patients , who took , at least six drugs per day , was four times higher compared to high SES patients with less complex drug management ( RR : 4.00 ; 95%CI : 2.22 - 7.17 ) . CONCLUSIONS Primary care physicians were more likely to access electronic information on current drug use for patients of low SES taking multiple medications and with fragmented care Objective To compare the efficacy of a short messaging service ( SMS ) text messaging and phone reminder to improve attendance rates at a health promotion center . Methods A total of 1 859 participants who had scheduled appointments in the health promotion center of our hospital from April 2007 to May 2007 were enrolled in the study and r and omly assigned into 3 groups : control ( no reminder ) group , SMS text messaging reminder group and telephone reminder group . Attendance rates and costs of interventions were collected . Results A total of 1848 participants were eligible for analysis . Attendance rates of control , SMS and telephone groups were 80.5 % , 87.5 % and 88.3 % , respectively . The attendance rates were significantly higher in SMS and telephone groups than that in the control group , with odds ratio 1.698 , 95 % confidence interval 1.224 to 2.316 , P=0.001 in the SMS group , and odds ratio 1.829 , 95 % confidence interval 1.333 to 2.509 , P<0.001 in the telephone group . However , there was no difference between the SMS group and the telephone group ( P=0.670 ) . The cost effectiveness analysis showed that the cost per attendance for the SMS group ( 0.31 Yuan ) was significantly lower than that for the telephone group ( 0.48 Yuan ) . ConclusionS MS and telephone are effective reminders for improving attendance rate at a health promotion center . SMS reminder may be more cost-effective compared with the telephone reminder Background Mobile phones are increasingly used in health systems in developing countries and innovative technical solutions have great potential to overcome barriers of access to reproductive and child health care . However , despite widespread support for the use of mobile health technologies , evidence for its role in health care is sparse . Objective We aim ed to evaluate the association between a mobile phone intervention and perinatal mortality in a re source -limited setting . Methods This study was a pragmatic , cluster-r and omized , controlled trial with primary health care facilities in Zanzibar as the unit of r and omization . At their first antenatal care visit , 2550 pregnant women ( 1311 interventions and 1239 controls ) who attended antenatal care at selected primary health care facilities were included in this study and followed until 42 days after delivery . Twenty-four primary health care facilities in six districts were r and omized to either mobile phone intervention or st and ard care . The intervention consisted of a mobile phone text message and voucher component . Secondary outcome measures included stillbirth , perinatal mortality , and death of a child within 42 days after birth as a proxy of neonatal mortality . Results Within the first 42 days of life , 2482 children were born alive , 54 were stillborn , and 36 died . The overall perinatal mortality rate in the study was 27 per 1000 total births . The rate was lower in the intervention clusters , 19 per 1000 births , than in the control clusters , 36 per 1000 births . The intervention was associated with a significant reduction in perinatal mortality with an odds ratio ( OR ) of 0.50 ( 95 % CI 0.27 - 0.93 ) . Other secondary outcomes showed an insignificant reduction in stillbirth ( OR 0.65 , 95 % CI 0.34 - 1.24 ) and an insignificant reduction in death within the first 42 days of life ( OR 0.79 , 95 % CI 0.36 - 1.74 ) . Conclusions Mobile phone applications may contribute to improved health of the newborn and should be considered by policy makers in re source -limited setting s. Trial Registration Clinical Trials.gov NCT01821222 ; http://www . clinical trials.gov/ct2/show/NCT01821222 ( Archived by WebCite at http://www.webcitation.org/6NqxnxYn0 ) BACKGROUND Half of patients with hypertension have poor blood pressure ( BP ) control . Recent models for treating hypertension have integrated disease monitoring and telephone-based interventions delivered in patients ' homes . This study evaluated the costs of the Hypertension Intervention Nurse Telemedicine Study ( HINTS ) , aim ed to improve BP control in veterans . METHODS Eligible veterans were r and omized to either usual care or 1 of 3 telephone-based intervention groups using home BP telemonitoring : ( 1 ) behavioral management , ( 2 ) medication management , or ( 3 ) combined . Intervention costs were derived from information collected during the trial . Direct medical costs ( inpatient , outpatient , and outpatient pharmacy , including hypertension-specific pharmacy ) at 18 months by group were calculated using Veterans Affairs ( VA ) Decision Support System data . Bootstrapped CIs were computed to compare intervention and medical costs between intervention groups and usual care . RESULTS Patients receiving behavior or medication management showed significant gains in BP control at 12 months ; there were no differences in BP control at 18 months . In subgroup analysis , patients with poor baseline BP control receiving combined intervention significantly improved BP at 12 and 18 months . In overall and subgroup sample s , average intervention costs were similar in the 3 study arms , and at 18 months , there were no statistically significant differences in direct VA medical costs or total VA costs between treatment arms and usual care . CONCLUSIONS To optimize investment in telephone-based home interventions such as the HINTS , it is important to identify groups of patients who are most likely to benefit from more intensive home BP management Objectives Adverse drug events ( ADEs ) are common in ambulatory care and may result from poor patient-physician communication about medication-related symptoms . A module was developed within an electronic patient portal that was design ed to enhance communication about medication symptoms and , in turn , reduce ADEs and health-care utilization . Methods The research ers conducted a r and omized , controlled clinical trial of MedCheck , an automated electronic message generated in a patient Internet portal . MedCheck asked intervention patients if they had filled a recent prescription and if they had experienced any problems with the medication . Patients ’ responses were forwarded automatically to primary care physicians . The study enrolled 375 intervention patients and 363 controls . After 3 months , the investigators review ed patients ’ medical records and conducted telephone interviews to identify ADEs and to assess health-care utilization . Results Among the 375 intervention patients , 184 ( 49 % ) responded to at least 1 MedCheck message . Patients reported 52 unfilled prescriptions and 56 medication problems . Patients responded to 72 % of messages within 1 day . There was no statistically significant difference between intervention and control groups in the rate of ADEs , preventable or ameliorable ADEs , serious ADEs , or in subjects ’ health-care utilization . Conclusions Internet portals have the potential to enhance patient-physician communication . However , additional development is required to demonstrate that such interventions can improve medication safety or health-care utilization . Clinical Trials.gov Background : Failure to attend appointments compromises health service efficiency . Despite considerable interest in using novel technologies to improve attendance , evidence from rigorously conducted controlled studies is lacking . Aim : To evaluate the effectiveness of texting appointment reminders to patients who persistently fail to attend appointments . Design : R and omised controlled study . Setting : Inner city general practice in Lothian , Scotl and . Method : We included 415 appointments made by patients ( n = 173 ) who had failed to attend two or more routine appointments in the preceding year . Patients whose appointments were r and omised to the intervention group received a text message reminder of the appointment . Patients whose appointments were in the control group received no reminder . Our primary outcome measure was non-attendance rates . We undertook an intention-to-treat analysis and multi-level analysis to take account of the lack of independence of the outcomes of repeated appointments for the same patient . Results : Of the 418 appointments originally included in the study , three were excluded due to clerical error ; 189 were r and omised to the intervention group and 226 to the control group . Twenty-two appointments ( 12 % ) were not attended in the intervention group compared with 39 ( 17 % ) in the control group . A chi-square analysis , considering the outcome of appointments as independent from one another , gave a non-significant difference of 5 % ( 95 % CI of difference −1.1 to 12.3 % , p = 0.13 ) . Multilevel analysis applied to the binary outcome data on non-attendance gave an odds ratio for non-attendance in the intervention group compared with the control group of 0.63 ( 95 % CI 0.36 to 1.1 , p = 0.11 ) . Conclusion : Although the intervention showed promise , we failed to demonstrate significant reduction in non-attendance rates , as a result of texting appointment reminders to patients who persistently fail to attend their general practice appointments BACKGROUND Few telemedicine programs have undergone cost analyses , impeding their implementation into practice . We report on the economic analysis of a nurse-administered intervention design ed to improve blood pressure control among hypertensive veterans . METHODS We r and omized hypertensive patients at the Durham Veterans Affairs Medical Center primary care clinic to behavioral ( n = 294 ) or nonbehavioral ( n = 294 ) interventions . Behavioral intervention patients received tailored information bimonthly for 2 years via telephone . To calculate intervention cost , we microcosted the nurse 's labor cost and computer hardware and software costs , applied a direct-to-indirect cost ratio , and distributed the costs over an estimated cohort of patients . We analyzed data from the Veterans Affairs Decision Support System to assess whether the intervention impacted overall health care utilization and costs . We used life expectancy estimates from the literature to develop decision models to calculate cost per life-year saved . RESULTS The mean annual intervention cost was $ 112 ( range $ 61-$259 ) . During 2 years of follow-up , patients in the intervention group incurred $ 7,800 in inpatient costs and $ 9,741 in outpatient costs ; the nonintervention group incurred $ 6,866 in inpatient costs and $ 9,599 in outpatient costs . The total cost difference was not statistically significant ( P = .56 ) . Cost-effectiveness of the behavioral intervention ranged from $ 42,457 per life-year saved for normal-weight women to $ 87,300 per life-year saved for normal-weight men . CONCLUSIONS The study results suggest that a nurse-administered , tailored behavioral intervention can be implemented at nominal cost and be cost-effective ; however , there was no apparent lowering of health care utilization and costs during the 2 years of follow-up BACKGROUND Obesity and its cardiovascular complications are extremely common medical problems , but evidence on how to accomplish weight loss in clinical practice is sparse . METHODS We conducted a r and omized , controlled trial to examine the effects of two behavioral weight-loss interventions in 415 obese patients with at least one cardiovascular risk factor . Participants were recruited from six primary care practice s ; 63.6 % were women , 41.0 % were black , and the mean age was 54.0 years . One intervention provided patients with weight-loss support remotely -- through the telephone , a study -specific Web site , and e-mail . The other intervention provided in-person support during group and individual sessions , along with the three remote means of support . There was also a control group in which weight loss was self-directed . Outcomes were compared between each intervention group and the control group and between the two intervention groups . For both interventions , primary care providers reinforced participation at routinely scheduled visits . The trial duration was 24 months . RESULTS At baseline , the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) for all participants was 36.6 , and the mean weight was 103.8 kg . At 24 months , the mean change in weight from baseline was -0.8 kg in the control group , -4.6 kg in the group receiving remote support only ( P<0.001 for the comparison with the control group ) , and -5.1 kg in the group receiving in-person support ( P<0.001 for the comparison with the control group ) . The percentage of participants who lost 5 % or more of their initial weight was 18.8 % in the control group , 38.2 % in the group receiving remote support only , and 41.4 % in the group receiving in-person support . The change in weight from baseline did not differ significantly between the two intervention groups . CONCLUSIONS In two behavioral interventions , one delivered with in-person support and the other delivered remotely , without face-to-face contact between participants and weight-loss coaches , obese patients achieved and sustained clinical ly significant weight loss over a period of 24 months . ( Funded by the National Heart , Lung , and Blood Institute and others ; Clinical Trials.gov number , NCT00783315 . ) Pesinet is a non-profit organisation which operates a microinsurance programme combined with a monitoring service in low-income countries to increase primary healthcare utilisation for children . We studied the association between enrolment in the Pesinet programme and changes in utilisation of health services . We conducted a prospect i ve controlled study in Bamako ( Mali ) in children under five years old . Participants in the Pesinet service were recruited from a neighbourhood of Bamako ( n = 91 ) and participants in the control group ( usual care ) came from two other neighbouring districts ( n = 89 ) . Eight question naires were completed at 2-week intervals for each child in the study . We performed logistic regression modelling to assess the effect of the Pesinet programme on health service utilisation , adjusting for confounding variables ( age and socio-economic status ) . During the study , families reported 206 episodes of disease in the intervention group and 168 in the control group . Children from the intervention group had 85 medical consultations and those in the control group had 28 . Based on the logistic regression model , there was increased utilisation of health care services among children enrolled in the Pesinet programme , with an adjusted Odds Ratio for medical consultations of 2.2 . Membership of the Pesinet telehealth programme increased primary healthcare utilisation among children under five years old in Mali Objectives : Evaluate the effectiveness of an online self-management programme ( EPP Online ) for Engl and residents with long-term conditions . Methods : A prospect i ve longitudinal study . Data were collected online at baseline , 6 and 12 months . The intervention was an asynchronous 6-week chronic-disease self-management programme offered online . We measured seven health status measures ( health distress , self-rated health , illness intrusiveness , disability , fatigue , pain and shortness of breath ) , four behaviours ( aerobic exercise , stretching exercise , stress management and communications with physician ) , and five utilization measures ( GP visits , pharmacy visits , PT/OT visits , emergency visits and hospitalizations ) . We also measured self-efficacy and satisfaction with the health care system . Results : A total of 568 completed baseline data : 546 ( 81 % ) completed 6 months and 443 ( 78 % ) completed 1 year . Significant improvements ( p<0.01 ) were found at 6 months for all variables except self-rated health , disability , stretching , hospitalizations and nights in hospital . At 12 months only decrease in disability , nights in hospital and hospitalizations were not significant with reduction in visits to emergency departments being marginally significant ( p = 0.012 ) . Both self-efficacy and satisfaction with the health care system improved significantly . Discussion : The peer-led online programme conditions appears to decrease symptoms , improve health behaviours , self-efficacy and satisfaction with the health care system and reducing health care utilization up to 1 year BACKGROUND AND AIM Electronic patient-provider communication promises to improve efficiency and effectiveness of clinical care . This study aims to explore whether a secure web-based messaging system is an effective way of providing patient care in general practice s. METHOD We conducted a r and omised controlled trail and recruited 200 patients from the waiting area in one primary clinic in Norway . Participants were r and omised to either the intervention group , which received access to a secure messaging system , or the control group receiving st and ard care without such access . Primary outcome measures were number of online consultations , telephone consultations and office visits in the two groups . Data were derived from patient records and collected 1 year prior to ( baseline ) , and 1 year after the intervention . RESULTS Forty-six percent of the patients who were given access to the messaging system ( n=99 ) used the online communication system on at least one occasion ( ranging from 1 to 17 messages per patient per year ) . A total of 147 electronic messages were sent to six general practitioners during a 1-year trial period . Eleven percent of the messages were to schedule an appointment . In 10 % of the messages , the GP was unable to respond adequately and recommended an office visit . The reduction in office visits over time was greater for the intervention group than for the control group ( P=0.034 ) . There was however no significant difference in the number of telephone consultations between the groups during the study ( P=0.258 ) . CONCLUSION The use of a secure electronic messaging system reduced the number of office visits at the general practice , but not phone consultations OBJECTIVE To examine the feasibility and efficacy of integrating home health monitoring into a primary care setting . DESIGN A mixed method was used for this pilot study . It included in-depth interviews , focus groups , and surveys . SETTING A semirural family health network in eastern Ontario comprising 8 physicians and 5 nurses caring for approximately 10 000 patients . PARTICIPANTS Purpose ful sample of 22 patients chosen from the experimental group of 120 patients 50 years old or older in a larger r and omized controlled trial ( N = 240 ) . These patients had chronic illnesses and were identified as being at risk based on objective criteria and physician assessment . INTERVENTIONS Between November 2004 and March 2006 , 3 nurse practitioners and a pharmacist installed telehomecare units with 1 or more peripheral devices ( eg , blood-pressure monitor , weight scale , glucometer ) in patients ' homes . The nurse practitioners incorporated individualized instructions for using the unit into each patient 's care plan . Patients used the units every morning for collecting data , entering values into the system either manually or directly through supplied peripherals . The information was transferred to a secure server and was then uploaded to a secure Web-based application that allowed care providers to access and review it from any location with Internet access . The devices were monitored in the office on weekdays by the nurse practitioners . MAIN OUTCOME MEASURES Acceptance and use of the units , patients ' and care providers ' satisfaction with the system , and patients ' demographic and health characteristics . RESULTS All 22 patients , 12 men and 10 women with an average age of 73 years ( range 60 to 88 years ) , agreed to participate . Most were retired , and a few were receiving community services . Common diagnoses included hypertension , diabetes , cardiovascular disease , and chronic obstructive pulmonary disease . All patients had blood pressure monitors installed , 11 had wired weight scales,5 had glucometers , and 5 had pulse oximeters . The units were in place for 9 to 339 days . Three patients asked to have the systems removed early because they did not use them or found them inconvenient . The other patients and their informal caregivers found the technology user-friendly and useful . Health care providers were satisfied with the technology and found the equipment useful . They thought it might reduce the number of office visits patients made and help track long-term trends . CONCLUSION These pilot results demonstrate that telehomecare monitoring in a collaborative care community family practice is feasible and well used , and might improve access to and quality of care BACKGROUND Only about a third of people with asthma attend an annual review . Clinicians need to identify cost-effective ways to improve access and ensure regular review . AIM To compare the cost-effectiveness of nurse-led telephone with face-to-face asthma review s. DESIGN OF STUDY Cost-effectiveness analysis based on a 3-month r and omised controlled trial . SETTING Four general practice s in Engl and . METHOD Adults due an asthma review were r and omised to telephone or face-to-face consultations . Trial nurses recorded proportion review ed , duration of consultation , and abortive calls/missed appointments . Data on use of healthcare re sources were extracted from GP records . Cost-effectiveness was assessed from the health service perspective ; sensitivity analyses were based on proportion review ed and duration of consultation . RESULTS A total of 278 people with asthma were r and omised to surgery ( n = 141 ) or telephone ( n = 137 ) review . Onehundred- and -one ( 74 % ) of those with asthma in the telephone group were review ed versus 68 ( 48 % ) in the surgery group ( P < 0.001 ) . Telephone consultations were significantly shorter ( mean duration telephone = 11.19 minutes [ st and ard deviation { SD } = 4.79 ] versus surgery = 21.87 minutes [ SD = 6.85 ] , P < 0.001 ) . Total respiratory healthcare costs per patient over 3 months were similar ( telephone = pounds sterling 64.49 [ SD = 73.33 ] versus surgery = pounds sterling 59.48 [ SD = 66.02 ] , P = 0.55 ) . Total costs of providing 101 telephone versus 68 face-to-face asthma review s were also similar ( telephone = pounds sterling 725.84 versus surgery = pounds sterling 755.70 ) , but mean cost per consultation achieved was lower in the telephone arm ( telephone = pounds sterling 7.19 [ SD = 2.49 ] versus surgery = pounds sterling 11.11 [ SD = 3.50 ] ; mean difference = - pounds sterling 3.92 [ 95 % confidence interval = - pounds sterling 4.84 to pounds sterling 3.01 ] , P < 0.001 ) . CONCLUSIONS Telephone consultations enable a greater proportion of asthma patients to be review ed at no additional cost to the health service . This mode of delivering care improves access and reduces cost per consultation achieved Background : Efforts to enhance patient-physician communication may improve management of underdiagnosed chronic conditions . Patient internet portals offer an efficient venue for coaching patients to discuss chronic conditions with their primary care physicians ( PCP ) . Objectives : We sought to test the effectiveness of an internet portal-based coaching intervention to promote patient-PCP discussion about chronic conditions . Research Design : We conducted a r and omized trial of a nurse coach intervention conducted entirely through a patient internet-portal . Subjects : Two hundred forty-one patients who were registered portal users with scheduled PCP appointments were screened through the portal for 3 target conditions , depression , chronic pain , mobility difficulty , and r and omized to intervention and control groups . Measures : One-week and 3-month patient surveys assessed visit experiences , target conditions , and quality of life ; chart abstract ions assessed diagnosis and management during PCP visit . Results : Similar high percentages of intervention ( 85 % ) and control ( 80 % ) participants reported discussing their screened condition during their PCP visit . More intervention than control patients reported their PCP gave them specific advice about their health ( 94 % vs. 84 % ; P = 0.03 ) and referred them to a specialist ( 51 % vs. 28 % ; P = 0.002 ) . Intervention participants reported somewhat higher satisfaction than controls ( P = 0.07 ) . Results showed no differences in detection or management of screened conditions , symptom ratings , and quality of life between groups . Conclusions : Internet portal-based coaching produced some possible benefits in care for chronic conditions but without significantly changing patient outcomes . Limited sample sizes may have contributed to insignificant findings . Further research should explore ways internet portals may improve patient outcomes in primary care . Clinical Trials.gov registration NCT00130416 BACKGROUND Emergency department ( ED ) visits for ambulatory care sensitive conditions ( ACSCs ) are common among older adults . The high-intensity telemedicine model of care has been proposed as an innovative approach to exp and access to acute illness care , thereby preventing ED visits . The aim of this study was to assess the effect of a high-intensity telemedicine program for senior living community ( SLC ) residents on the rate of ED use for ACSCs . METHODS We performed a prospect i ve cohort study at a primary care geriatrics practice that provides care to 22 SLCs . Six SLCs selected as intervention facilities , with the remaining SLCs serving as controls . Consenting practice patients at intervention facilities could have patient-to-provider , real-time , or store- and -forward high-intensity telemedicine services to diagnose and treat illnesses . The primary outcome was the rate of ED visits for which the primary diagnosis was an " ambulatory-care-sensitive " condition by the Institute of Medicine , which we compared between control and intervention participants . RESULTS During the study period , control participants had 310 ED visits for ACSCs , for a rate of 0.195 visits/person-year . Intervention participants visited the ED for ACSCs 85 times , for a rate of 0.138 visits/person-year [ unadjusted rate ratio ( RR ) : 0.71 , 95 % confidence interval ( CI ) : 0.53 - 0.94 ] . Among intervention participants , ED use for ACSCs decreased at an annual rate of 34 % ( RR : 0.661 , 95 % CI : 0.444 - 0.982 ) , whereas , in the control group there was no statistically significant change in ED use over time ( RR : 1.01 , 95 % CI : 0.90 - 1.14 ) . CONCLUSIONS Providing acute illness care by high-intensity telemedicine to older adults residing in SLCs significantly decreases the rate of ED use for ACSCs over 1 year , compared with no change in the rate of ED use for ACSCs among the control group Please cite this paper as : Lund S , Hemed M , Nielsen B , Said A , Said K , Makungu M , Rasch V. Mobile phones as a health communication tool to improve skilled attendance at delivery in Zanzibar : a cluster‐r and omised controlled trial . BJOG 2012;119:1256–1264 IMPORTANCE Chronic musculoskeletal pain is among the most prevalent , costly , and disabling medical disorders . However , few clinical trials have examined interventions to improve chronic pain in primary care . OBJECTIVE To determine the effectiveness of a telecare intervention for chronic pain . DESIGN , SETTING , AND PARTICIPANTS The Stepped Care to Optimize Pain Care Effectiveness ( SCOPE ) study was a r and omized trial comparing a telephone-delivered collaborative care management intervention vs usual care in 250 patients with chronic ( ≥3 months ) musculoskeletal pain of at least moderate intensity ( Brief Pain Inventory [ BPI ] score ≥5 ) . Patients were enrolled from 5 primary care clinics in a single Veterans Affairs medical center from June 2010 through May 2012 , with 12-month follow-up completed by June 2013 . INTERVENTIONS Patients were r and omized either to an intervention group ( n = 124 ) or to a usual care group whose members received all pain care as usual from their primary care physicians ( n = 126 ) . The intervention group received 12 months of telecare management that coupled automated symptom monitoring with an algorithm-guided stepped care approach to optimizing analgesics . MAIN OUTCOMES AND MEASURES Primary outcome was the BPI total score , which ranges from 0 ( " no pain " ) to 10 ( " pain as bad as you can imagine " ) and for which a 1-point change is considered clinical ly important . Secondary pain outcomes included BPI interference and severity , global pain improvement , treatment satisfaction , and use of opioids and other analgesics . RESULTS Overall , mean ( SD ) baseline BPI scores in the intervention and control groups were 5.31 ( 1.81 ) and 5.12 ( 1.80 ) , respectively . Compared with usual care , the intervention group had a 1.02-point lower ( 95 % CI , -1.58 to -0.47 ) BPI score at 12 months ( 3.57 vs 4.59 ) . Patients in the intervention group were nearly twice as likely to report at least a 30 % improvement in their pain score by 12 months ( 51.7 % vs 27.1 % ; relative risk , 1.9 [ 95 % CI , 1.4 to 2.7 ] ) , with a number needed to treat of 4.1 ( 95 % CI , 3.0 to 6.4 ) for a 30 % improvement . Secondary pain outcomes also improved . Few patients in either group required opioid initiation or dose escalation . CONCLUSIONS AND RELEVANCE Telecare collaborative management increased the proportion of primary care patients with improved chronic musculoskeletal pain . This was accomplished by optimizing nonopioid analgesic medications using a stepped care algorithm and monitoring . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00926588 Background Approximately half of American adults do not meet recommended physical activity guidelines . Face-to-face lifestyle interventions improve health outcomes but are unlikely to yield population -level improvements because they can be difficult to disseminate , expensive to maintain , and inconvenient for the recipient . In contrast , Internet-based behavior change interventions can be disseminated widely at a lower cost . However , the impact of some Internet-mediated programs is limited by high attrition rates . Online communities that allow participants to communicate with each other by posting and reading messages may decrease participant attrition . Objective Our objective was to measure the impact of adding online community features to an Internet-mediated walking program on participant attrition and average daily step counts . Methods This r and omized controlled trial included sedentary , ambulatory adults who used email regularly and had at least 1 of the following : overweight ( body mass index [ BMI ] ≥ 25 ) , type 2 diabetes , or coronary artery disease . All participants ( n = 324 ) wore enhanced pedometers throughout the 16-week intervention and uploaded step-count data to the study server . Participants could log in to the study website to view graphs of their walking progress , individually-tailored motivational messages , and weekly calculated goals . Participants were r and omized to 1 of 2 versions of a Web-based walking program . Those r and omized to the “ online community ” arm could post and read messages with other participants while those r and omized to the “ no online community " arm could not read or post messages . The main outcome measures were participant attrition and average daily step counts over 16 weeks . Multiple regression analyses assessed the effect of the online community access controlling for age , sex , disease status , BMI , and baseline step counts . Results Both arms significantly increased their average daily steps between baseline and the end of the intervention period , but there were no significant differences in increase in step counts between arms using either intention-to-treat or completers analysis . In the intention-to-treat analysis , the average step count increase across both arms was 1888 ± 2400 steps . The percentage of completers was 13 % higher in the online community arm than the no online community arm ( online community arm , 79 % , no online community arm , 66 % , P = .02 ) . In addition , online community arm participants remained engaged in the program longer than no online community arm participants ( hazard ratio = 0.47 , 95 % CI = 0.25 - 0.90 , P = .02 ) . Participants with lower baseline social support posted more messages to the online community ( P < .001 ) and viewed more posts ( P < .001 ) than participants with higher baseline social support . Conclusion Adding online community features to an Internet-mediated walking program did not increase average daily step counts but did reduce participant attrition . Participants with low baseline social support used the online community features more than those with high baseline social support . Thus , online communities may be a promising approach to reducing attrition from online health behavior change interventions , particularly in population s with low social support . Trial Registration NCT00729040 ; http:// clinical trials.gov/ct2/show/NCT00729040 ( Archived by WebCite at http://www.webcitation.org/5v1VH3n0A OBJECTIVES Patients discharged from the emergency department ( ED ) are often referred for primary care , specialty , or other disease-specific follow-up appointments . Attendance at these scheduled follow-up appointments has been found to improve patient outcomes , decrease ED bounce-backs , and reduce mal practice risk . Reasons for missing follow-up visits are complex , but the most commonly reason cited by patients is simply forgetting . In this study the authors evaluated the ability of an automated text message reminder system to increase attendance at post-ED discharge follow-up appointments in a predominantly Hispanic safety-net population . METHODS This was a r and omized controlled trial of ED patients with outpatient follow-up visits scheduled at the time of ED discharge . A total of 374 English- and Spanish-speaking patients with text-capable mobile phones were enrolled . Patients in the intervention arm received automated , personalized text message appointment reminders including date , time , and clinic location at 7 , 3 , and 1 day before scheduled visits . A t-test of proportions was used to compare outcomes between intervention and control groups . Both an intention-to-treat ( ITT ) and a per- protocol analysis of the data were performed . The ITT more accurately reflects real-world conditions where errors such as number entry errors are bound to occur . The per- protocol analysis adds value by isolating the effect of the intervention by comparing patients who actually received it compared with those who did not . RESULTS In the per- protocol analysis of the primary outcome , the overall appointment adherence rate was 72.6 % in the intervention group compared with 62.1 % in the control group ( difference between groups = 10.5 % , 95 % confidence interval [ CI ] = 0.3 % to 20.8 % ; p = 0.045 ; number needed to treat = 9.5 ) . In the ITT analysis , the overall appointment attendance rate 70.2 % in the intervention group compared with 62.1 % in the control group ( difference between groups = 8.2 % ; 95 % CI = -1.6 % to 17.7 % ; p = 0.100 ) . In a secondary largely exploratory analysis , the intervention was found to have the most benefit in patients with the lowest baseline follow-up rate ( English speakers with specialty care appointments ) . CONCLUSIONS Automated text message appointment reminders result ed in improvement in attendance at scheduled post-ED discharge outpatient follow-up visits and represent a low-cost and highly scalable solution to increase attendance at post-ED follow-up appointments , which should be further explored in larger sample sizes and diverse patient population Background : Electronic information exchange is believed to improve efficiency and reduce re source utilization . We developed a Web-based st and ardized communication system ( SCS ) that enables family physicians to receive detailed reports of their patients ' care in the emergency department . We sought to determine the impact of the SCS on measures of re source utilization in the emergency department and family physician offices . Methods : We used an open 4-period crossover cluster-r and omized controlled design . During 2 separate 10-week intervention phases , family physicians received detailed reports of their patients ' emergency department visits over the Internet , and in the alternating control phases they received a 1-page copy of the emergency department notes by mail . The primary outcome was the number of repeat visits to the emergency department within 14 days of the initial visit . Secondary outcomes included duplication of test and specialty consultation requests by the emergency and family physician . Outcomes were measured using the hospital data base and question naires sent to the family physicians . Results : A total of 2022 patient visits to the emergency department from 23 practice s were used in the study . Use of the SCS failed to reduce the number of repeat visits to the emergency department within 14 days ( odds ratio [ OR ] 1.10 , 95 % confidence interval [ CI ] 0.8–1.51 ) and 28 days ( OR 1.01 , 95 % CI 0.8–1.27 ) . There was no significant duplication of requests for diagnostic tests between the emergency and family physician during the intervention and control phases ( 24 v. 22 , p = 0.93 ) , but there was significantly greater duplication in specialty consultation requests in the intervention phase than in the control phase ( 20 v. 8 , p = 0.049 ) . Interpretation : An electronic link between emergency and family physicians did not result in a significant reduction in re source utilization at either service point . Investments in improved electronic information exchange between emergency departments and family physician offices may not be substantiated by a reduction in re source utilization We compared desktop videoconferencing to conventional face-to-face visits for a range of commonly presenting problems in a general practice . A total of 175 patients were recruited . Patients were r and omized to one of two arms of the study . In the first arm , the patients completed a visit ( virtual or face-to-face ) with a physician ; they then completed a second visit via the other modality with another physician . In the second arm of the study , subjects had both visits face-to-face ; different physicians conducted the two face-to-face consultations . Patients found virtual visits similar to face-to-face visits on most measures , including time spent with the physician , ease of interaction and personal aspects of the interaction . Physicians were also highly satisfied with the virtual visit modality . The diagnostic agreement between physicians was 84 % between face-to-face and virtual visits ; it was 80 % between the two face-to-face visits . The study suggests that both patients and physicians could benefit if virtual visits were used as an alternative method of accessing primary care services Background With the public ’s increased use of the Internet , the use of email as a means of communication between patients and physicians will likely increase . Yet , despite evidence of increased interest by patients , email use by physicians for clinical care has been slow . Objective To examine the factors associated with physician-patient email , and report on the physicians ’ adherence to recognized guidelines for email communication . Methods Cross-sectional survey ( March – May , 2005 ) of all primary care physicians ( n = 10253 ) , and a 25 % stratified , r and om sample of all ambulatory clinical specialists ( n = 3954 ) in the state of Florida . Physicians were surveyed on email use with patients , adherence to recognized guidelines , and demographics . Results The 4203 physicians completed the question naire ( a 28.2 % participation rate ) . Of these , 689 ( 16.6 % ) had personally used email to communicate with patients . Only 120 ( 2.9 % ) used email with patients frequently . In univariate analysis , email use correlated with physician age ( decreased use : age > 61 ; P = .014 ) , race ( decreased use : Asian background ; P < .001 ) , medical training ( increased use : family medicine , P = .001 ; or surgical specialty , P = .007 ; but not internal medicine , P = .112 ) , practice size ( > 50 physicians , P < .001 ) , and geographic location ( urban 17.2 % vs. rural , 7.9 % ; P < .001 ) . Multivariate modeling showed that only practice size greater than 50 ( OR = 1.94 ; 95 % CI = 1.01 - 3.79 ) and Asian-American race ( OR = 0.26 ; 95 % CI = 0.14 - 0.49 ) were related to email use with patients . Remarkably , only 46 physicians ( 6.7 % ) adhered to at least half of the 13 selected guidelines for email communication . Conclusions This large survey of physicians , practicing in ambulatory setting s , shows only modest advances in the adoption of email communication , and little adherence to recognized guidelines for email correspondence . Further efforts are required to educate both patients and physicians on the advantages and limitations of email communication , and to remove fiscal and legal barriers to its adoption Background Healthcare information provided by telephone service and internet sources is growing but has not been shown to reduce inappropriate emergency department ( ED ) visits . Objective To describe the use of advice or healthcare information among patients with non-urgent illnesses seeking care before attendance at an ED , or primary care ( PC ) centres in an urban region in Sweden . Design Patients with non-urgent illnesses seeking care at an ED or patients attending the PC were followed up with a combination of patient interviews , a question naire to the treating physician and a prospect i ve follow-up of healthcare use through a population -based registry . Results Half of the non-urgent patients attending the ED had used healthcare information or advice before the visit , mainly from a healthcare professional source . In PC , men were more likely to have used information or advice compared with women ( OR 2.5 95 % CI 1.3 to 5.0 ) , whereas the situation was reversed among ED patients ( OR=0.4 95 % CI 0.2 to 0.9 ) . Men with no previous healthcare experience attending the ED had the lowest use of healthcare information ( p<0.01 ) . Very few in both groups had utilised healthcare information on the internet in a case of perceived emergency . Conclusion ED patients rated as non-urgent by the triage nurse used more advice and healthcare information than PC patients , irrespective of the physician-rated urgency of the symptoms . The problem seems not to be lack of information about appropriate ED use , but to find ways to direct the information to the right target group |
11,351 | 26,416,143 | Recruiter training programmes were well received and some increased recruiters ’ self-confidence in communicating key RCT concepts to patients .
There was , however , little evidence that this training increased actual recruitment rates or patient underst and ing , satisfaction , or levels of informed consent .
Conclusions There is a need to develop recruiter training programmes that can lead to improved recruitment and informed consent in r and omised trials | Background Recruitment to r and omised controlled trials ( RCTs ) is often difficult .
Clinician related factors have been implicated as important reasons for low rates of recruitment .
Clinicians ( doctors and other health professionals ) can experience discomfort with some underlying principles of RCTs and experience difficulties in conveying them positively to potential trial participants .
Recruiter training has been suggested to address identified problems but a synthesis of this research is lacking .
The aim of our study was to systematic ally review the available evidence on training interventions for recruiters to r and omised trials . | Background A commonly reported problem with the conduct of multicentre r and omised controlled trials ( RCTs ) is that recruitment is often slower or more difficult than expected , with many trials failing to reach their planned sample size within the timescale and funding originally envisaged . The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies : the UK Medical Research Council ( MRC ) and the Health Technology Assessment ( HTA ) Programme . Methods The cohort of trials was identified from the administrative data bases held by the two funding bodies . 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria . The full scientific applications and subsequent trial reports su bmi tted by the trial teams to the funders provided the principal data sources . Associations between trial characteristics and recruitment success were tested using the Chi-squared test , or Fisher 's exact test where appropriate . Results Less than a third ( 31 % ) of the trials achieved their original recruitment target and half ( 53 % ) were awarded an extension . The proportion achieving targets did not appear to improve over time . The overall start to recruitment was delayed in 47 ( 41 % ) trials and early recruitment problems were identified in 77 ( 63 % ) trials . The inter-relationship between trial features and recruitment success was complex . A variety of strategies were employed to try to increase recruitment , but their success could not be assessed . Conclusion Recruitment problems are complex and challenging . Many of the trials in the cohort experienced recruitment difficulties . Trials often required extended recruitment periods ( sometimes supported by additional funds ) . While this is of continuing concern , success in addressing the trial question may be more important than recruitment alone 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 BACKGROUND Previous research has shown that communication between members of multidisciplinary teams ( MDTs ) is often suboptimal and communication about trials between MDTs and their patients is difficult . Educational interventions can help dyadic exchanges with different aspects of trial recruitment but less work has focussed on team interventions . METHODS 22 multidisciplinary cancer teams in the UK participated in an RCT of a novel Teams Talking Trials ( TTT ) Workshop aim ed at improving the following : awareness , involvement , communication and recruitment to cancer trials . MDTs were r and omised following either 6 or 12 months of audits , which were repeated after the intervention . Audits included numbers approached about trials , team members ' attitudes , involvement and awareness of their teams ' trial portfolios . RESULTS There was no significant difference in the rate of approaching patients about trials post workshop ( estimated improvement 22 % higher regression coefficient of 0.2 , exp . (0.2)=1.22 ) . There was improvement in team members ' involvement in trials in 4 areas ( p≤0.04 ) : the pressure to enter patients into RCTs , the likelihood of a start-up meeting to discuss a newly accepted trial , the informational role played by individuals and recognition of this HCP 's role by other team members . Also , confidence in communication about RCTS increased and awareness of different aspects of trial management improved on all 14 aspects ( p=0.001 ) . CONCLUSION Attendance by teams at focussed workshops design ed to enhance communication and trial recruitment improved several aspects of team functioning , but a significant impact on the number of patients approached could not be demonstrated Background Poor recruitment to r and omised controlled trials ( RCTs ) is a widespread problem . Provision of interventions aim ed at supporting or incentivising clinicians may improve recruitment to RCTs . Objectives To quantify the effects of strategies aim ed at improving the recruitment activity of clinicians in RCTs , complemented with a synthesis of qualitative evidence related to clinicians ' attitudes towards recruiting to RCTs . Data sources A systematic review of English and non-English articles identified from : The Cochrane Library , Ovid MEDLINE , Ovid EMBASE , Ovid PsycINFO , Ebsco CINAHL , Index to Theses and Open SIGLE from 2001 to March 2011 . Additional reports were identified through citation search es of included articles . Study eligibility criteria Quantitative studies were included if they evaluated interventions aim ed at improving the recruitment activity of clinicians or compared recruitment by different groups of clinicians . Information about host trial , study design , participants , interventions , outcomes and host RCT was extracted by one research er and checked by another . Studies that met the inclusion criteria were assessed for quality using a st and ardised tool , the Effective Public Health Practice Project tool . Qualitative studies were included if they investigated clinicians ' attitudes to recruiting patients to RCTs . All results / findings were extracted , and content analysis was carried out . Overarching themes were abstract ed , followed by a meta summary analysis . Studies that met the inclusion criteria were assessed for quality using the Critical Appraisal Skills Programme qualitative checklist . Data extraction Data extraction was carried out by one research er using predefined data fields , including study quality indicators , and verified by another . Results Eight quantitative studies were included describing four interventions and a comparison of recruiting clinicians . One study was rated as strong , one as moderate and the remaining six as weak when assessed for quality using the Effective Public Health Practice Project tool . Effective interventions included the use of qualitative research to identify and overcome barriers to recruitment , reduction of the clinical workload associated with participation in RCTs and the provision of extra training and protected research time . Eleven qualitative studies were identified , and eight themes were abstract ed from the data : underst and ing of research , communication , perceived patient barriers , patient – clinician relationship , effect on patients , effect on clinical practice , individual benefits for clinicians and methods associated with successful recruitment . Meta summary analysis identified the most frequently reported subthemes to be : difficulty communicating trial methods , poor underst and ing of research and priority given to patient well-being . Overall , the qualitative studies were found to be of good quality when assessed using the Critical Appraisal Skills Programme checklist . Conclusions There were few high- quality trials that tested interventions to improve clinicians ' recruitment activity in RCTs . The most promising intervention was the use of qualitative methods to identify and overcome barriers to clinician recruitment activity . More good quality studies of interventions are needed to add to the evidence base . The meta summary of qualitative findings identified underst and ing and communicating RCT methods as a key target for future interventions to improve recruitment . Reinforcement of the potential benefits , both for clinicians and for their patients , could also be a successful factor in improving recruitment . A bias was found towards investigating barriers to recruitment , so future work should also encompass a focus on successfully recruiting trials Abstract Objective To evaluate a training intervention aim ed at improving healthcare professionals ' communication with cancer patients about r and omised clinical trials . Design Before and after evaluation of training programme . Setting Members of the National Cancer Research Network , Scottish Trials Network , and the Welsh Cancer Trials Network Participants 101 healthcare professionals ( 33 clinicians and 68 research nurses ) . Intervention Four modules delivered by a trained facilitator using videotapes and interactive exercises to cover general issues about discussing r and omised clinical trials with patients , problems specific to adjuvant trials , trials with palliation as the goal , and trials where patients had a strong preference for one treatment arm . Main outcome measures Before and after the intervention , participants were videotaped discussing a trial with an actor portraying a patient . These consultations were assessed for presence of information required by good clinical practice guidelines . The actor patients gave an assessment after each interview . Participants reported their self confidence about key aspects of trial discussion . Results Analysis of the videotaped consultations showed that , after intervention , significantly more participants displayed key communication behaviours such as explaining r and omisation ( 69 v 81 , odds ratio 2.33 , P = 0.033 ) , checking patients ' underst and ing ( 11 v 31 , odds ratio 3.22 , P = 0.002 ) , and discussing st and ard treatment ( 73 v 88 , odds ratio 4.75 , P = 0.005 ) and side effects ( 69 v 85 , odds ratio 3.29 , P = 0.006 ) . Participants ' self confidence increased significantly ( P < 0.001 ) across all areas . Actor patients ' ratings of participants ' communication showed significant improvements for 12/15 key items . Conclusion This intensive 8 hour intervention significantly improved participants ' confidence and competence when communicating about r and omised clinical trials Objective The aim of the study was to investigate how doctors considered and experienced the concept of equipoise while recruiting patients to r and omized controlled trials ( RCTs ) . Study Design and Setting In-depth interviews with 32 doctors in six publicly funded pragmatic RCTs explored their perceptions of equipoise as they undertook RCT recruitment . The RCTs varied in size , duration , type of complex intervention , and clinical specialties . Interview data were analyzed using qualitative content and thematic analytical methods derived from grounded theory and synthesized across six RCTs . Results All six RCTs suffered from poor recruitment . Doctors wanted to gather robust evidence but experienced considerable discomfort and emotion in relation to their clinical instincts and concerns about patient eligibility and safety . Although they relied on a sense of community equipoise to justify participation , most acknowledged having “ hunches ” about particular treatments and patients , some of which undermined recruitment . Surgeons experienced these issues most intensely . Training and support promoted greater confidence in equipoise and improved engagement and recruitment . Conclusion Recruitment to RCTs is a fragile process and difficult for doctors intellectually and emotionally . Training and support can enable most doctors to become comfortable with key RCT concepts including equipoise , uncertainty , patient eligibility , and r and omization , promoting a more resilient recruitment process in partnership with patients Background : The optimal treatment for localised oesophageal squamous cell carcinoma ( SCC ) is uncertain . We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy . Methods : A feasibility RCT in three centres examined incident patients and reasons for in eligibility using multi-disciplinary team meeting records . Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff . Results : Of 375 patients with oesophageal SCC , 42 ( 11.2 % ) were eligible . Reasons for eligibility varied between centres , with significantly differing proportions of patients excluded because of total tumour length ( P=0.002 ) . Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms , balancing treatment arms and explaining the need for r and omisation . Before analyses of the qualitative data and recruiter training no patients were r and omised . Following training in one centre 5 of 16 eligible patients were r and omised . Conclusions : An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients . A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process Purpose Few studies have compared the instructiveness of real patient contacts with simulated patient ( SP ) contacts . Although most of these studies found no difference , students often comment that the instructiveness of both encounters is dissimilar . The aims of this study were to evaluate which contact ( real patient or SP ) is perceived as most instructive by students and which variables contribute to this . Method The authors performed an experiment involving 163 first-year medical students , r and omized to having a real patient contact ( n = 61 ) or SP contact ( n = 102 ) . Quantitative ( question naires ) and qualitative ( focus groups ) methods were used to evaluate the perceived instructiveness of the contact . Results The general instructiveness of both real patient contacts and SP contacts was marked high . Several differences between the evaluations of real patient contacts and SP contacts were found . For example , students considered real patient contacts less helpful in practicing communication skills and considered the real patients ' feedback less relevant . The focus group interviews yielded explanations for many of the differences found . Students regarded real patients as more authentic . However , SPs were better informed about the purpose of the consultation and provided the student with more specific feedback . Conclusions Students consider authenticity an important advantage of real patients . Their difficult recruitment is an important disadvantage , however , SPs have important advantages compared with real patients —for example , their feedback . The choice of real patient contacts or SP contacts for medical education depends on factors like the phase of the curriculum and the aim of the encounter This paper reports on the reasons why patients agreed to or declined entry into r and omized trials of cancer following discussion s conducted by clinicians in both District General and University Hospitals . Two hundred and four patients completed a 16-item question naire following the consultation , of these 112 ( 55 % ) were women with breast cancer . Overall results showed that 147 ( 72.1 % ) patients accepted entry to a r and omized clinical trial ( RCT ) . The main reasons nominated for participating in a trial were that ‘ others will benefit ’ ( 23.1 % ) and ‘ trust in the doctor ’ ( 21.1 % ) . One of the main reasons for declining trial entry was that patients were ‘ worried about r and omization ’ ( 19.6 % ) . There was a significantly higher acceptance rate for trials providing active treatment in every arm 98 ( 80.6 % ) compared with those trials with a no treatment arm 46 ( 60.5 % ) , χ2test P = 0.003 . The study outlines a number of factors that appear to influence a patient ’s decision to accept or decline entry into an RCT of cancer therapy . An important factor is whether or not the trial offers active treatment in all arms of the study . Communication that promotes trust and confidence in the doctor is also a powerful motivating influence . © 2000 Cancer Research Background There are many barriers to patient participation in r and omised controlled trials of cancer treatments . To increase participation in trials , strategies need to be identified to overcome these barriers . Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in r and omised controlled trials ( RCTs ) of cancer treatments . Methods A systematic review was conducted . Published and unpublished studies in any language were search ed for in fifteen electronic data bases , including MEDLINE , EMBASE , CINAHL and PsycINFO , from inception to the end of 2004 . Studies of any interventions to improve cancer patient participation in RCTs , which reported the change in recruitment rates , were eligible for inclusion . RCTs and non-r and omised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included . Data were extracted by one review er into structured summary tables and checked for accuracy by a second review er . Each included study was assessed against a checklist for method ological quality by one review er and checked by a second review er . A narrative synthesis was conducted . Results Eight studies were identified that met the inclusion criteria : three RCTs , two non-r and omised controlled trials and three observational studies . Six of the studies had an intervention that had some relevance to the UK . There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs , though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer . Although there was no evidence of an effect in any of the studies , the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work . Conclusion There is not a strong evidence -base for interventions that increase cancer patient participation in r and omised trials . Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials INTRODUCTION Strategies to improve recruitment to RCTs ( r and omised controlled trials ) are limited . The ProtecT ( Prostate testing for cancer and Treatment ) study successfully developed a complex intervention based on qualitative research methods to increase recruitment rates . The Quartet study ( Qualitative Research to Improve Recruitment to RCTs ) was established to evaluate whether the ProtecT qualitative methods could be transferred into other RCTs . This paper reports on the barriers and facilitators in setting up these collaborations . METHODS The Quartet study collaborated with five RCTs . Qualitative methods used were : interviews and focus groups with RCT staff ; audio-recording recruitment interactions ; and feedback sessions for RCT staff based on qualitative findings . Data were audio-recorded , transcribed and analysed using content and thematic analyses . Issues arising during establishment of collaborations were recorded and analysed . RESULTS Establishing collaborations proved challenging and not always surmountable . Difficulties were encountered in gaining agreement of RCT staff to participate because of central RCT staff 's lack of authority over recruitment staff , poor communication within RCTs and recruiters ' reluctance to have their practice scrutinised . The complexity of the recruitment process also hindered translation of ProtecT methods . Although Quartet enabled significant recruitment issues to surface , the bureaucratic tasks involved in securing governance approval delayed onset of collaborations , reducing the time to address issues and evaluate Quartet 's impact . DISCUSSION The Quartet study established collaborations with a range of RCTs and gained valuable insights for future collaborations between qualitative research ers and RCTs . Qualitative research methods need to be included at the feasibility stage of a RCT or fully integrated into the RCT , as in the ProtecT study , with routine audio-recording for monitoring and training purpose s. Quartet-like collaborations could then be established without delay , and recruitment processes of RCTs could become transparent , monitored and improved Background Recruitment of sufficient participants in an efficient manner is still widely acknowledged to be a major challenge to the mounting and completion of r and omised controlled trials ( RCTs ) . Few recruitment interventions have involved staff undertaking recruitment . This study aim ed i ) to underst and the recruitment process from the perspective of recruiters actively recruiting RCT participants in six pragmatic RCTs , and ii ) to identify opportunities for interventions to improve recruitment . Methods Interviews were undertaken with 72 individuals ( 32 doctors or RCT Chief investigators ( CIs ) ; 40 nurses/other health professionals ) who were actively recruiting participants in six RCTs to explore their experiences of recruitment . The RCTs varied in scale , duration , and clinical context s. Interviews were fully transcribed and analysed using qualitative content and thematic analytic methods derived from grounded theory . For this analysis , data were systematic ally extracted from each RCT and synthesis ed across all six RCTs to produce a detailed and nuanced underst and ing of the recruitment process from the perspectives of the recruiters . Results Recruiters readily identified organisational difficulties , fewer than expected eligible patients , and patients ’ treatment preferences as the key barriers to recruitment . As they described their experiences of recruitment , several previously hidden issues related to their roles as research ers and clinicians emerged , imbued with discomfort and emotion . The synthesis across the RCTs showed that doctors were uncomfortable about aspects of patient eligibility and the effectiveness of interventions , whereas nurses were anxious about approaching potential RCT participants and conflicts between the research and their clinical responsibilities . Recruiters seemed unaware that their views contributed to recruitment difficulties . Their views were not known to RCT CIs . Training and support needs were identified for both groups of staff . Conclusions The synthesis showed that recruitment to these RCTs was a complex and fragile process . Clear obstacles were identified but hidden challenges related to recruiters ’ roles undermined recruitment , unbeknown to RCT CIs . Qualitative research can elicit and identify the hidden challenges . Training and support are then needed for recruiters to become more comfortable with the design and principles of RCTs , so that they can engage more openly with potentially eligible participants and create a more resilient recruitment process Background Recruitment to r and omised controlled trials ( RCTs ) with very different treatment arms is often difficult . The ProtecT ( Prostate testing for cancer and Treatment ) study successfully used qualitative research methods to improve recruitment and these methods were replicated in five other RCTs facing recruitment difficulties . A similar qualitative recruitment investigation was undertaken in the SPARE ( Selective bladder Preservation Against Radical Excision ) feasibility study to explore reasons for low recruitment and attempt to improve recruitment rates by implementing changes suggested by qualitative findings . Methods In Phase I of the investigation , reasons for low levels of recruitment were explored through content analysis of RCT documents , thematic analysis of interviews with trial staff and recruiters , and conversation analysis of audio-recordings of recruitment appointments . Findings were presented to the trial management group and a plan of action was agreed . In Phase II , changes to design and conduct were implemented , with training and feedback provided for recruitment staff . Results Five key challenges to trial recruitment were identified in Phase I : ( a ) Investigators and recruiters had considerable difficulty articulating the trial design in simple terms ; ( b ) The recruitment pathway was complicated , involving staff across different specialties/centres and communication often broke down ; ( c ) Recruiters inadvertently used ' loaded ' terminology such as ' gold st and ard ' in study information , leading to unbalanced presentation ; ( d ) Fewer eligible patients were identified than had been anticipated ; ( e ) Strong treatment preferences were expressed by potential participants and trial staff in some centres . In Phase II , study information ( patient information sheet and flowchart ) was simplified , the recruitment pathway was focused around lead recruiters , and training sessions and ' tips ' were provided for recruiters . Issues of patient eligibility were insurmountable , however , and the independent Trial Steering Committee advised closure of the SPARE trial in February 2010 . Conclusions The qualitative investigation identified the key aspects of trial design and conduct that were hindering recruitment , and a plan of action that was acceptable to trial investigators and recruiters was implemented . Qualitative investigations can thus be used to eluci date challenges to recruitment in trials with very different treatment arms , but require sufficient time to be undertaken successfully . Trial Registration CRUK/07/011 ; IS RCT BACKGROUND The International Breast Cancer Study Group conducted a phase III trial in Australian/New Zeal and ( ANZ ) and Swiss/German/Austrian ( SGA ) centres on training doctors in clear and ethical information delivery about treatment options and strategies to encourage shared decision making . METHODS Medical , surgical , gynaecological and radiation oncologists , and their patients for whom adjuvant breast cancer therapy was indicated , were eligible . Doctors were r and omised to participate in a workshop with st and ardised teaching material and role playing . Patients were recruited in the experimental and control groups before and after the workshop . RESULTS In ANZ centres , 21 eligible doctors recruited a total of 304 assessable patients . In SGA centres , 41 doctors recruited 390 patients . The training was well accepted . There was no overall effect on patient decisional conflict ( primary endpoint ) 2 weeks after the consultation . Overall , patients were satisfied with their treatment decision , their consultation and their doctors ' consultation skills . Considerable variation was observed in patient outcomes between SGA and ANZ centres ; the effect sizes of the intervention were marginal ( < 0.2 ) . CONCLUSIONS Shared decision making remains a challenge . A sustained training effect may require more intensive training tailored to the local setting . Cross-cultural differences need attention in conducting trials on communication interventions Background R and omized clinical trials often encounter slow enrollment . Failing to meet sample size requirements has scientific , financial , and ethical implication s. Aims We report interventions used to accelerate recruitment in a large multicenter clinical trial that was not meeting prespecified enrollment commitments . Methods The Carotid Revascularization Endarterectomy vs. Stenting Trial began r and omization in December 2000 . To accelerate enrollment , multiple recruitment tactics were initiated , which included exp and ing the number of sites , hiring a recruitment director ( May 2003 ) , broadening eligibility criteria ( April 2005 ) , br and ing with a study logo , Web site , and recruitment material s , increasing site visits by study leadership , sending e-mails to the site teams after every enrollment , distributing electronic newsletters , and implementing investigator and coordinator conferences . Results From December 2000 through May 2003 , 14 sites became active ( 54 patients r and omized ) , from June 2003 through April 2005 , 44 sites were added ( 404 patients r and omized ) , and from May 2005 through July 2008 , 54 sites were added ( 2044 patients r and omized ) . During these time intervals , the number of patients enrolled per site per year was 1.5 , 3.6 , and 5.6 . For the single years 2004 to 2008 , the mean monthly r and omization rates per year were 19.7 , 38.1 , 56.4 , 53.0 , and 54.7 ( annualized ) , respectively . Enrollment was highest after recruitment tactics were implemented : 677 patients in 2006 , 636 in 2007 , and 657 in 2008 ( annualized ) . The prespecified sample size of 2502 patients , 47 % asymptomatic , was accomplished on July 2008 . Conclusions Aggressive recruitment tactics and investment in a full-time recruitment director who can lead implementation may be effective in accelerating recruitment in multicenter trials PURPOSE To investigate how communication among physicians , patients , and family/companions influences patients ' decision making about participation in clinical trials . PATIENTS AND METHODS We video recorded 235 outpatient interactions occurring among oncologists , patients , and family/companions ( if present ) at two comprehensive cancer centers . We combined interaction analysis of the real-time video-recorded observations ( collected at Time 1 ) with patient self-reports ( Time 2 ) to determine how communication about trial offers influenced accrual decisions . RESULTS Clinical trials were explicitly offered in 20 % of the interactions . When offers were made and patients perceived they were offered a trial , 75 % of patients assented . Observed messages ( at Time 1 ) directly related to patients ' self-reports regarding their decisions ( 2 weeks later ) , and how they felt about their decisions and their physicians . Specifically , messages that help build a sense of an alliance ( among all parties , including the family/companions ) , provide support ( tangible assistance and reassurance about managing adverse effects ) , and provide medical content in language that patients and family/companions underst and are associated with the patient 's decision and decision-making process . CONCLUSION In two urban , National Cancer Institute- design ated comprehensive cancer centers , a large percentage of patients are not offered trials . When offered a trial , most patients enroll . The quality and quantity of communication occurring among the oncologist , patient , and family/companion when trials are discussed matter in the patient 's decision-making process . These findings can help increase physician awareness of the ways that messages and communication behaviors can be observed and evaluated to improve clinical practice and research Clinical trials have come to be regarded as the gold st and ard for treatment evaluation . However , many doctors and their patients experience difficulties when discussing trials , leading to poor accrual to trials and question able quality of informed consent . We have previously developed a typology for ethical communication about Phase II and III clinical trials within four domains : ( a ) shared decision making , ( b ) sequencing information , ( c ) type and clarity of information , and ( d ) disclosure/coercion . The aim of this study was to compare current clinical practice when seeking informed consent with this typology . Fifty-nine consultations in which 10 participating oncologists sought informed consent were audiotaped . Verbatim transcripts were analysed using a coding system to ( a ) identify the presence or absence of aspects of the four domains and ( b ) rate the quality of aspects of two domains : ( i ) shared decision-making and ( ii ) type and clarity of information . Oncologists rarely addressed aspects of shared decision-making , other than offering to delay a treatment decision ( 78 % ) . Moreover , many of these discussion s scored poorly with respect to ideal content . The oncologists were rarely consistent with the sequence of information provision . A general rationale for r and omising was only described in 46 % of consultations . In almost one third of the consultations ( 28.8 % ) doctors made implicit statements favouring one option over another , either st and ard or clinical trial treatment . Doctors complied with some but not other aspects of a st and ard procedure for discussing clinical trials . This reflects the difficulty inherent in seeking ethical informed consent and the need for communication skills training for oncologists This study examined the use of lay advocates ( i.e. , women enrolled in a study who advocate to others ) to improve recruitment among Hispanic women in the Arizona recruitment sites for a large-scale , national prevention study , the Women 's Health Initiative ( WHI ) . We examined whether trained , Hispanic lay advocates ( called Embajadoras ) brought more women into the study than a matched group of Hispanic and Anglo enrollees in the WHI who were supplied with brochures . Fifty-six Hispanic participants in the WHI were r and omized to receive training or no training on advocacy , and continued to meet quarterly for 18 months . Also , 42 Anglo women were assigned to control . All groups received brochures to use for advocating the WHI . The number of women referred and enrolled was tracked as well as other factors expected to influence outcomes . Embajadoras were more successful at referral and enrollment than untrained Hispanic women and more successful at enrollment than untrained Anglo controls . Embajadoras were also found to distribute significantly more brochures than control groups . Therefore , a culturally aligned training program to encourage current Hispanic participants in a clinical trial to advocate the study to others may be an effective way to boost referrals and enrollments . Other potential influences on enrollment or referral success could not be determined due to the small sample size . Further study is needed to examine the best methods to encourage enrollment for women referred to the study INTRODUCTION Clinical trials have come to be regarded as the gold st and ard for treatment evaluation . However , many doctors and their patients experience difficulties when discussing trial participation , leading to poor accrual to trials and question able quality of informed consent . We have previously developed a communication skills training program based on a typology for ethical communication about Phase II and III clinical trials within four categories . The training program consisted of a 1 day experiential workshop that included didactic teaching , exemplary video and role play . The aim of this study was to evaluate the effectiveness of the communication skills training workshop . METHOD Oncologists were recruited from three major teaching hospitals conducting oncology outpatient clinics in three Australian capital cities . Ten oncologists and 90 of their adult cancer patients who were eligible for a Phase II or III clinical trial participated . Ninety informed consent consultations were audiotaped before ( n = 59 ) and after ( n = 31 ) training , and fully transcribed . The presence or absence of each domain component was coded and these were summed within categories . A coding manual was produced which enabled st and ardization of the coding procedure . Patients completed question naires before and after the consultation , and doctors completed a short measure of satisfaction after the consultation . RESULTS Doctors increased their use of some aspects of shared decision-making behavior ( t(87 ) = -1.945 , p = 0.05 ) and described some aspects of essential ethical/ clinical information more commonly . In addition they used less coercive behaviors ( z = -1.976 , p = 0.048 ) . However , they did not provide more clinical information or structure their consultations in the recommended fashion . Patients in the post-training cohort reported more positive attitudes to clinical trials , but other outcomes were not affected by the intervention . CONCLUSIONS This short training programme demonstrated limited success in improving the oncologist 's communication skills when gaining informed consent . A larger r and omized controlled trial of extended training is now underway Background The conduct of current cardiovascular outcome trials requires investigation of thous and s of patients at hundreds of investigator sites . Such large trials are clinical ly and logistically highly dem and ing and often tend to finish with significant delays , consequently delaying patient access to new medicines . Purpose To address this issue , we design ed and implemented a novel approach – a Clinical Trial Educator ( CTE ) program – to accelerate enrollment in the Thrombin-Receptor Antagonist for Clinical Event Reduction ( TRA•CER ) trial . This article analyzes the effect of this approach on the study milestones : patient recruitment , site start-up time , and recruitment rate . Methods Scientifically qualified and specifically trained CTEs regularly visited TRA•CER investigator sites in 18 European countries where they trained and educated investigators and site personnel to support them address recruitment challenges . Patient recruitment was assessed in absolute numbers and as recruitment rates , both in relation to CTE site visits . Results CTEs performed 2184 visits at 373 European TRA•CER sites ( out of 921 global sites ) . Of sites visited by a CTE , significantly less remained without enrolling any patient than of sites not visited by a CTE ( 5.9 % vs. 15.3 % ; p < 0.001 ) . Sites visited within 30 days after initiation showed a significantly shortened median time to recruitment of the first patient ( 28 vs. 59 days with visits ≤30 or > 30 days after initiation ; p < 0.001 ) . Mean patient recruitment rates were significantly higher at visited than at not-visited sites ( 1.13 vs. 0.89 patients per site per month , p < 0.001 ) and significantly increased after the first CTE site visit ( from 0.70 to 1.17 patients per site per month ; p < 0.001 ) . Finally , there were fewer low-recruiting sites and more high-recruiting sites among the CTE-visited sites compared to the not-visited sites , and the mean recruitment rate at high-recruiting sites visited by CTEs was significantly higher than at high-recruiting sites without CTE visits ( 2.07 vs. 1.64 patients per site per month ; p < 0.01 ) . Limitations The possibility for selection bias is inherent to this post hoc analysis of a nonr and omized data set . The European focus of the CTE program described here might add some geographical bias . Also , other activities such as investigator meetings conducted in parallel with CTE activities might have partly masked the results of our analysis . Finally , the analysis is limited to recruitment-related parameters , and the aspect of cost-effectiveness has not been quantitatively assessed . Conclusion We found a significant positive association between CTE site visits and the assessed recruitment-related study milestones in the TRA•CER trial , and enrollment finished ahead of plan . We propose that a CTE program could efficiently accelerate enrollment in other clinical trials and therapeutic areas and could contribute to shortening patient access time to novel and potential lifesaving treatments in cardiovascular medicine and beyond PURPOSE To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials . METHODS Main member institutions of the Cancer and Leukemia Group B ( CALGB ) and its affiliates were r and omly assigned to receive st and ard information ( n = 73 ) or educational intervention ( n = 53 ) . St and ard information included CALGB Web site access and periodic notification about existing trials . The geriatric educational intervention included st and ard information plus : ( 1 ) an educational seminar ; ( 2 ) educational material s ; ( 3 ) a list of available protocol s for use on charts ; ( 4 ) a monthly e-mail and mail reminders for 1 year ; and ( 5 ) a case discussion seminar . The main outcome was percentage of accrual of older persons to phase II and III treatment protocol s after study initiation compared with baseline . RESULTS There were 3,032 patients entered onto trials in the baseline year , and 2,160 and 1,239 during the 2 years postintervention , respectively . Overall percentage of accrual of older patients was 37 % at baseline , and 33 % and 31 % during the first and second years after intervention . There was no improvement in accrual in the intervention versus control arm : 36 % v 32 % in the first year and 31 % v 31 % in the second year . CONCLUSION Accrual of older patients was not increased by this intervention . Reasons for lack of effect include low intervention intensity , high baseline accrual rates , and closure of several high-accruing protocol s during the study . More intense and multifaceted approaches will be needed to change physician ( and patient ) behavior and to increase accrual of older persons to clinical trials R and omised controlled trials ( RCTs ) represent the gold st and ard methodology for determining effectiveness of healthcare interventions . Poor recruitment to RCTs can threaten external validity and waste re sources . An inherent tension exists between safeguarding informed decision-making by participants and maximising numbers enrolled . This study investigated what occurs during informed consent appointments in an ongoing multi-centre RCT in the UK . Objectives were to investigate : 1 ] how study staff presented study information to participants ; 2 ] what evidence emerged as to how well-informed participants were when proceeding to r and omisation or treatment selection ; and 3 ] what aspects of the communication process may facilitate improvements in providing evidence of informed consent . Qualitative analysis of a purposive sample of 23 recruitment appointments from three study centres and involving several recruitment staff applied techniques of thematic , content and conversation analysis ( CA ) . Thematic analysis and CA revealed variation in appointment content and structure . Appointments were mostly recruiter-led or participant-led , and this structure was associated with what evidence emerged as to how participants understood information provided and whether they were in equipoise . Participant-led appointments provided this evidence more consistently . Detailed CA identified communication techniques which , when employed by recruiters , provided evidence as to how participants understood the choices before them . Strategic use of open questions , pauses and ceding the floor in the interaction facilitated detailed and systematic exploration of each participant 's concerns and position regarding equipoise . We conclude that the current focus on content to be provided to achieve informed consent should be broadened to encompass consideration of how information is best conveyed to potential participants . A model of tailored information provision using the communication techniques identified and centred on eliciting and addressing participants ' concerns is proposed . Use of these techniques is necessary to make potential participants ' underst and ing of key issues and their position regarding equipoise explicit in order to facilitate truly informed consent When physicians disclose information about r and omised controlled trials , they have to balance the requirements of conducting high st and ard research and the respect for patients ' rights . Physicians need training in this difficult matter . An individualised communication skills training ( CST ) about r and omised controlled trials for oncologists has been developed . The aim of this publication is to describe the concept of our CST and present data of evaluation by the participants : First , a theoretical introduction about a communication model and important ethical and legal issues was presented . Individual learning goals of participants were then derived through video assessment with actor- patients . The learning goals were the basis for practicing in role play . Individual coaching helped physicians to transfer the made experience into their daily work . Forty physicians have been trained . The acceptance of the training concept was assessed by a question naire consisting of 14 items and using a 6-point scale from 1 ( very best ) to 6 ( very bad ) : the individualised CST was highly accepted ( mean = 1.33 ) . Practicing with actor- patients ( mean = 1.4 ) , providing constructive feedback ( mean = 1.3 ) and assessing individual learning goals ( mean = 1.85 ) were seen as helpful . Our CST trains physicians to realise best research st and ards and incorporate patients ' rights AIM A discussion and qualitative evaluation of the use of peer- review to train nurses and optimize recruitment practice in a r and omized controlled trial . BACKGROUND Sound recruitment processes are critical to the success of r and omized controlled trials . Nurses recruiting to trials must obtain consent for an intervention that is administered for reasons other than anticipated benefit to the patient . This requires not only patients ' acquiescence but also evidence that they have weighed the relevant information in reaching their decision . How trial information is explained is vital , but communication and training can be inadequate . DESIGN A discussion of a new process to train nurses recruiting to a r and omized controlled trial . DATA SOURCES Literature from 1999 - 2013 about consenting to trials is included . Over 3 months from 2009 - 2010 , recruiting nurses review ed recruitment interviews recorded during the pilot phase of a single-site r and omized controlled trial and noted content , communication style and interactions . They discussed their findings during peer- review meetings , which were audio-recorded and analysed using qualitative methodology . IMPLICATION S FOR NURSING Peer- review can enhance nurses ' training in trial recruitment procedures by supporting development of the necessary communication skills , facilitating consistency in information provision and sharing best practice . CONCLUSIONS Nurse-led peer- review can provide a forum to share communication strategies that will elicit and address participant concerns and obtain evidence of participant underst and ing prior to consent . Comparing practice can improve consistency and accuracy of trial information and facilitate identification of recruitment issues . Internal peer- review was well accepted and promoted team cohesion . Further evaluation is needed |
11,352 | 28,263,392 | The analysis of data showed that CTLA‐4 inhibitors seem to be associated with a higher risk of all‐ and high‐ grade hepatotoxicity compared with control regimens , whereas PD‐1 inhibitors seem to be associated with a lower risk of all‐ and high‐ grade hepatotoxicity compared with control regimens | & NA ; Although existing evidence from clinical trials has demonstrated manifestation of hepatic adverse events with the use of immune checkpoint inhibitors ( ICPIs ) , overall risks have yet to be reported .
Therefore , we assessed the risk of hepatotoxicity associated with inhibitors of the immune checkpoint . | BACKGROUND Treatments for small-cell lung cancer ( SCLC ) after failure of platinum-based chemotherapy are limited . We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens . METHODS The SCLC cohort of this phase 1/2 multicentre , multi-arm , open-label trial was conducted at 23 sites ( academic centres and hospitals ) in six countries . Eligible patients were 18 years of age or older , had limited-stage or extensive-stage SCLC , and had disease progression after at least one previous platinum-containing regimen . Patients received nivolumab ( 3 mg/kg bodyweight intravenously ) every 2 weeks ( given until disease progression or unacceptable toxicity ) , or nivolumab plus ipilimumab ( 1 mg/kg plus 1 mg/kg , 1 mg/kg plus 3 mg/kg , or 3 mg/kg plus 1 mg/kg , intravenously ) every 3 weeks for four cycles , followed by nivolumab 3 mg/kg every 2 weeks . Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg . Depending on tolerability , patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . The primary endpoint was objective response by investigator assessment . All analyses included patients who were enrolled at least 90 days before data base lock . This trial is ongoing ; here , we report an interim analysis of the SCLC cohort . This study is registered with Clinical Trials.gov , number NCT01928394 . FINDINGS Between Nov 18 , 2013 , and July 28 , 2015 , 216 patients were enrolled and treated ( 98 with nivolumab 3 mg/kg , three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg ) . At data base lock on Nov 6 , 2015 , median follow-up for patients continuing in the study ( including those who had died or discontinued treatment ) was 198·5 days ( IQR 163·0 - 464·0 ) for nivolumab 3 mg/kg , 302 days ( IQR not calculable ) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 361·0 days ( 273·0 - 470·0 ) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 260·5 days ( 248·0 - 288·0 ) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . An objective response was achieved in ten ( 10 % ) of 98 patients receiving nivolumab 3 mg/kg , one ( 33 % ) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 14 ( 23 % ) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and ten ( 19 % ) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . Grade 3 or 4 treatment-related adverse events occurred in 13 ( 13 % ) patients in the nivolumab 3 mg/kg cohort , 18 ( 30 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort , and ten ( 19 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( none vs 5 [ 8 % ] vs none ) and diarrhoea ( none vs 3 [ 5 % ] vs 1 [ 2 % ] ) . No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-related adverse event . Six ( 6 % ) patients in the nivolumab 3 mg/kg group , seven ( 11 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group , and four ( 7 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events . Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events ( myasthenia gravis and worsening of renal failure ) , and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis . INTERPRETATION Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC . These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 r and omised controlled trials in SCLC . FUNDING Bristol-Myers Squibb BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) PURPOSE In phase I/II trials , the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma . This phase III study evaluated overall survival ( OS ) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or st and ard-of-care chemotherapy . PATIENTS AND METHODS Patients with treatment-naive , unresectable stage IIIc or IV melanoma were r and omly assigned at a ratio of one to one to tremelimumab ( 15 mg/kg once every 90 days ) or physician 's choice of st and ard-of-care chemotherapy ( temozolomide or dacarbazine ) . RESULTS In all , 655 patients were enrolled and r and omly assigned . The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths , but survival follow-up continued . At final analysis with 534 events , median OS by intent to treat was 12.6 months ( 95 % CI , 10.8 to 14.3 ) for tremelimumab and 10.7 months ( 95 % CI , 9.36 to 11.96 ) for chemotherapy ( hazard ratio , 0.88 ; P = .127 ) . Objective response rates were similar in the two arms : 10.7 % in the tremelimumab arm and 9.8 % in the chemotherapy arm . However , response duration ( measured from date of r and om assignment ) was significantly longer after tremelimumab ( 35.8 v 13.7 months ; P = .0011 ) . Diarrhea , pruritus , and rash were the most common treatment-related adverse events in the tremelimumab arm ; 7.4 % had endocrine toxicities . Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor . CONCLUSION This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over st and ard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma . The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study . METHODS We r and omly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks ) . The primary end point was overall survival . RESULTS At 1 year , the overall rate of survival was 72.9 % ( 95 % confidence interval [ CI ] , 65.5 to 78.9 ) in the nivolumab group , as compared with 42.1 % ( 95 % CI , 33.0 to 50.9 ) in the dacarbazine group ( hazard ratio for death , 0.42 ; 99.79 % CI , 0.25 to 0.73 ; P<0.001 ) . The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group ( hazard ratio for death or progression of disease , 0.43 ; 95 % CI , 0.34 to 0.56 ; P<0.001 ) . The objective response rate was 40.0 % ( 95 % CI , 33.3 to 47.0 ) in the nivolumab group versus 13.9 % ( 95 % CI , 9.5 to 19.4 ) in the dacarbazine group ( odds ratio , 4.06 ; P<0.001 ) . The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups , including subgroups defined by status regarding the programmed death lig and 1 ( PD-L1 ) . Common adverse events associated with nivolumab included fatigue , pruritus , and nausea . Drug-related adverse events of grade 3 or 4 occurred in 11.7 % of the patients treated with nivolumab and 17.6 % of those treated with dacarbazine . CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival , as compared with dacarbazine , among previously untreated patients who had metastatic melanoma without a BRAF mutation . ( Funded by Bristol-Myers Squibb ; CheckMate 066 Clinical Trials.gov number , NCT01721772 . ) BACKGROUND Endogenous or iatrogenic antitumour immune responses can improve the course of follicular lymphoma , but might be diminished by immune checkpoints in the tumour microenvironment . These checkpoints might include effects of programmed cell death 1 ( PD1 ) , a co-inhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells . We did this phase 2 trial to investigate the activity of pidilizumab , a humanised anti-PD1 monoclonal antibody , with rituximab in patients with relapsed follicular lymphoma . METHODS We did this open-label , non-r and omised trial at the University of Texas MD And erson Cancer Center ( Houston , TX , USA ) . Adult ( ≥18 years ) patients with rituximab-sensitive follicular lymphoma relapsing after one to four previous therapies were eligible . Pidilizumab was administered at 3 mg/kg intravenously every 4 weeks for four infusions , plus eight optional infusions every 4 weeks for patients with stable disease or better . Starting 17 days after the first infusion of pidilizumab , rituximab was given at 375 mg/m(2 ) intravenously weekly for 4 weeks . The primary endpoint was the proportion of patients who achieved an objective response ( complete response plus partial response according to Revised Response Criteria for Malignant Lymphoma ) . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00904722 . FINDINGS We enrolled 32 patients between Jan 13 , 2010 , and Jan 20 , 2012 . Median follow-up was 15.4 months ( IQR 10.1 - 21.0 ) . The combination of pidilizumab and rituximab was well tolerated , with no autoimmune or treatment-related adverse events of grade 3 or 4 . The most common adverse events of grade 1 were anaemia ( 14 patients ) and fatigue ( 13 patients ) , and the most common adverse event of grade 2 was respiratory infection ( five patients ) . Of the 29 patients evaluable for activity , 19 ( 66 % ) achieved an objective response : complete responses were noted in 15 ( 52 % ) patients and partial responses in four ( 14 % ) . INTERPRETATION The combination of pidilizumab plus rituximab is well tolerated and active in patients with relapsed follicular lymphoma . Our results suggest that immune checkpoint blockade is worthy of further study in follicular lymphoma . FUNDING National Institutes of Health , Leukemia and Lymphoma Society , Cure Tech , and University of Texas MD And erson Cancer Center BACKGROUND Despite recent advances in the treatment of advanced non-small-cell lung cancer , there remains a need for effective treatments for progressive disease . We assessed the efficacy of pembrolizumab for patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . METHODS We did this r and omised , open-label , phase 2/3 study at 202 academic medical centres in 24 countries . Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells were r and omly assigned ( 1:1:1 ) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg , pembrolizumab 10 mg/kg , or docetaxel 75 mg/m(2 ) every 3 weeks . The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50 % of tumour cells . We used a threshold for significance of p<0.00825 ( one-sided ) for the analysis of overall survival and a threshold of p<0.001 for progression-free survival . This trial is registered at Clinical Trials.gov , number NCT01905657 . FINDINGS Between Aug 28 , 2013 , and Feb 27 , 2015 , we enrolled 1034 patients : 345 allocated to pembrolizumab 2 mg/kg , 346 allocated to pembrolizumab 10 mg/kg , and 343 allocated to docetaxel . By Sept 30 , 2015 , 521 patients had died . In the total population , median overall survival was 10.4 months with pembrolizumab 2 mg/kg , 12.7 months with pembrolizumab 10 mg/kg , and 8.5 months with docetaxel . Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel ( hazard ratio [ HR ] 0.71 , 95 % CI 0.58 - 0.88 ; p=0.0008 ) and for pembrolizumab 10 mg/kg versus docetaxel ( 0.61 , 0.49 - 0.75 ; p<0.0001 ) . Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg , 4.0 months with pembrolizumab 10 mg/kg , and 4.0 months with docetaxel , with no significant difference for pembrolizumab 2 mg/kg versus docetaxel ( 0.88 , 0.74 - 1.05 ; p=0.07 ) or for pembrolizumab 10 mg/kg versus docetaxel ( HR 0.79 , 95 % CI 0.66 - 0.94 ; p=0.004 ) . Among patients with at least 50 % of tumour cells expressing PD-L1 , overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 14.9 months vs 8.2 months ; HR 0.54 , 95 % CI 0.38 - 0.77 ; p=0.0002 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 17.3 months vs 8.2 months ; 0.50 , 0.36 - 0.70 ; p<0.0001 ) . Likewise , for this patient population , progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 5.0 months vs 4.1 months ; HR 0.59 , 95 % CI 0.44 - 0.78 ; p=0.0001 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 5.2 months vs 4.1 months ; 0.59 , 0.45 - 0.78 ; p<0.0001 ) . Grade 3 - 5 treatment-related adverse events were less common with pembrolizumab than with docetaxel ( 43 [ 13 % ] of 339 patients given 2 mg/kg , 55 [ 16 % ] of 343 given 10 mg/kg , and 109 [ 35 % ] of 309 given docetaxel ) . INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . These data establish pembrolizumab as a new treatment option for this population and vali date the use of PD-L1 selection . FUNDING Merck & BACKGROUND Ipilimumab , an anti-CTLA4 monoclonal antibody , demonstrated survival benefit in melanoma with immune-related ( ir ) adverse events ( irAEs ) managed by the protocol -defined guidelines . This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer ( ED-SCLC ) . DESIGN Patients ( n=130 ) with chemotherapy-naïve ED-SCLC were r and omized 1 : 1 : 1 to receive paclitaxel ( 175 mg/m2)/carboplatin ( area under the curve=6 ) with either placebo ( control ) or ipilimumab 10 mg/kg in two alternative regimens , concurrent ipilimumab ( ipilimumab+paclitaxel/carboplatin followed by placebo+paclitaxel/carboplatin ) or phased ipilimumab ( placebo+paclitaxel/carboplatin followed by ipilimumab+paclitaxel/carboplatin ) . Treatment was administered every 3 weeks for a maximum of 18 weeks ( induction ) , followed by maintenance ipilimumab or placebo every 12 weeks . End points included progression-free survival ( PFS ) , irPFS , best overall response rate ( BORR ) ; irBORR , overall survival ( OS ) , and safety . RESULTS Phased ipilimumab , but not concurrent ipilimumab , improved irPFS versus control [ HR ( hazard ratio)=0.64 ; P=0.03 ] . No improvement in PFS ( HR=0.93 ; P=0.37 ) or OS ( HR=0.75 ; P=0.13 ) occurred . Phased ipilimumab , concurrent ipilimumab and control , respectively , were associated with median irPFS of 6.4 , 5.7 and 5.3 months ; median PFS of 5.2 , 3.9 and 5.2 months ; median OS of 12.9 , 9.1 and 9.9 months . Overall rates of grade 3/4 irAEs were 17 , 21 and 9 % for phased ipilimumab , concurrent ipilimumab and control , respectively . CONCLUSION These results suggest further investigation of ipilimumab in ED-SCLC BACKGROUND Patients with melanoma that progresses on ipilimumab and , if BRAF(V600 ) mutant-positive , a BRAF or MEK inhibitor or both , have few treatment options . We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma . METHODS We carried out a r and omised phase 2 trial of patients aged 18 years or older from 73 hospitals , clinics , and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and , if BRAF(V600 ) mutant-positive , previous treatment with a BRAF or MEK inhibitor or both . Patients had to have resolution of all ipilimumab-related adverse events to grade 0 - 1 and prednisone 10 mg/day or less for at least 2 weeks , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , and at least one measurable lesion to be eligible . Using a central ised interactive voice response system , we r and omly assigned ( 1:1:1 ) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy ( paclitaxel plus carboplatin , paclitaxel , carboplatin , dacarbazine , or oral temozolomide ) . R and omisation was stratified by ECOG performance status , lactate dehydrogenase concentration , and BRAF(V600 ) mutation status . Individual treatment assignment between pembrolizumab and chemotherapy was open label , but investigators and patients were masked to assignment of the dose of pembrolizumab . We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01704287 . The study is closed to enrolment but continues to follow up and treat patients . FINDINGS Between Nov 30 , 2012 , and Nov 13 , 2013 , we enrolled 540 patients : 180 patients were r and omly assigned to receive pembrolizumab 2 mg/kg , 181 to receive pembrolizumab 10 mg/kg , and 179 to receive chemotherapy . Based on 410 progression-free survival events , progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg ( HR 0·57 , 95 % CI 0·45 - 0·73 ; p<0·0001 ) and those assigned to pembrolizumab 10 mg/kg ( 0·50 , 0·39 - 0·64 ; p<0·0001 ) compared with those assigned to chemotherapy . 6-month progression-free survival was 34 % ( 95 % CI 27 - 41 ) in the pembrolizumab 2 mg/kg group , 38 % ( 31 - 45 ) in the 10 mg/kg group , and 16 % ( 10 - 22 ) in the chemotherapy group . Treatment-related grade 3 - 4 adverse events occurred in 20 ( 11 % ) patients in the pembrolizumab 2 mg/kg group , 25 ( 14 % ) in the pembrolizumab 10 mg/kg group , and 45 ( 26 % ) in the chemotherapy group . The most common treatment-related grade 3 - 4 adverse event in the pembrolizumab groups was fatigue ( two [ 1 % ] of 178 patients in the 2 mg/kg group and one [ < 1 % ] of 179 patients in the 10 mg/kg group , compared with eight [ 5 % ] of 171 in the chemotherapy group ) . Other treatment-related grade 3 - 4 adverse events include generalised oedema and myalgia ( each in two [ 1 % ] patients ) in those given pembrolizumab 2 mg/kg ; hypopituitarism , colitis , diarrhoea , decreased appetite , hyponatremia , and pneumonitis ( each in two [ 1 % ] ) in those given pembrolizumab 10 mg/kg ; and anaemia ( nine [ 5 % ] ) , fatigue ( eight [ 5 % ] ) , neutropenia ( six [ 4 % ] ) , and leucopenia ( six [ 4 % ] ) in those assigned to chemotherapy . INTERPRETATION These findings establish pembrolizumab as a new st and ard of care for the treatment of ipilimumab-refractory melanoma . FUNDING Merck Sharp & Dohme BACKGROUND In patients with melanoma , ipilimumab ( an antibody against cytotoxic T-lymphocyte-associated antigen 4 [ CTLA-4 ] ) prolongs overall survival , and nivolumab ( an antibody against the programmed death 1 [ PD-1 ] receptor ) produced durable tumor regression in a phase 1 trial . On the basis of their distinct immunologic mechanisms of action and supportive pre clinical data , we conducted a phase 1 trial of nivolumab combined with ipilimumab in patients with advanced melanoma . METHODS We administered intravenous doses of nivolumab and ipilimumab in patients every 3 weeks for 4 doses , followed by nivolumab alone every 3 weeks for 4 doses ( concurrent regimen ) . The combined treatment was subsequently administered every 12 weeks for up to 8 doses . In a sequenced regimen , patients previously treated with ipilimumab received nivolumab every 2 weeks for up to 48 doses . RESULTS A total of 53 patients received concurrent therapy with nivolumab and ipilimumab , and 33 received sequenced treatment . The objective -response rate ( according to modified World Health Organization criteria ) for all patients in the concurrent-regimen group was 40 % . Evidence of clinical activity ( conventional , unconfirmed , or immune-related response or stable disease for ≥24 weeks ) was observed in 65 % of patients . At the maximum doses that were associated with an acceptable level of adverse events ( nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram ) , 53 % of patients had an objective response , all with tumor reduction of 80 % or more . Grade 3 or 4 adverse events related to therapy occurred in 53 % of patients in the concurrent-regimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible . Among patients in the sequenced-regimen group , 18 % had grade 3 or 4 adverse events related to therapy and the objective -response rate was 20 % . CONCLUSIONS Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy , with rapid and deep tumor regression in a substantial proportion of patients . ( Funded by Bristol-Myers Squibb and Ono Pharmaceutical ; Clinical Trials.gov number , NCT01024231 . ) BACKGROUND In a phase 1 dose-escalation study , combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response , including complete responses , among patients with advanced melanoma . METHODS In this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment , we r and omly assigned patients in a 2:1 ratio to receive ipilimumab ( 3 mg per kilogram of body weight ) combined with either nivolumab ( 1 mg per kilogram ) or placebo once every 3 weeks for four doses , followed by nivolumab ( 3 mg per kilogram ) or placebo every 2 weeks until the occurrence of disease progression or unacceptable toxic effects . The primary end point was the rate of investigator-assessed , confirmed objective response among patients with BRAF V600 wild-type tumors . RESULTS Among patients with BRAF wild-type tumors , the rate of confirmed objective response was 61 % ( 44 of 72 patients ) in the group that received both ipilimumab and nivolumab ( combination group ) versus 11 % ( 4 of 37 patients ) in the group that received ipilimumab and placebo ( ipilimumab-monotherapy group ) ( P<0.001 ) , with complete responses reported in 16 patients ( 22 % ) in the combination group and no patients in the ipilimumab-monotherapy group . The median duration of response was not reached in either group . The median progression-free survival was not reached with the combination therapy and was 4.4 months with ipilimumab monotherapy ( hazard ratio associated with combination therapy as compared with ipilimumab monotherapy for disease progression or death , 0.40 ; 95 % confidence interval , 0.23 to 0.68 ; P<0.001 ) . Similar results for response rate and progression-free survival were observed in 33 patients with BRAF mutation-positive tumors . Drug-related adverse events of grade 3 or 4 were reported in 54 % of the patients who received the combination therapy as compared with 24 % of the patients who received ipilimumab monotherapy . Select adverse events with potential immunologic causes were consistent with those in a phase 1 study , and most of these events resolved with immune-modulating medication . CONCLUSIONS The objective -response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy . Combination therapy had an acceptable safety profile . ( Funded by Bristol-Myers Squibb ; Clinical Trials.gov number , NCT01927419 . ) PURPOSE Ipilimumab , which is an anti-cytotoxic T-cell lymphocyte-4 monoclonal antibody , showed a survival benefit in melanoma with adverse events ( AEs ) managed by protocol -defined guidelines . A phase II study in lung cancer assessed the activity of ipilimumab plus paclitaxel and carboplatin . PATIENTS AND METHODS Patients ( N = 204 ) with chemotherapy-naive non-small-cell lung cancer ( NSCLC ) were r and omly assigned 1:1:1 to receive paclitaxel ( 175 mg/m(2 ) ) and carboplatin ( area under the curve , 6 ) with either placebo ( control ) or ipilimumab in one of the following two regimens : concurrent ipilimumab ( four doses of ipilimumab plus paclitaxel and carboplatin followed by two doses of placebo plus paclitaxel and carboplatin ) or phased ipilimumab ( two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimumab plus paclitaxel and carboplatin).Treatment was administered intravenously every 3 weeks for ≤ 18 weeks ( induction ) . Eligible patients continued ipilimumab or placebo every 12 weeks as maintenance therapy . Response was assessed by using immune-related response criteria and modified WHO criteria . The primary end point was immune-related progression-free survival ( irPFS ) . Other end points were progression-free survival ( PFS ) , best overall response rate ( BORR ) , immune-related BORR ( irBORR ) , overall survival ( OS ) , and safety . RESULTS The study met its primary end point of improved irPFS for phased ipilimumab versus the control ( hazard ratio [ HR ] , 0.72 ; P = .05 ) , but not for concurrent ipilimumab ( HR , 0.81 ; P = .13 ) . Phased ipilimumab also improved PFS according to modified WHO criteria ( HR , 0.69 ; P = .02 ) . Phased ipilimumab , concurrent ipilimumab , and control treatments were associated with a median irPFS of 5.7 , 5.5 , and 4.6 months , respectively , a median PFS of 5.1 , 4.1 , and 4.2 months , respectively , an irBORR of 32 % , 21 % and 18 % , respectively , a BORR of 32 % , 21 % and 14 % , respectively , and a median OS of 12.2 , 9.7 , and 8.3 months . Overall rates of grade 3 and 4 immune-related AEs were 15 % , 20 % , and 6 % for phased ipilimumab , concurrent ipilimumab , and the control , respectively . Two patients ( concurrent , one patient ; control , one patient ) died from treatment-related toxicity . CONCLUSION Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS , which supports additional investigation of ipilimumab in NSCLC |
11,353 | 21,680,196 | Initially , reverse transcriptase polymerase chain reaction ( RT-PCR ) based methods were utilized with weak correlation between their positive detection and patients ' outcome .
More recent immunological techniques have indicated a reproducible correlation with outcome . | Prostate-specific antigen ( PSA ) levels in blood are widely used in prostate cancer ( PCa ) for the management of this disease at every stage of progression .
Currently , PSA levels combined with clinical stage and Gleason score provide the best predictor of survival and the main element to monitor treatment efficiency .
However , these areas could be improved by utilizing emerging biomarkers .
Recently , circulating tumor cells ( CTCs ) and disseminating tumor cells ( DTCs ) have been detected in PCa and may be a new surrogate c and i date .
Here we provide a systematic review of the literature in order to describe the current evidence of CTC/DTC surrogacy regarding outcome of prostate cancer patients .
We also discuss several markers that could be used to increase the sensitivity and specificity of CTC/DTC detection . | BACKGROUND Intermediate or surrogate endpoints for survival can shorten time lines for drug approval . We aim ed to assess circulating tumour cell ( CTC ) count as a prognostic factor for survival in patients with progressive , metastatic , castration-resistant prostate cancer receiving first-line chemotherapy . METHODS We identified patients with progressive metastatic castration-resistant prostate cancer starting first-line chemotherapy in the IMMC38 trial . CTCs were isolated by immunomagnetic capture from blood sample s at baseline and after treatment . Baseline variables , including CTC count , titre of prostate-specific antigen ( PSA ) , and concentration of lactate dehydrogenase ( LDH ) , and post-treatment variables ( change in CTCs and PSA ) were tested for association with survival with Cox proportional hazards models . Concordance probability estimates were used to gauge discriminatory strength of the informative factors in identifying patients at low-risk and high-risk of survival . FINDINGS Variables associated with high risk of death were high LDH concentration ( hazard ratio 6.44 , 95 % CI 4.24 - 9.79 ) , high CTC count ( 1.58 , 1.41 - 1.77 ) , and high PSA titre ( 1.26 , 1.10 - 1.45 ) , low albumin ( 0.10 , 0.03 - 0.39 ) , and low haemoglobin ( 0.72 , 0.64 - 0.81 ) at baseline . At 4 weeks , 8 weeks , and 12 weeks after treatment , changes in CTC number were strongly associated with risk , whereas changes in PSA titre were weakly or not associated ( p>0.04 ) . The most predictive factors for survival were LDH concentration and CTC counts ( concordance probability estimate 0.72 - 0.75 ) . INTERPRETATION CTC number , analysed as a continuous variable , can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials . Prospect i ve recording of CTC number as an intermediate endpoint of survival in r and omised clinical trials is warranted Purpose : To detect insulin-like growth factor-IR ( IGF-IR ) on circulating tumor cells ( CTC ) as a biomarker in the clinical development of a monoclonal human antibody , CP-751,871 , targeting IGF-IR . Experimental Design : An automated sample preparation and analysis system for enumerating CTCs ( CellTracks ) was adapted for detecting IGF-IR – positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871 . This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was vali date d using cell lines and blood sample s from healthy volunteers and patients with metastatic carcinoma . Results : There was no interference between the analytic and therapeutic antibodies . Eighty patients were enrolled on phase I studies of CP-751,871 , with 47 ( 59 % ) patients having CTCs detected during the study . Before treatment , 26 patients ( 33 % ) had CTCs , with 23 having detectable IGF-IR – positive CTCs . CP-751,871 alone , and CP-751,871 with cytotoxic chemotherapy , decreased CTCs and IGF-IR – positive CTCs ; these increased toward the end of the 21-day cycle in some patients , falling again with retreatment . CTCs were commonest in advanced hormone refractory prostate cancer ( 11 of 20 ) . Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by > 50 % ( 6 of 10 versus 2 of 8 patients ) . A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by > 50 % . Conclusions : IGF-IR expression is detectable by immunofluorescence on CTCs . These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection , particularly in advanced prostate cancer In clinical ly organ-confined prostate cancer patients , bloodstream tumour cell dissemination generally occurs , and may be enhanced by surgical prostate manipulation . To evaluate cancer-cell seeding impact upon patient recurrence-free survival , 155 patients were prospect ively enrolled then followed . Here , 57 patients presented blood prostate cell shedding preoperatively and intraoperatively ( group I ) . Of the 98 preoperatively negative patients , 53 ( 54 % ) remained negative ( group II ) and 45 ( 46 % ) became intraoperatively positive ( group III ) . Median biological and clinical recurrence-free time was far shorter in group I ( 36.2 months , P<0.0001 ) than in group II ( 69.6 months ) but did not significantly differ in group II and III ( 69.6 months vs 65.0 ) . Such 5-year follow-up data show that preoperative circulating prostate cells are an independent prognosis factor of recurrence . Moreover , tumour h and ling induces cancer-cell seeding but surgical blood dissemination does not accelerate cancer evolution BACKGROUND The purpose of this study was to evaluate the association of circulating tumour cell ( CTC ) counts , before and after commencing treatment , with overall survival ( OS ) in patients with castration-resistant prostate cancer ( CRPC ) . EXPERIMENTAL DESIGN A 7.5 ml of blood was collected before and after treatment in 119 patients with CRPC . CTCs were enumerated using the Cell Search System . RESULTS Higher CTC counts associated with baseline characteristics portending aggressive disease . Multivariate analyses indicated that a CTC > or=5 was an independent prognostic factor at all time points evaluated . Patients with baseline CTC > or=5 had shorter OS than those with < 5 [ median OS 19.5 versus > 30 months , hazard ratio ( HR ) 3.25 , P=0.012 ] ; patients with CTC > 50 had a poorer OS than those with CTCs 5 - 50 ( median OS 6.3 versus 21.1 months , HR 4.1 , P<0.001 ) . Patients whose CTC counts reduced from > or=5 at baseline to < 5 following treatment had a better OS compared with those who did not . CTC counts showed a similar , but earlier and independent , ability to time to disease progression to predict OS . CONCLUSION CTC counts predict OS and provide independent prognostic information to time to disease progression ; CTC dynamics following therapy need to be evaluated as an intermediate end point of outcome in r and omised phase III trials Purpose : The TAX-327 study r and omized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel , weekly docetaxel , or mitoxantrone , each with prednisone . Experimental Design : We used the TAX-327 data base to address ( a ) the relationship between quality of life ( QoL ) and pain ; ( b ) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL ; ( c ) the relationships between prostate-specific antigen ( PSA ) response , pain response , and QoL response ; ( d ) the times at which these responses are first observed ; and ( e ) whether PSA , pain , and /or QoL response predict for overall survival . Results : At baseline , 374 of 815 men assessed for QoL had major pain ; of these , 92 % had substantial impairment of QoL compared with 75 % without major pain ( P < 0.001 ) . Men with minimal symptoms had prolonged survival ( median , 25.6 months ) compared with symptomatic patients ( median , 17.1 months ; P = 0.009 ) ; they were more likely to have initial deterioration of QoL if treated with weekly docetaxel . PSA response and pain response , but not QoL response , were independently associated with survival in l and mark analysis . Median times to PSA and pain response were 44 and 27 days , respectively ; some men had initial increase in serum PSA before subsequent decline . Conclusions : Symptoms other than pain contribute to impaired QoL in men with hormone-refractory prostate cancer . Those with minimal symptoms have prolonged survival . Both pain and PSA response are associated with survival but are not adequate to use as surrogate end points in phase 3 studies . Early increases in serum PSA ( up to 12 weeks ) should be ignored when determining response or progression PURPOSE We report a prospect i ve study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction ( RT-PCR ) for prostate-specific antigen ( PSA ) and prostate-specific membrane antigen ( PSM ) to predict pathologic stage and biochemical recurrence in patients with clinical ly localized prostate cancer treated with radical prostatectomy . PATIENTS AND METHODS One hundred forty-one patients were entered onto the study . Preoperative evaluation included clinical T stage , serum PSA , biopsy Gleason score , and serum RT-PCR for PSA/PSM . Univariate and multivariate logistic regression models , Kaplan-Meier estimates , and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure . RESULTS Seventy-three patients ( 51.8 % ) were RT-PCR positive for PSA , PSM , or both . In the multivariate logistic regression model , only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease ( odds ratio [ OR ] , 1.06 ; 95 % confidence interval [ CI ] , 1.00 to 1.13 ; P = .026 ) or organ-/specimen-confined disease ( OR , 1.09 ; 95 % CI , 1.02 to 1.16 ; P = .009 ) . Overall Kaplan-Meier biochemical relapse-free survival ( bRFS ) was 85 % at 59 months . Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA ( OR , 1.05 ; 95 % CI , 1.02 to 1.09 ; P = .004 ) and biopsy Gleason score ( OR , 3.57 ; 95 % CI , 1.37 to 9.58 ; P = .009 ) were independent predictors of biochemical failure . RT-PCR status did not predict pathologic stage or biochemical failure . Repeat analysis excluding 27 patients who received preoperative and rogen-deprivation therapy did not change the results . CONCLUSION Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy . This assay has no clinical utility in this patient population The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies PURPOSE We previously reported evidence of hematogenous dissemination of prostate cells during radical retropubic prostatectomy , and we now provide clinical and molecular reverse transcriptase-polymerase chain reaction ( RT-PCR ) followup of that patient cohort . MATERIAL S AND METHODS A total of 101 men with clinical ly localized prostate cancer were prospect ively enrolled in the study . The prostate specific antigen ( PSA ) RT-PCR assay was performed on peripheral venous blood sample s preoperatively in 101 , during surgery in 29 , during and up to 12 weeks after surgery in 50 and at least 1 year postoperatively in 65 patients . Correlation with clinical ( PSA ) indicators of recurrence was performed . RESULTS Of the 101 patients 9 demonstrated biochemical evidence of prostate cancer progression ( median followup 22 months ) . Of the 50 men with perioperative molecular results the RT-PCR positive rate increased from 22 % preoperatively in 11 to 48 % in 24 ( p = 0.02 ) and then decreased to 10 % in 4 of 40 men at 1 year postoperatively ( p = 0.07 ) . Molecular followup at a minimum of 1 year after radical retropubic prostatectomy was obtained in 65 men , of whom the RT-PCR positive rate decreased from 23 % preoperatively in 14 to 9.2 % in 6 ( p = 0.05 ) . No significant correlation was observed between a persistently positive RT-PCR result and biochemical failure . CONCLUSIONS Although a significant proportion of men have molecular evidence of hematogenous prostate cell dissemination intraoperatively , longitudinal molecular and clinical followup demonstrates reconversion to a negative status as the predominant trend . At relatively short followup no significant correlation was identified between the RT-PCR result and the PSA progression-free survival CONTEXT Interstitial radiation ( implant ) therapy is used to treat clinical ly localized adenocarcinoma of the prostate , but how it compares with other treatments is not known . OBJECTIVE To estimate control of prostate-specific antigen ( PSA ) after radical prostatectomy ( RP ) , external beam radiation ( RT ) , or implant with or without neoadjuvant and rogen deprivation therapy in patients with clinical ly localized prostate cancer . DESIGN Retrospective cohort study of outcome data compared using Cox regression multivariable analyses . SETTING AND PATIENTS A total of 1872 men treated between January 1989 and October 1997 with an RP ( n = 888 ) or implant with or without neoadjuvant and rogen deprivation therapy ( n = 218 ) at the Hospital of the University of Pennsylvania , Philadelphia , or RT ( n = 766 ) at the Joint Center for Radiation Therapy , Boston , Mass , were enrolled . MAIN OUTCOME MEASURE Actuarial freedom from PSA failure ( defined as PSA outcome ) . RESULTS The relative risk ( RR ) of PSA failure in low-risk patients ( stage T1c , T2a and PSA level < or = 10 ng/mL and Gleason score < or = 6 ) treated using RT , implant plus and rogen deprivation therapy , or implant therapy was 1.1 ( 95 % confidence interval [ CI ] , 0.5 - 2.7 ) , 0.5 ( 95 % CI , 0.1 - 1.9 ) , and 1.1 ( 95 % CI , 0.3 - 3.6 ) , respectively , compared with those patients treated with RP . The RRs of PSA failure in the intermediate-risk patients ( stage T2b or Gleason score of 7 or PSA level > 10 and < or = 20 ng/mL ) and high-risk patients ( stage T2c or PSA level > 20 ng/mL or Gleason score > or = 8) treated with implant compared with RP were 3.1 ( 95 % CI , 1.5 - 6.1 ) and 3.0 ( 95 % CI , 1.8 - 5.0 ) , respectively . The addition of and rogen deprivation to implant therapy did not improve PSA outcome in high-risk patients but result ed in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients . These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10 . CONCLUSIONS Low-risk patients had estimates of 5-year PSA outcome after treatment with RP , RT , or implant with or without neoadjuvant and rogen deprivation that were not statistically different , whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant . Prospect i ve r and omized trials are needed to verify these findings Clinical biomarker tests that aid in making treatment decisions will play an important role in achieving personalized medicine for cancer patients . Definitive evaluation of the clinical utility of these biomarkers requires conducting large r and omized clinical trials ( RCTs ) . Efficient RCT design is therefore crucial for timely introduction of these medical advances into clinical practice , and a variety of design s have been proposed for this purpose . To guide design and interpretation of RCTs evaluating biomarkers , we present an in-depth comparison of advantages and disadvantages of the commonly used design s. Key aspects of the discussion include efficiency comparisons and special interim monitoring issues that arise because of the complexity of these RCTs . Important ongoing and completed trials are used as examples . We conclude that , in most setting s , r and omized biomarker-stratified design s ( ie , design s that use the biomarker to guide analysis but not treatment assignment ) should be used to obtain a rigorous assessment of biomarker clinical utility CONTEXT Combined treatment using radiation therapy ( RT ) and and rogen suppression therapy ( AST ) is used to treat men with clinical ly localized adenocarcinoma of the prostate , but outcome using this combined therapy compared with RT alone is not known . OBJECTIVE To determine the relative efficacy of RT plus AST vs RT alone among men with clinical ly localized prostate cancer . DESIGN , SETTING , AND PATIENTS Retrospective cohort study of 1586 men with prostate cancer who were treated between January 1989 and August 1999 using 3-dimensional conformal RT with ( n = 276 ) or without ( n = 1310 ) 6 months of AST . MAIN OUTCOME MEASURE Relative risk ( RR ) of prostate-specific antigen ( PSA ) failure ( defined according to the American Society for Therapeutic Radiology and Oncology consensus statement ) , by treatment and high- , intermediate- , or low-risk group based on serum PSA level , biopsy Gleason score , and 1992 American Joint Commission on Cancer clinical tumor category . RESULTS Estimates of 5-year PSA outcome after RT with or without AST were not statistically different among low-risk patients ( P = .09 ) , whereas intermediate- and high-risk patients treated with RT plus AST had significantly better outcomes than those treated with RT alone ( P<.001 and = .009 , respectively ) . The RR of PSA failure in low-risk patients treated with RT plus AST was 0.5 ( 95 % confidence interval [ CI ] , 0.3 - 1.1 ) compared with patients treated with RT alone . The RRs of PSA failure in intermediate-risk and high-risk patients treated with RT plus AST compared with RT alone were 0.2 ( 95 % CI , 0 . 1 - 0.3 ) and 0.4 ( 95 % CI , 0.2 - 0.8 ) , respectively . CONCLUSIONS Our data suggest a significant benefit in 5-year PSA outcomes for men with clinical ly localized prostate cancer in intermediate- and high-risk groups treated with RT plus AST vs those treated with RT alone . Results from prospect i ve r and omized trials currently under way are needed to vali date these findings . JAMA . 2000;284:1280 - Radical prostatectomy should ideally be curative for all patients with clinical ly localized prostate cancer ( PrCa ) , yet a sizeable proportion of them eventually relapse . We examined in this setting the feasibility of pre-operative risk stratification for early post-operative relapse using reverse transcriptase polymerase chain reaction ( RT-PCR ) for prostate-specific antigen ( PSA ) and prostate-specific membrane antigen ( PSMA ) transcripts in pre-operative bone marrow ( BM ) biopsies and peripheral blood ( PBL ) sample s. Nested RT-PCR for PSA and PSMA transcripts were performed in RNA from BM biopsies and PBL sample s prospect ively obtained from 111 men newly diagnosed , by trans-rectal ultrasound (TRUS)-guided biopsy , with clinical ly localized PrCa and scheduled to undergo radical prostatectomy , according to their respective doctors ' recommendation . Molecular analysis for each sample ( PBL or BM ) was considered positive only if both PSA and PSMA transcripts were detectable . Serial serum PSA level measurements served for biochemical follow-up and detection of biochemical failure ( PSA > 0.2 ng/ml ) . PBL and BM RT-PCR molecular staging delineated three groups of patients ( a ) PBL−BM− ( 72 patients , 65 % ) , ( b ) PBL+BM+ ( 29 patients , 26 % ) , and ( c ) PBL+BM− ( 10 patients , 9 % ) . These three groups corresponded to low , high , and intermediate risk for early post-prostatectomy recurrence ( median time to biochemical failure of > 38 , 8 , and > 28 months , respectively ) . Multivariate analysis confirmed that molecular staging status was independent predictor of disease-free survival , after adjusting for PSA levels and Gleason score . In clinical ly localized PrCa , combined PSA/PSMA RT-PCR in PBL and BM is an independent predictor of time to biochemical failure following radical prostatectomy PURPOSE We investigated whether serum markers of angiogenesis endothelin-1 ( ET-1 ) and tissue factor ( TF ) , and /or markers of vascular damage such as circulating endothelial cells ( CECs ) , or their relative changes during treatment , were prognostic for overall survival ( OS ) in castration resistant prostate cancer ( CRPC ) patients . Additionally , we combined these markers with circulating tumour cells ( CTCs ) to construct a predictive nomogram for treatment outcome . PATIENTS AND METHODS One hundred and sixty two CRPC patients treated with a docetaxel containing regimen had blood drawn before and at 2 - 5 weeks and 6 - 8 weeks after treatment start . Prospect ively determined CTC and CEC levels , and retrospectively measured serum concentrations of ET-1 ( pg/mL ) and TF ( pg/mL ) were evaluated to determine their prognostic value for OS . RESULTS Baseline CEC , TF and ET-1 were not prognostic for OS . A > or = 3.8-fold increase in CEC 2 - 5 weeks after treatment initiation was associated with decreased OS ( median 10.9 versus 16.8 months ; P=0.015 ) , as was any decrease in TF levels compared to baseline levels ( median 11.9 versus 21.5 months ; P=0.0005 ) . As previously published , baseline and CTC counts > or = 5 at 2 - 5 weeks were also predictive of decreased OS . Combining CTC with changes in TF and CEC 2 - 5 weeks after treatment initiation yielded four groups differing in OS ( median OS 24.2 versus 16.0 versus 11.4 versus 6.1 months ; P<0.0001 ) . CONCLUSION CEC , CTC and TF levels alone and combined can predict early on OS in CRPC patients treated with docetaxel-based therapy . A prospect i ve study to confirm the use of these markers for patient management is needed PURPOSE Time to progression ( TTP ) , overall survival , and quality of life ( QL ) were compared in patients with hormone-resistant prostate cancer ( HRPC ) treated with prednisone ( 5 mg orally , four times a day ) or flutamide ( 250 mg orally , three times a day ) . PATIENTS AND METHODS Symptomatic patients were r and omized to receive either prednisone ( 101 patients ) or flutamide ( 100 patients ) . Subjective response was assessed based on performance status , the use of analgesics , and the need to apply alternative palliative treatment . Prostate-specific antigen (PSA)-based biochemical response ( > or= 50 % reduction of baseline PSA ) was recorded . At baseline and at 6-week intervals during follow-up , patients completed the European Organization for Research and Treatment of Cancer Quality of Life Question naire C-30 . RESULTS There was no difference between the groups in median TTP ( prednisone , 3.4 months ; flutamide , 2.3 months ) or overall survival ( prednisone , 10.6 months ; flutamide , 11.2 months ) . In the prednisone group , 56 % of the patients experienced a subjective response , compared with 45 % in the flutamide group ( P : = .18 ) . The median response duration was 4.8 months for prednisone and 4.2 months for flutamide . A biochemical response was observed in 21 % and 23 % of the prednisone and flutamide groups , respectively . Gastrointestinal toxicity was the reason for trial discontinuation in seven patients receiving flutamide and two patients receiving prednisone . The QL assessment parameters favored the use of prednisone with statistically significant differences in pain , fatigue , role functioning , appetite loss , gastrointestinal distress , and overall QL . CONCLUSION In symptomatic HRPC , treatment with prednisone or flutamide leads to similar rates of TTP and overall survival and no difference in subjective or biochemical response . The QL results favor the use of low-cost prednisone in patients with HRPC PURPOSE It has been postulated that castration-resistant prostate cancer ( CRPC ) commonly remains hormone dependent . Abiraterone acetate is a potent , selective , and orally available inhibitor of CYP17 , the key enzyme in and rogen and estrogen bio synthesis . PATIENTS AND METHODS This was a phase I/II study of abiraterone acetate in castrate , chemotherapy-naive CRPC patients ( n = 54 ) with phase II expansion at 1,000 mg ( n = 42 ) using a two-stage design to reject the null hypothesis if more than seven patients had a prostate-specific antigen ( PSA ) decline of > or = 50 % ( null hypothesis = 0.1 ; alternative hypothesis = 0.3 ; alpha = .05 ; beta = .14 ) . Computed tomography scans every 12 weeks and circulating tumor cell ( CTC ) enumeration were performed . Prospect i ve reversal of resistance at progression by adding dexamethasone 0.5 mg/d to suppress adrenocorticotropic hormone and upstream steroids was pursued . RESULTS A decline in PSA of > or = 50 % was observed in 28 ( 67 % ) of 42 phase II patients , and declines of > or = 90 % were observed in eight ( 19 % ) of 42 patients . Independent radiologic evaluation reported partial responses ( Response Evaluation Criteria in Solid Tumors ) in nine ( 37.5 % ) of 24 phase II patients with measurable disease . Decreases in CTC counts were also documented . The median time to PSA progression ( TTPP ) on abiraterone acetate alone for all phase II patients was 225 days ( 95 % CI , 162 to 287 days ) . Exploratory analyses were performed on all 54 phase I/II patients ; the addition of dexamethasone at disease progression reversed resistance in 33 % of patients regardless of prior treatment with dexamethasone , and pretreatment serum and rogen and estradiol levels were associated with a probability of > or = 50 % PSA decline and TTPP on abiraterone acetate and dexamethasone . CONCLUSION CYP17 blockade by abiraterone acetate results in declines in PSA and CTC counts and radiologic responses , confirming that CRPC commonly remains hormone driven BACKGROUND The identification of surrogate endpoints that can replace true outcome endpoints is crucial to the rapid evaluation of new cancer drugs . Retrospective analyses of phase II and III trials in metastatic and rogen-independent prostate cancer have shown associations between declines in serum prostate-specific antigen ( PSA ) levels and survival . We evaluated PSA changes as potential surrogate markers for survival by using data from a clinical trial . METHODS Men with and rogen-independent prostate cancer were r and omly assigned to either docetaxel/estramustine ( D/E ) or mitoxantrone/prednisone ( M/P ) treatment on Southwest Oncology Group Protocol 99 - 16 . Of 674 eligible patients , 551 had a baseline PSA measurement and at least one PSA measurement during the first 3 months on protocol . PSA level declines of 5%-90 % and PSA velocity at 1 , 2 , and 3 months were tested for surrogacy by using three statistical criteria : Prentice 's criteria , the proportion of treatment effect explained , and the proportion of variation explained . All statistical tests were two-sided . RESULTS Three-month PSA level declines of 20%-40 % , a 2-month PSA decline of 30 % , and PSA velocity at 2 and 3 months met all three surrogacy criteria . For example , a 3-month PSA decline of at least 30 % was associated with a more than 50 % decrease in the risk of death compared with the lack of such a decline ( hazard ratio [ HR ] = 0.43 , 95 % confidence interval [ CI ] = 0.34 to 0.55 ; P < .001 ) , and the increased risk of death for men treated with M/P compared with D/E ( HR = 1.24 , 95 % CI = 1.02 to 1.51 ; P = .032 ) lost statistical significance after adjustment for this surrogate , whereas the decrease in risk of death associated with a 3-month 30 % PSA decline remained statistically significant after adjustment for treatment . PSA level declines of 50 % , commonly reported in clinical trials , did not meet the criteria for surrogacy . CONCLUSIONS Several PSA measures satisfied the surrogacy criteria for survival in a retrospective analysis of data from SWOG 99 - 16 . However , these measures await prospect i ve validation in future clinical trials of chemotherapy in men with and rogen-independent prostate cancer BACKGROUND The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer . We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92 - 02 r and omized trial . METHODS Patients ( n = 1554 r and omly assigned and 1521 evaluable for this analysis ) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent and rogen deprivation therapy with external beam radiation therapy and then r and omly assigned to no additional therapy ( control arm ) or 24 additional months of and rogen deprivation therapy ( experimental arm ) . Data from l and mark analyses at 3 and 5 years for general clinical treatment failure ( defined as documented local disease progression , regional or distant metastasis , initiation of and rogen deprivation therapy , or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy ) and /or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice 's four criteria . All statistical tests were two-sided . RESULTS At 3 years , 1364 patients were alive and contributed data for analysis . Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice 's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years . At 5 years , 1178 patients were alive and contributed data for analysis . Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years ( P = .08 ) , both endpoints were consistent with Prentice 's remaining criteria . CONCLUSIONS Distant metastasis and general clinical treatment failure at 3 years may be c and i date surrogate endpoints for prostate cancer-specific survival at 10 years . These endpoints , however , must be vali date d in other data sets PURPOSE Suramin is a novel agent that has demonstrated preliminary evidence of antitumor activity in hormone-refractory prostate cancer ( HRPC ) . A prospect i ve r and omized clinical trial was design ed to evaluate pain and opioid analgesic intake as surrogates for antitumor response in HRPC patients with significant , opioid analgesic-dependent pain . PATIENTS AND METHODS A double-blind , placebo-controlled trial r and omized patients to receive a 78-day , outpatient regimen of either suramin plus hydrocortisone ( HC , 40 mg/d ) or placebo plus HC . Treatment assignment was unblinded when either disease progression or dose-limiting toxicity occurred ; placebo patients were allowed to cross-over to open-label suramin plus HC . In addition to pain and opioid analgesic intake , prostate-specific antigen ( PSA ) response , time to disease progression , quality of life , performance status , and survival were compared . RESULTS Overall mean reductions in combined pain and opioid analgesic intake were greater for suramin plus HC ( rank sum P = .0001 ) . Pain response was achieved in a higher proportion of patients receiving suramin than placebo ( 43 % v 28 % ; P = .001 ) , and duration of response was longer for suramin responders ( median , 240 v 69 days ; P = .0027 ) . Time to disease progression was longer ( relative risk = 1.5 ; 95 % confidence interval , 1.2 to 1.9 ) and the proportion of patients with a greater than 50 % decline in PSA was higher ( 33 % v 16 % ; P = .01 ) in patients who received suramin . Neither quality of life nor performance status was decreased by suramin treatment , and overall survival was similar . Most adverse events were of mild or moderate intensity and were easily managed medically . CONCLUSION Outpatient treatment with suramin plus HC is well tolerated and provides moderate palliative benefit and delay in disease progression for patients with symptomatic HRPC |
11,354 | 27,707,980 | Persistent RV dysfunction , impaired functional status , diminished exercise capacity , and reduced QoL are common in PE survivors . | Long-term right ventricular ( RV ) function , functional capacity , exercise capacity , and quality of life following pulmonary embolism ( PE ) , and the impact of thrombolysis , are unclear . | BACKGROUND Acute pulmonary embolism ( PE ) can worsen quality of life due to persistent dyspnea or exercise intolerance . OBJECTIVE Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE . METHODS Normotensive patients with PE and right ventricular ( RV ) strain ( by echocardiography or biomarkers ) were enrolled from eight hospitals . All patients received low-molecular-weight heparin followed by r and om assignment to either a single weight-based bolus of tenecteplase or placebo , administered in a double-blinded fashion . The primary composite outcome included : ( i ) death , circulatory shock , intubation or major bleeding within 5 days or ( ii ) recurrent PE , poor functional capacity ( RV dysfunction with either dyspnea at rest or exercise intolerance ) or an SF36 ( ® ) Physical Component Summary ( PCS ) score < 30 at 90-day follow-up . RESULTS Eighty-three patients were r and omized ; 40 to tenecteplase and 43 to placebo . The trial was terminated prematurely . Within 5 days , adverse outcomes occurred in three placebo-treated patients ( death in one and intubation in two ) and one tenecteplase-treated patient ( fatal intracranial hemorrhage ) . At 90 days , adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus , 16 ( 37 % ) placebo-treated and six ( 15 % ) tenecteplase-treated patients had at least one adverse outcome ( exact two-sided P = 0.017 ) . CONCLUSIONS Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome BACKGROUND The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial . METHODS In a r and omized , double-blind trial , we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism . Eligible patients had right ventricular dysfunction on echocardiography or computed tomography , as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation ( or collapse ) within 7 days after r and omization . The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after r and omization . RESULTS Of 1006 patients who underwent r and omization , 1005 were included in the intention-to-treat analysis . Death or hemodynamic decompensation occurred in 13 of 506 patients ( 2.6 % ) in the tenecteplase group as compared with 28 of 499 ( 5.6 % ) in the placebo group ( odds ratio , 0.44 ; 95 % confidence interval , 0.23 to 0.87 ; P=0.02 ) . Between r and omization and day 7 , a total of 6 patients ( 1.2 % ) in the tenecteplase group and 9 ( 1.8 % ) in the placebo group died ( P=0.42 ) . Extracranial bleeding occurred in 32 patients ( 6.3 % ) in the tenecteplase group and 6 patients ( 1.2 % ) in the placebo group ( P<0.001 ) . Stroke occurred in 12 patients ( 2.4 % ) in the tenecteplase group and was hemorrhagic in 10 patients ; 1 patient ( 0.2 % ) in the placebo group had a stroke , which was hemorrhagic ( P=0.003 ) . By day 30 , a total of 12 patients ( 2.4 % ) in the tenecteplase group and 16 patients ( 3.2 % ) in the placebo group had died ( P=0.42 ) . CONCLUSIONS In patients with intermediate-risk pulmonary embolism , fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke . ( Funded by the Programme Hospitalier de Recherche Clinique in France and others ; PEITHO EudraCT number , 2006 - 005328 - 18 ; Clinical Trials.gov number , NCT00639743 . ) BACKGROUND Elevated blood concentrations of troponin proteins or brain natriuretic peptide ( BNP ) worsen the prognosis of patients with pulmonary embolism ( PE ) . Novel biomarkers that reflect mechanisms of right ventricle ( RV ) damage from PE may provide additional prognostic value . We compare the prognostic use of BNP , troponin I , D-dimer , monocyte chemoattractant protein-1 , matrix metalloproteinase , myeloperoxidase , C-reactive protein , and caspase 3 as biomarkers of RV damage and adverse outcomes in submassive PE . METHODS This article used a prospect i ve cohort study of normotensive ( systolic blood pressure always > 100 mm Hg ) patients with computed tomographic angiography-diagnosed PE . All patients underwent echocardiography and phlebotomy at diagnosis , and survivors had another echocardiography 6 months later . We tested each biomarker for prognostic significance , requiring a lower limit 95 % CI > 0.50 for the area under the receiver operating characteristic curve ( AUROC ) with a reference st and ard positive of RV hypokinesis on either echocardiogram . Biomarkers with prognostic significance were dichotomized at the concentration that yielded highest likelihood ratio positive and mortality rates compared ( Fisher exact test ) . RESULTS We enrolled 152 patients with complete data . Thirty-seven ( 24 % , 95 % CI 18%-32 % ) had RV hypokinesis . Only BNP and troponin had significant AUROC values as follows : 0.71 ( 95 % CI 0.60 - 0.81 ) and 0.71 ( 95 % CI 0.62 - 0.82 ) , respectively . Overall mortality was 13/153 ( 8.5 % ) ; mortality rate for BNP > 100 versus < or = 100 pg/mL was 23 % versus 3 % ( P = .003 ) , respectively . Mortality rate for troponin I > 0.1 versus < or = 0.1 ng/mL was 13 % versus 6 % ( P = .205 ) , respectively . CONCLUSIONS Of 8 mechanistically plausible biomarkers , only BNP and troponin I had significant prognostic use with BNP having an advantage for predicting mortality BACKGROUND The Pulmonary Embolism Quality of Life question naire ( PEmb-QoL ) is a 40-item question naire to measure health-related quality of life in patients with pulmonary embolism . It covers six 6 dimensions : frequency of complaints , limitations in activities of daily living , work-related problems , social limitations , intensity of complaints , and emotional complaints . Originally developed in Dutch and English , we prospect ively vali date d a German version of the PEmb-QoL. METHODS A forward-backward translation of the English version of the PEmb-QoL into German was performed . German-speaking consecutive adult patients aged ≥18 years with an acute , objective ly confirmed pulmonary embolism discharged from a Swiss university hospital ( 01/2011 - 06/2013 ) were recruited telephonically . Established psychometric tests and criteria were used to evaluate the acceptability , reliability , and validity of the German PEmb-QoL question naire . To assess the underlying dimensions , an exploratory factor analysis was performed . RESULTS Overall , 102 patients were enrolled in the study . The German version of the PEmb-QoL showed a good internal consistency ( Cronbach 's alpha ranging from 0.72 to 0.96 ) , item-total ( 0.53 - 0.95 ) and inter-item correlations ( > 0.4 ) , and test-retest reliability ( intra-class correlation coefficients 0.59 - 0.89 ) for the dimension scores . A moderate correlation of the PEmb-QoL with SF-36 dimension and summary scores ( 0.21 - 0.83 ) indicated convergent validity , while low correlations of PEmb-QoL dimensions with clinical characteristics ( -0.16 - 0.37 ) supported discriminant validity . The exploratory factor analysis suggested four underlying dimensions : limitations in daily activities , symptoms , work-related problems , and emotional complaints . CONCLUSION The German version of the PEmb-QoL question naire is a valid and reliable disease-specific measure for quality of life in patients with pulmonary embolism Over the ensuing seven months she had three more clinical relapses , each accompanied by reappearance in the stools of either the organism or its cytotoxin , or both . Each improvement after vancomycin ( eight to 14-daycourses ) was accompanied by disappearance of the organism . At one point she was given cholestyramine , but she was unable to tolerate it . Her illness was punctuated by malnutrition and episodes of heart failure . She was given no other antibiotics . After the sixth relapse maintenance treatment with oral vancomycin 125 mg eight-hourly was begun . With this regimen diarrhoea was controlled and stools over the next 10 weeks remained negative for C difficile and its cytotoxin . There was no adverse reaction to vancomycin throughout The role of low-dose thrombolysis in the reduction of pulmonary artery pressure in moderate pulmonary embolism ( PE ) has not been investigated . Because the lungs are very sensitive to thrombolysis , we postulated that effective and safe thrombolysis might be achieved by a lower dose of tissue plasminogen activator . The purpose of the present study was to evaluate the role of this " safe dose " thrombolysis in the reduction of pulmonary artery pressure in moderate PE . During a 22-month period , 121 patients with moderate PE were r and omized to receive a " safe dose " of tissue plasminogen activator plus anticoagulation ( thrombolysis group [ TG ] , n = 61 patients ) or anticoagulation alone ( control group [ CG ] , n = 60 ) . The primary end points consisted of pulmonary hypertension and the composite end point of pulmonary hypertension and recurrent PE at 28 months . Pulmonary hypertension and the composite end point developed in 9 of 58 patients ( 16 % ) in the TG and 32 of 56 patients ( 57 % ) in the CG ( p < 0.001 ) and 9 of 58 patients ( 16 % ) in the TG and 35 of 56 patients ( 63 % ) in the CG ( p < 0.001 ) , respectively . The secondary end points were total mortality , the duration of hospital stay , bleeding at the index hospitalization , recurrent PE , and the combination of mortality and recurrent PE . The duration of hospitalization was 2.2 ± 0.5 days in the TG and 4.9 ± 0.8 days in the CG ( p < 0.001 ) . The combination of death plus recurrent PE was 1 ( 1.6 % ) in TG and 6 ( 10 % ) in the CG ( p = 0.0489 ) . No bleeding occurred in any group , and despite a positive trend in favor of a " safe dose " thrombolysis , no significant difference was noted in the rate of individual outcomes of death and recurrent PE when assessed independently . In conclusion , the results from the present prospect i ve r and omized trial suggests that " safe dose " thrombolysis is safe and effective in the treatment of moderate PE , with a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months Background The PEmb-QoL is a vali date d 40-item question naire to quantify health-related quality of life in patients having experienced pulmonary embolism ( PE ) . It covers six health dimensions : frequency of complaints , activities of daily living limitations , work-related problems , social limitations , intensity of complaints , and emotional complaints . Originally developed in Dutch and English , we sought to prospect ively vali date the psychometric properties of a French version of the PEmb-QoL. Methods We performed a forward and backward translation of the English version of the PEmb-QoL into French . French-speaking consecutive adult patients with an acute , objective ly confirmed PE admitted to the emergency department of a Swiss university hospital between 08/2009 and 09/2011 were recruited telephonically . We used st and ard psychometric tests and criteria to evaluate the acceptability , reliability , and validity of the French version of the PEmb-QoL. We also performed an exploratory factor analysis . Results Overall , 102 patients were enrolled in the study . The French version of the PEmb-QoL showed good reliability ( internal consistency , item – total and inter-item correlations ) , reproducibility ( test-retest reliability ) , and validity ( convergent , discriminant ) in French-speaking patients with PE . The exploratory factor analysis suggested three underlying dimensions : limitations in daily activity ( items 4b-m , 5a-d ) , symptoms ( items 1a-h and 7 ) , and emotional complaints ( items 9a-f and j ) . Conclusion We successfully vali date d the French version of the PEmb-QoL question naire in patients with PE . Our results show that the PEmb-QoL is a valuable tool for assessing health-related quality of life after PE in French-speaking patients AIMS We hypothesized that first-time submassive pulmonary embolism ( PE ) can cause persistent , significant cardiopulmonary problems , including right ventricular damage and worsened quality of life in patients with no prior cardiopulmonary disease . METHODS AND RESULTS We prospect ively enrolled 205 patients without end-stage comorbidity diagnosed with submassive PE ( systolic blood pressure always > 100 mmHg ) . Using explicit criteria , we identified a subgroup of 127 ' previously healthy ' patients who were free of cardiopulmonary disease or other disabling process . All patients had transthoracic echocardiography ( echo ) at the time of diagnosis . Six months later , survivors returned for repeat echo , 6 min walk distance ( 6MWD ) , and a quality -of-life survey . We defined a significant cardiopulmonary problem as either : ( i ) abnormal RV on echo ( RV dilation or RV hypokinesis ) ; or ( ii ) NYHA score > II or a 6MWD < 330 m at 6 months . Of 127 study patients , five had inadequate echos , nine were lost to follow-up , and four died , leaving 109 with complete data . Of 109 patients , 45 ( 41 % ) had cardiopulmonary problems 6 months after PE : 18 of 109 ( 17 % ) had only an abnormal RV , 18 of 109 ( 17 % ) had only functional limitation , and nine of 109 ( 8 % ) had both . Twenty-two patients ( 20 % ) indicated at least one index of poor quality -of-life : health status worse , not currently shopping , or perceived need for oxygen at home . Patients with cardiopulmonary problems demonstrated a significant decrease in SaO(2)% after 6MWD ( 97 + /- 1.3 pre-6MWD vs. 96 + /- 1.8 % post-6MWD , P = 0.004 by paired t-test ) . CONCLUSION Six months after first-time PE , 41 % of previously healthy patients had either an abnormal RV on echo , an NYHA score > II or a 6MWD < 330 m. Treatment studies of PE should include these persistent cardiopulmonary problems as study endpoints BACKGROUND Chronic thromboembolic pulmonary hypertension ( CTPH ) is associated with considerable morbidity and mortality . Its incidence after pulmonary embolism and associated risk factors are not well documented . METHODS We conducted a prospect i ve , long-term , follow-up study to assess the incidence of symptomatic CTPH in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism . Patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography and , if supportive findings were present , ventilation-perfusion lung scanning and pulmonary angiography . CTPH was considered to be present if systolic and mean pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg , respectively ; pulmonary-capillary wedge pressure was normal ; and there was angiographic evidence of disease . RESULTS The cumulative incidence of symptomatic CTPH was 1.0 percent ( 95 percent confidence interval , 0.0 to 2.4 ) at six months , 3.1 percent ( 95 percent confidence interval , 0.7 to 5.5 ) at one year , and 3.8 percent ( 95 percent confidence interval , 1.1 to 6.5 ) at two years . No cases occurred after two years among the patients with more than two years of follow-up data . The following increased the risk of CTPH : a previous pulmonary embolism ( odds ratio , 19.0 ) , younger age ( odds ratio , 1.79 per decade ) , a larger perfusion defect ( odds ratio , 2.22 per decile decrement in perfusion ) , and idiopathic pulmonary embolism at presentation ( odds ratio , 5.70 ) . CONCLUSIONS CTPH is a relatively common , serious complication of pulmonary embolism . Diagnostic and therapeutic strategies for the early identification and prevention of CTPH are needed Background Pulmonary embolism ( PE ) is a severe condition with nonspecific symptoms . Diagnosis relies on medical imaging but follow-up is currently based on clinical symptoms and general risk factors . The duration of anticoagulant treatment after an acute episode of PE is still subject to debate and the best method of identifying the risk of recurrence in individual patients is undefined . Tomographic lung scintigraphy [ ventilation/perfusion single photon emission computed tomography ( V/P SPECT ) ] has improved the diagnostic accuracy with regard to PE but has not been evaluated for PE follow-up . Aim The aim of this prospect i ve study was to quantitatively follow the natural history of treated PE using V/P SPECT , which could prove helpful in defining an anticoagulant treatment regime for individual patients . Methods Of 83 consecutive patients with clinical ly suspected PE examined with V/P SPECT , 23 patients with confirmed PE were followed by serial V/P SPECT examinations over a 6-month period . All patients were also followed clinical ly . Results The mean relative decrease in PE extent compared with the time of diagnosis was 54±26 % at 2 weeks , 79±30 % at 3 months , and 82±30 % at 6 months . Significant resolution of mismatched perfusion defects occurred between V/P SPECT controls within the first 3 months of anticoagulation ( P<0.001 ) but not thereafter . V/P SPECT identified four patients with chronic PE , even though all patients were free from symptoms at 3-month follow-up . Conclusion Follow-up of PE with V/P SPECT is feasible to evaluate treatment effectiveness in individual patients and to identify patients that develop chronic PE . This study also confirms that resolution of perfusion defects after PE occurs within the first 3 months of treatment . It is therefore recommended that V/P SPECT follow-up should be considered at 3 months after diagnosis RATIONALE Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension ( PAH ) , the minimal important difference ( MID ) of the 6-minute walk test ( 6MWT ) has not been well defined for this population of patients . OBJECTIVES To estimate the MID in the 6MWT in patients with PAH . METHODS Study subjects from the clinical trial of tadalafil in PAH , a 16-week , parallel-group , r and omized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist , were eligible . 6MWT was performed using a st and ardized protocol . Distributional and anchor-based methods were used to estimate the MID ; the latter method used the Physical Component Summary Score ( PCS ) of the Medical Outcomes Study 36-item short form ( SF-36 ) . MEASUREMENTS AND MAIN RESULTS Four hundred five subjects were analyzed . Domains of the SF-36 were weakly to modestly associated with 6MWT . Change in the PCS of the SF-36 was most strongly associated with change in 6MWT ( r = 0.40 , P < 0.001 ) and thus was selected as the anchor for subsequent anchor-based analyses . Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m , whereas anchor-based analyses yielded an estimate of 38.6 m. CONCLUSIONS Using both distributional and anchor-based methods , the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implication s for ( 1 ) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy , and ( 2 ) sample size calculations for future study design BACKGROUND The main objectives of this study were to determine the incidence of echocardiography-detected right ventricle dysfunction ( RVD ) or pulmonary hypertension ( PHT ) and its correlation with computed tomography pulmonary angiography ( CTPA ) in hemodynamically stable patients with pulmonary embolism ( PE ) , both at diagnosis and after 6 months follow-up . METHODS Prospect i ve , descriptive , single-center follow-up study . STUDY POPULATION 103 consecutive patients , with a life expectancy of > 6 months , presenting with PE and a systolic blood pressure > or = 90mmHg . Echocardiography and CTPA were performed at diagnosis and after 6 months . RESULTS At diagnosis , RVD and isolated PHT were found in 24.5 % and 19.6 % of patients , respectively . CTPA and echocardiography correlated significantly at diagnosis . However , CTPA could not predict accurately RVD or PHT . Persistence of RVD and isolated PHT was observed in 7.9 % and 11.8 % of cases , respectively , 6 months later . Intraluminal filling defects disappeared in 79 % . No new filling defects were seen in any patient . Excluding cases with comorbidities that might account for PHT , CTPA was normal at the 6th month in 23.1 % of patients with and in 87.8 % of cases without persistent RVD or PHT , respectively ( p<0.0001 ) . CONCLUSIONS RVD or PHT are a frequent finding at diagnosis in patients with hemodynamically stable pulmonary embolism and they persist at 6 months in a significant proportion of cases . We have observed a relationship between the persistence of residual vascular obstruction in CTPA and RVD or PHT 6 months after PE Background and hypothesis : Hemodynamic and functional consequences of acute pulmonary embolism ( APE ) are believed to be reversible with antithrombotic treatment . To verify this hypothesis , we reassessed our patients at least 1 year after an episode of APE BACKGROUND Little is known about residual abnormalities after pulmonary embolism ( PE ) . OBJECTIVES To assess risk factors and the clinical significance of perfusion defects in patients with PE . PATIENTS / METHODS Consecutive patients receiving at least 3 months of anticoagulant for an acute PE were included in a prospect i ve cohort study . Ventilation/perfusion lung scan , echocardiography , 6-min walk test , thrombophilia and hemostatic variables were performed 6 - 12 months after PE . Perfusion defect was defined as a perfusion defect in at least two segments . RESULTS Seventy-three out of 254 patients ( 29 % ) had perfusion defects during follow-up ( median 12 months ) and were more likely to have dyspnea , had a higher systolic pulmonary arterial pressure [ 39 mmHg ( SD ) ( 12 ) vs. 31 mmHg ( 8) ; P < 0.001 ] and walked a shorter distance during the 6-min walk test [ 374 m ( 122 ) vs. 427 m ( 99 ) ; P = 0.004 ] . Age [ odds ratio ( OR ) 1.35 ; 95 % confidence interval ( CI ) , 1.11 - 1.63 ] , the time interval between symptom onset and diagnosis ( OR , 1.17 ; 95 % CI , 1.04 - 1.31 ) , pulmonary vascular obstruction at the onset of PE ( OR , 1.34 ; 95 % CI , 1.16 - 1.55 ) and previous venous thromboembolism ( OR 2.06 ; 95 % CI , 1.03 - 4.11 ) were independent predictors of perfusion defect after treatment of acute PE . Total tissue factor pathway inhibitor concentration was associated with perfusion defects . CONCLUSIONS Perfusion defects are associated with an increase in pulmonary artery pressure ( PAP ) and functional limitation . Age , longer times between symptom onset and diagnosis , initial pulmonary vascular obstruction and previous venous thromboembolism were associated with perfusion defects STUDY OBJECTIVE To assess the incidence of chronic thromboembolic pulmonary hypertension ( CTPH ) after the first episode of objective ly confirmed pulmonary embolism ( PE ) . DESIGN Prospect i ve cohort study in 12 Italian medical centers . PATIENTS Consecutive patients treated with oral anticoagulants for the first episode of PE , either idiopathic or associated with temporary risk factors , were followed up for at least 3 years . Patients were excluded from the study if they had a known persistent risk factor for venous thromboembolism ( VTE ) . INTERVENTIONS At the follow-up visits , patients were evaluated for persistent dyspnea , either at rest or on exertion . All patients who were referred with dyspnea were assessed by transthoracic echocardiography , with evaluation of the systolic and mean pulmonary artery pressures . Patients with evidence of pulmonary hypertension on echocardiography underwent perfusion lung scans and pulmonary angiography to confirm the diagnosis of CTPH . RESULTS Overall , 259 patients were included in the study . PE was idiopathic in 135 patients , while it was associated with at least a temporary risk factor for VTE in 124 patients . After an average follow-up period of 46 months , 37 patients were found to have persistent dyspnea that was unexplained in 5 patients . Among these patients , a diagnosis of CTPH was confirmed in two patients with idiopathic PE ( 0.8 % of the overall study population [ 95 % confidence interval ( CI ) , 0.0 to 1.9 ] ; 1.5 % of patients with idiopathic PE [ 95 % CI , 0.0 to 3.6 ] ) . The diagnosis was made 14 and 22 months , respectively , after the acute PE . CONCLUSIONS The incidence of CTPH observed in this study was about 1 % . CTPH was observed in two patients with idiopathic PE A total of 23 of the 40 patients who had angiographically proven pulmonary embolism and who had initially been r and omized to an IV infusion of heparin ( n = 11 ) or a thrombolytic agent ( urokinase or streptokinase , n = 12 ) were restudied after a mean follow-up of 7.4 years to measure the right-sided pressures and to evaluate their response to exercise during supine bicycle ergometry . Results showed that , at rest , the pulmonary artery ( PA ) mean pressure and the pulmonary vascular resistance ( PVR ) were significantly higher in the heparin group compared with the thrombolytic group ( 22 vs. 17 mmHg , p < 0.05 , and 351 vs. 171 dynes s- 1 cm- 5 , p < 0.02 , respectively ) . During exercise both parameters rose to a significantly higher level in the heparin group ( from rest to exercise , PA : 22 - 32 mmHg , p < 0.01 ; PVR : 351 - 437 dynes s- 1 cm- 5 , p < 0.01 , respectively ) , but not in the thrombolytic group ( rest to exercise , PA : 17 - 19 mmHg , p = NS ; PVR : 171 - 179 dynes s- 1 cm- 5 , p = NS ) . It is concluded that thrombolytic therapy preserves the normal hemodynamic response to exercise in the long term and may prevent recurrences of venous thromboembolism and the development of pulmonary hypertension BACKGROUND The functional capacity of long-term survivors of submassive pulmonary embolism ( PE ) is unreported . A six-minute walk distance ( 6MWD ) < 350 m and reduced heart rate recovery ( HRR ) indicate adverse prognosis in various chronic diseases . METHODS Long-term survivors of acute PE ( January 2000-June 2005 ) were invited to undergo prospect ively planned six-minute walk test ( 6MWT ) , transthoracic echocardiogram ( TTE ) , clinical and biochemical evaluation with cardiac biomarkers . HRR was calculated as the difference between heart rate at 6-min during and at 1-min post 6MWT . RESULTS 120 patients ( 52 males ; mean age [ ±st and ard deviation ] - 65 ± 14 years ) were identified 7.7 ± 1.4 years after PE . 6MWD was significantly lower than that predicted after adjustment for age , sex , and height ( 448 ± 114 m vs 475 ± 89 m , p = 0.005 ) , and 16 % ( 17/104 ) had 6MWD < 350 m. Among patients with no baseline comorbidities at follow-up ( Charlson comorbidity index = 0 ) , 8 % ( 4/52 ) had 6MWD < 350 m. Resting TTE identified 29 % of patients had raised right ventricular ( RV ) pulmonary pressure ( pulmonary arterial systolic pressure [ PASP ] > 36 mmHg ) and 13 % had impaired RV function . Patients with 6MWD < 85 % predicted had significantly greater impairment of RV longitudinal function ( p < 0.001 ) , higher PASP ( p < 0.001 ) and pulmonary vascular resistance ( p < 0.001 ) , elevated NT-proBNP ( p = 0.03 ) and high-sensitivity troponin-T ( HsTropT , p = 0.03 ) , but similar left ventricular systolic and diastolic function , to those with normal 6MWT . CONCLUSIONS Apparently well , long-term survivors of PE demonstrate impaired exercise capacity , heart rate recovery , mild pulmonary hypertension , raised PVR and right ventricular dysfunction associated with elevated NT-proBNP and Introduction : The aim of this study was to assess the effect of thrombolysis versus heparin treatment on echocardiographic parameters and clinical outcome , during hospitalization and within the first 180 days after admission , in patients with first episode of submassive pulmonary embolism ( SPE ) and right ventricle dysfunction ( RVD ) . Methods : Consecutive patients ( age , 18–75 years ) with a first episode of SPE , symptoms onset since no more than 6 hours , normal blood pressure ( > 100 mm Hg ) , echocardiographic evidence of RVD and positive lung spiral computed tomography were double-blind r and omized : 1 group received 100 mg of alteplase ( 10-mg bolus , followed by a 90-mg intravenous infusion over a period of 2 hours ) , while the other group received matching placebo . In addition to alteplase or placebo , both groups received an unfractionated heparin treatment . Echocardiogram was performed at admission , at 24 , 48 and 72 hours , at discharge and at 3 and at 6 months after r and omization . Results : Seventy-two patients were included into the study ; 37 were assigned to thrombolysis and 35 to placebo . Both groups were well matched with regard to features and clinical presentation . Thrombolysis group showed a significant early improvement of RV function compared with heparin group , and this improvement was observed also during the follow-up ( 180 days ) . The same group also showed significant reduction in clinical events during the hospitalization and follow-up . Conclusions : Our data suggest that , in hemodynamically stable patients with SPE , thrombolysis shows an earliest reduction of RVD and a more favorable trend in clinical outcome , so , it could merit consideration in SPE Background — In patients with acute pulmonary embolism , systemic thrombolysis improves right ventricular ( RV ) dilatation , is associated with major bleeding , and is withheld in many patients at risk . This multicenter r and omized , controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis ( USAT ) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients . Methods and Results — Fifty-nine patients ( 63±14 years ) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension ( RV/LV ) ratio ≥1.0 were r and omized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours ( n=30 ; USAT group ) or unfractionated heparin alone ( n=29 ; heparin group ) . Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours . Safety outcomes included death , major and minor bleeding , and recurrent venous thromboembolism at 90 days . In the USAT group , the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours ( P<0.001 ) ; in the heparin group , mean RV/LV ratios were 1.20±0.14 and 1.17±0.20 , respectively ( P=0.31 ) . The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 ( P<0.001 ) , respectively . At 90 days , there was 1 death ( in the heparin group ) , no major bleeding , 4 minor bleeding episodes ( 3 in the USAT group and 1 in the heparin group ; P=0.61 ) , and no recurrent venous thromboembolism . Conclusions — In patients with pulmonary embolism at intermediate risk , a st and ardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours , without an increase in bleeding complications . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01166997 |
11,355 | 25,316,645 | RESULTS There were evidence s that rhGH in burned pediatric patients can reduce exogenous albumin requirement , with a improvement in Lean Body Mass , and accelerate site-donor wound healing , with no effects on mortality .
Possibly can reduce the length of hospital stay .
Hyperglycemia was the most frequently reported adverse event .
This review suggests that the early application of rhGH to st and ard treatment in pediatric severe burned patients has the potential to improve some aspects from outcome . | BACKGROUND AND OBJECTIVES To assess the use of recombinant human growth hormone ( rhGH ) in pediatric patients with hypercatabolic state in the pediatric intensive care unit . | Objectives : Dopamine , a natural catecholamine with hypophysiotropic properties , is used as a first choice drug for inotropic and vasoactive support in pediatric intensive care . In infants and children , the pituitary gl and plays a crucial role as a regulator of growth , metabolism , maturation and , possibly , immune function . We evaluated the effect of dopamine infusion ( 5 & mgr;g/kg/min iv ) on the dynamics of prolactin , growth hormone , and thyrotropin secretion and on the thyroid axis in critically ill infants and children . Design : Prospect i ve , r and omized , controlled , open‐labeled , clinical study . Setting : Intensive care unit of a university hospital over a 9‐month period . Patients and Methods : The study population consisted of infants and children recovering from cardiovascular surgery . The group was stratified into two age groups ( infants aged 12 to 90 days [ n = 18 ] and children aged 0.3 to 6.7 yrs [ n = 15 ] ) and was studied dynamically ( blood sampling every 20 mins for 3 hrs ) on two consecutive days , after r and omization for dopamine withdrawal on the first or the second day . Serum prolactin , growth hormone , insulin‐like growth factor‐1 , thyrotropin , thyroxine ( T4 ) , triiodothyronine ( T3 ) , and reverse triiodothyronine ( reverse T3 ) concentrations were measured . Measurements and Main Results : In the newborns , dopamine was found to suppress prolactin , growth hormone , and thyrotropin secretion consistently , rebound releases starting within 20 mins after dopamine withdrawal . One day later , prolactin concentrations were ten times higher , pulsatile growth hormone secretion was augmented , thyrotropin was unchanged , but T3 was increased by 30 % and the T3/reverse T3 ratio was inverted . In the children , dopamine suppressed prolactin and thyrotropin ( but not growth hormone ) secretion , rebound releases starting within 20 mins after dopamine withdrawal . One day later , prolactin concentrations were at least twice as high , thyrotropin was increased ten‐fold , T4 was augmented by 14 % , T3 by 30 % and the T3/reverse T3 ratio had doubled . Neither in newborns nor in children did dopamine withdrawal appear to affect the low serum insulin‐like growth factor‐1 concentrations . Conclusions : The data indicate that dopamine infusion induces or aggravates partial hypopituitarism and the euthyroid sick syndrome in critically ill infants and children . ( Crit Care Med 1994 ; 22:1747–1753 We tested the hypothesis that the administration of recombinant human growth hormone ( rHGH ) and exercise would increase lean body mass ( LBM ) and muscle strength in burned children to a greater extent than rHGH or exercise separately . Children , ages 7 - 17 yr , with > 40 % body surface area burned , were r and omized into groups . One group ( GHEX , n = 10 ) participated in a 12-wk in-hospital physical rehabilitation program supplemented with an exercise program and received 0.05 mg . kg(-1 ) . day(-1 ) of rHGH . A second exercising group ( SALEX , n = 13 ) received saline . A third group ( GH , n = 10 ) received a similar dose of rHGH as GHEX and participated in a 12-wk , home-based physical rehabilitation program without exercise . The fourth group ( Saline , n = 11 ) received saline and participated in a 12-wk , home-based physical rehabilitation program without exercise . The mean ( + /-SE ) percent change in lean body mass after 12 wk was not significantly different between GHEX ( 9.0 + /- 2.1 % ) , SALEX ( 5.4 + /- 1.6 % ) , and GH ( 5.8 + /- 1.8 % ) groups ( P = 0.33 ) . However , the mean percent change in muscle strength was significantly greater in the GHEX ( 36.2 + /- 5.4 % ) and SALEX ( 42.6 + /- 10.0 % ) groups than in the GH ( -7.4 + /- 4.7 % ) or Saline ( 6.7 + /- 4.4 % ) groups ( P = 0.008 ) . In summary , rHGH GHEX , SALEX , and GH alone produced similar improvements in LBM . However , muscle strength was only increased via exercise BACKGROUND Recombinant human growth hormone ( rhGH ) has been shown to favorably modulate the acute-phase response and may improve the clinical outcome . OBJECTIVE To examine whether rhGH attenuates the elevated tumor necrosis factor alpha ( TNF-alpha ) levels that correlate with increased multiorgan failure and mortality in burned adults and children . DESIGN Twenty children with burns of greater than 40 % of the total body surface area were r and omly divided into 2 groups to receive placebo ( n = 10 ) or rhGH , 0.2 mg/kg per day intramuscularly ( n = 10 ) . SETTING Pediatric burn hospital . MAIN OUTCOME MEASURE Serum TNF-alpha levels by enzyme-linked immunoassay at baseline ( day 0 ) and at 21 and 42 days after injury . For statistical analysis , we used the Kruskal-Wallis and Friedman tests . RESULTS No significant differences in age ( mean + /- SD , 6.2+/-1.6 vs 5.0+/-1.2 years ) or percentage of total body surface area burn ( mean + /- SD , 65.1%+/-8.2 % vs 57.1%+/-5.2 % ) could be shown between the groups given rhGH and placebo . Baseline TNF-alpha levels were elevated from reference values in both groups . Twenty-one and 42 days after rhGH administration , serum TNF-alpha levels were significantly decreased from those at baseline ( P<.05 ) . No significant decrease in TNF-alpha levels was observed in the placebo group ( P = .5 ) . CONCLUSIONS Recombinant human growth hormone significantly lowers serum TNF-alpha levels after burn injury . This is consistent with the beneficial effect that rhGH has on the acute-phase response Objective To determine whether the beneficial effects of growth hormone persist throughout the prolonged hypermetabolic and hypercatabolic response to severe burn . Summary Background Data The hypermetabolic response to severe burn is associated with increased energy expenditure , insulin resistance , immunodeficiency , and whole body catabolism that persists for months after injury . Growth hormone is a potent anabolic agent and salutary modulator of posttraumatic metabolic responses . Methods Seventy-two severely burned children were enrolled in a placebo-controlled double-blind trial investigating the effects of growth hormone ( 0.05 mg/kg per day ) on muscle accretion and bone growth . Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after burn . Total body weight , height , dual-energy x-ray absorptiometry , indirect calorimetry , and hormone values were measured at discharge , then at 6 months , 9 months , and 12 months after burn . Results were compared between groups . Results Growth hormone subjects gained more weight than placebo subjects at the 9-month study point ; this disparity in weight gain continued to exp and throughout the remainder of the study . Height also increased in the growth hormone group compared with controls at 12 months . Change in lean body mass was greater in those treated with growth hormone at 6 , 9 , and 12 months . Bone mineral content was increased at 9 and 12 months ; this was associated with higher parathormone levels . Conclusions Low-dose recombinant human growth hormone successfully abates muscle catabolism and osteopenia induced by severe burn The beneficial effects of growth hormone on wound healing in severely burned children were studied . Forty patients who were 2 to 18 years old , with 40 % or more total body surface area ( TBSA ) and 20 % or more TBSA full-thickness flame or scald burns , were r and omized in a double-blind study to receive placebo or 0.1 mg/kg/day recombinant human growth hormone ( rHGH ) until the first donor site healed or to receive 0.2 mg/kg/day rHGH or placebo from admission throughout hospitalization . Patients receiving 0.2 mg/kg/day rHGH demonstrated significantly higher serum IGF-1 levels at 4.8 + /- 1.7 U/mL compared to placebos at 1.6 + /- 0.4 U/mL ( p less than 0.05 ) and a significant decrease in donor-site healing times compared to placebo ( p less than 0.05 ) . Length of hospital stay ( LOS/%TBSA ) was decreased from 0.80 + /- 0.10 days/%TBSA burned in the placebo group to 0.54 + /- 0.04 days/%TBSA burned in the 0.2 mg/kg/day treatment group ( p less than 0.05 ) . This translates , for the average 60 % TBSA burned patient , to a decrease in LOS from 46 to 32 days Objectives To describe the sequential changes in the growth hormone (GH)/insulin-like growth factors axis and their relationship with nitrogen balance in children following cardiac surgery . Design Prospect i ve , descriptive study . Setting Pediatric intensive care unit of a university hospital . Patients Twenty three postoperative cardiac surgical patients after bypass . Interventions Blood and urine sample s were taken on days 1 , 2 , and 7 of pediatric intensive care unit admission . An intraanesthesia , presurgery sample was also obtained . Measurements and Main Results Serum concentrations of insulin , insulin growth factor-I ( IGF-I ) , insulin growth factor binding proteins 1 and 3 ( IGFBP-1 and IGFBP-3 ) , growth hormone binding protein ( GHBP ) , and urinary concentrations of GH and free cortisol ( UFC ) were measured on days 1 , 2 , and 7 of the study period . C-reactive protein and prealbumin , were also measured in blood sample s as conventional markers of inflammatory or nutritional status . Pediatric Risk of Mortality II score and UFC were used as indicators of acute stress . The nitrogen balance and urinary nitrogen urea excretion were used as markers of catabolic state . Urinary concentrations of GH were high from days 1 to 7 . Plasma concentrations of IGF-I and GHBP were low and remained low throughout the study period . IGFBP-3 levels were below normal but without reaching statistical significance . The IGFBP-1 levels were initially high but descended progressively toward normal values . Urinary nitrogen urea production was persistently elevated and was associated with a negative nitrogen balance . No relationship was found between nitrogen balance and IGF-I , prealbumin , or C-reactive protein . Conclusions A GH-resistant state is observed in postoperative children following cardiac surgery . Stress response is characterized by an elevation of growth hormone secretion that is not followed by the corresponding increment in IGF-I and IGFBP-3 concentrations . These hormonal changes may be permissive for the catabolic state of these patients . IGF-I and IGFBP-1 and -3 are not related to either nitrogen balance or urinary nitrogen urea excretion Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator . The aim of this study was to evaluate the short-term effect of dexamethasone ( DEXA ) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia . We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [ median ( range ) gestational age 27.5 wk ( 25.9 - 32.0 wk ) , median ( range ) birth weight 970 g ( 610 - 2150 g ) ] immediately before and 2 d after the start of DEXA treatment . On both days of study , serum GH profiles were obtained , and serum IGF-I and IGF binding protein ( IGFBP ) −1 and −3 levels were measured . The ventilation score and the nutritional intake were calculated . Before the start of DEXA treatment , the median serum mean GH level was 12.0 μg/L ( 6 - 28.4 μg/L ) , whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 μg/L ( 1.7 - 11.9 μg/L ) . During DEXA treatment , mean , baseline , and maximal GH levels ( Pulsar analysis ) were significantly lower compared with pretreatment levels ( p < 0.01 , p < 0.01 , and p < 0.05 , respectively ) . Serum IGF-I and IGFBP-3 levels did not decline during DEXA . Serum IGFBP-1 levels were significantly lower compared with pretreatment levels ( p < 0.01 ) . Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered . Ventilation score and nutritional intake did not significantly correlate with serum GH , IGF-I , or IGFBP-1 or -3 levels , either before or after the start of DEXA . Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels , without an acute decline in serum IGF-I levels . A concomitant decrease in serum IGFBP-1 levels was found Burn injury in children is associated with low bone formation and long-term bone loss . Because recombinant human GH ( rHGH ) may accelerate burn wound healing , and because rHGH increases bone formation and density in GH-deficient patients , we studied the short-term effects of rHGH on bone fomation , reflected by osteocalcin and type I procollagen propeptide levels in a r and omized , double-blind , placebo-controlled study . Nineteen patients were enrolled and received either rHGH ( 0.2 mg/kg.day ) or an equal volume of saline . Mean burn size and age were not different between the groups , and test substances were given from admission to time of wound healing ( mean : 43 + /- 22 days ) . At wound healing , serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229 % and 187 % of the respective means of the placebo group ( P < 0.025 ) . Serum osteocalcin concentrations remained below normal in both groups , and type I procollagen propeptide levels achieved a low normal level IGFBR-4 levels were twice that of normal on admission and doubled further at wound healing ; IGFBP-5 levels were low on admission but rose to normal at wound healing . We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3 . The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child Objective Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated . Summary Background Data Growth hormone has been shown to reduce wound healing times in burned pediatric patients . Through genetic engineering , several different forms have been synthesized ; however , not all are marketed currently . Two forms of growth hormone were used in these studies , Protropin ( Genentech , Inc. , San Francisco , GA ) , a commercially available product that possesses a N-terminal methionine residue not found in the second form Nutropin ( Genentech , Inc. , San Francisco , CA ) , which , as yet , is not commercially available . Through the use of recombinant human growth hormone , rapid wound healing may reduce the hypermetabolic period , the risk of infection , and accelerate the healing of donor sites used for grafting onto burned areas . The two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children . Methods Forty-six children , with a > 40 % total body surface area and > 20 % total body surface area full-thickness burn were entered in a double-bind , r and omized study to receive rhGH within 8 days of injury . Twenty received ( 0.2 mg/kg/day ) Nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision . Eighteen patients who failed the entry criteria for receiving Nutropin received Protropin therapeutically ( 0.2 mg/kg/day ) . Donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with Scarlet Red impregnated fine mesh gauze ( Sherwood Medical , St. Louis , MO ) . The initial donor site healing time , in days , was reached when the gauze could be removed without any trauma to the healed site . Results Donor sites in patients receiving Nutropin ( n = 20 ) or Protropin ( n = 18 ) healed at 6.8 ± 1.5 and 6.0 ± 1.5 ( mean ± SD ) days , respectively , whereas those receiving placebo ( n = 26 ) had a first donor site healing time of 8.5 ± 2.3 days . Both groups receiving rhGH showed a significant reduction in donor site healing time compared with placebo at p < 0.01 . When subgroups were compared , no difference in healing times could be shown with regards to age or time of admission after injury Useful information about hydration and the size of the body cell mass ( BCM ) can be obtained by monitoring changes in the amount of total body water ( TBW ) and its components , extracellular water ( ECW ) and intracellular water ( ICW ) . A combined tracer dilution method with deuterium to measure TBW and bromide to measure ECW was used to assess changes in ICW ( as a proxy for the BCM ) and in the ECW/ICW ratio ( an indicator of water distribution ) over the course of recovery in nine severely burned children . During the acute phase of recovery , ICW losses averaged ( mean + /- SD ) 2.2 + /- 2.0 liters ( P = .02 ) or 18.5 + /- 0.4 % . During the rehabilitative phase , mean ICW increased by 3.4 + /- 3.7 liters or 31.9 + /- 14 % . The ECW/ICW ratio varied widely both between patients and during the course of the study . During the acute phase of recovery , the mean ECW/ICW ratio increased from 1.06 + /- 0.15 liters to 1.20 + /- 0.14 liters because the ECW compartment had exp and ed relative to the ICW compartment . During rehabilitation , the ECW/ICW ratio decreased from 1.20 + /- 0.14 liters to 0.86 + /- 0.20 liters , with a recoup of ICW and continued ECW losses . Tracking ICW and the ECW/ICW ratio using the combined tracer dilution method is practical for monitoring BCM and water distribution in severely burned children . Taken together , the indices provide useful information about hydration and nutritional status in individuals recovering from severe burn injury The catabolic state is a major contributor to the morbidity and mortality of critical illness . The underlying mechanism is poorly understood . We examined the endogenous secretion of an anabolic protein , GH , and studied the effect exerted on its secretion by dopamine , a catecholamine that is frequently administered for cardiovascular purpose s in critical care . In a r and omized controlled study of critically ill adult polytrauma patients ( n = 11 ) , we evaluated the effect of prolonged ( 83- to 296-h ) dopamine infusion ( 5 micrograms/kg.min , iv ) on the dynamics of GH secretion and on serum insulin-like growth factor-I , cortisol , and insulin concentrations . The effect of brief ( 15- to 21-h ) dopamine administration was documented in an additional r and omized controlled cross-over study involving nine patients . The GH profiles , obtained by blood sampling every 20 min for 9 h during 2 consecutive nights , were examined by deconvolution analysis . GH release was found to be exclusively pulsatile in all patients . Prolonged and brief dopamine infusions appeared to have similar effects . Twenty-four hours before initiation or after withdrawal of dopamine infusion , mean serum GH concentrations , mean secretion rate , amount of GH per secretory burst , and secretory burst amplitude were low , but , respectively , a median of 17 % ( P = 0.028 ) , 36 % ( P = 0.046 ) , 40 % ( P = 0.008 ) , and 94 % ( P = 0.002 ) higher than those during dopamine infusion . After dopamine withdrawal , increased GH secretion was detectable within 3 h. Dopamine 's effect on GH release was specific , as this agent had no discernable effect on the elevated serum cortisol and insulin concentrations or the low plasma insulin-like growth factor-I levels within 24 h. In conclusion , the present data suggest that pulsatile GH secretion is low during critical illness and that dopamine infusion further attenuates GH secretion through amplitude modulation , possibly as a result of a direct inhibitory action on the somatotropes . The latter iatrogenic effect might further aggravate the catabolic state of critical illness OBJECTIVE To determine the effects of recombinant human insulin-like growth factor-1 ( IGF-1 ) complexed with its principal binding protein , IGFBP-3 , on skeletal muscle metabolism in severely burned children . SUMMARY BACKGROUND DATA Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting . Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned . The use of these agents , however , has several adverse side effects . A new combination of IGF-1 and IGFBP-3 is now available for clinical study . METHODS Twenty-nine severely burned children were prospect ively studied before and after treatment with 0.5 , 1 , 2 , or 4 mg/kg/day IGF-1/IGFBP-3 to determine net balance of protein across the leg , muscle protein fractional synthetic rates , and glucose metabolism . Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls . RESULTS Seventeen of 29 children were catabolic before starting treatment . The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1 , which did not further increase with 2.0 and 4.0 mg/kg/day . IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates . This effect was more pronounced in catabolic children . IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization . CONCLUSIONS IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects OBJECTIVE To determine the safety and efficacy of recombinant human growth hormone ( rhGH ) in the treatment of children who are severely burned . SUMMARY BACKGROUND DATA During the last decade , we have used recombinant human growth hormone ( rhGH ; 0.2 mg/kg/day s.q . ) to successfully treat 130 children with more than 40 % total body surface area ( TBSA ) burns to enhance wound healing and decrease protein loss . A significant increase in the mortality of adult patients in the intensive care unit who were given rhGH has recently been reported in two large European trials which questions the therapeutic safety of rhGH . METHODS The records of 263 children who were burned were review ed . Patients receiving either rhGH at 0.2 mg/kg/day subcutaneously as part of a r and omized clinical trial ( n = 48 ) or therapeutically ( n = 82 ) were compared with r and omized placebo-administered controls ( n = 54 ) , contiguous matched controls ( n = 48 ) , and matched patients admitted after August 1997 , after which no patients were treated with rhGH ( n = 31 ) . Morbidity and mortality , which might be altered by rhGH therapy , were considered with specific attention to organ function or failure , infection , hemodynamics , and calcium , phosphorous , and albumin balance . RESULTS A 2 % mortality was observed in both rhGH and saline placebo groups in the controlled studies , with no differences in septic complications , organ dysfunction , or heart rate pressure product identified . In addition , no difference in mortality could be shown for those given rhGH therapeutically versus their controls . No patient deaths were attributed to rhGH in autopsies review ed by observers blinded to treatment . Hyperglycemic episodes and exogenous insulin requirements were higher among rhGH recipients , whereas exogenous albumin requirements and the development of hypocalcemia was reduced . CONCLUSIONS Data indicate that rhGH used in the treatment of children who were severely burned is safe and efficacious Objective : Recombinant human growth hormone ( rHGH ) has been shown to increase mortality in adult trauma patients ; however , little has been reported on its side effects in children . The acute phase response has been suggested to be a contributing factor to trauma mortality . Therefore , the purpose of this study was to examine the effects of exogenous rHGH on the acute phase response in pediatric burn patients . Design : Prospect i ve , r and omized , double‐blind study . Setting : Shriners Hospital for Children . Patients : Thermally injured pediatric patients , ranging in age from 0.1 to 16 yrs . Interventions : Twenty‐eight thermally injured children received either 0.2 mg/kg/day of rHGH or saline ( placebo ) within 3 days of admission and for at least 25 days . Measurements and Main Results : Measurements were patient demographics , incidence of sepsis , inhalation injury , mortality , serum constitutive proteins , acute phase proteins , proinflammatory cytokines and insulin‐like growth factor‐I ( IGF‐I ) , insulin‐like growth factor binding protein (IGFBP)‐1 , and IGFBP‐3 . No differences could be demonstrated in age , gender , burn size , incidence in sepsis ( 20 % vs. 26 % ) , inhalation injury ( 46 % vs. 27 % ) , or mortality ( 8 % vs. 7 % ) between those receiving rHGH or placebo . Serum IGF‐I and IGFBP‐3 increased with rHGH treatment , whereas serum IGFBP‐1 decreased compared with placebo ( p < .05 ) . Burned children treated with rHGH required significantly less albumin substitution to maintain normal levels compared with placebo ( p < .05 ) . Those receiving rHGH demonstrated a decrease in serum C‐reactive protein and serum amyloid‐A and an increase in serum retinol‐binding protein compared with placebo ( p < .05 ) . rHGH decreased serum tumor necrosis factor‐α and interleukin (IL)‐1β , whereas no changes were found for serum IL‐1α , IL‐6 , and IL‐10 compared with placebo ( p < .05 ) . Free fatty acids were elevated in burned children who received rHGH ( p < .05 ) . Conclusion : Data indicate that rHGH does not increase mortality . rHGH decreased acute phase proteins , tumor necrosis factor‐α , and IL‐1β , which is associated with increases in constitutive hepatic proteins and Objective To evaluate postoperative serum concentrations of growth hormone ( GH ) , insulin-like growth factor I ( IGF-I ) , C-reactive protein ( CRP ) , and prealbumin as predictors of clinical outcome as defined by the incidence of 30-day postoperative mortality , the postoperative length of pediatric intensive care unit ( PICU ) stay , and the risk of postoperative infection in infants of high surgical risk undergoing operative correction of congenital cardiac defects . Design Prospect i ve , observational study . Setting PICU of a university hospital . Patients A high surgical risk group of 36 children admitted for elective cardiac surgery . Intervention Measures of serum levels of IGF-I , basal GH , prealbumin , and CRP . These parameters were followed from the hospital admission until the discharge from the PICU at specific time points : preoperative and on the second , fifth , and tenth postoperative days . Measurements and Main Results Surgical stress response was marked by an increase of GH and CRP levels and a fall in prealbumin levels on the second postoperative day . Prealbumin , CRP , and GH returned to preoperative levels on average 10 days following surgery ; the values of IGF-I , which had decreased on the fifth day , remained below those values observed before the surgery . Patients whose PICU stay was ≤ 10 days showed significant decreases in GH and CRP serum levels and an increase in IGF-I and prealbumin levels on postoperative day 5 compared with the patients who stayed > 10 days . The sustained high CRP ( ≥ 8.4 mg/dL , p < .05 ) and GH ( ≥ 66 mIU/L , p < .03 ) values on the fifth day were associated with increased mortality in contrast with patients in whom the values were returning to preoperative levels . Conclusions Serial monitoring of serum GH , IGF-I , CRP , and prealbumin levels may be useful as a means to a ) stratify the acute metabolic response to surgically induced injury insult and b ) predict clinical outcome as defined by the length of stay in the PICU and the likelihood of 30-day survival following open-heart surgery in infants |
11,356 | 16,253,049 | Across conditions , PRE was shown to improve the ability to generate force , with moderate to large effect sizes that may carry over into an improved ability to perform daily activities . | Progressive resistance exercise ( PRE ) is a method of increasing the ability of muscles to generate force .
However , the effectiveness and safety of PRE for clients of physical therapists are not well known .
The purpose of this article is to review the evidence on positive and negative effects of PRE as a physical therapy intervention . | OBJECTIVE To determine the effects of stopping and restarting two types of exercise programs in older adults . DESIGN A controlled , longitudinal study that utilized r and om assignment of volunteers . Treatments were exercise programs design ed to improve cardiovascular or neuromuscular fitness . MEASUREMENTS Dependent variables measured before and after implementation of treatments were : maximum oxygen consumption , oxygen pulse , treadmill and cycle training workloads , quadriceps isokinetic peak torque , quadriceps isokinetic total work , and quadriceps training workload . MAIN RESULTS Exercise training was highly effective in improving cardiovascular endurance or muscular strength . Ten weeks of exercise detraining result ed in small losses in newly gained cardiovascular capacity but more noticeable losses in muscular strength . Exercise retraining was accomplished easily using cardiovascular or resistive exercises . The functional benefits of restarting a cardiovascular exercise program appeared additive despite a 10-week intervening period of exercise detraining . In this age group , cardiovascular exercise produced limited improvements in muscular strength , and resistive exercise training positively influenced cardiovascular exercise performance . CONCLUSIONS Older adults are fairly resilient to 10 weeks of cardiovascular detraining and retain newly gained muscular strength for at least 5 weeks , despite an interruption of formal exercise . An occasional missed exercise session or temporary cessation of habitual exercise should not be a cause for distress in exercising older adults . Instead , they should realize the case with which they may restart their exercise program and also appreciate the generalized fitness benefits that can be ascribed to becoming more active BACKGROUND Intensive exercise training can lead to improvement in strength and functional performance in older people living at home and nursing home residents . There is little information whether intensive physical exercise may be applicable and effective in elderly patients suffering from the acute sequelae of injurious falls or hip surgery . OBJECTIVE To assess the feasibility , safety and efficacy of intensive , progressive physical training in rehabilitation after hip surgery . DESIGN Prospect i ve , r and omised , placebo-controlled intervention study of a 3-months training intervention and a 3-months ' follow-up . SETTING Physical training 6 - 8 weeks after hip surgery . SUBJECTS Twenty-eight ( 15 intervention , 13 control ) elderly patients with a history of injurious falls admitted to acute care or inpatient rehabilitation because of acute fall-related hip fracture or elective hip replacement . METHODS Progressive resistance and functional training to improve strength and functional performance . RESULTS No training-related medical problems occurred in the study group . Twenty-four patients ( 86 % ) completed all assessment s during the intervention and follow-up period . Adherence was excellent in both groups ( intervention : 93 , 0+/-13 , 5 % versus control : 96 , 7+/-6 , 2 % ) . Training significantly increased strength , functional motor performance and balance and reduced fall-related behavioural and emotional problems . Some improvements in strength persisted during 3-months follow-up while other strength variables and functional performances were lost after cessation of training . Patients in the control group showed no change in strength , functional performance and emotional state during intervention and follow-up . CONCLUSIONS Progressive resistance training and progressive functional training are safe and effective methods to increase strength and functional performance during rehabilitation in patients after hip surgery and a history of injurious falls . Because part of the training improvements were lost after stopping the training , a continuing training regime should be established OBJECTIVE To determine clinical effectiveness of strength training in children with spastic cerebral palsy . DESIGN Prospect i ve before and after trial in which subjects participated in a 6-week strength training program . All received before and after isometric strength evaluation of eight muscle groups in both lower extremities with a h and -held dynamometer , 3-D gait analysis at free and fast speeds , administration of the Gross Motor Function Measure ( GMFM ) , and assessment of energy expenditure during gait . SETTING Pediatric rehabilitation center at a tertiary care hospital . PATIENTS Eleven children met inclusion criteria for participation . Six had spastic diplegia , were limited community ambulators , and demonstrated less than 50 % of normal muscle strength . Five had spastic hemiplegia and demonstrated a 20 % strength asymmetry in at least two muscles across extremities . RESULTS Each group had significant strength gains in the muscles targeted . The entire cohort had higher gait velocity primarily as a result of increased cadence , with greater capacity to walk faster . GMFM Dimension 5 also improved , with no change in energy expenditure . Asymmetry in strength improved in hemiplegia , with no change in asymmetry in support times or joint motion across extremities . CONCLUSIONS This study reinforced the relationship of strength to motor function in cerebral palsy and further demonstrated the effectiveness of strengthening in this population Background and Purpose — To evaluate the efficacy of supervised high-intensity progressive resistance training ( PRT ) on lower extremity strength , function , and disability in older , long-term stroke survivors . Methods — Forty-two volunteers aged 50 years and above , 6 months to 6 years after a single mild to moderate stroke , were r and omized into either a control group of upper extremity stretching or a PRT group that received a 12-week supervised high-intensity resistance training program consisting of bilateral leg press ( LP ) , unilateral paretic and nonparetic knee extension ( KE ) , ankle dorsiflexion ( DF ) , and plantarflexion ( PF ) exercises . Functional performance was assessed using the 6-minute walk , stair-climb time , repeated chair-rise time , and habitual and maximal gait velocities . Self-reported changes in function and disability were evaluated using the Late Life Function and Disability Instrument ( LLFDI ) . Results — Single-repetition maximum strength significantly improved in the PRT group for LP ( 16.2 % ) , paretic KE ( 31.4 % ) , and nonparetic KE ( 38.2 % ) with no change in the control group . Paretic ankle DF ( 66.7 % versus −24.0 % ) , paretic ankle PF ( 35.5 % versus −20.3 % ) , and nonparetic ankle PF ( 14.7 % versus −13.8 % ) significantly improved in the PRT group compared with the control . The PRT group showed significant improvement in self-reported function and disability with no change in the control . There was no significant difference between groups for any performance-based measure of function . Conclusions — High-intensity PRT improves both paretic and nonparetic lower extremity strength after stroke , and results in reductions in functional limitations and disability STUDY DESIGN A r and omized clinical trial . OBJECTIVES To examine the relative efficacy of three active therapies for chronic low back pain . SUMMARY OF BACKGROUND DATA There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain , but many questions remain regarding its exact prescription and method of application . The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider . METHODS One hundred forty-eight patients with chronic low back pain were r and omized to one of the following treatments , which they attended twice a week for 3 months : 1 ) modern active physiotherapy , 2 ) muscle reconditioning on training devices , or 3 ) low-impact aerobics . Pretherapy and posttherapy , objective measurements of lumbar mobility were performed , and question naires were administered inquiring about self-rated pain and disability , and psychosocial factors . Similar question naires were administered 6 months after therapy . The data were analyzed using the intention-to-treat principle . RESULTS Of the 148 patients , 16 ( 10.8 % ) dropped out of the therapy . One hundred thirty-seven question naires ( 93 % ) were available for analysis at all three time points . After therapy , significant reductions were observed in pain intensity , frequency , and disability ; Fear-Avoidance Beliefs about physical activity ( FABQactivity ) ; and " praying/hoping , " " catastrophizing , " and " pain behavior " coping strategies -- each with no group differences in the extent of the response . These effects were maintained over the subsequent 6 months , with the exception of disability and FABQactivity for the physiotherapy group . There were small but significant posttherapy increases in lumbar mobility , with aerobics and devices showing a greater response than physiotherapy . CONCLUSION The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality , but rather through some " central " effect , perhaps involving an adjustment of perception in relation to pain and disability . The direct costs associated with administering physiotherapy were three times as great , and devices four times as great , as those for aerobics . Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition OBJECTIVE To test the effects of a high intensity home-based progressive strength training program on the clinical signs and symptoms of osteoarthritis ( OA ) of the knee . METHODS Forty-six community dwelling patients , aged 55 years or older with knee pain and radiographic evidence of knee OA , were r and omized to a 4 month home based progressive strength training program or a nutrition education program ( attention control ) . Thirty-eight patients completed the trial with an adherence of 84 % to the intervention and 65 % to the attention control . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index pain and physical function subscales . Secondary outcomes included clinical knee examination , muscle strength , physical performance measures , and question naires to measure quality of life variables . RESULTS Patients in the strength training group who completed the trial had a 71 % improvement in knee extension strength in the leg reported as most painful versus a 3 % improvement in the control group ( p < 0.01 ) . In a modified intent to treat analysis , self-reported pain improved by 36 % and physical function by 38 % in the strength training group versus 11 and 21 % , respectively , in the control group ( p = 0.01 for between group comparison ) . In addition , those patients in the strength training group who completed the trial had a 43 % mean reduction in pain ( p = 0.01 vs controls ) , a 44 % mean improvement in self-reported physical function ( p < 0.01 vs controls ) , and improvements in physical performance , quality of life , and self-efficacy when compared to the control group . CONCLUSION High intensity , home based strength training can produce substantial improvements in strength , pain , physical function and quality of life in patients with knee OA Bourbonnais D , Bilodeau S , Lepage Y , Beaudoin N , Gravel D , Forget R : Effect of force-feedback treatments in patients with chronic motor deficits after a stroke . Am J Phys Med Rehabil 2002;81:890–897 . Objective To assess the effects a motor reeducation approach based on static dynamometers used to provide feedback on the force produced . Design The study design was a single-blind , r and omized , controlled trial . Chronic stroke subjects participated in a 6-wk , thrice-weekly , force-feedback program of either the upper paretic limb ( n = 13 ) or the lower paretic limb ( n = 12 ) . Baseline and postintervention assessment s of the performance of both the upper and the lower limb were measured for each subject , the untreated paretic limb of each group serving as a control for the other group . Results With the exception of the h and grip force , strength measurements of the treated limb increased after completion of the treatment . The outcome measurements of the upper limb of the subjects included in the upper paretic limb were not significantly different after treatment from those measured in the lower paretic limb . In contrast , gait velocity and the distance walked in 2 min increased after treatment in the lower paretic limb as compared with the upper paretic limb , whereas the scores in the Fugl-Meyer test for the lower limb and the timed up- and -go test did not increase for either group after treatment . Conclusion The results indicate that treatment of the lower limb based on force feedback produces an improvement of gait velocity PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P < 0.05 ) . At 18 months all these differences persisted ( P < 0.05 ) , except for inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program OBJECTIVE To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Sedentary , overweight men and women with type 2 diabetes , aged 60 - 80 years ( n = 36 ) , were r and omized to high-intensity progressive resistance training plus moderate weight loss ( RT & WL group ) or moderate weight loss plus a control program ( WL group ) . Clinical and laboratory measurements were assessed at 0 , 3 , and 6 months . RESULTS HbA(1c ) fell significantly more in RT & WL than WL at 3 months ( 0.6 + /- 0.7 vs. 0.07 + /- 0.8 % , P < 0.05 ) and 6 months ( 1.2 + /- 1.0 vs. 0.4 + /- 0.8 % , P < 0.05 ) . Similar reductions in body weight ( RT & WL 2.5 + /- 2.9 vs. WL 3.1 + /- 2.1 kg ) and fat mass ( RT & WL 2.4 + /- 2.7 vs. WL 2.7 + /- 2.5 kg ) were observed after 6 months . In contrast , lean body mass ( LBM ) increased in the RT & WL group ( 0.5 + /- 1.1 kg ) and decreased in the WL group ( 0.4 + /- 1.0 ) after 6 months ( P < 0.05 ) . There were no between-group differences for fasting glucose , insulin , serum lipids and lipoproteins , or resting blood pressure . CONCLUSIONS High-intensity progressive resistance training , in combination with moderate weight loss , was effective in improving glycemic control in older patients with type 2 diabetes . Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes This r and omized clinical trial evaluated the effects of a home-based , six-week strength-training programme on lower limb strength and physical activity of 21 young people ( 11 females , 10 males ; mean age 13 years 1 month , SD 3 years 1 month ; range 8 to 18 years ) with spastic diplegic cerebral palsy ( CP ) with independent ambulation , with or without gait aids ; ( Gross Motor Function Classification System levels I to III ) . Compared with the 10 controls , the 11 participants in the strength-training programme increased their lower limb strength ( combined ankle plantarflexor and knee extensor strength as measured by a h and -held dynamometer ) at 6 weeks ( F(1,19)=4.58 , p=0.046 ) and at a follow-up 12 weeks later ( F(1,18)=6.25 , p=0.041 ) . At 6 weeks , trends were also evident for improved scores in Gross Motor Function Measure dimensions D and E for st and ing , running and jumping , and faster stair climbing . A relatively short clinical ly feasible home-based training programme can lead to lasting changes in the strength of key lower-limb muscles that may impact on the daily function of young people with CP BACKGROUND Training therapy with its manifold effects should be part of a modern and multi modular treatment of the COPD . Because of the specific symptoms ( e. g. muscle atrophy , dyspnea , low testosterone levels ) and the deconditioning of these patients , a resistance training might meet the dem and s of a COPD -exercise-therapy rather than an endurance training . The aim of this research project was to evaluate the efficiency of a hypertrophic maximal strength training on various COPD relevant parameters . METHODS 28 patients with moderate to severe COPD ( m12/f16 ) were r and omized and divided in a treatment and a control group . The patients in the treatment group underwent a resistance training ( hypertrophic maximal strength training ) for 12 weeks , initially two times , then three times a week . RESULTS Considering the results of the daily Peak-Flow-Measurement , there was no significant change in both groups , but a trend towards an improvement could be found in the treatment group . There was no difference in the change of FEV 1 . The performance on the ergo cycle showed a highly significant improvement ( p < 0.001 ) in the treatment group of 18.7 % ( 21.9 Watt ) . The results of the SGRQ showed a significant improvement ( p < 0.05 ) of the HRQL in the treatment group . A change of the HRQL in the control group was not found . CONCLUSIONS These data support the hypotheses that a short term high intensity strength training programme is suitable to improve performance measures of patients with moderate to severe COPD and it might also improve pulmonary function . The conclusion can be drawn , that this kind of resistance training can be prefered as COPD -specific training therapy and offers new treatment perspectives Study Design . A r and omized , parallel-group , single-blinded clinical trial was performed . After a 1-week baseline period , patients were r and omized to 11 weeks of therapy , with posttreatment follow-up assessment 3 , 6 , and 12 months later . Objectives . To compare the relative efficacy of rehabilitative neck exercise and spinal manipulation for the management of patients with chronic neck pain . Summary of Background Data . Mechanical neck pain is a common condition associated with substantial morbidity and cost . Relatively little is known about the efficacy of spinal manipulation and exercise for chronic neck pain . Also , the combination of both therapies has yet to be explored . Methods . Altogether , 191 patients with chronic mechanical neck pain were r and omized to receive 20 sessions of spinal manipulation combined with rehabilitative neck exercise ( spinal manipulation with exercise ) , MedX rehabilitative neck exercise , or spinal manipulation alone . The main outcome measures were patient-rated neck pain , neck disability , functional health status ( as measured by Short Form-36 [ SF-36 ] ) , global improvement , satisfaction with care , and medication use . Range of motion , muscle strength , and muscle endurance were assessed by examiners blinded to patients ’ treatment assignment . Results . Clinical and demographic characteristics were similar among groups at baseline . A total of 93 % of the patients completed the intervention phase . The response rate for the 12-month follow-up period was 84 % . Except for patient satisfaction , where spinal manipulative therapy and exercise were superior to spinal manipulation with ( P = 0.03 ) , the group differences in patient-rated outcomes after 11 weeks of treatment were not statistically significant ( P = 0.13 ) . However , the spinal manipulative therapy and exercise group showed greater gains in all measures of strength , endurance , and range of motion than the spinal manipulation group ( P < 0.05 ) . The spinal manipulation with exercise group also demonstrated more improvement in flexion endurance and in flexion and rotation strength than the MedX group ( P < 0.03 ) . The MedX exercise group had larger gains in extension strength and flexion – extension range of motion than the spinal manipulation group ( P < 0.05 ) . During the follow-up year , a greater improvement in patient-rated outcomes were observed for spinal manipulation with exercise and for MedX exercise than for spinal manipulation alone ( P = 0.01 ) . Both exercise groups showed very similar levels of improvement in patient-rated outcomes , although the spinal manipulation and exercise group reported greater satisfaction with care ( P < 0.01 ) . Conclusions . For chronic neck pain , the use of strengthening exercise , whether in combination with spinal manipulation or in the form of a high-technology MedX program , appears to be more beneficial to patients with chronic neck pain than the use of spinal manipulation alone . The effect of low-technology exercise or spinal manipulative therapy alone , as compared with no treatment or placebo , and the optimal dose and relative cost effectiveness of these therapies , need to be evaluated in future studies The effects of exercise for isolated lumbar extensor muscles were examined in 54 chronic low-back pain patients . Subjects were r and omly assigned to a 10-week exercise program ( N = 31 ) or a wait-list control group ( N = 23 ) . Results indicated a significant increase in isometric lumbar extension strength for the treatment group and a significant reduction in reported pain compared with the control group ( P 0.05 ) . Treated subjects reported less physical and psychosocial dysfunction whereas the control group increased in pain , and physical and psychosocial dysfunction . There were no concomitant changes in reported daily activity levels . These results show that lumbar extension exercise is beneficial for strengthening the lumbar extensors and results in decreased pain and improved perceptions of physical and psychosocial functioning in chronic back pain patients . However , these improvements were not related to changes in activities or psychological distress BACKGROUND AND PURPOSE The goal of this investigation was to study the recovery of ankle plantar-flexor peak torque , fatigue resistance , and functional ability ( stair climbing , walking ) following cast immobilization in patients with ankle fractures . SUBJECTS The participants were 10 patients who underwent open reduction-internal fixation and 8 weeks of cast immobilization following a fracture of the ankle mortise and 10 age- and sex-matched , noninjured comparison subjects . METHODS Plantar-flexor torque and fatigue resistance were measured at 1 , 5 , and 10 weeks of rehabilitation using an isokinetic dynamometer . Ankle plantar-flexor peak torque and fatigue resistance were correlated to timed ambulation , timed stair climbing , and unilateral heel-rises . RESULTS Following immobilization , plantar-flexor peak torque was decreased at all angular speeds and positions . The decrease in peak torque was associated with an increase in fatigue resistance . With rehabilitation , ankle plantar-flexor torque and fatigue resistance normalized . Regression analysis revealed a strong relationship between plantar-flexor peak torque and functional measures . By 10 weeks post-immobilization , peak torque , fatigue resistance , and all measures of functional performance had returned to control levels . CONCLUSION AND DISCUSSION The decrease in muscle performance , functional ability , and fatigue resistance induced by 8 weeks of cast immobilization can be reversed with 10 weeks of supervised physical therapy . In addition , this study demonstrated that ankle-plantar flexor torque is a good predictor of stair-climbing and walking performance in patients with ankle fractures OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P<.001 ) , a 12 % lower score on the knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P<.001 ) , mean ( + /-SE ) time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P<.001 ) , and mean ( + /-SE ) time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P<.001 ) than the health education group . The resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis Study Design . A r and omized , controlled trial , test‐retest design , with a 3‐ , 6‐ , and 30‐month postal question naire follow‐up . Objective . To determine the efficacy of a specific exercise intervention in the treatment of patients with chronic low back pain and a radiologic diagnosis of spondylolysis or spondylolisthesis . Summary of Background Data . A recent focus in the physiotherapy management of patients with back pain has been the specific training of muscles surrounding the spine ( deep abdominal muscles and lumbar multifidus ) , considered to provide dynamic stability and fine control to the lumbar spine . In no study have research ers evaluated the efficacy of this intervention in a population with chronic low back pain where the anatomic stability of the spine was compromised . Methods . Forty‐four patients with this condition were assigned r and omly to two treatment groups . The first group underwent a 10‐week specific exercise treatment program involving the specific training of the deep abdominal muscles , with co‐activation of the lumbar multifidus proximal to the pars defects . The activation of these muscles was incorporated into previously aggravating static postures and functional tasks . The control group underwent treatment as directed by their treating practitioner . Results . After intervention , the specific exercise group showed a statistically significant reduction in pain intensity and functional disability levels , which was maintained at a 30‐month follow‐up . The control group showed no significant change in these parameters after intervention or at follow‐up . Summary . A " specific exercise " treatment approach appears more effective than other commonly prescribed conservative treatment programs in patients with chronically symptomatic spondylolysis or spondylolisthesis The purpose of this study was to evaluate effects of a progressive strength training programme on walking ability in adults with cerebral palsy . Ten individuals with spastic diplegia ( seven males , three females ; mean age 31 , range 23 - 44 years ) participated twice a week over 10 weeks . Seven individuals with spastic diplegia ( four males , three females ; mean age 33 , range 25 - 47 years ) who did not receive strength training served as controls . All individuals were ambulatory but motor ability ranged from functional walkers to individuals who always required walking aids and used a wheelchair regularly . Significant improvements were seen in isometric strength ( hip extensors p=0.006 , hip abductors p=0.01 ) , and in isokinetic concentric work at 30 degrees/s ( knee extensors p=0.02 ) but not in eccentric work . Results also showed significant improvements in Gross Motor Function Measure ( GMFM ) dimensions D and E ( p=0.005 ) , walking velocity ( p=0.005 ) , and Timed Up and Go ( p=0.01 ) . There was no increase in spasticity for those who underwent strength training . Individuals in the control group did not show any significant improvement in any measured variable . The groups were small , however , and there was no significant difference between the groups in any measured variable . These findings suggest that a 10-week progressive strength training programme improves muscle strength and walking ability without increasing spasticity OBJECTIVE To evaluate the effects of a progressive resistance strength training program on changes in muscle strength , gait , and balance in older individuals 1 yr after stroke , seven individuals were recruited who were greater than 60-yr-old , 1 yr after stroke , living at home , and able to follow verbal comm and s. DESIGN Subjects participated in a 12-wk 2x per wk resistance training program at 70 % of 1 repetition maximum . RESULTS Lower limb strength improved 68 % on the affected side and 48 % on the intact side during training , with the largest increases observed for hip extension ( affected side : 88 % , P < 0.01 ; intact side : 103 % , P < 0.001 ) . Repeated chair st and time decreased 21 % ( P < 0.02 ) . Motor performance assessed by the Motor Assessment Scale improved 9 % ( P < 0.04 ) and static and dynamic balance ( Berg balance scale ) improved 12 % ( P < 0.004 ) . Progressive resistance training in individuals 1 yr after stroke improves affected and intact side lower limb strength and was associated with gains in chair st and time , balance , and motor performance . CONCLUSIONS These results support the concept that strength training is an appropriate intervention to improve the quality of physical function in older community dwelling stroke survivors This study determined the effects of endurance or resistance exercise training on maximal O2 consumption ( VO2max ) and the cardiovascular responses to exercise of 70- to 79-yr-old men and women . Healthy untrained subjects were r and omly assigned to a control group ( n = 12 ) or to an endurance ( n = 16 ) or resistance training group ( n = 19 ) . Training consisted of three sessions per week for 26 wk . Resistance training consisted of one set of 8 - 12 repetitions on 10 Nautilus machines . Endurance training consisted of 40 min at 50 - 70 % VO2max and at 75 - 85 % VO2max for the first and last 13 wk of training , respectively . The endurance training group increased its VO2max by 16 % during the first 13 wk of training and by a total of 22 % after 26 wk of training ; this group also increased its maximal O2 pulse , systolic blood pressure , and ventilation , and decreased its heart rate and perceived exertion during submaximal exercise . The resistance training group did not elicit significant changes in VO2max or in other maximal or submaximal cardiovascular responses despite eliciting 9 and 18 % increases in lower and upper body strength , respectively . Thus healthy men and women in their 70s can respond to prolonged endurance exercise training with adaptations similar to those of younger individuals . Resistance training in older individuals has no effect on cardiovascular responses to submaximal or maximal treadmill exercise Sixty-two older adults ( 68.4+/-6 years ) were r and omized into a control group ( n=16 ) , low-intensity exercise group ( n=22 , LEX ; 50 % 1-repetition maximum ; 13 repetitions per exercise ) , or a high-intensity exercise group ( n=24 , HEX ; 80 % 1-repetition maximum ; eight repetitions per exercise ) group . Subjects trained for 24 weeks , performing 1 set for each of 13 exercises . Subjects performed a grade d exercise test ( GXT ) at baseline and after 24 weeks of strength training . Heart rate , systolic , and diastolic blood pressures were measured at rest , during the GXT and 1 , 3 , and 5-min post-GXT . Mean arterial pressure was also calculated . Post-training , time to peak systolic and diastolic blood pressures and heart rate was increased in the LEX and HEX groups by 22.9 % and 44.5 % , respectively ( p<0.05 ) . Diastolic blood pressure , heart rate , and mean arterial pressure during the GXT were significantly decreased ( p<0.05 ) in the HEX group following training . Post-GXT heart rate was lower in the HEX and LEX groups compared to control ( p<0.05 ) indicating a more rapid recovery . Resistance exercise prolongs the onset of peak cardiovascular responses , decreases the cardiovascular response to exertion , and improves recovery from maximal exertion Eight hundred ninety-five consecutive chronic low back pain patients were evaluated . Six hundred twenty-seven completed the program . One hundred sixty-one began , but dropped out , and 107 were recommended for treatment but did not undergo treatment for various reasons . Average duration of symptoms prior to evaluation was 26 months . Forty-seven percent of patients were workers ' compensation patients . The primary treatment was intensive , specific exercise using firm pelvic stabilization to isolate and rehabilitate the lumbar spine musculature . Patients were encouraged to work hard to achieve specific goals . Seventy-six percent of patients completing the program had excellent or good results . At 1-year follow up 94 % of patients with good or excellent results reported maintaining their improvement . Results in the control group were significantly poorer in all areas surveyed except employment This study assessed the effects of short-term circuit weight training ( CWT ) on glycaemic control in NIDDM . Twenty-seven untrained , sedentary subjects ( mean age , 51 ) with NIDDM participated in an 8-week r and omised , controlled study , involving either CWT 3 days/week ( n = 15 ) or no formal exercise ( control ) ( n = 12 ) . All subjects performed regular self-blood glucose monitoring throughout . Fasting serum glucose and insulin were measured following a 12-h fast and during an oral glucose tolerance test ( 75 g ) before and after 8 weeks . Twenty-one subjects completed the study ( CWT , n = 11 ) ( Control , n = 10 ) . Strength for all exercises improved significantly after CWT . Pooled time-series analysis , using a r and om effects model , revealed an overall decrease in self-monitored glucose levels with CWT compared to controls . Significant reductions from baseline values were observed in both the glucose ( -213 mmol l-1 per 120 min , P < 0.05 ) and insulin ( -6130 pmol l-1 per 120 min , P < 0.05 ) area under the curve following CWT relative to controls . After adjustment for body mass changes , the change in self-monitored glucose levels and insulin area under the curve , but not glucose area under the curve , remained significant . Short-term CWT therefore may provide a practical exercise alternative in the lifestyle management of this condition Objective : To determine whether systematic progressive high-intensity quadriceps training increases leg extensor power and reduces disability in patients rehabilitating after proximal femoral fracture . Design : Open parallel group r and omized controlled trial comparing the addition of six weeks quadriceps training ( 40 patients ) with st and ard physiotherapy alone ( 40 patients ) . The training group exercised twice weekly , with six sets of 12 repetitions of knee extension ( both legs ) , progressing up to 80 % of their one-repetition maximum . Setting : Orthogeriatric unit , and community follow-up . Subjects : Eighty patients rehabilitating after proximal femoral fracture . Main outcome measures : Measurements of leg extensor power ( Nottingham Power Rig ) , functional mobility ( elderly mobility score ) , disability ( Barthel Index ) and quality of life ( Nottingham Health Profile ) were made at baseline , after six weeks ( at the end of the intervention ) and at 16 weeks . Results : Leg extensor power increased significantly in the quadriceps training group ( fractured leg mean improvement at six weeks 157 % ( st and ard error 16 ) , nonfractured leg 80 % ( 12 ) ) compared with the control group ( 63 % ( 11 ) and 26 % ( 8) respectively , unpaired Student 's t-test p = 0.007 and p = 0.01 for between-group comparisons ) . Significant benefits were maintained at 16 weeks . Quadriceps training result ed in a greater increase in elderly mobility scale score compared with st and ard rehabilitation ( between-group difference of 2.5 ( 95 % CI 1.1,3.8 ) at week 6 and 1.9 ( 0.4,3.4 ) at week 16 ) . Barthel score increased significantly from week 0 to 6 in the quadriceps training group compared with controls ( Mann – Whitney U-test p = 0.05 ) . Patients in the quadriceps training group scored significantly better in the energy subscore of the Nottingham Health Profile at the end of follow-up ( Mann – Whitney U-test p = 0.0185 ) . Conclusions : Progressive high-intensity quadriceps training in elderly proximal femoral fracture patients increased leg extensor power and reduced disability . This was accompanied by an increase in energy as measured by the Nottingham Health Profile . This intervention may provide a simple practical way of improving outcome in these patients Abstract The effects of three resistance training programs on muscular strength and on absolute and relative muscular endurance were investigated . Forty-three male college students were r and omly assigned to the training protocol s. The high resistance-low repetition group ( n = 15 ) performed three sets of 6–8 RM ( repetition maximum ) per session . The medium resistance-medium repetition subjects ( n = 16 ) trained by doing two sets of 30–40 RM per session , while the low resistance-high repetition group ( n = 12 ) used a single set of 100–150 RM . All subjects trained with the bench press exercise three times per week for nine weeks . Tests of strength ( 1-RM ) , absolute and relative endurance were administered before and after training . Statistical analyses revealed that the 20 % improvement in maximum strength by the high resistance-low repetition group was greater than the 8 and 5 % gains reported for the medium resistance-medium repetition and low resistance-high repetition groups , respectively . Relative to absolute STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up Objectives —To determine the effect of different training schedules on the cross sectional area ( CSA ) of the lumbar multifidus muscle in patients with chronic low back pain . Methods —Each of 59 nine patients was r and omly assigned to one of three programmes : 10 weeks of stabilisation training ( group 1 ; n = 19 ) ; 10 weeks of stabilisation training combined with dynamic resistance training ( group 2 ; n = 20 ) ; 10 weeks of stabilisation training combined with dynamic-static resistance training ( group 3 ; n = 20 ) . Before and after 10 weeks of training , multifidus CSAs were measured from st and ard computed tomography images at three different levels ( upper end plate of L3 and L4 , and lower end plate of L4 ) . Results —The CSA of the multifidus muscle was significantly increased at all levels after training in group 3 . In contrast , no significant differences were found in groups 1 and 2 . Conclusions —General stabilisation exercises and dynamic intensive lumbar resistance training have no significant effect on the CSA of the lumbar multifidus muscle in patients with chronic low back pain . The static holding component between the concentric and eccentric phase was found to be critical in inducing muscle hypertrophy during the first 10 weeks . Treatment consisting of stabilisation training combined with an intensive lumbar dynamic-static strengthening programme seems to be the most appropriate method of restoring the size of the multifidus muscle OBJECTIVE To determine the effectiveness of progressive resistance strengthening exercises to improve gross motor function and walking in patients receiving intensive rehabilitation after stroke . DESIGN R and omized controlled trial . SETTING Five inpatient rehabilitation programs affiliated with teaching hospitals . PARTICIPANTS Inclusion criteria included less than 6 months poststroke and recovery of the leg stages 3 to 5 on the Chedoke-McMaster Stroke Assessment ( CMSA ) . INTERVENTIONS Both groups received conventional physical therapy programs . In addition , the experimental group performed 9 lower-extremity progressive resistance exercises 3 times a week for the duration of their stay , whereas the control group did the same exercises and for the same duration but without resistance . MAIN OUTCOME MEASURES The Disability Inventory of the CMSA and the 2-minute walk test ( 2MWT ) at baseline , 4 weeks , discharge , and 6 months after discharge . RESULTS Over the length of stay , the rate of change in the Disability Inventory was.27 points per day in the experimental group and .29 points per day in the control group ; the between-group difference was -.02 points per day ( 95 % confidence interval [ CI ] , -.10 to.06 ; P=.62 ) . At discharge , the rate of change in the 2MWT was -.01 m in the experimental group and .15 m in the control group ; the between-group difference was -.16 m ( 95 % CI , -.37 to.05 ; P=.14 ) . CONCLUSIONS Progressive resistance strengthening exercises as applied in our study were not effective when compared with the same exercises given without resistance OBJECTIVE To determine the effectiveness of exercise therapy in patients with osteoarthritis ( OA ) of the hip or knee . METHODS A r and omized single blind , clinical trial was conducted in a primary care setting . Patients with hip or knee OA by American College of Rheumatology criteria were selected . Two intervention groups were compared . Both groups received treatment from the patients ' general practitioner , including patient education and medication if necessary . The experimental group also received exercise therapy from a physiotherapist in primary care . The treatment period was 12 weeks . The main outcome measures were pain , medication use ( nonsteroidal antiinflammatory drugs , NSAID ) and observed disability . RESULTS A total of 201 patients were r and omized . Exercise therapy was associated with a reduction of pain in the past week ( difference in change -17.0 ; 95 % CI -23.6 , -10.4 ) and observed disability ( -0.19 ; 95 % CI -0.38 ; -0.01 ) . Effect sizes were medium ( 0.58 ) and small ( 0.28 ) , respectively . No effect of exercise therapy was found for the use of NSAID . Additional beneficial effects ( p = 0.05 ) were found for the use of paracetamol ( effect size 0.33 ) , global effect as perceived by the patient ( effect size 0.68 ) , and muscle strength of the hip ( effect size 0.34 ) . CONCLUSION After 12 weeks , exercise therapy is effective in reducing pain and disability . The size of the effects is medium and small , respectively OBJECTIVES The goal most often stated by persons with stroke is improved walking function . The purpose of this study was to determine the effects of isokinetic strength training on walking performance , muscle strength , and health-related quality of life in survivors of chronic stroke . METHODS Twenty participants ( age , 61.2 + /- 8.4 years ) with chronic stroke were r and omized into 2 groups . The experimental group undertook maximal concentric isokinetic strength training , whereas the control group received passive range of motion of the paretic lower extremity 3 times a week for 6 weeks . The Kin-Com Isokinetic Dynamometer ( Chattanooga Group Inc. , TN ) was used for both the strengthening and passive range of motion exercises . The Mann-Whitney U test was used to compare the changes in scores ( postintervention minus baseline ) between the control and experimental groups for a composite lower extremity strength score , walking speed ( level-walking and stair-walking ) and health-related quality of life measure ( 36-Item Short Form Health Survey [ SF-36 ] ) . RESULTS Both the experimental and control groups increased their strength and walking speed postintervention ; however , there were no differences in the changes in walking speed between the groups . There was a trend ( P = .06 ) toward greater strength improvement in the experimental group compared with the control group . No changes in SF-36 scores were found in either group . CONCLUSIONS Intervention aim ed at increasing strength did not result in improvements in walking . The results of this study stress the importance of controlled clinical trials in determining the effect of specific treatment approaches . Strength training in conjunction with other task-related training may be indicated |
11,357 | 30,764,813 | The dedicated mental health treatments targeting depression or alcohol misuse consistently reduced levels of these outcomes .
In contrast to the dedicated mental health interventions , the integrated interventions did not consistently reduce mental ill health or alcohol misuse compared to control conditions .
Conclusions Too few studies have been conducted to judge whether mental health treatments may provide a beneficial strategy to prevent or reduce IPV in LMIC . | Background Epidemiological research suggests an interrelationship between mental health problems and the (re)occurrence of intimate partner violence ( IPV ) .
However , little is known about the impact of mental health treatments on IPV victimization or perpetration , especially in low- and middle-income countries ( LMIC ) . | Women who exchange sex for money or other goods , that is , female sex workers , are at increased risk of experiencing physical and sexual violence from both paying and intimate partners . Exposure to violence can be exacerbated by alcohol use and HIV/STI risk . The purpose of this study is to examine the efficacy of a HIV/STI risk reduction and enhanced HIV/STI risk reduction intervention at decreasing paying and intimate partner violence against Mongolian women who exchange sex and engage in harmful alcohol use . Women are recruited and r and omized to either ( a ) four sessions of a relationship-based HIV/STI risk reduction intervention ( n = 49 ) , ( b ) the same HIV/STI risk reduction intervention plus two additional motivational interviewing sessions ( n = 58 ) , or ( c ) a four session control condition focused on wellness promotion ( n = 59 ) . All the respondents complete assessment s at baseline ( preintervention ) as well as at immediate posttest , 3 and 6 months postintervention . A multilevel logistic model finds that women who participated in the HIV/STI risk reduction group ( OR = 0.14 , p < .00 ) , HIV/STI risk reduction and motivational interview group ( OR = 0.46 , p = .02 ) , and wellness ( OR = 0.20 , p < .00 ) group reduced their exposure to physical and sexual violence in the past 90 days . No significant differences in effects are observed between conditions . This study demonstrates the efficacy of a relationship-based HIV/STI risk reduction intervention , a relationship-based HIV/STI risk reduction intervention combined with motivational interviewing , and a wellness promotion intervention in reducing intimate and paying partner violence against women who exchange sex in Mongolia . The findings have significant implication s for the impact of minimal intervention and the potential role of peer networks and social support in reducing women ’s experiences of violence in re source poor setting Summary Background Although structured psychological treatments are recommended as first-line interventions for depression , only a small fraction of people globally receive these treatments because of poor access in routine primary care . We assessed the effectiveness and cost-effectiveness of a brief psychological treatment ( Healthy Activity Program [ HAP ] ) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care setting s. Methods In this r and omised controlled trial , we recruited participants aged 18–65 years scoring more than 14 on the Patient Health Question naire 9 ( PHQ-9 ) indicating moderately severe to severe depression from ten primary health centres in Goa , India . Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible . Participants were r and omly allocated ( 1:1 ) to enhanced usual care ( EUC ) alone or EUC combined with HAP in r and omly sized blocks ( block size four to six [ two to four for men ] ) , stratified by primary health centre and sex , and allocation was concealed with use of sequential numbered opaque envelopes . Physicians providing EUC were masked . Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression ( PHQ-9 score of < 10 ) at 3 months in the intention-to-treat population , assessed by masked field research ers . Secondary outcomes were disability , days unable to work , behavioural activation , suicidal thoughts or attempts , intimate partner violence , and re source use and costs of illness . We assessed serious adverse events in the per- protocol population . This trial is registered with the IS RCT N registry , number IS RCT N95149997 . Findings Between Oct 28 , 2013 , and July 29 , 2015 , we enrolled and r and omly allocated 495 participants ( 247 [ 50 % ] to the EUC plus HAP group [ two of whom were subsequently excluded because of protocol violations ] and 248 [ 50 % ] to the EUC alone group ) , of whom 466 ( 95 % ) completed the 3 month primary outcome assessment ( 230 [ 49 % ] in the EUC plus HAP group and 236 [ 51 % ] in the EUC alone group ) . Participants in the EUC plus HAP group had significantly lower symptom severity ( Beck Depression Inventory version II in EUC plus HAP group 19·99 [ SD 15·70 ] vs 27·52 [ 13·26 ] in EUC alone group ; adjusted mean difference −7·57 [ 95 % CI −10·27 to −4·86 ] ; p<0·0001 ) and higher remission ( 147 [ 64 % ] of 230 had a PHQ-9 score of < 10 in the HAP plus EUC group vs 91 [ 39 % ] of 236 in the EUC alone group ; adjusted prevalence ratio 1·61 [ 1·34–1·93 ] ) than did those in the EUC alone group . EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability ( adjusted mean difference −2·73 [ –4·39 to −1·06 ] ; p=0·001 ) , days out of work ( −2·29 [ –3·84 to −0·73 ] ; p=0·004 ) , intimate partner physical violence in women ( 0·53 [ 0·29–0·96 ] ; p=0·04 ) , behavioural activation ( 2·17 [ 1·34–3·00 ] ; p<0·0001 ) , and suicidal thoughts or attempts ( 0·61 [ 0·45–0·83 ] ; p=0·001 ) . The incremental cost per quality -adjusted life-year gained was $ 9333 ( 95 % CI 3862–28 169 ; 2015 international dollars ) , with an 87 % chance of being cost-effective in the study setting . Serious adverse events were infrequent and similar between groups ( nine [ 4 % ] in the EUC plus HAP group vs ten [ 4 % ] in the EUC alone group ; p=1·00 ) . Interpretation HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa , India . HAP was readily accepted by this previously untreated population and was cost-effective in this setting . HAP could be a key strategy to reduce the treatment gap for depressive disorders , the leading mental health disorder worldwide . Funding Wellcome Trust Background The Healthy Activity Programme ( HAP ) , a brief behavioural intervention delivered by lay counsellors , enhanced remission over 3 months among primary care attendees with depression in peri-urban and rural setting s in India . We evaluated the sustainability of the effects after treatment termination , the cost-effectiveness of HAP over 12 months , and the effects of the hypothesized mediator of activation on clinical outcomes . Methods and findings Primary care attendees aged 18–65 years screened with moderately severe to severe depression on the Patient Health Question naire 9 ( PHQ-9 ) were r and omised to either HAP plus enhanced usual care ( EUC ) ( n = 247 ) or EUC alone ( n = 248 ) , of whom 95 % completed assessment s at 3 months , and 91 % at 12 months . Primary outcomes were severity on the Beck Depression Inventory – II ( BDI-II ) and remission on the PHQ-9 . HAP participants maintained the gains they showed at the end of treatment through the 12-month follow-up ( difference in mean BDI-II score between 3 and 12 months = −0.34 ; 95 % CI −2.37 , 1.69 ; p = 0.74 ) , with lower symptom severity scores than participants who received EUC alone ( adjusted mean difference in BDI-II score = −4.45 ; 95 % CI −7.26 , −1.63 ; p = 0.002 ) and higher rates of remission ( adjusted prevalence ratio [ aPR ] = 1.36 ; 95 % CI 1.15 , 1.61 ; p < 0.009 ) . They also fared better on most secondary outcomes , including recovery ( aPR = 1.98 ; 95 % CI 1.29 , 3.03 ; p = 0.002 ) , any response over time ( aPR = 1.45 ; 95 % CI 1.27 , 1.66 ; p < 0.001 ) , higher likelihood of reporting a minimal clinical ly important difference ( aPR = 1.42 ; 95 % CI 1.17 , 1.71 ; p < 0.001 ) , and lower likelihood of reporting suicidal behaviour ( aPR = 0.71 ; 95 % CI 0.51 , 1.01 ; p = 0.06 ) . HAP plus EUC also had a marginal effect on WHO Disability Assessment Schedule score at 12 months ( aPR = −1.58 ; 95 % CI −3.33 , 0.17 ; p = 0.08 ) ; other outcomes ( days unable to work , intimate partner violence toward females ) did not statistically significantly differ between the two arms . Economic analyses indicated that HAP plus EUC was dominant over EUC alone , with lower costs and better outcomes ; uncertainty analysis showed that from this health system perspective there was a 95 % chance of HAP being cost-effective , given a willingness to pay threshold of Intl$16,060—equivalent to GDP per capita in Goa — per quality -adjusted life year gained . Patient-reported behavioural activation level at 3 months mediated the effect of the HAP intervention on the 12-month depression score ( β = −2.62 ; 95 % CI −3.28 , −1.97 ; p < 0.001 ) . Serious adverse events were infrequent , and prevalence was similar by arm . We were unable to assess possible episodes of remission and relapse that may have occurred between our outcome assessment time points of 3 and 12 months after r and omisation . We did not account for or evaluate the effect of mediators other than behavioural activation . Conclusions HAP ’s superiority over EUC at the end of treatment was largely stable over time and was mediated by patient activation . HAP provides better outcomes at lower costs from a perspective covering publicly funded healthcare services and productivity impacts on patients and their families . Trial registration IS RCT N registry IS RCT Background Violence against women and girls ( VAWG ) is an urgent global health problem . Root causes for VAWG include the individual- and family-level factors of alcohol abuse , mental health problems , violence exposure , and related adverse experiences . Few studies in low- and middle-income countries ( LMIC ) have assessed the effectiveness of psychological interventions for reducing VAWG . This r and omized controlled trial , part of the What Works to Prevent Violence Against Women and Girls consortium , examines the effectiveness of a common elements treatment approach ( CETA ) for reducing VAWG and comorbid alcohol abuse among families in Zambia . Methods / design Study participants are families consisting of three persons : an adult woman , her male husb and or partner , and one of her children aged 8–17 ( if available ) . Eligibility criteria include experience of moderate-to-severe intimate partner violence by the woman and hazardous alcohol use by her male partner . Family units are r and omized to receive CETA or treatment as usual . The primary outcome is VAWG as measured by the Severity of Violence Against Women Scale , assessed along with secondary outcomes at 24 months post-baseline . Interim assessment s are also conducted at 4–5 months ( following CETA completion ) and 12 months post-baseline . Conclusions This ongoing trial is one of the first in sub-Saharan Africa to evaluate the use of an evidence -based common elements approach for reducing VAWG by targeting a range of individual- and family-level factors , including alcohol abuse . Results of this trial will inform policy on what interventions work to prevent VAWG in LMIC with local perspectives on scale up and wider implementation Background Counselling for Alcohol Problems ( CAP ) , a brief intervention delivered by lay counsellors , enhanced remission and abstinence over 3 months among male primary care attendees with harmful drinking in a setting in India . We evaluated the sustainability of the effects after treatment termination , the cost-effectiveness of CAP over 12 months , and the effects of the hypothesized mediator ‘ readiness to change ’ on clinical outcomes . Methods and findings Male primary care attendees aged 18–65 years screening with harmful drinking on the Alcohol Use Disorders Identification Test ( AUDIT ) were r and omised to either CAP plus enhanced usual care ( EUC ) ( n = 188 ) or EUC alone ( n = 189 ) , of whom 89 % completed assessment s at 3 months , and 84 % at 12 months . Primary outcomes were remission and mean st and ard ethanol consumed in the past 14 days , and the proposed mediating variable was readiness to change at 3 months . CAP participants maintained the gains they showed at the end of treatment through the 12-month follow-up , with the proportion with remission ( AUDIT score < 8 : 54.3 % versus 31.9 % ; adjusted prevalence ratio [ aPR ] 1.71 [ 95 % CI 1.32 , 2.22 ] ; p < 0.001 ) and abstinence in the past 14 days ( 45.1 % versus 26.4 % ; adjusted odds ratio 1.92 [ 95 % CI 1.19 , 3.10 ] ; p = 0.008 ) being significantly higher in the CAP plus EUC arm than in the EUC alone arm . CAP participants also fared better on secondary outcomes including recovery ( AUDIT score < 8 at 3 and 12 months : 27.4 % versus 15.1 % ; aPR 1.90 [ 95 % CI 1.21 , 3.00 ] ; p = 0.006 ) and percent of days abstinent ( mean percent [ SD ] 71.0 % [ 38.2 ] versus 55.0 % [ 39.8 ] ; adjusted mean difference 16.1 [ 95 % CI 7.1 , 25.0 ] ; p = 0.001 ) . The intervention effect for remission was higher at 12 months than at 3 months ( aPR 1.50 [ 95 % CI 1.09 , 2.07 ] ) . There was no evidence of an intervention effect on Patient Health Question naire 9 score , suicidal behaviour , percentage of days of heavy drinking , Short Inventory of Problems score , WHO Disability Assessment Schedule 2.0 score , days unable to work , or perpetration of intimate partner violence . Economic analyses indicated that CAP plus EUC was dominant over EUC alone , with lower costs and better outcomes ; uncertainty analysis showed a 99 % chance of CAP being cost-effective per remission achieved from a health system perspective , using a willingness to pay threshold equivalent to 1 month ’s wages for an unskilled manual worker in Goa . Readiness to change level at 3 months mediated the effect of CAP on mean st and ard ethanol consumption at 12 months ( indirect effect −6.014 [ 95 % CI −13.99 , −0.046 ] ) . Serious adverse events were infrequent , and prevalence was similar by arm . The method ological limitations of this trial are the susceptibility of self-reported drinking to social desirability bias , the modest participation rates of eligible patients , and the examination of mediation effects of only 1 mediator and in only half of our sample . Conclusions CAP ’s superiority over EUC at the end of treatment was largely stable over time and was mediated by readiness to change . CAP provides better outcomes at lower costs from a societal perspective . Trial registration IS RCT N registry IS RCT Importance The mental health consequences of conflict and violence are wide-ranging and pervasive . Scalable interventions to address a range of mental health problems are needed . Objective To test the effectiveness of a multicomponent behavioral intervention delivered by lay health workers to adults with psychological distress in primary care setting s. Design , Setting , and Participants A r and omized clinical trial was conducted from November 1 , 2014 , through January 28 , 2016 , in 3 primary care centers in Peshawar , Pakistan , that included 346 adult primary care attendees with high levels of both psychological distress and functional impairment according to the 12-item General Health Question naire and the World Health Organization Disability Assessment Schedule 2.0 ( WHODAS 2.0 ) . Interventions Lay health workers administered 5 weekly 90-minute individual sessions that included empirically supported strategies of problem solving , behavioral activation , strengthening social support , and stress management . The control was enhanced usual care . Main Outcomes and Measures Primary outcomes , anxiety and depression symptoms , were independently measured at 3 months with the Hospital Anxiety and Depression Scale ( HADS ) . Secondary outcomes were posttraumatic stress symptoms ( Posttraumatic Stress Disorder Checklist for DSM-5 ) , functional impairment ( WHODAS 2.0 ) , progress on problems for which the person sought help ( Psychological Outcome Profiles ) , and symptoms of depressive disorder ( 9-item Patient Health Question naire ) . Results Among 346 patients ( mean [ SD ] age , 33.0 [ 11.8 ] years ; 78.9 % women ) , 172 were r and omly assigned to the intervention and 174 to enhanced usual care ; among them , 146 and 160 completed the study , respectively . At baseline , the intervention and control groups had similar mean ( SD ) HADS scores on symptoms of anxiety ( 14.16 [ 3.17 ] vs 13.64 [ 3.20 ] ; adjusted mean difference [ AMD ] , 0.52 ; 95 % CI , -0.22 to 1.27 ) and depression ( 12.67 [ 3.27 ] vs 12.49 [ 3.34 ] ; AMD , 0.17 , 95 % CI , -0.54 to 0.89 ) . After 3 months of treatment , the intervention group had significantly lower mean ( SD ) HADS scores than the control group for anxiety ( 7.25 [ 3.63 ] vs 10.03 [ 3.87 ] ; AMD , -2.77 ; 95 % CI , -3.56 to -1.98 ) and depression ( 6.30 [ 3.40 ] vs 9.27 [ 3.56 ] ; AMD , -2.98 ; 95 % CI , -3.74 to -2.22 ) . At 3 months , there were also significant differences in scores of posttraumatic stress ( AMD , -5.86 ; 95 % CI , -8.53 to -3.19 ) , functional impairment ( AMD , -4.17 ; 95 % CI , -5.84 to -2.51 ) , problems for which the person sought help ( AMD , -1.58 ; 95 % CI , -2.40 to -0.77 ) , and symptoms of depressive disorder ( AMD , -3.41 ; 95 % CI , -4.49 to -2.34 ) . Conclusions and Relevance Among adults impaired by psychological distress in a conflict-affected area , lay health worker administration of a brief multicomponent intervention based on established behavioral strategies , compared with enhanced usual care , result ed in clinical ly significant reductions in anxiety and depressive symptoms at 3 months . Trial Registration anzctr.org.au Identifier : ANZCTR12614001235695 Background Violence against women by intimate partners remains unacceptably common worldwide . The evidence base for the assumed psychological impacts of intimate partner violence ( IPV ) is derived primarily from studies conducted in high-income countries . A recently published systematic review identified 13 studies linking IPV to incident depression , none of which were conducted in sub-Saharan Africa . To address this gap in the literature , we analyzed longitudinal data collected during the course of a 3-y cluster-r and omized trial with the aim of estimating the association between IPV and depression symptom severity . Methods and Findings We conducted a secondary analysis of population -based , longitudinal data collected from 1,238 pregnant women during a 3-y cluster-r and omized trial of a home visiting intervention in Cape Town , South Africa . Surveys were conducted at baseline , 6 mo , 18 mo , and 36 mo ( 85 % retention ) . The primary explanatory variable of interest was exposure to four types of physical IPV in the past year . Depression symptom severity was measured using the Xhosa version of the ten-item Edinburgh Postnatal Depression Scale . In a pooled cross-sectional multivariable regression model adjusting for potentially confounding time-fixed and time-varying covariates , lagged IPV intensity had a statistically significant association with depression symptom severity ( regression coefficient b = 1.04 ; 95 % CI , 0.61–1.47 ) , with estimates from a quantile regression model showing greater adverse impacts at the upper end of the conditional depression distribution . Fitting a fixed effects regression model accounting for all time-invariant confounding ( e.g. , history of childhood sexual abuse ) yielded similar findings ( b = 1.54 ; 95 % CI , 1.13–1.96 ) . The magnitudes of the coefficients indicated that a one – st and ard-deviation increase in IPV intensity was associated with a 12.3 % relative increase in depression symptom severity over the same time period . The most important limitations of our study include exposure assessment that lacked measurement of sexual violence , which could have caused us to underestimate the severity of exposure ; the extended latency period in the lagged analysis , which could have caused us to underestimate the strength of the association ; and outcome assessment that was limited to the use of a screening instrument for depression symptom severity . Conclusions In this secondary analysis of data from a population -based , 3-y cluster-r and omized controlled trial , IPV had a statistically significant association with depression symptom severity . The estimated associations were relatively large in magnitude , consistent with findings from high-income countries , and robust to potential confounding by time-invariant factors . Intensive health sector responses to reduce IPV and improve women ’s mental health should be explored This study examined the efficacy of an enhanced intervention to reduce sexual risk of HIV/STI and harmful alcohol use among female sex workers in Mongolia . Women ( n = 166 ) were recruited and r and omized to either ( 1 ) a relationship-based HIV sexual risk reduction intervention ; ( 2 ) the same sexual risk reduction intervention plus motivational interviewing ; or ( 3 ) a control condition focused on wellness promotion . At three and six month follow-up , both treatment interventions and the wellness promotion condition were effective in reducing the percentage and the number of unprotected acts of vaginal sex with paying partners in the past 90 days . All three conditions demonstrated efficacy in reducing harmful alcohol use . No significant differences in effects were observed between conditions . Findings suggest that even low impact behavioral interventions can achieve considerable reductions of HIV/STI risk and harmful alcohol use with a highly vulnerable population in a low re source d setting Background Without effective treatment , PTSD and depression can cause persistent disability in disaster-affected population s. Methods Our objective was to test the efficacy of Interpersonal Psychotherapy ( IPT ) delivered by trained local personnel compared with treatment as usual ( TAU ) for Posttraumatic Stress Disorder ( PTSD ) and Major Depressive Disorder ( MDD ) among adults affected by the Sichuan 2008 earthquake . A small r and omized controlled trial of IPT + TAU versus TAU alone was delivered by local mental health personnel in Shifang , China . Between July 2011 and January 2012 , 49 adults ≥ 18 years with PTSD , MDD or both were enrolled and r and omized to 12 weekly sessions of IPT + TAU ( 27 ) or TAU ( 22 ) alone x 12 weeks . IPT was then offered to the TAU group . Unblinded follow up assessment s were conducted at three and six months . IPT was a 12 session , weekly one hour treatment delivered by local personnel who were trained and supervised in IPT . TAU was continuation of prescribed psychotropic medication ( if applicable ) and crisis counseling , as needed . Main Outcome ( s ) and Measures ( s ) : Clinician Administered PTSD Scale ( CAPS ) PTSD diagnosis ; Structured Clinical Interview for DSM-IV ( SCID ) for MDD diagnosis . Secondary measures included PTSD/depression symptoms , interpersonal conflict/anger , social support , self-efficacy and functioning . Results Using an intent-to-treat analysis , 22 IPT + TAU and 19 TAU participants were compared at three months post-baseline . A significantly greater reduction of PTSD and MDD diagnoses was found in the IPT group ( 51.9 % , 30.1 % , respectively ) versus the TAU group ( 3.4 % , 3.4 % , respectively ) . Despite the small sample , the estimates for time-by-condition analyses of target outcomes ( 2.37 for PTSD ( p = .018 ) and 1.91 for MDD ( p = .056 ) ) indicate the improvement was better in the IPT + TAU condition versus the TAU group . Treatment gains were maintained at 6 months for the IPT group . A similar treatment response was observed in the TAU group upon receipt of IPT . Conclusions This initial study shows that IPT is a promising treatment for reducing PTSD and depression , the two major mental health disorders affecting population s surviving natural disaster , using a design that builds local mental health care capacity . Trial Registration Clinical Trials . Gov number , NCT01624935 OBJECTIVES This study examined the efficacy of a relationship-based HIV/sexually transmitted disease prevention program for heterosexual couples and whether it is more effective when delivered to the couple or to the woman alone . METHODS Couples ( n = 217 ) were recruited and r and omized to ( 1 ) 6 sessions provided to couples together ( n = 81 ) , ( 2 ) the same intervention provided to the woman alone ( n = 73 ) , or ( 3 ) a 1-session control condition provided to the woman alone ( n = 63 ) . RESULTS The intervention was effective in reducing the proportion of unprotected and increasing the proportion of protected sexual acts . No significant differences in effects were observed between couples receiving the intervention together and those in which the woman received it alone . CONCLUSIONS This study demonstrates the efficacy of a relationship-based prevention program for couples at risk for HIV infection Background Intimate partner violence ( IPV ) is a critical public health and human rights concern globally , including for refugee women in low-re source setting s. Little is known about effective interventions for this population . IPV and psychological distress have a bi-directional relationship , indicating the potential benefit of a structured psychological component as part of efforts to reduce IPV for women currently in violent relationships . Methods This protocol describes a cluster r and omized controlled trial aim ed at evaluating an 8-session integrated psychological and advocacy intervention ( Nguvu ) with female adult survivors of past-year IPV displaying moderate to severe psychological distress . Outcomes are reductions in : recurrence of IPV ; symptoms of anxiety , depression and post-traumatic stress ( primary ) ; and functional impairment ( secondary ) . Hypothesized mediators of the intervention are improvements in social support , coping skills and support seeking . We will recruit 400 participants from existing women ’s support groups operating within villages in Nyarugusu refugee camp , Tanzania . Women ’s groups will be r and omized to receive the intervention ( Nguvu and usual care ) or usual care alone . All eligible women will complete a baseline assessment ( week 0 ) followed by a post-treatment ( week 9 ) and a 3-month post-treatment assessment ( week 20 ) . The efficacy of the intervention will be determined by between-group differences in the longitudinal trajectories of primary outcomes evaluated using mixed-effects models . Study procedures have been approved by Institutional Review Boards in the United States and Tanzania . Discussion This trial will provide evidence on the efficacy of a novel integrated group intervention aim ed at secondary prevention of IPV that includes a structured psychological component to address psychological distress . The psychological and advocacy components of the proposed intervention have been shown to be efficacious for their respective outcomes when delivered in isolation ; however , administering these approaches through a single , integrated intervention may result in synergistic effects given the interrelated , bidirectional relationship between IPV and mental health . Furthermore , this trial will provide information regarding the feasibility of implementing a structured intervention for IPV and mental health in a protracted humanitarian setting .Trial registration IS RCT N65771265 , June 27 , 2016 This paper describes the Common Elements Treatment Approach ( CETA ) for adults presenting with mood or anxiety problems developed specifically for use with lay counselors in low- and middle-income countries ( LMIC ) . Details of the intervention development , training , supervision , and decision-making process are presented . Case vignettes are used as examples throughout . Preliminary findings are presented on counselor/supervisor performance and client outcomes from practice cases completed prior to r and omized controlled trials ( RCT ) conducted at two sites for adult survivors of torture and /or systematic violence in ( a ) southern Iraq and ( b ) Thail and -Burma border . Data suggest that local supervisors and lay counselors with little prior mental health training or experience maintained fidelity to the model . The majority of pilot clients were retained in treatment , suggesting acceptability . Using the Reliable Change Index ( RCI ) for each individual we examined the number of clients above a minimal threshold ( z > 1.96 ) for each outcome . In Iraq 100 % of clients had RCIs above the threshold for depression and posttraumatic stress , and 81.8 % for impaired function . In Thail and , 81.3 % of clients had RCIs above minimum threshold for depression , 68.8 % for posttraumatic stress , and 37.5 % for impaired function . Implementation of CETA is discussed in relation to cultural issues within LMIC . These findings , combined with US-based evidence , suggest that a common elements approach warrants further development and testing as a means for addressing the treatment gap for mental health problems in LMIC Objective To assess the impact of the Women 's Health CoOp ( WHC ) on drug abstinence among vulnerable women having HIV counselling and testing ( HCT ) . Design R and omised trial conducted with multiple follow-ups . Setting 15 communities in Cape Town , South Africa . Participants 720 drug-using women aged 18–33 , r and omised to an intervention ( 360 ) or one of two control arms ( 181 and 179 ) with 91.9 % retained at follow-up . Interventions The WHC brief peer-facilitated intervention consisted of four modules ( two sessions ) , 2 h addressing knowledge and skills to reduce drug use , sex risk and violence ; and included role-playing and rehearsal , an equal attention nutrition intervention , and an HCT-only control . Primary outcome measures Biologically confirmed drug abstinence measured at 12-month follow-up , sober at last sex act , condom use with main and casual sex partners , and intimate partner violence . Results At the 12-month endpoint , 26.9 % ( n=83/309 ) of the women in the WHC arm were abstinent from drugs , compared with 16.9 % ( n=27/160 ) in the Nutrition arm and 20 % ( n=31/155 ) in the HCT-only control arm . In the r and om effects model , this translated to an effect size on the log odds scale with an OR of 1.54 ( 95 % CI 1.07 to 2.22 ) comparing the WHC arm with the combined control arms . Other 12-month comparison measures between arms were non-significant for sex risk and victimisation outcomes . At 6-month follow-up , women in the WHC arm ( 65.9 % , 197/299 ) were more likely to be sober at the last sex act ( OR1.32 ( 95 % CI 1.02 to 1.84 ) ) than women in the Nutrition arm ( 54.3 % , n=82/152 ) . Conclusions This is the first trial among drug-using women in South Africa showing that a brief intervention added to HCT results in greater abstinence from drug use at 12 months and a larger percentage of sexual activity not under the influence of substances . Trial registration number NCT00729391 Clinical OBJECTIVE Women who develop symptoms of posttraumatic stress disorder ( PTSD ) and depression subsequent to interpersonal trauma are at heightened risk for future intimate partner violence ( IPV ) victimization . Cognitive-behavioral therapy ( CBT ) is effective in reducing PTSD and depression symptoms , yet limited research has investigated the effectiveness of CBT in reducing risk for future IPV among interpersonal trauma survivors . METHOD This study examined the effect of CBT for PTSD and depressive symptoms on the risk of future IPV victimization in a sample of women survivors of interpersonal violence . The current sample included 150 women diagnosed with PTSD secondary to an array of interpersonal traumatic events ; they were participating in a r and omized clinical trial of different forms of cognitive processing therapy for the treatment of PTSD . Participants were assessed at 9 time points as part of the larger trial : pretreatment , 6 times during treatment , posttreatment , and 6-month follow-up . RESULTS As hypothesized , reductions in PTSD and in depressive symptoms during treatment were associated with a decreased likelihood of IPV victimization at a 6-month follow-up even after controlling for recent IPV ( i.e. , IPV from a current partner within the year prior to beginning the study ) and prior interpersonal traumas . CONCLUSIONS These findings highlight the importance of identifying and treating PTSD and depressive symptoms among interpersonal trauma survivors as a method for reducing risk for future IPV AIMS To evaluate whether an alcohol harm reduction intervention was associated with reduced interpersonal violence or engagement in sex work among female sex workers ( FSWs ) in Mombasa , Kenya . DESIGN R and omized controlled trial . SETTING HIV prevention drop-in centers in Mombasa , Kenya . PARTICIPANTS 818 women 18 or older in Mombasa who visited HIV prevention drop-in centers , were moderate-risk drinkers and engaged in transactional sex in past six months ( 410 and 408 in intervention and control arms , respectively ) . INTERVENTION 6 session alcohol harm reduction intervention . COMPARATOR 6 session non-alcohol related nutrition intervention . MEASUREMENTS In-person interviews were conducted at enrollment , immediately post-intervention and 6-months post-intervention . General linear mixed models examined associations between intervention assignment and recent violence ( physical violence , verbal abuse , and being robbed in the past 30 days ) from paying and non-paying sex partners and engagement in sex work in the past 30 days . FINDINGS The alcohol intervention was associated with statistically significant decreases in physical violence from paying partners at 6 months post-intervention and verbal abuse from paying partners immediately post-intervention and 6-months post-intervention . Those assigned to the alcohol intervention had significantly reduced odds of engaging in sex work immediately post-intervention and 6-months post-intervention . CONCLUSIONS The alcohol intervention was associated with reductions in some forms of violence and with reductions in engagement in sex work among FSWs in Mombasa , Kenya Background Gender-based violence and HIV are highly prevalent in the harsh environment of informal settlements and reducing violence here is very challenging . The group intervention Stepping Stones has been shown to reduce men ’s perpetration of violence in more rural areas , but violence experienced by women in the study was not affected . Economic empowerment interventions with gender training can protect older women from violence , but microloan interventions have proved challenging with young women . We investigated whether combining a broad economic empowerment intervention and Stepping Stones could impact on violence among young men and women . The intervention , Creating Futures , was developed as a new generation of economic empowerment intervention , which enabled livelihood strengthening though helping participants find work or set up a business , and did not give cash or make loans . Methods We piloted Stepping Stones with Creating Futures in two informal settlements of Durban with 232 out of school youth , mostly aged 18–30 and evaluated with a shortened interrupted time series of two baseline surveys and at 28 and 58 weeks post-baseline . 94/110 men and 111/122 women completed the last assessment , 85.5 % and 90.2 % respectively of those enrolled . To determine trend , we built r and om effects regression models with each individual as the cluster for each variable , and measured the slope of the line across the time points . Results Men ’s mean earnings in the past month increased by 247 % from R411 ( ~$40 ) to R1015 ( ~$102 , and women ’s by 278 % R 174 ( ~$17 ) to R 484 ( about $ 48 ) ( trend test , p < 0.0001 ) . There was a significant reduction in women ’s experience of the combined measure of physical and /or sexual IPV in the prior three months from 30.3 % to 18.9 % ( p = 0.037 ) . This was not seen for men . However both men and women scored significantly better on gender attitudes and men significantly reduced their controlling practice s in their relationship . The prevalence of moderate or severe depression symptomatology among men and suicidal thoughts decreased significantly ( p < 0.0001 and p = 0.01 ) . Conclusions These findings are very positive for an exploratory study and indicate that the Creating Futures/Stepping Stones intervention has potential for impact in these difficult areas with young men and women . Further evaluation is needed Summary Background Although structured psychological treatments are recommended as first-line interventions for harmful drinking , only a small fraction of people globally receive these treatments because of poor access in routine primary care . We assessed the effectiveness and cost-effectiveness of Counselling for Alcohol Problems ( CAP ) , a brief psychological treatment delivered by lay counsellors to patients with harmful drinking attending routine primary health-care setting s. Methods In this r and omised controlled trial , we recruited male harmful drinkers defined by an Alcohol Use Disorders Identification Test ( AUDIT ) score of 12–19 who were aged 18–65 years from ten primary health centres in Goa , India . We excluded patients who needed emergency medical treatment or inpatient admission , who were unable to communicate clearly , and who were intoxicated at the time of screening . Participants were r and omly allocated ( 1:1 ) by trained health assistants based at the primary health centres to enhanced usual care ( EUC ) alone or EUC combined with CAP , in r and omly sized blocks of four to six , stratified by primary health centre , and allocation was concealed with use of sequential numbered opaque envelopes . Physicians providing EUC and those assessing outcomes were masked . Primary outcomes were remission ( AUDIT score of < 8) and mean daily alcohol consumed in the past 14 days , at 3 months . Secondary outcomes were the effect of drinking , disability score , days unable to work , suicide attempts , intimate partner violence , and re source use and costs of illness . Analyses were on an intention-to-treat basis . We used logistic regression analysis for remission and zero-inflated negative binomial regression analysis for alcohol consumption . We assessed serious adverse events in the per- protocol population . This trial is registered with the ISCRTN registry , number IS RCT N76465238 . Findings Between Oct 28 , 2013 , and July 29 , 2015 , we enrolled and r and omly allocated 377 participants ( 188 [ 50 % ] to the EUC plus CAP group and 190 [ 50 % ] to the EUC alone group [ one of whom was subsequently excluded because of a protocol violation ] ) , of whom 336 ( 89 % ) completed the 3 month primary outcome assessment ( 164 [ 87 % ] in the EUC plus CAP group and 172 [ 91 % ] in the EUC alone group ) . The proportion with remission ( 59 [ 36 % ] of 164 in the EUC plus CAP group vs 44 [ 26 % ] of 172 in the EUC alone group ; adjusted prevalence ratio 1·50 [ 95 % CI 1·09–2·07 ] ; p=0·01 ) and the proportion abstinent in the past 14 days ( 68 [ 42 % ] vs 31 [ 18 % ] ; adjusted odds ratio 3·00 [ 1·76–5·13 ] ; p<0·0001 ) were significantly higher in the EUC plus CAP group than in the EUC alone group , but we noted no effect on mean daily alcohol consumed in the past 14 days among those who reported drinking in this period ( 37·0 g [ SD 44·2 ] vs 31·0 g [ 27·8 ] ; count ratio 1·08 [ 0·79–1·49 ] ; p=0·62 ) . We noted an effect on the percentage of days abstinent in the past 14 days ( adjusted mean difference [ AMD ] 16·0 % [ 8·1–24·1 ] ; p<0·0001 ) , but no effect on the percentage of days of heavy drinking ( AMD −0·4 % [ –5·7 to 4·9 ] ; p=0·88 ) , the effect of drinking ( Short Inventory of Problems score AMD–0·03 [ –1·93 to 1·86 ] ; p=0.97 ) , disability score ( WHO Disability Assessment Schedule score AMD 0·62 [ –0·62 to 1·87 ] ; p=0·32 ) , days unable to work ( no days unable to work adjusted odds ratio 1·02 [ 0·61–1·69 ] ; p=0.95 ) , suicide attempts ( adjusted prevalence ratio 1·8 [ –2·4 to 6·0 ] ; p=0·25 ) , and intimate partner violence ( adjusted prevalence ratio 3·0 [ –10·4 to 4·4 ] ; p=0·57 ) . The incremental cost per additional remission was $ 217 ( 95 % CI 50–1073 ) , with an 85 % chance of being cost-effective in the study setting . We noted no significant difference in the number of serious adverse events between the two groups ( six [ 4 % ] in the EUC plus CAP group vs 13 [ 8 % ] in the EUC alone group ; p=0·11 ) . Interpretation CAP delivered by lay counsellors plus EUC was better than EUC alone was for harmful drinkers in routine primary health-care setting s , and might be cost-effective . CAP could be a key strategy to reduce the treatment gap for alcohol use disorders , one of the leading causes of the global burden among men worldwide . Funding Wellcome Trust This r and omized clinical trial examined the relative efficacy of a relationship-based HIV/STI prevention intervention for women and their regular male sexual partners at 12 months post-intervention . A total of 217 couples were r and omized to ( 1 ) a six-session intervention provided to the woman and her sexual partner together ( n = 81 ) ; ( 2 ) the same intervention provided to the woman alone ( n = 73 ) ; or ( 3 ) a one-session health information education “ control ” provided to the woman alone ( n = 63 ) . Findings suggest the intervention was efficacious in reducing unprotected sex at 12 months post-intervention , compared with the education control group . No significant differences were observed when comparing whether couples received the intervention together or when the woman received it alone This study aim ed to examine the bi-directional relationship between intimate partner violence ( IPV ) and depression using prospect i ve data . Data from the Korean Welfare Panel Study ( KOWEPS ) were used to test whether IPV was associated with an increased overall level of depression and with the rate of change over time in depressive symptoms and whether this model of change in depressive symptoms was associated with subsequent incidences of IPV . This study utilized data from 3153 married women who participated in the KOWEPS from 2006 through 2009 . The KOWEPS is a panel study of a nationally representative sample of Korean households . The women 's responses to multiple questions adopted from the Conflict Tactics Scale ( CTS ) were used to create a dichotomous IPV variable at Wave1 and Wave4 . The CESD-11 was used to measure the women 's level of depression . We utilized a latent growth model ( LGM ) of depression using IPV at Wave1 as a predictor and IPV at Wave4 as an outcome predicted by the model parameters of the LGM of depression . We found that after controlling for the effects of age , education , social support and income , IPV at Wave1 was positively associated with overall depression levels and negatively associated with the growth rate of depression . Further , IPV at Wave4 was associated with the intercept and the slope of the depression LGM and with IPV at Wave1 . The overall model fit the data well . This study indicated that experiencing IPV influences a woman 's level of depression in terms of its overall level and rate of change , which , in turn , influences the victim 's likelihood of experiencing subsequent IPV This prospect i ve study examines the impact of four posttraumatic stress disorder ( PTSD ) symptom clusters ( hyperarousal , reexperiencing , numbing , and avoidance ) on reabuse over 1 year among women exposed to intimate partner violence ( IPV ) . The covariates include severity of IPV , a history of childhood violence , and characteristics of the abusive relationship . Although both hyperarousal and numbing symptoms were higher at baseline among women subsequently reabused , only numbing symptoms increased the odds of reabuse after controlling for the covariates . Greater IPV severity and shorter relationship duration also increased the risk of reabuse . Results indicate that specific symptoms of PTSD , especially numbing , need to be addressed to increase the safety of women seeking services for IPV OBJECTIVES We evaluated changes in social capital following group-based cognitive processing therapy ( CPT ) for female survivors of sexual violence . METHODS We compared CPT with individual support in a cluster-r and omized trial in villages in South Kivu province , Democratic Republic of the Congo . Local psychosocial assistants delivered the interventions from April through July 2011 . We evaluated differences between CPT and individual support conditions for structural social capital ( i.e. , time spent with nonkin social network , group membership and participation , and the size of financial and instrumental support networks ) and emotional support seeking . We analyzed intervention effects with longitudinal r and om effects models . RESULTS We obtained small to medium effect size differences for 2 study outcomes . Women in the CPT villages increased group membership and participation at 6-month follow-up and emotional support seeking after the intervention compared with women in the individual support villages . CONCLUSIONS Results support the efficacy of group CPT to increase dimensions of social capital among survivors of sexual violence in a low-income conflict-affected context BACKGROUND Few population -based studies have assessed the physical and mental health consequences of both psychological and physical intimate partner violence ( IPV ) among women or men victims . This study estimated IPV prevalence by type ( physical , sexual , and psychological ) and associated physical and mental health consequences among women and men . METHODS The study analyzed data from the National Violence Against Women Survey ( NVAWS ) of women and men aged 18 to 65 . This r and om-digit-dial telephone survey included questions about violent victimization and health status indicators . RESULTS A total of 28.9 % of 6790 women and 22.9 % of 7122 men had experienced physical , sexual , or psychological IPV during their lifetime . Women were significantly more likely than men to experience physical or sexual IPV ( relative risk [RR]=2.2 , 95 % confidence interval [CI]=2.1 , 2.4 ) and abuse of power and control ( RR=1.1 , 95 % CI=1.0 , 1.2 ) , but less likely than men to report verbal abuse alone ( RR=0.8 , 95 % CI=0.7 , 0.9 ) . For both men and women , physical IPV victimization was associated with increased risk of current poor health ; depressive symptoms ; substance use ; and developing a chronic disease , chronic mental illness , and injury . In general , abuse of power and control was more strongly associated with these health outcomes than was verbal abuse . When physical and psychological IPV scores were both included in logistic regression models , higher psychological IPV scores were more strongly associated with these health outcomes than were physical IPV scores . CONCLUSIONS Both physical and psychological IPV are associated with significant physical and mental health consequences for both male and female victims |
11,358 | 31,446,536 | In conclusion , TTS has significantly different clinical characteristics than ACS .
However , the in-hospital and long-term overall mortality rates are not trivial for TTS patients , and some presenting features ( underlying diseases , male sex , advanced age , low LVEF and shock ) were significantly associated with all-cause mortality | null | null |
11,359 | 28,332,385 | A recent systematic review of 21 r and omized , controlled trials suggested that fish-oil supplementation during pregnancy reduces the risk of both preterm delivery and low birth weight.2 It is therefore possible that the positive effect in relation to preterm birth might outweigh the potential for an increased risk of hemorrhage | In relation to preterm birth and low birth weight , it has been hypothesized that fish-oil supplementation during pregnancy might prevent both outcomes . | Background Susceptibility variants identified by genome-wide association studies ( GWAS ) have modest effect sizes . Whether such variants provide incremental information in assessing risk for common ' complex ' diseases is unclear . We investigated whether measured and imputed genotypes from a GWAS data set linked to the electronic medical record alter estimates of coronary heart disease ( CHD ) risk . Methods Study participants ( n = 1243 ) had no known cardiovascular disease and were considered to be at high , intermediate , or low 10-year risk of CHD based on the Framingham risk score ( FRS ) which includes age , sex , total and HDL cholesterol , blood pressure , diabetes , and smoking status . Of twelve SNPs identified in prior GWAS to be associated with CHD , four were genotyped in the participants as part of a GWAS . Genotypes for seven SNPs were imputed from HapMap CEU population using the program MACH . We calculated a multiplex genetic risk score for each patient based on the odds ratios of the susceptibility SNPs and incorporated this into the FRS . Results The mean ( SD ) number of risk alleles was 12.31 ( 1.95 ) , range 6 - 18 . The mean ( SD ) of the weighted genetic risk score was 12.64 ( 2.05 ) , range 5.75 - 18.20 . The CHD genetic risk score was not correlated with the FRS ( P = 0.78 ) . After incorporating the genetic risk score into the FRS , a total of 380 individuals ( 30.6 % ) were reclassified into higher-(188 ) or lower-risk groups ( 192 ) . Conclusion A genetic risk score based on measured/imputed genotypes at 11 susceptibility SNPs , led to significant reclassification in the 10-y CHD risk categories . Additional prospect i ve studies are needed to assess accuracy and clinical utility of such reclassification BACKGROUND Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease . The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown . METHODS Using a polygenic score of DNA sequence polymorphisms , we quantified genetic risk for coronary artery disease in three prospect i ve cohorts - 7814 participants in the Atherosclerosis Risk in Communities ( ARIC ) study , 21,222 in the Women 's Genome Health Study ( WGHS ) , and 22,389 in the Malmö Diet and Cancer Study ( MDCS ) - and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available . We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors : no current smoking , no obesity , regular physical activity , and a healthy diet . RESULTS The relative risk of incident coronary events was 91 % higher among participants at high genetic risk ( top quintile of polygenic scores ) than among those at low genetic risk ( bottom quintile of polygenic scores ) ( hazard ratio , 1.91 ; 95 % confidence interval [ CI ] , 1.75 to 2.09 ) . A favorable lifestyle ( defined as at least three of the four healthy lifestyle factors ) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle ( defined as no or only one healthy lifestyle factor ) , regardless of the genetic risk category . Among participants at high genetic risk , a favorable lifestyle was associated with a 46 % lower relative risk of coronary events than an unfavorable lifestyle ( hazard ratio , 0.54 ; 95 % CI , 0.47 to 0.63 ) . This finding corresponded to a reduction in the st and ardized 10-year incidence of coronary events from 10.7 % for an unfavorable lifestyle to 5.1 % for a favorable lifestyle in ARIC , from 4.6 % to 2.0 % in WGHS , and from 8.2 % to 5.3 % in MDCS . In the BioImage Study , a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category . CONCLUSIONS Across four studies involving 55,685 participants , genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease . Among participants at high genetic risk , a favorable lifestyle was associated with a nearly 50 % lower relative risk of coronary artery disease than was an unfavorable lifestyle . ( Funded by the National Institutes of Health and others . ) BACKGROUND Effective medical therapies are lacking for the treatment of neurofibromatosis type 1-related plexiform neurofibromas , which are characterized by elevated RAS-mitogen-activated protein kinase ( MAPK ) signaling . METHODS We conducted a phase 1 trial of selumetinib ( AZD6244 or ARRY-142886 ) , an oral selective inhibitor of MAPK kinase ( MEK ) 1 and 2 , in children who had neurofibromatosis type 1 and inoperable plexiform neurofibromas to determine the maximum tolerated dose and to evaluate plasma pharmacokinetics . Selumetinib was administered twice daily at a dose of 20 to 30 mg per square meter of body-surface area on a continuous dosing schedule ( in 28-day cycles ) . We also tested selumetinib using a mouse model of neurofibromatosis type 1-related neurofibroma . Response to treatment ( i.e. , an increase or decrease from baseline in the volume of plexiform neurofibromas ) was monitored by using volumetric magnetic resonance imaging analysis to measure the change in size of the plexiform neurofibroma . RESULTS A total of 24 children ( median age , 10.9 years ; range , 3.0 to 18.5 ) with a median tumor volume of 1205 ml ( range , 29 to 8744 ) received selumetinib . Patients were able to receive selumetinib on a long-term basis ; the median number of cycles was 30 ( range , 6 to 56 ) . The maximum tolerated dose was 25 mg per square meter ( approximately 60 % of the recommended adult dose ) . The most common toxic effects associated with selumetinib included acneiform rash , gastrointestinal effects , and asymptomatic creatine kinase elevation . The results of pharmacokinetic evaluations of selumetinib among the children in this trial were similar to those published for adults . Treatment with selumetinib result ed in confirmed partial responses ( tumor volume decreases from baseline of ≥20 % ) in 17 of the 24 children ( 71 % ) and decreases from baseline in neurofibroma volume in 12 of 18 mice ( 67 % ) . Disease progression ( tumor volume increase from baseline of ≥20 % ) has not been observed to date . Anecdotal evidence of decreases in tumor-related pain , disfigurement , and functional impairment was observed . CONCLUSIONS Our early-phase data suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT01362803 . ) IMPORTANCE The use of mitogen-activated protein kinase ( MAPK ) kinase ( MEK ) inhibitors has become more common in the treatment of systemic cancer . These agents have been associated with a central serous-like retinopathy in some patients . Recognition of such retinal findings and the relatively benign nature of these events is important to avoid unnecessary intervention , including the cessation of a potentially life-prolonging medication . OBJECTIVES To evaluate the presence and characteristics of subretinal fluid ( SRF ) associated with the use of MEK inhibitors in the treatment of systemic cancer and to correlate the presence of SRF with visual acuity and symptoms over time . DESIGN , SETTING , AND PARTICIPANTS Post hoc analysis was conducted of prospect ively collected data from 51 patients with locally advanced or metastatic cancer undergoing treatment with the MEK inhibitor binimetinib in 1 of 4 clinical trials . All clinical trial participants underwent complete ophthalmic examination by retina specialists at a private practice in Boston , Massachusetts , and were monitored between February 29 , 2012 , and January 8 , 2014 . The examination included Snellen-measured visual acuity , dilated fundus examination , and spectral-domain optical coherence tomography at baseline , biweekly for 2 months , then monthly for the remainder of their trial participation . Post hoc design and data analysis were performed between December 1 , 2013 , and June 20 , 2014 . MAIN OUTCOMES AND MEASURES Visual symptoms , visual acuity , fundus appearance , and the presence and characteristics of SRF noted on optical coherence tomography . The characteristics of angiograms performed at the discretion of the treating physician were review ed . RESULTS Of the 51 participants , 18 ( 35 % ) were men ; the mean ( SD ) age was 60 ( 13 ) years ( range , 32 - 87 years ) . Forty-six ( 90 % ) study participants developed SRF during the study period , with 9 ( 20 % ) experiencing symptoms at any point . The mean ( SD ) central retinal thickness of 39 study participants who developed SRF at the first visit increased from 280 ( 26 ) µm at baseline to 316 ( 43 ) µm at the first visit after starting binimetinib treatment ( paired t test , P < .001 ) . On examination , SRF appeared as elevated , yellow-orange pockets in the fovea and /or along the arcades . Corresponding optical coherence tomographic imaging revealed SRF beneath the interdigitation zone . The fovea was affected in 37 of 46 ( 80 % ) individuals ; the location of SRF accumulation varied . Visual symptoms were mild and mainly transient , occurring in 9 participants with SRF ( 20 % ; 95 % CI , 10%-33 % ) . Only 2 participants ( 4 % ) were found to have SRF at the last study visit after discontinuation of treatment with binimetinib . Both had Snellen-measured visual acuity of 20/25 or better . CONCLUSIONS AND RELEVANCE The presence of SRF was common in study participants undergoing treatment with the MEK inhibitor binimetinib . Visual symptoms were mild and mainly transient . The presence of SRF did not lead to permanent ocular sequelae . Cessation of life-extending treatment with MEK inhibitors is not indicated when SRF is present Background — Whether knowledge of genetic risk for coronary heart disease ( CHD ) affects health-related outcomes is unknown . We investigated whether incorporating a genetic risk score ( GRS ) in CHD risk estimates lowers low-density lipoprotein cholesterol ( LDL-C ) levels . Methods and Results — Participants ( n=203 , 45–65 years of age , at intermediate risk for CHD , and not on statins ) were r and omly assigned to receive their 10-year probability of CHD based either on a conventional risk score ( CRS ) or CRS + GRS ( + GRS ) . Participants in the + GRS group were stratified as having high or average/low GRS . Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician . We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake , physical activity levels , or statin use . Participants ( mean age , 59.4±5 years ; 48 % men ; mean 10-year CHD risk , 8.5±4.1 % ) were allocated to receive either CRS ( n=100 ) or + GRS ( n=103 ) . At the end of the study period , the + GRS group had a lower LDL-C than the CRS group ( 96.5±32.7 versus 105.9±33.3 mg/dL ; P=0.04 ) . Participants with high GRS had lower LDL-C levels ( 92.3±32.9 mg/dL ) than CRS participants ( P=0.02 ) but not participants with low GRS ( 100.9±32.2 mg/dL ; P=0.18 ) . Statins were initiated more often in the + GRS group than in the CRS group ( 39 % versus 22 % , P<0.01 ) . No significant differences in dietary fat intake and physical activity levels were noted . Conclusions — Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01936675 |
11,360 | 22,071,813 | No effects for the composite process-of-care indicators for either condition were found , but there were some improvements in the individual process-of-care indicators .
There was an effect on the mortality rates for acute myocardial infa rct ion .
The small body of evidence available provides no consistent evidence that the public release of performance data changes consumer behaviour or improves care .
Evidence that the public release of performance data may have an impact on the behaviour of healthcare professionals or organisations is lacking | BACKGROUND It is becoming increasingly common to release information about the performance of hospitals , health professionals or providers , and healthcare organisations into the public domain .
However , we do not know how this information is used and to what extent such reporting leads to quality improvement by changing the behaviour of healthcare consumers , providers and purchasers , or to what extent the performance of professionals and providers can be affected .
OBJECTIVES To determine the effectiveness of the public release of performance data in changing the behaviour of healthcare consumers , professionals and organisations . | OBJECTIVE To assess the effects of CAHPS health plan performance information on plan choices and decision processes by New Jersey Medicaid beneficiaries . DATA SOURCES / STUDY SETTING The study sample was a statewide sample of all new Medicaid cases that chose Medicaid health plans during April 1998 . The study used state data on health maintenance organization ( HMO ) enrollments and survey data for a subset of these cases . STUDY DESIGN An experimental design was used , with new Medicaid cases r and omly assigned to experimental or control groups . The experimental group received a CAHPS report along with the st and ard enrollment material s , and the control group did not . DATA COLLECTION The HMO enrollment data were obtained from the state in June 1998 , and evaluation survey data were collected from July to October 1998 . PRINCIPAL FINDINGS No effects of CAHPS information on HMO choices were found for the total sample . Further examination revealed that only about half the Medicaid cases said they received and read the plan report and there was an HMO with dominant Medicaid market share but low CAHPS performance scores . The subset of cases who read the report and did not choose this dominant HMO chose HMOs with higher CAHPS scores , on average , than did those in an equivalent control group . CONCLUSIONS Health plan performance information can influence plan choices by Medicaid beneficiaries , but will do so only if they actually read it . These findings suggest a need for enhancing dissemination of the information as well as further education to encourage informed choices Most plan report cards that compare the performance of health plans have framed the decision about plan choice as an opportunity to get better- quality care . This study uses a controlled experimental design to examine the effect of reframing the health plan choice decision to one that emphasizes protecting oneself from possible risk . The findings show that framing the health plan decision using a risk message has a consistent and significant positive impact on how consumers comprehend , value , and weight comparative performance information OBJECTIVE To assess whether presentation approaches design ed to be more meaningful result in greater weighting of quality information in decisions . An emerging body of research indicates that the way information is presented affects how it is interpreted and how it is weighted in decisions . Comparative health plan performance reports are not being used by consumers possibly because the information presented is difficult to use . The next generation of these reports should be design ed to support decision making . DESIGN AND STUDY PARTICIPANTS The study uses a controlled experimental design . Participants ( n = 162 ) were r and omly assigned to different conditions and asked to complete tasks related to using quality information and making health plan selection s. Dependent variables included the amount of weight given to quality information in choices and decision accuracy . RESULTS Some presentation approaches make it easier for users to process and integrate quality data into their choices . However , other presentation formats influence consumers ' decisions in ways that undermine their self-interest . CONCLUSIONS Findings indicate that presenting quality data in a more evaluable format increases the weight it carries in consumer decisions . Every change made in the presentation of comparative data has the potential to influence decisions . Those who disseminate information have a responsibility to be aware of how they use that influence and to direct it in productive and defensible ways . The alternative is to manipulate people in ways that are unknown , are not thought out , or are not defensible , but are no less manipulative Many consumers are offered two or more employer-sponsored health insurance plans , and competition among health plans for subscribers is promoted as a mechanism for balancing health care costs and quality . Yet consumers may not receive the information necessary to make informed health plan choices . This study tests the effects on health plan choice of providing supplemental decision-support material s to inform consumers about expected health plan costs . Our main finding is that such information induces consumers to bear more risk , especially those in relatively good health . Thus our results suggest that working-age , privately insured consumers currently may be over-insuring for medical care Abstract Objective : To assess whether crude league tables of mortality and league tables of risk adjusted mortality accurately reflect the performance of hospitals . Design : Longitudinal study of mortality occurring in hospital . Setting : 9 neonatal intensive care units in the United Kingdom . Subjects : 2671 very low birth weight or preterm infants admitted to neonatal intensive care units between 1988 and 1994 . Main outcome measures : Crude hospital mortality and hospital mortality adjusted using the clinical risk index for babies ( CRIB ) score . Results : Hospitals had wide and overlapping confidence intervals when ranked by mortality in annual league tables ; this made it impossible to discriminate between hospitals reliably . In most years there was no significant difference between hospitals , only r and om variation . The apparent performance of individual hospitals fluctuated substantially from year to year . Conclusions : Annual league tables are not reliable indicators of performance or best practice ; they do not reflect consistent differences between hospitals . Any action prompted by the annual league tables would have been equally likely to have been beneficial , detrimental , or irrelevant . Mortality should be compared between groups of hospitals using specific criteria —such as differences in the volume of patients , staffing policy , training of staff , or aspects of clinical practice —after adjusting for risk . This will produce more reliable estimates with narrower confidence intervals , and more reliable and rapid conclusions . Key messages League tables are being used increasingly to evaluate hospital performance in the United Kingdom In annual league tables the rankings of nine neonatal intensive care units in different hospitals had wide and overlapping confidence intervals and their rankings fluctuated substantially over six years Annual league tables of hospital mortality were inherently unreliable for comparing hospital performance or for indicating best practice s The UK government 's commitment to using annual league tables of outcomes such as mortality to monitor services and the spread of best practice s should be reconsidered Prospect i ve studies of risk adjusted outcome in hospitals grouped according to specific characteristics would provide better information and be a better use of re OBJECTIVE To determine whether an intervention design ed to inform and guide patients in choosing a primary care provider ( PCP ) could increase satisfaction and trust . DESIGN A r and omized controlled trial conducted at the Santa Clara Medical Center of the Kaiser Permanente Medical Care Program in Northern California . PATIENTS AND METHODS Patients needing a PCP were r and omly assigned to Informed Choice ( provider-level information offered ) , Guided Choice ( PCP names provided based on the similarity of patients ' and practitioners ' patient-centered beliefs , and patients then chose ) , or Usual Care . One year later , mailed question naires asked about patients ' trust and satisfaction , perceptions of the choice process , and trust and satisfaction with Kaiser Permanente . More than 5000 adult patients were linked with a PCP as part of the project , and completed surveys were returned by 2437 patients . RESULTS Neither intervention arm generated better matches on patient-practitioner beliefs than Usual Care ; however , trust and satisfaction were higher among Guided Choice patients . Across study arms , patient-practitioner belief discrepancy showed a consistent positive association with trust , satisfaction , and attitudes toward Kaiser Permanente . CONCLUSIONS The discrepancy between patient and practitioner beliefs about care is an important determinant of trust and satisfaction , and involving patients in the selection of their PCP can have an independent positive effect . It should be possible to build on the experience of this project to develop programs that better match patients and practitioners within managed care plans OBJECTIVE To examine the effect of providing the Medicare & You h and book on consumers ' attitudes and behavior regarding health plan decision making . DATA SOURCE A national sample of 3,738 Medicare beneficiaries who were surveyed in late 1999 and early 2000 was employed . Data were collected using a mail survey with telephone follow-up ; the response rate was 76 percent . STUDY DESIGN Medicare beneficiaries were r and omly assigned to a control group that received no Medicare-related in formation as part of the study , or to a treatment group that received a copy of the 2000 version of the Medicare & You h and book as part of a national mailing . Half of the treat men t group ( the " re-mail " group ) received a second copy of the h and book along wit h their mail survey instrument . PRINCIPAL FINDINGS The control and treatment groups did not differ regarding their level of satisfaction with or confidence in their current choice of health plan according to predicted mean values . Treatment group beneficiaries had a significantly higher propensity to either change or consider changing health plans relative to beneficiaries in the control group . Controlling for other factors , 5 percent of treatment group members switched health insurance plans during the prior month compared to 3 percent of control group members . there were no significant differences in predicted values between the re-mail and no re-mail groups in any of the models . Type of supplemental insurance was also highly related to all three outcomes . CONCLUSIONS Findings from this and a prior parallel study suggest th at messages contained in the Medicare & You h and book can have an influence on beneficiaries and the Medicare market . Thus , careful attention should be given to the wording and intent of these messages . This is particularly relevant given the current administration 's emphasis on increasing enrollment in Medicare+Choice plans and findings from earlier research reporting that beneficiaries felt the h and book was pressuring them to enroll in managed care OBJECTIVE To examine the effect of providing new Medicare information material s on consumers ' attitudes and behavior about health plan choice . DATA SOURCE New and experienced Medicare beneficiaries who resided in the Kansas City metropolitan statistical area during winter 1998 - 99 were surveyed . More than 2,000 computer-assisted telephone interviews were completed across the two beneficiary population s with a mean response rate of 60 percent . STUDY DESIGN Medicare beneficiaries were r and omly assigned to a control group or one of three treatment groups that received varying amounts and types of new Medicare information material s. One treatment group received the Health Care Financing Administrations 's pilot Medicare & You 1999 h and book , a second group received the same version of the h and book and a Medicare version of the Consumer Assessment of Health Plans ( CAHPS ) report , and a third treatment group received the Medicare & You bulletin , an abbreviated version of the h and book . PRINCIPAL FINDINGS Results of the study suggest that the federal government 's new consumer information material s are having some influence on Medicare beneficiaries ' attitudes and behaviors about health plan decision making . Experienced beneficiary treatment group members were significantly more confident with their current health plan choice than control group members , but new beneficiaries were significantly less likely to use the new material s to choose or change health plans than control group members . In general the effects on confidence and health plan switching did not vary across the different treatment material s. CONCLUSIONS The 1999 version of the Medicare & You material s contained a message that it is not necessary to change health plans . This message appears to have decreased the likelihood of using the new material s to choose or change plans , whereas other material s to which beneficiaries are exposed may encourage plan switching . Because providing more information to beneficiaries did not result in commensurate increases in confidence levels or rate of health plan switching , factors other than the amount of information , such as how the information is presented , may be more critical than volume This evaluation tested if Consumer Assessment of Health Plans Study ( CAHPS ) information on plan performance affected health plan choices by new beneficiaries in Iowa Medicaid . New cases entering Medicaid in selected counties during February through May 2000 were assigned r and omly to experimental or control groups . The control group received st and ard Medicaid enrollment material s , and the experimental group received these material s plus a CAHPS report . We found that CAHPS information did not affect health plan choices by Iowa Medicaid beneficiaries , similar to previously reported findings for New Jersey Medicaid . However , it did affect plan choice in an earlier laboratory experiment . The value of this information may be limited to a subset of We assessed the efficacy of material s that integrated comparative information on cost , benefits , and quality for employer-based retiree health plans and Medicare Advantage plans in a r and omized experiment to test the impact of content and format . Results indicate that older consumers who received the intervention material s found the material s easier to use , gained greater knowledge about Medicare from them , were more likely to value comparative quality information , were more likely to select higher quality plans , and were more likely to choose a plan that reflected the dimensions they found most important compared to older consumers receiving the control material CONTEXT Publicly released report cards on hospital performance are increasingly common , but whether they are an effective method for improving quality of care remains uncertain . OBJECTIVE To evaluate whether the public release of data on cardiac quality indicators effectively stimulates hospitals to undertake quality improvement activities that improve health care processes and patient outcomes . DESIGN , SETTING , AND PATIENTS Population -based cluster r and omized trial ( Enhanced Feedback for Effective Cardiac Treatment [ EFFECT ] ) of 86 hospital corporations in Ontario , Canada , with patients admitted for acute myocardial infa rct ion ( AMI ) or congestive heart failure ( CHF ) . INTERVENTION Participating hospital corporations were r and omized to early ( January 2004 ) or delayed ( September 2005 ) feedback of a public report card on their baseline performance ( between April 1999 and March 2001 ) on a set of 12 process-of-care indicators for AMI and 6 for CHF . Follow-up performance data ( between April 2004 and March 2005 ) also were collected . MAIN OUTCOME MEASURES The co primary outcomes were composite AMI and CHF indicators based on 12 AMI and 6 CHF process-of-care indicators . Secondary outcomes were the individual process-of-care indicators , a hospital report card impact survey , and all-cause AMI and CHF mortality . RESULTS The publication of the early feedback hospital report card did not result in a significant systemwide improvement in the early feedback group in either the composite AMI process-of-care indicator ( absolute change , 1.5 % ; 95 % confidence interval [ CI ] , -2.2 % to 5.1 % ; P = .43 ) or the composite CHF process-of-care indicator ( absolute change , 0.6 % ; 95 % CI , -4.5 % to 5.7 % ; P = .81 ) . During the follow-up period , the mean 30-day AMI mortality rates were 2.5 % lower ( 95 % CI , 0.1 % to 4.9 % ; P = .045 ) in the early feedback group compared with the delayed feedback group . The hospital mortality rates for CHF were not significantly different . CONCLUSION Public release of hospital-specific quality indicators did not significantly improve composite process-of-care indicators for AMI or CHF . TRIAL REGISTRATION http:// clinical trials.gov Identifier : NCT00187460 BACKGROUND Although there is evidence that consumers want comparative quality information , most studies indicate that consumers make limited use of the data in decision making . The reasons for the limited use appear to be the complexity of the information and the difficulty of processing and using the amount of information in reports . The purpose of this investigation was to determine whether there are approaches to reporting comparative information that make it easier for consumers to comprehend the information . Further , the degree to which consumers who have a low level of skill can accurately use that information when it is presented in a format that is easier to use was examined . METHODS The study used an experimental design to examine how different presentation approaches affect the use of information . Participants were r and omly assigned to different conditions and were asked to review information and complete a decision task related to using comparative information and making health plan selection s. Two separate convenience sample s were used in the study : an elderly Medicare sample ( N = 253 ) , and a nonelderly sample ( N = 239 ) . RESULTS The findings indicate that there are data presentation approaches that help consumers who have lower skills use information more accurately . Some of these presentation strategies ( for example , relative stars ) improve comprehension among the lower skilled , and other strategies ( for example , evaluative labels ) appear to aid those in the midrange of comprehension skill . CONCLUSIONS Using these approaches in reporting would likely increase the use of the comparative information and increase the efficacy of reporting efforts Abstract Objective To learn how patients in Medicare , the US medical insurance programme that covers elderly patients , made decisions about where to undergo major surgery and how they would make future decisions . Design National telephone interview study . Setting United States . Participants 510 r and omly selected Medicare beneficiaries who had undergone an elective , high risk procedure about 3 years earlier — abdominal aneurysm repair ( n = 103 ) , heart valve replacement surgery ( n = 96 ) , or resection of the bladder ( n = 119 ) , lung ( n = 128 ) , or stomach ( n = 64 ) for cancer . Response rates were 48 % among eligible survivors and 68 % among those able to participate . Results Although all participants could choose where to have surgery , only 55 % said there was an alternative hospital in their area where they could have gone . Overall , only 10 % of respondents seriously considered going elsewhere for surgery . Few respondents ( 11 % ) looked for information to compare hospitals . Almost all respondents thought their hospital and surgeon had good reputations ( 94 % and 88 % , respectively ) , beliefs mostly determined by what their referring doctors said . When asked how much various factors would influence their advice to a friend about choosing where to go for major surgery , surgeon reputation was the most influential ( 78 % said it would influence their advice “ a lot ” ) , followed by the hospital having “ nationally recognised ” surgeons ( 63 % ) , and then various performance data ( surgeon volume ( 58 % ) , nurse : patient ratios ( 49 % ) , number of operations carried out by the hospital ( 48 % ) , and hospital operative mortality ( 45 % ) ) . Forty per cent said they would act on mortality data , indicating that they would switch from their initial choice of hospital to a different one if its mortality was a percentage point lower ( that is , 3 % v 4 % ) . Conclusion Some respondents cl aim ed they would switch hospital for elective surgery on the basis of mortality data . Since most respondents relied on their referring physician 's opinion to decide where to have surgery , surgical performance data ought to be accessible to referring physicians |
11,361 | 25,192,153 | When comparing the percentage of newly formed bone using various grafting material s with NH , calcium sulfate , magnesium enriched hydroxyapatite , and porcine-derived bone grafts offered the best outcomes .
However , due to the heterogeneity of the included studies , the search was extended to determine which type of graft result ed in greatest bone formation . | INTRODUCTION The aim of this systematic review was to evaluate , from a histological point of view , the amount of newly formed bone in ridge preservation procedures using various graft material s in comparison with natural healing ( NH ) and to determine which is the ideal type of graft to be used . | The aim of the study was to determine the fate of demineralized freeze-dried bone allograft ( DFDBA ) used in conjunction with a barrier membrane in the management of extraction sockets and deficient alveolar ridges , and to compare the amount of bone formed with that found in untreated sites . Ten biopsies were obtained from 8 grafted patients . Five biopsies were harvested from untreated sites during routine implant placement and analyzed for comparison . In the socket management procedure , DFDBA was packed tightly into the socket and covered with an exp and ed polytetrafluoroethylene ( e-PTFE ) membrane . Primary closure was achieved in all cases . In the ridge regeneration procedure , cortical columns were placed in the ridge projecting outward approximately 3 mm to create and maintain space for DFDBA particles packed between them ; the columns were then covered by an e-PTFE membrane . Healing time ranged from 8 to 23 months . At the time of implant placement , bone cores ( 7 mm x 2 mm ) were harvested , fixed in 10 % formalin solution , and prepared for histologic examination . At the light microscopic level , no inflammation or fibrous encapsulation was observed . New bone formation on and around DFDBA particles was widespread . Histomorphometric analysis of the grafted specimens and untreated sites was carried out using the trabecular bone volume ( TBV ) index . The TBV in the maxillary test specimens was 55.03 % , as compared to 57.33 % of control cores . Unaltered DFDBA made up 8.7 % of the test specimens . In the m and ibular biopsies , the TBV was 56.6 % , while for the controls it was 40.9 % . The volume of DFDBA still present was 2.45 % . The results tended to indicate that treatment with DFDBA in conjunction with cell occlusive membranes will result in new bone formation , predominantly by the process of conduction , which appears to be similar in amount and nature to that found in cores harvested from healed nonfunctional edentulous areas BACKGROUND Reduction of alveolar height and width after tooth extraction may present problems for implant placement , especially in the anterior maxilla where bone volume is important for biologic and esthetic reasons . Different graft material s have been proposed to minimize the reduction in ridge volume . The aim of this study was to compare radiographic and histomorphometric results of magnesium-enriched hydroxyapatite ( MHA ) and calcium sulfate ( CS ) grafts in fresh sockets after tooth extraction s. METHODS Forty-five fresh extraction sockets with three bone walls were selected in 15 patients . A split-mouth design was used : 15 sockets on the right side of the jaw received MHA , 15 sockets on the left side received CS , and 15 r and om unfilled sockets were considered the control ( C ) group . Intraoral digital radiographs were taken at baseline and at 3 months after graft material placement . At 3 months , cylinder bone sample s were obtained for histology and histomorphometry analysis . RESULTS The difference in mean radiographic vertical bone level from baseline to 3 months was -2.48 + /- 0.65 mm in the CS group , -0.48 + /- 0.21 mm in the MHA group , and -3.75 + /- 0.63 mm in the unfilled C group . Statistically significant differences ( P < 0.05 ) were found between CS and MHA groups and between MHA and C groups . Histologic examination revealed bone formation in all treated sites ; trabecular bone assessment did not differ among apical , mesial , and coronal portions of the specimens . Mean vital bone measurements for CS , MHA , and C groups were 45.0 % + /- 6.5 % , 40.0 % + /- 2.7 % , and 32.8 % + /- 5.8 % , respectively . Statistically significant differences ( P < 0.05 ) were found among all groups . Connective tissue percentages averaged 41.5 % + /- 6.7 % for the CS group , 41.3 % + /- 1.3 % for the MHA group , and 64.6 % + /- 6.8 % for the C group . Statistically significant differences ( P < 0.05 ) were found between CS and C groups and between MHA and C groups . The CS-grafted sockets showed 13.9 % + /- 3.4 % residual implant material , whereas the MHA-treated sockets showed 20.2 % + /- 3.2 % residual material . The difference between the groups was statistically significant ( P < 0.05 ) . CONCLUSIONS Radiographs revealed a greater reduction of alveolar ridge in the CS group than in the MHA group . Histologic examination showed more bone formation and faster resorption in the CS group and more residual implant material in the MHA group BACKGROUND The placement of different graft material s and /or the use of occlusive membranes to cover the extraction socket entrance are techniques aim ed at preserving/reducing alveolar ridge resorption . The use of grafting material s in fresh extraction sockets has , however , been question ed because particles of the grafted material have been found in alveolar sockets 6 - 9 months following their insertion . AIM The aims of the study were to ( i ) . evaluate whether alveolar ridge resorption following tooth extraction could be prevented or reduced by the application of a bioabsorbable polylactide-polyglycolide sponge used as a space filler , compared to natural healing by clot formation , and ( ii ) . evaluate histologically the amount and quality of bone tissue formed in the sockets , 6 months after the use of the bioabsorbable material . MATERIAL AND METHODS Thirty-six patients , undergoing periodontal therapy , participated in this study . All patients were scheduled for extraction of one or more compromised teeth . Following elevation of full-thickness flaps and extraction of teeth , measurements were taken to evaluate the distance between three l and marks ( mesio-buccal , mid-buccal , disto-buccal ) on individually prefabricated stents , and the alveolar crest . Twenty-six alveolar sockets ( test ) were filled with a bioabsorbable polylactide-polyglycolide acid sponge ( Fisiograft ) , while 13 sockets ( controls ) were allowed to heal without any filling material . The flaps were sutured with no attempt to achieve primary closure of the surgical wound . Re-entry for implant surgery was performed 6 months following the extraction s. Thirteen biopsies ( 10 test and three control sites ) were harvested from the sites scheduled for implant placement . RESULTS The clinical measurements at 6 months revealed , in the mesial-buccal site , a loss of bone height of 0.2 mm ( 1.4 SD ) in the test and 0.6 mm ( 1.1 SD ) in the controls ; in the mid-buccal portion a gain of 1.3 mm ( 1.9 SD ) in the test and a loss of 0.8 mm ( 1.6 SD ) in the controls ; and in the distal portion a loss of 0.1 mm ( 1.1 SD ) in the test and of 0.8 ( 1.5 SD ) mm in the controls . The biopsies harvested from the test sites revealed that the new bone formed at 6 months was mineralized , mature and well structured . Particles of the grafted material could not be identified in any of the 10 test biopsies . The bone formed in the control sites was also mature and well structured . CONCLUSION The results of this study indicate that alveolar bone resorption following tooth extraction may be prevented or reduced by the use of a bioabsorbable synthetic sponge of polylactide-polyglycolide acid . The quality of bone formed seemed to be optimal for dental implant insertion OBJECTIVES To histologically analyze the early angiogenesis-osteogenesis interplay in post- extraction sockets augmented with magnesium-enriched hydroxyapatite ( Mg-enriched HA ) . MATERIAL AND METHODS Ten post- extraction sites underwent post- extraction ridge preservation procedure . According to r and omization , sites were divided into two balanced groups and bone specimens were collected 2 or 4 months after surgery . Sections were stained with hematoxylin/eosin , Masson-Goldner trichrome , and tartrate-resistant acid phosphatase ( TRAP ) , respectively . Furthermore , indirect immunohistochemistry was performed using alkaline phosphatase , CD34 and caveolin-1 antibodies . Mean values and st and ard deviations were calculated for each outcome variable . Data were then compared using one-way ANOVA test . P < 0.05 was considered statistically significant . RESULTS Histomorphometric analysis presented 15.0 % ( ±3.5 ) regenerated bone after 2 months of healing . After 4 months , regenerated bone increased 5.1-fold up to 77.4 % ( ± 8.6 ) ( P < 0.001 ) . On the contrary , vessels and capillary reduced from 645 ( ±33 ) to 255 ( ± 94 ) ( caveolin-1 expression , P = 0.008 ) . These findings were confirmed by CD34 expression ( 301 ± 95 and 88 ( ±24 ) , respectively , at 2 and 4 months ( P = 0.046 ) . CONCLUSIONS Within the limits of the present r and omized controlled study , it can be concluded that Mg-enriched HA is a suitable material for socket preservation and ensures early angiogenesis and early osteogenesis The aim of this study was to investigate the healing of human extraction sockets filled with Bio-Oss particles ( Geistlich Pharma AG , Wolhusen , Switzerl and ) . In 21 subjects , providing a total of 31 healing sites , at least one tooth was scheduled for extraction and the extraction sites for implant therapy . The dimensions of the alveolar ridge at the extraction sites were considered insufficient and required augmentation concomitant with tooth extraction . There were three treatment groups . In group A , the extraction sockets were covered with a Bio-Gide membrane ( Geistlich Pharma AG ) and in group B the extraction sockets were filled with Bio-Oss . The extraction sockets in group C were left to heal spontaneously . Biopsies from the extraction sites were collected at the time of implant installation . Sample s from group A showed large amounts of lamellar bone and bone marrow and small proportions of woven bone . Sites grafted with Bio-Oss ( group B ) were comprised of connective tissue and small amounts of newly formed bone surrounding the graft particles . Only 40 % of the circumference of the Bio-Oss particles was in contact with woven bone . Sites from group C were characterized by the presence of mineralized bone and bone marrow BACKGROUND Various material s have been used immediately following tooth extraction to fill and /or cover the socket in an attempt to limit or prevent ridge resorption . The purpose of the present pilot study was to establish a reliable model to investigate the effect of various bone graft and bone replacement material s on extraction socket healing . This study also compared healing extraction sockets 6 to 8 months postimplantation of a bioactive glass ( BG ) or demineralized freeze-dried bone allograft ( DFDBA ) to an unfilled socket control ( C ) . METHODS Following tooth extraction , a total of 30 sockets in 19 patients were r and omly divided into 3 treatment groups : 10 sockets received BG , 10 sockets DFDBA , and 10 sockets served as unfilled controls . Primary coverage was achieved by flap advancement over each socket . Six to 8 months post extraction at time of implant placement , histological cores of the treatment sites were obtained . These cores were processed , undecalcified sections prepared and stained with Stevenel blue/van Gieson 's picric fuchsin , and histomorphometrically analyzed . Vital bone , connective tissue and marrow , and residual graft particles were reported as a percentage of the total core . RESULTS A model system was described in humans and used to evaluate the healing response in the 3 treatment groups . Results concluded that mean vital bone present was 59.5 % for BG- , 34.7 % for DFDBA- , and 32.4 % for C-treated sites . These differences were not statistically significant . However , the residual implant material was significantly higher in DFDBA-treated ( 13.5 % ) versus BG-treated sockets ( 5.5 % ) . CONCLUSIONS Although the differences in percent vital bone were not statistically significant among the 3 treatment groups in this pilot study , BG material was observed to act as an osteoconductive material which had a positive effect on socket healing at 6 to 8 months post extraction . Further research following implant placement in treated and control sockets is warranted to determine if bone implant contact is improved in BG-filled versus unfilled sockets To solve some of the problems inherent in bone regeneration , various types of graft material s , matrix , putty , and gel delivery systems have been developed . These deliver demineralized bone matrix ( DBM ) to a graft site and maintain it in an appropriate position to achieve favorable results . This prospect i ve study review ed 10 cases of extraction immediate grafting with a putty – DBM delivery system . Five patients were male and 5 female . At intervals ranging from 4 to 21 months post extraction grafting , bone cores were harvested at the time of surgical insertion of Replace endosteal two-stage implants . All patients were restored with single-tooth self-st and ing prostheses . Bone quality and quantity in each of the bone cores were evaluated . All 10 cases were completed with favorable outcomes BACKGROUND Tooth extraction typically leads to loss of ridge width and height . The primary aim of this 6-month r and omized , controlled , blinded , clinical study was to determine whether ridge preservation would prevent post- extraction resorptive changes as assessed by clinical and histologic parameters . METHODS Twenty-four patients , 10 males and 14 females , aged 28 to 76 ( mean 51.5 + /- 13.6 ) , requiring a non-molar extraction and delayed implant placement were r and omly selected to receive either extraction alone ( EXT ) or ridge preservation ( RP ) using tetracycline hydrated freeze-dried bone allograft ( FDBA ) and a collagen membrane . A replaced flap , which did not completely cover the sockets , was used . Following extraction , horizontal and vertical ridge dimensions were determined using a modified digital caliper and an acrylic stent , respectively . Prior to implant placement , a 2.7 x 6.0 mm trephine core was obtained and preserved in formalin for histologic analysis . RESULTS The width of the RP group decreased from 9.2 + /- 1.2 mm to 8.0 + /- 1.4 mm ( P<0.05 ) , while the width of the EXT group decreased from 9.1 + /- 1.0 mm to 6.4 + /- 2.2 mm ( P<0.05 ) , a difference of 1.6 mm . Both the EXT and RP groups lost ridge width , although an improved result was obtained in the RP group . Most of the resorption occurred from the buccal ; maxillary sites lost more width than m and ibular sites . The vertical change for the RP group was a gain of 1.3 + /- 2.0 mm versus a loss of 0.9 + /- 1.6 mm for the EXT group ( P<0.05 ) , a height difference of 2.2 mm . Histologic analysis revealed more bone in the RP group : about 65 + /- 10 % versus 54 + /- 12 % in the EXT group . The RP group included both vital bone ( 28 % ) and non-vital ( 37 % ) FDBA fragments . CONCLUSIONS Ridge preservation using FDBA and a collagen membrane improved ridge height and width dimensions when compared to extraction alone . These dimensions may be more suitable for implant placement , especially in areas where loss of ridge height would compromise the esthetic result . The quantity of bone observed on histologic analysis was slightly greater in preservation sites , although these sites included both vital and non-vital bone . The most predictable maintenance of ridge width , height , and position was achieved when a ridge preservation procedure was employed After tooth extraction , varying amounts of bone resorption occur because of qualitative and quantitative changes at the edentulous site of the alveolar process . The aims of this r and omized controlled clinical trial were ( 1 ) to compare the post extraction changes in residual ridge dimensions during spontaneous healing with those during socket preservation , ( 2 ) to analyze the histologic and histomorphometric aspects of the grafted sockets , and ( 3 ) to compare probing procket depth ( PPD ) and clinical attachment level ( CAL ) changes at teeth adjacent to extraction sites . Forty-eight teeth were extracted from 41 patients referred for extraction of 1 or more maxillary or m and ibular premolars or molars . The edentulous sites were r and omly assigned to the control ( EXT , extraction alone ) or experimental groups ( SP , extraction and socket preservation ) . In the SP group , the sockets were filled with bovine bone mineral and covered with porcine collagen membrane . At baseline and after 4 months , PPD , gingival recession ( REC ) , and CAL were measured at teeth adjacent to the edentulous sites . The changes in ridge dimensions from baseline to 4 months were assessed on dental casts . At 4 months , bone was harvested from the grafted areas in the SP group and the edentulous areas in the EXT group . PPD , REC , and CAL were comparable between groups . However , from baseline to 4 months , the SP group showed significantly less reduction in ridge width ( 1.04 ± 1.08 mm vs 4.48 ± 0.65 mm , P < .001 ) and height ( 0.46 ± 0.46 mm vs 1.54 ± 0.33 mm , P < .001 ) . Histologically , the grafted sockets exhibited various stages of bone maturation and formation without inflammatory responses . No significant difference in the mineralized and nonmineralized fractions was noted between the groups . Socket preservation using bovine bone mineral and porcine collagen membrane considerably limits the amount of horizontal and vertical bone resorption when compared with extraction alone OBJECTIVE This systematic review aims to evaluate the scientific evidence on the efficacy in the surgical protocol s design ed for preserving the alveolar ridge after tooth extraction and to evaluate how these techniques affect the placement of dental implants and the final implant supported restoration . MATERIAL AND METHODS A thorough search in MEDLINE - PubMed , Embase and the Cochrane Central Register of controlled trials ( CENTRAL ) was conducted up to February 2011 . R and omized clinical trials and prospect i ve cohort studies with a follow-up of at least 3 months reporting changes on both the hard and soft tissues ( height and /or width ) of the alveolar process ( mm or % ) after tooth extraction were considered for inclusion . RESULTS The screening of titles and abstract s result ed in 14 publications meeting the eligibility criteria . Data from nine of these 14 studies could be grouped in the meta-analyses . Results from the meta-analyses showed a statistically significant greater ridge reduction in bone height for control groups as compared to test groups ( weighted mean differences , WMD = -1.47 mm ; 95 % CI [ -1.982 , -0.953 ] ; P < 0.001 ; heterogeneity : I(2 ) = 13.1 % ; χ(2 ) P-value = 0.314 ) and a significant greater reduction in bone width for control groups compared to the test groups ( WMD = -1.830 mm ; 95 % CI [ -2.947 , -0.732 ] ; P = 0.001 ; heterogeneity : I(2 ) = 0 % ; χ(2 ) P-value = 0.837 ) . Subgroup analysis was based on the surgical protocol used for the socket preservation ( flapless/flapped , barrier membrane/no membrane , primary intention healing/no primary healing ) and on the measurement method utilized to evaluate morphological changes . Meta-regression analyses demonstrated a statistically significant difference favoring the flapped subgroup in terms of bone width ( meta-regression ; slope = 2.26 ; 95 % IC [ 1.01 ; 3.51 ] ; P = 0.003 ) . CONCLUSIONS The potential benefit of socket preservation therapies was demonstrated result ing in significantly less vertical and horizontal contraction of the alveolar bone crest . The scientific evidence does not provide clear guidelines in regards to the type of bio material , or surgical procedure , although a significant positive effect of the flapped surgery was observed . There are no data available to draw conclusions on the consequences of such benefits on the long-term outcomes of implant therapy BACKGROUND Animal and human research es have shown that immediate implant placement into extraction sockets failed to prevent socket dimensional changes following tooth extraction . It has been suggested that a minimal width of 1 - 2 mm of buccal bone is necessary to maintain a stable vertical dimension of the alveolar crest . AIM To determine the dimensions of the bony wall at extraction sites in the esthetic zone ( anterior teeth and premolars in the maxilla ) and relate it to immediate implant placement . METHODS As part of an ongoing prospect i ve r and omized-controlled multicenter clinical study on immediate implant placement , the width of the buccal and palatal bony walls was recorded at 93 extraction sites . RESULTS The mean width of the buccal and palatal bony walls was 1 and 1.2 mm , respectively ( P<0.05 ) . For the anterior sites ( canine to canine ) , the mean width of the buccal bony wall was 0.8 mm . For the posterior ( premolar ) sites , it was 1.1 mm ( P<0.05 ) . In the anterior sites , 87 % of the buccal bony walls had a width < or = 1 mm and 3 % of the walls were 2 mm wide . In the posterior sites , the corresponding values were 59 % and 9 % , respectively . CONCLUSIONS If the criterion of a minimal buccal bone width of 2 mm to maintain a stable buccal bony wall is valid , only a limited number of sites in the anterior maxilla display such a clinical situation . The data suggested that in the majority of extraction sites in the anterior maxilla , thin ( < or = 1 mm ) buccal walls were present . This , in turn , means that in most clinical situations encountered , augmentation procedures are needed to achieve adequate bony contours around the implant PURPOSE The aim of this r and omized , controlled , blinded clinical study was to compare ridge dimensions and histologic characteristics of ridges preserved with 2 different graft material s. MATERIAL S AND METHODS Twenty-four subjects , each requiring a nonmolar extraction and delayed implant placement , were r and omly selected to receive ridge preservation treatment with either an allograft in an experimental putty carrier plus a calcium sulfate barrier ( PUT ) or a bovine-derived xenograft ( BDX ) plus a collagen membrane . Horizontal and vertical ridge dimensions were determined using a digital caliper and a template . At 4 months post extraction , a trephine core was obtained for histologic analysis . RESULTS The average ridge width decreased by 0.50 mm for both groups ( P < .05 ) . The midbuccal vertical change for the PUT group was a loss of 0.3+/-0.7 mm versus a gain of 0.7+/-1.2 mm for the BDX group , a difference of 1.0 mm ( P > .05 ) . Histologic analysis revealed vital bone in the PUT group of about 61%+/-9 % versus 26%+/-20 % for the BDX group ( P < .05 ) . DISCUSSION Greater vital bone fill in the PUT group may be attributable to earlier and greater vascular invasion of the carrier material . The putty material was characterized by ease of h and ling , simple placement , and enhanced graft particle containment . CONCLUSIONS Allograft mixed with an experimental putty carrier produced significantly more vital bone fill than did the use of a xenograft with no carrier material . Ridge width and height dimensions were similarly preserved with both graft material BACKGROUND The preservation of bone volume immediately after tooth removal might be necessary to optimize the success of implant placement in terms of esthetics and function . The objectives of this r and omized clinical trial were two-fold : 1 ) to compare the bone dimensional changes following tooth extraction with extraction plus ridge preservation using corticocancellous porcine bone and a collagen membrane ; and 2 ) to analyze and compare histologic and histomorphometric aspects of the extraction -alone sites to the grafted sites . METHODS Forty subjects who required tooth extraction and implant placement were enrolled in this study . Using a computer-generated r and omization list , the subjects were r and omly assigned to the control group ( EXT ; extraction alone ) or to the test group ( RP ; ridge-preservation procedure with corticocancellous porcine bone and collagen membrane ) . The following parameters were assessed immediately after extraction and 7 months prior to implant placement : plaque index , gingival index , bleeding on probing , horizontal ridge width , and vertical ridge changes . A bone biopsy was taken from the control and test sites 7 months after the surgical treatment . Histologic and histomorphometric analyses were also performed . RESULTS A significantly greater horizontal reabsorption was observed at EXT sites ( 4.3+/-0.8 mm ) compared to RP sites ( 2.5+/-1.2 mm ) . The ridge height reduction at the buccal side was 3.6+/-1.5 mm for the extraction -alone group , whereas it was 0.7+/-1.4 mm for the ridge-preservation group . Moreover , the vertical change at the lingual sites was 0.4 mm in the ridge-preservation group and 3 mm in the extraction -alone group . Forty biopsies were harvested from the experimental sites ( test and control sites ) . The biopsies harvested from the grafted sites revealed the presence of trabecular bone , which was highly mineralized and well structured . Particles of the grafted material could be identified in all sample s. The bone formed in the control sites was also well structured with a minor percentage of mineralized bone . The amount of connective tissue was significantly higher in the extraction -alone group than in the ridge-preservation group . CONCLUSIONS The ridge-preservation approach using porcine bone in combination with collagen membrane significantly limited the resorption of hard tissue ridge after tooth extraction compared to extraction alone . Furthermore , the histologic analysis showed a significantly higher percentage of trabecular bone and total mineralized tissue in ridge-preservation sites compared to extraction -alone sites 7 months after tooth removal PURPOSE In this prospect i ve study , bone formation in human extraction sockets augmented with Bio-Oss Collagen after a 12-week healing period was quantified and compared to bone formation in unaugmented extraction sockets . MATERIAL S AND METHODS Selected patients with four-walled extraction sockets were included in this prospect i ve study . After extraction , the sockets were r and omly augmented using Bio-Oss Collagen or left to heal unfilled without raising a mucoperiosteal flap . At the time of implant placement , histologic specimens were obtained from the socket and analyzed . Statistical analysis was performed using the Wilcoxon signed-rank test . RESULTS Twenty-five patients with a total of 39 sockets ( 20 augmented , 19 unaugmented ) were included in the study and the histologic specimens analyzed . All specimens were free of inflammatory cells . The mean overall new bone formation in the augmented sites was 25 % ( range , 8%-41 % ) and in the unaugmented sockets it was 44 % ( range , 3%-79 % ) . There was a significant difference in the rate of new bone formation between the grafted and ungrafted sockets and a significant difference in the bone formation rate in the apical compared to the coronal regions of all sockets , independent of the healing mode . CONCLUSION This descriptive study demonstrated that bone formation in Bio-Oss Collagen-grafted human extraction sockets was lower than bone formation in ungrafted sockets . Bone formation occurred in all specimens with varying degrees of maturation independent of the grafting material and was initiated from the apical region OBJECTIVES The aim of this study was to evaluate ( i ) the degree of bone mineralization in the alveolar sockets 3 months following the use of a bio-absorbable graft material and ( ii ) the degree of resorption of the grafted material . MATERIAL S Twenty patients , undergoing periodontal therapy , participated in this study . All patients were scheduled for extraction of one or more compromised monoradicular teeth and scheduled for replacement of the extracted teeth with dental implants . METHODS Following elevation of full-thickness flaps and extraction of teeth , the alveolar sockets were filled with a bioabsorbable polylactide-polyglycolide acid sponge ( Fisiograft ) ( Test group - T ) or natural healing by clot formation was allowed ( Control group - C ) . The flaps were sutured with no attempt to achieve primary closure of the surgical wound . Re-entry for implant surgery was performed 3 months following the extraction s. RESULTS Fifteen biopsies ( seven T and nine C ) were harvested from the sites where the implants were placed . The biopsies harvested from the T sites revealed that the alveolar sockets healed with newly trabecular bone , highly mineralized and well structured . Particles of the grafted material could not be identified in any of the T biopsies . The bone formed in the C sites was also well structured , with a slightly minor percentage of mineralized bone . In both T and C biopsies , the apical portion presented a higher degree of mineralization compared with the coronal portion . CONCLUSIONS The results of this study indicated that the use of a bio-absorbable synthetic sponge of polylactide-polyglycolide acid did not interfere with the formation of new bone in the alveolar sockets and that the characteristics of the 3-month newly formed bone seemed to be optimal for dental implants ' insertion . The biocompatibility , safety and characteristics of Fisiograft suggest that the material is suitable for filling alveolar sockets following extraction s , to prevent volume reduction and collapse of the overlying soft tissue flaps BACKGROUND The objectives of this study are to compare differences in histologic and clinical healing following tooth extraction and ridge preservation using two different xenograft treatment protocol s. METHODS Forty-four patients with a non-molar tooth that required extraction and planned implant placement were r and omly allocated into two ridge preservation protocol groups . Protocol 1 used a xenograft material consisting of 90 % anorganic bovine bone in combination with 10 % porcine collagen fibers combined with a resorbable bilayer membrane composed of non-cross-linked porcine types I and III collagen . Protocol 2 used a xenograft sponge composed of 70 % cross-linked type I bovine collagen coated with a layer of non-sintered hydroxyapatite mineral on its surface combined with a resorbable membrane composed of type I porcine collagen cross-linked by natural ribose glycation . Following 21 weeks of healing , clinical measurements were repeated , and a core biopsy was obtained and prepared for histologic evaluation of percentages of vital bone , residual graft , and connective tissue/other ( CT/other ) . RESULTS Similar percentages of CT/other were detected between protocol s , with no significant difference between groups ( P = 0.763 ) . A significantly greater percentage of vital bone was detected in specimens in protocol 2 ( P < 0.001 ) . Protocol 1 presented with a mean of 32.83 % ± 14.72 % vital bone , 13.44 % ± 11.57 % residual graft material , and 53.73 % ± 6.76 % CT/other . Protocol 2 presented with a mean of 47.03 % ± 9.09 % vital bone , no detectable residual graft material , and 52.97 % ± 9.09 % CT/other . Clinical ly , no significant differences in dimensional changes were evident between ridge preservation protocol s. CONCLUSION To the best of our knowledge , this study represents the first r and omized controlled trial to evaluate clinical and histologic differences seen when using these two xenograft protocol s for ridge preservation BACKGROUND Various grafting material s have been used for preservation of the dimensions of the residual alveolar ridge following tooth extraction . The purpose of this study was to evaluate clinical , histomorphometric , and radiographic healing 4 months after tooth extraction with or without placement of a putty-form anorganic bovine-derived hydroxyapatite matrix combined with a synthetic cell-binding peptide P-15 ( Putty P15 ) to determine the effect on alveolar ridge preservation following exodontia . METHODS Twenty-four consecutive subjects in need of extraction of maxillary premolars were recruited . Recruited subjects were r and omly assigned to the test ( Putty P15 and bioabsorbable collagen wound dressing material ) or control ( bioabsorbable collagen wound dressing material only ) group . Data were recorded at 1 , 2 , 4 , 8 , and 16 weeks after ridge preservation procedures . At 16 weeks , a reentry surgery was performed , clinical measurements were repeated , and bone core biopsies were obtained for histomorphometric analysis prior to dental implant placement . RESULTS The control group had a mean reduction in ridge height of -0.56 + /- 1.04 mm , whereas alveolar ridge height appeared to remain unchanged in the test group ( 0.15 + /- 1.76 ) . The test group showed a mean reduction in ridge width of -1.31 + /- 0.96 mm , whereas the mean value for the control group was -1.43 + /- 1.05 mm . No statistical significance was observed between the groups . Mean bone density was significantly superior in the test group ( 2.08 + /- 0.65 versus 3.33 + /- 0.65 ) . Histomorphometric analyses revealed similar percentages of bone vitality ( test : 29.92 % + /- 8.46 % ; control : 36.54 % + /- 7.73 % ) . Comparable percentages of bone marrow and fibrous tissue also were observed ( test : 65.25 % + /- 6.41 % ; control : 62.67 % + /- 7.41 % ) . Only 6.25 % of the Putty P15 particles remained at 4 months in the analyzed biopsies . CONCLUSION A favorable response was observed when Putty P15 was applied to extraction sockets , suggesting that it may be useful for alveolar ridge preservation prior to dental implant placement BACKGROUND The aim of this r and omized , controlled clinical trial is to determine whether ridge preservation using an osteoinductive allograft ( test ) would prevent ridge resorption and promote bone maturation compared to extraction alone ( control ) . METHODS Seventeen patients ( 20 total sites ) , in need of a non-molar extraction and delayed implant placement were r and omly selected to receive either ridge preservation or extraction alone . A cone-beam computed tomography was completed with a radiographic stent in place before extraction and 10 to 12 weeks postoperatively for dimensional and buccal plate analyses . Bone cores were taken for micro-computed tomography ( microCT ) and histologic analyses . RESULTS Resorption of the alveolar ridge occurred at all sites with no statistically significant differences found between test and control sites . A significant correlation was found between the initial buccal plate thickness and the loss of vertical ridge height . microCT and histologic analyses found a mean new bone volume of 44.9 % with microCT and 37.4 % with histology in test sites and 39 % and 35.5 % , respectively , in control sites . The residual graft volume was 2.4 % with microCT and 4.5 % with histology . CONCLUSIONS Test and control sites lost similar amounts of alveolar ridge , with the loss of buccolingual width occurring predominantly at the expense of the buccal bone . A thicker buccal plate was associated with less ridge loss in the vertical dimension . The percentage of new bone was not statistically significant between either the test or control sites , using either microCT or histologic analyses BACKGROUND The ridge-preservation technique has been applied with membrane alone or membrane plus graft . Synthetic peptides , mimicking bioactive growth factor or extracellular matrix protein , have been attempted to provide an active surface of the bio material s in inducing bone formation while alleviating the limitations of whole protein such as short half-life , immunologic responses . The aim of the present clinical study is to examine the osteogenic effect of synthetic oligopeptide-coated bone mineral compared to bone graft without peptide when applied with collagen membrane in a ridge-preservation technique . METHODS Synthetic oligopeptide from the collagen-binding domain of osteopontin was chemically synthesized and coated onto the surface of bone mineral particulates . Ridge preservations were performed at 44 extraction sites in 42 patients ( 20 males and 22 females ) . Analyses of clinical parameters and histomorphometric evaluations were conducted to compare the osteogenic effects of the grafts between baseline and 6 months . RESULTS In the bone grafts of the control group treated without synthetic peptide , new bone formation was only seen around borders and basal areas . However , new bone was observed broadly in the defects of the test group treated with synthetic peptide-coated bone mineral , as seen not only at peripheries but also in the central and coronal parts of bone cores in the defects . The average percentage of new bone formation was significantly higher in the test group ( 5.3 % ± 8.3 % versus 10.4 % ± 4.6 % ) . The contact percentages between the graft particles and the new bone were 8.2 % ± 11.3 % for the control group and 20.4 % ± 7.5 % for the test group ( P < 0.05 ) . CONCLUSIONS The ridge-preservation approach using synthetic oligopeptide-coated bone mineral with collagen membrane effectively prevented the resorption of hard tissue with higher bone-to-graft contact , and the oligopeptide-coated bone may be a choice for ridge-preservation procedures while assuring new bone formation OBJECTIVE The aim of this study was to clinical ly and histologically analyze the healing of grafted sockets by mineralized human bone allograft ( MHBA ) and nongrafted sockets , correlating the results with buccal plate thickness . MATERIAL AND METHODS Thirty-one sockets were r and omly split into control ( CG ) and treatment ( MHBA grafted ) ( TG ) groups and , subsequently , into four subgroups according to buccal plate thickness : a ≤ 1 mm and b > 1 mm . Ridge thickness , depth , and height were monitored . Four months after , at implant placement , a bone core biopsy for histologic and morphometric analyses was taken . RESULTS The differences of buccal height ( TG-a -0.27 and CG-a -1.17 mm ) and width ( TG-a 0.55 and CG-a 2.67 mm , TG-b 0.12 and CG-b 1.17 mm ) were statistically significant . The increase in bone amount CG-b ( 28.17 % ) compared with CG-a ( 16.98 % ) was statistically significant . Soft tissue amount of TG-b ( 54.21 % ) and TG-a ( 56.91 % ) was lower than that of CG-b ( 71.83 % ) and CG-a ( 83.01 % ) , both being statistically significant ( P = 0.002 ) . CONCLUSIONS The results proved that thin buccal plates had a worse outcome on socket healing and that network formation by MBHA not only predisposes a successful implant insertion but also acts as size keeper BACKGROUND The objective of this study is to compare histologic and clinical healing following tooth extraction and ridge preservation with either cortical or cancellous freeze-dried bone allograft ( FDBA ) in non-molar extraction sockets . METHODS Forty patients requiring implant placement were enrolled , with 20 patients r and omly assigned to each group ( cortical versus cancellous FDBA ) . All of the allograft material s were obtained from the same donor to control for variability between donors and processing . Patients returned after 17 to 21 weeks ( average : 18.2 weeks ) , and a 2-mm-diameter core biopsy was obtained before implant placement . Histomorphometric analysis was performed to determine percentage of new bone formation , residual graft material , and non-mineralized connective tissue (CT)/other material . Clinical measurements of ridge dimensions were taken at the time of tooth extraction and again at implant placement . RESULTS There was no significant difference in new bone formation between the cortical and cancellous FDBA groups ( P = 0.857 ) . A significantly greater percentage of residual graft material was detected in the cortical FDBA group compared with the cancellous FDBA group ( P = 0.019 ) . A significantly greater percentage of non-mineralized CT/other material was found in the cancellous FDBA group compared with the cortical FDBA group ( P = 0.040 ) . The only significant clinical difference between groups was a greater loss of lingual ridge height in the cancellous group . CONCLUSIONS This is the first reported study to compare the histologic changes following tooth extraction with ridge preservation in humans using cortical versus cancellous FDBA . There were no differences in the percentage of new bone formation between the groups The goal of the present clinical study was to evaluate new bone formation in human extraction sockets augmented with enamel matrix derivatives ( EMD ) and Bio-Oss Collagen . Patients with symmetrical single-rooted teeth in the bilateral quadrants of the upper jaw condemned for extraction participated in this study . Following extraction , the sockets ( 20 sockets ) were r and omly augmented using either EMD or Bio-Oss Collagen . After 3 months of healing , bone biopsies were obtained and prepared for histological analyses . Dental implants were then placed . Implant stability quotient ( ISQ ) readings were obtained for each implant at the time of surgery and at 1 and 3 months postoperatively . The mean new bone formation was 34.57 ± 25.67 % in the EMD sites and 28.80 ± 16.14 % in the Bio-Oss Collagen sites . There was no significant difference between the groups . The ISQ values were significantly higher for the implants placed in the EMD sites at the first and third months , but no significant differences were observed in the ISQ values for the implants placed in the Bio-Oss Collagen sites . The augmentation of the extraction sockets with EMD or Bio-Oss Collagen leads to similar behaviour in bone regeneration PURPOSE The aim of this study was to evaluate the potential of an autologous bone marrow graft in preserving the alveolar ridges following tooth extraction . MATERIAL S Thirteen patients requiring extraction s of 30 upper anterior teeth were enrolled in this study . They were r and omized into two groups : seven patients with 15 teeth to be extracted in the test group and six patients with 15 teeth to be extracted in the control group . Hematologists collected 5 ml of bone marrow from the iliac crest of the patients in the test group immediately before the extraction s. Following tooth extraction and elevation of a buccal full-thickness flap , titanium screws were positioned throughout the buccal to the lingual plate and were used as reference points for measurement purpose s. The sockets were grafted with an autologous bone marrow in the test sites and nothing was grafted in the control sites . After 6 months , the sites were re-opened and bone loss measurements for thickness and height were taken . Additionally , before implant placement , bone cores were harvested and prepared for histologic and histomorphometric evaluation . RESULTS The test group showed better results ( P<0.05 ) in preserving alveolar ridges for thickness , with 1.14+/-0.87 mm ( median 1 ) of bone loss , compared with the control group , which had 2.46+/-0.4 mm ( median 2.5 ) of bone loss . The height of bone loss on the buccal plate was also greater in the control group than in the test group ( P<0.05 ) , 1.17+/-0.26 mm ( median 1 ) and 0.62 + 0.51 ( median 0.5 ) , respectively . In five locations in the control group , expansion or bone grafting complementary procedures were required to install implants while these procedures were not required for any of the locations in the test group . The histomorphometric analysis showed similar amounts of mineralized bone in both the control and the test groups , 42.87+/-11.33 % ( median 43.75 % ) and 45.47+/-7.21 % ( median 45 % ) , respectively . CONCLUSION These findings suggest that the autologous bone marrow graft can contribute to alveolar bone repair after tooth extraction BACKGROUND The aim of this investigation is to evaluate clinical and histologic outcome of using medical- grade calcium sulfate hemihydrate ( MGCSH ) mixed with platelet-rich plasma ( PRP ) for extraction socket preservation graft before implant placement . METHODS This study is a single-site , r and omized and controlled investigation . Sixteen patients with a non-restorable tooth requiring extraction followed by implant placement were enrolled in this study . After extraction of a tooth , eight selected patients r and omly received MGCSH mixed with PRP in the extraction sockets ( test group ) , and eight selected patients r and omly received collagen resorbable plug dressing material ( control group ) . At the time of extraction and 3 months later ( at implant placement surgery ) , vertical and horizontal socket dimensions were measured . Bone core sample s were retrieved from the center of the healed socket before implant placement for histomorphometric analysis . RESULTS There was a statistically significant difference between the two groups based on histomorphometric analysis ( P < 0.05 ) . New vital bone percentage regenerated after 3 months of healing was 66.5 % ± 10.4 % in sockets grafted with MGCSH mixed with PRP compared to 38.3 % ± 9.3 % collagen resorbable plug . There was no statistically significant difference in the amount of vertical and horizontal bone resorption ( P > 0.05 ) between groups . In all cases but two in the control group , implants were placed with primary stability . CONCLUSION MGCSH mixed with PRP showed greater vital bone volume at 3 months with rapid enhancement of bone healing compared to PRP-free collagen resorbable graft BACKGROUND Allografts , such as demineralized freeze-dried bone allograft ( DFDBA ) and mineralized freeze-dried bone allograft ( FDBA ) are commonly used by clinicians for ridge preservation procedures . The primary objective of this study is to histologically evaluate and compare the healing of non-molar extraction sockets grafted with DFDBA versus FDBA for ridge preservation . The secondary aim of this study is to compare dimensional changes in ridge height and width after grafting with these two material s. MATERIAL S Forty patients were r and omly divided into two groups of 20 . Extraction sockets were filled with either FDBA or DFDBA . To minimize variables associated with the organ donor and with tissue processing , all of the graft material was procured from a single donor ; the only difference in the two material s was the percentage mineralization of the final bone graft . A 2-mm-diameter core biopsy was taken from each grafted site ≈19 weeks after grafting . Histomorphometric analysis was performed to determine percentage of vital bone , residual graft particles , and connective tissue (CT)/other non-bone components . RESULTS There were no significant differences when comparing changes in alveolar ridge dimensions of the two groups . There was no significant difference in percentage CT/other between groups . DFDBA had a significantly greater percentage of vital bone at 38.42 % versus FDBA at 24.63 % . The DFDBA group also had a significantly lower mean percentage of residual graft particles at 8.88 % compared to FDBA at 25.42 % . CONCLUSION This study provides the first histologic and clinical evidence directly comparing ridge preservation with DFDBA versus FDBA in humans and demonstrates significantly greater new bone formation with DFDBA BACKGROUND Many material s have been found to be effective in ridge preservation . The purpose of this study is to determine whether calcium sulfate ( CS ) is as effective as freeze-dried bone allograft ( FDBA ) in preserving post extraction ridge dimensions and to evaluate the amount of new bone formation and graft clearance through histologic analysis . METHODS Thirty-one extraction sites were selected . Post extraction clinical measurements were made , and sites were divided r and omly into the test group ( CS ) or the control group ( FDBA ) . After graft placement , all individuals received the same postoperative treatment and instructions . Participants were recalled after 3 months , measurements were made , and sites were re-entered . Bone sample s were harvested and analyzed with histologic methodology for new bone formation and remaining residual graft . RESULTS Thirteen test and 15 control sites were evaluated . There was no significant change in vertical ridge height before or after surgery within the test and control groups ( P = 0.57 , P = 0.68 , respectively ) . There was a significant decrease in bucco-lingual ridge width for both groups ( P = 0.0003 , P = 0.0075 , respectively ) , but the difference between groups was not significant ( P = 0.11 ) . Histologic analysis revealed an average of 32 % new bone formation with 2.5 % graft remaining for the test group and 16.7 % new bone formation with 21 % graft remaining for the control . CONCLUSIONS Results indicate that CS is as effective as FDBA in preserving post extraction ridge dimensions in non-molar extraction sites . There is greater clearance of CS with more new bone formation after ≈3 months compared with FDBA in these sites . This paper received the Maynard K. Hine Award for Excellence in Dental Research presented by the Indiana Section of the American Association for Dental Research and supported by Procter & Gamble |
11,362 | 29,702,936 | Providing EPO for a hemoglobin level of more than 10 to 11 g/dl had a cost-effectiveness higher than that of doing so for other hemoglobin levels . | OBJECTIVE To compare the cost utility of using erythropoietin ( EPO ) to maintain different hemoglobin ( Hb ) target levels in hemodialysis patients from a societal perspective . | BACKGROUND The optimal haemoglobin concentration ( [ Hb ] ) for patients with end-stage renal failure is uncertain . In particular , it is unclear whether Hb normalization may be an advantage to such patients who are otherwise well . METHODS A prospect i ve , r and omized , double-blind cross-over study was completed in 14 haemodialysis patients ( 12 male ) aged between 23 and 65 years over a period of 18 months , using a variety of measures to examine the effect of epoetin at target [ Hb ] of 10 g/dl ( [Hb](10 ) ) and 14 g/dl ( [Hb](14 ) ) . Patients were r and omized to maintain one or other of the target levels for 6 weeks before being crossed over to the alternative [ Hb ] . Baseline data ( mean [ Hb ] : 8.5+/-0.2 g/dl ) were also included selectively . Six patients were known to be hypertensive . Comparisons were made between 24-h ambulatory blood pressure levels ( ABP ) , echocardiographic findings and estimates of blood volume ( BV ) , plasma volume ( PV ) and Hb mass . Quality of life estimates were obtained using the Sickness Impact Profile ( SIP ) , and epoetin dosage requirements at target [ Hb ] were assessed . RESULTS Daytime and nocturnal ABP ( systolic and diastolic ) were not different at the respective target [ Hb ] , although nocturnal diastolic levels were higher compared with baseline ( 73+/-4 mmHg ) at both [Hb](10 ) ( 83+/-3 , P:<0.01 ) and [Hb](14 ) ( 81+/-6 , P:<0.05 ) . Significant reductions in cardiac output ( 5.2+/-0.3 vs 6.6+/-0.5 l/min , P:<0.01 ) and left ventricular end-diastolic diameter ( 4.8+/-0.2 vs 5.2+/-0.2 cm , P:<0 . 001 ) were found at [Hb](14 ) compared with [Hb](10 ) . Left ventricular mass index was correlated with both PV ( P:<0.001 ) and BV ( P:<0.01 ) , but not with Hb mass . The PV decreased as the [ Hb ] rose ( P:<0.001 ) but BV remained unchanged . Quality of life was significantly improved at [Hb](14 ) compared with [Hb](10 ) for both total score ( 6 . 5+/-1.7 vs 13.4+/-3.0 , P:=0.01 ) and psychosocial dimension score ( 5 . 4+/-1.9 vs 15.4+/-4.0 , P:<0.01 ) . The maintenance weekly dose of epoetin required was 80 % higher at [Hb](14 ) compared with [Hb](10 ) ( P:<0.001 ) . CONCLUSION These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [ Hb ] in haemodialysis patients . Although untoward effects were not identified in this study at [Hb](14 ) , a substantially higher dose of epoetin is required to maintain this level BACKGROUND Renal anemia is an important determinant for left ventricular hypertrophy in dialysis patients and an independent prognosis parameter for the cardiovascular survival in dialysis patients . In addition , an autonomic dysfunction is associated with the uremic state and influences the cardiovascular risk in patients with end-stage renal disease ( ESRD ) . METHODS We investigated in this prospect i ve longitudinal study the effect of hemoglobin normalization by a chronic treatment with recombinant human erythropoietin ( rhEPO ) on cardiovascular prognosis parameters in 23 patients on chronic hemodialysis with renal anemia ( hemoglobin concentration < or = 10.5 g/dL ) and echocardiographically proven left ventricular hypertrophy . We studied muscle sympathetic nerve activity measured by microneurography ; cardiopulmonary baroreflex activity by lower-body negative pressure ( LBNP- ) testing ; left ventricular structure and mass index ( LVMI ) by echocardiography ; blood pressure by 24-hour readings ; peripheral blood flow and vascular resistance by plethysmography before ( U1 ) and after 7 months of chronic rhEPO treatment ( U2 ) . RESULTS In the anemic state , mean ( + /- SD ) muscle sympathetic nerve activity in ESRD was elevated ( U1 rest , 34 + /- 13 bursts per minute ) and cardiopulmonary baroreflex response during LBNP markedly lacking ( U1 -15 mm Hg , 34 + /- 13 bursts per minute ) reflecting a severely impaired autonomic function . Normalization of the hemoglobin concentration by chronic rhEPO treatment ( U1 , 10.5 + /- 0.9 g/dL versus U2 , 13.4 + /- 3.1 g/dL , P < 0.001 ) did not influence sympathetic nerve activity ( U2 , 34 + /- 15 bursts per minute , NS ) and cardiopulmonary baroreflex sensitivity did not change ( U2 -15 mm Hg , 37 + /- 16 bursts per minute , NS ) . LVMI decreased significantly after chronic treatment with rhEPO ( U1 , 134 + /- 26 g/m2 versus U2 , 97 + /- 25 g/m2 , P < 0.001 ) and left ventricular geometry developed from an asymmetric to a symmetric configuration ( U1 , relative wall thickness 0.58 versus U2 , 0.43 , P < 0.001 ) . Under treatment with rhEPO , 24-hour systolic and diastolic blood pressure did not increase ( systolic U1 , 132 + /- 4 mm Hg versus U2 , 128 + /- 3 mm Hg , NS , and diastolic U1 , 76 + /- 2 mm Hg versus U2 , 73 + /- 2 mm Hg , NS ) . Peripheral blood flow ( U1 , 6.1 + /- 3.3 mL/100 mL/min versus U2 , 6.2 + /- 0.6 mL/100 mL/min , NS ) as well as forearm vascular resistance ( U1 , 15.7 + /- 3.3 mm Hg/mL/100 mL versus U2 , 14.9 + /- 3.1 mm Hg/mL/100 mL , NS ) did not change by chronic rhEPO treatment . CONCLUSION Normalization of hemoglobin by chronic rhEPO treatment in dialysis patients has beneficial cardiovascular effects with regression of left ventricular hypertrophy and improvement of left ventricular geometry . However , a reduction of sympathetic overactivity or a re setting of baroreceptor sensitivity by a rhEPO treatment in dialysis patients in the medium-term could not be demonstrated . The reason for this may be the complex and multifactorial pathomechanism of autonomic dysfunction and cardiovascular disease in ESRD Target hematocrit/hemoglobin values in dialysis patients are still controversial . The Spanish Cooperative Renal Patients Quality of Life Study Group ( including 34 hemodialysis units ) conducted a prospect i ve , 6-mo study of the effect on patient functional status and quality of life of using epoetin to achieve normal hematocrit in hemodialysis patients with anemia . The possible adverse effects of increased hematocrit , patient hospitalization , and epoetin requirements were also studied . The study included 156 patients ( age range , 18 to 65 yr ) . Given the minimal experience in the safety of increasing hematocrit in dialysis patients to normal levels with epoetin , stable patients on hemodialysis who had received epoetin treatment for at least 3 mo and had a stable hemoglobin level of > or = 9 g/dl were included in the study . Patients with antecedents of congestive cardiac failure , ischemic cardiopathy , diabetes mellitus , uncontrolled hypertension , cerebrovascular accident or seizures , malfunction of the vascular access or severe comorbidity ( defined by a comorbidity index ) , and those over 65 yr of age were excluded from the study . Quality of life was measured with the Sickness Impact Profile ( SIP ) and Karnofsky scale . Patients completed question naires at home at onset and conclusion of the 6-mo study . Mean hematocrit increased from 30.9 to 38.4 % and hemoglobin from 10.2 to 12.5 g/dl during the study . Health indicator scores improved significantly : mean Physical Dimension ( SIP ) from 5.38 to 4.1 ( P < 0.005 ) ; mean Psychosocial Dimension from 9.2 to 7 ( P < 0.001 ) ; mean global SIP from 8.9 to 7.25 ( P < 0.001 ) ; mean Karnofsky scale score from 75.6 to 78.4 ( P < 0.01 ) . ( SIP is scaled so that lower scores represent better functional status , and vice versa for the Karnofsky scale ) . Therefore , functional status and quality of life improved with increased hematocrit . No deaths occurred . Three patients ( 2 % ) were censored for hypertension and nine ( 5.7 % ) for thrombosis of the vascular access . The cumulative probability of thrombosis of the vascular access was 0.067 . The average epoetin dose rose from 93 + /- 62 U/kg per wk at onset to 141 + /- 80 U/kg per wk at conclusion , a 51 % increase . The number of patients hospitalized decreased and hospital lengths of stay were shorter during the study period than in the same patients in the 6-mo period preceding the study ( P < 0.05 ) . Nine patients ( 5.7 % ) had thrombosis of the vascular access . There were no changes in the prevalence of arterial hypertension , but three patients ( 2 % ) showed hypertension that was difficult to control . It is concluded that normalization of hematocrit in selected hemodialysis patients , i.e. , nondiabetic patients without severe cardiovascular or cerebrovascular comorbidities , improves quality of life and decreases morbidity without significant adverse effects BACKGROUND In patients with end-stage renal disease , anemia develops as a result of erythropoietin deficiency , and recombinant human erythropoietin ( epoetin ) is prescribed to correct the anemia partially . We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis . METHODS We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis : 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent , and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study . The median duration of treatment was 14 months . The primary end point was the length of time to death or a first nonfatal myocardial infa rct ion . RESULTS After 29 months , there were 183 deaths and 19 first nonfatal myocardial infa rct ions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infa rct ions among those in the low-hematocrit group ( risk ratio for the normal-hematocrit group as compared with the low-hematocrit group , 1.3 ; 95 percent confidence interval , 0.9 to 1.9 ) . Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary , the study was halted . The causes of death in the two groups were similar . The mortality rates decreased with increasing hematocrit values in both groups . The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group . CONCLUSIONS In patients with clinical ly evident congestive heart failure or ischemic heart disease who are receiving hemodialysis , administration of epoetin to raise their hematocrit to 42 percent is not recommended We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis . The recombinant human erythropoietin was given intravenously three times weekly after dialysis , and transfusion requirements , hematocrit , ferrokinetics , and reticulocyte responses were monitored . Over a range of doses between 15 and 500 units per kilogram of body weight , dose-dependent increases in effective erythropoiesis were noted . At 500 units per kilogram , changes in the hematocrit of as much as 10 percentage points were seen within three weeks , and increases in ferrokinetics of three to four times basal values , as measured by erythron transferrin uptake , were observed . Of 18 patients receiving effective doses of recombinant human erythropoietin , 12 who had required transfusions no longer needed them , and in 11 the hematocrit increased to 35 percent or more . Along with the rise in hematocrit , four patients had an increase in blood pressure , and a majority had increases in serum creatinine and potassium levels . No organ dysfunction or other toxic effects were observed , and no antibodies to the recombinant hormone were formed . These results demonstrate that recombinant human erythropoietin is effective , can eliminate the need for transfusions with their risks of immunologic sensitization , infection , and iron overload , and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease BACKGROUND Health-related quality of life ( QOL ) is an important measure of how disease affects patients ' lives . Dialysis patients have decreased QOL relative to healthy controls . Little is known about QOL in patients with chronic kidney disease ( CKD ) before renal replacement therapy . METHODS The Medical Outcomes Study Short Form-36 ( SF-36 ) , a st and ard QOL instrument , was used to evaluate 634 patients ( mean glomerular filtration rate [ GFR ] , 23.6 + /- 9.6 mL/min/1.73 m2 [ 0.39 + /- 0.16 mL/s/1.73 m2 ] ) enrolled in a 4-center , prospect i ve , observational study of CKD . SF-36 scores in these patients were compared with those in a prevalent cohort of hemodialysis ( HD ) patients and healthy controls ( both from historical data ) . QOL data also were analyzed for correlations with GFR and albumin and hemoglobin levels in multivariable analyses . RESULTS Patients with CKD had higher SF-36 scores than a large cohort of HD patients ( P < 0.0001 for 8 scales and 2 summary scales ) , but lower scores than those reported for the US adult population ( P < 0.0001 for 7 of 8 scales and 1 of 2 summary scales ) . Patients with CKD stage 4 had lower QOL scores than patients with CKD stage 5 , although differences were not significant . Hemoglobin level was associated positively with higher mental and physical QOL scores ( P < 0.05 ) in all individual and component scales except Pain . CONCLUSION SF-36 scores were higher in this CKD cohort compared with HD patients , but lower than in healthy controls . GFR was not significantly associated with QOL . Hemoglobin level predicted both physical and mental domains of the SF-36 . Longitudinal studies are needed to define at-risk periods for decreases in QOL during progression of CKD BACKGROUND Hemoglobin levels below 10 g/dL lead to left ventricular ( LV ) hypertrophy , LV dilation , a lower quality of life , higher cardiac morbidity , and a higher mortality rate in end-stage renal disease . The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown . METHODS One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were r and omly assigned to receive doses of epoetin alpha design ed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks . The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation . RESULTS In patients with concentric LV hypertrophy , the changes in LV mass index were similar in the normal and low target hemoglobin groups . The changes in cavity volume index were similar in both targets in the LV dilation group . Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved ( 8 mL/m2 per 1 g/dL hemoglobin decrement , P = 0.009 ) . Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation . Normalization of hemoglobin led to improvements in fatigue ( P = 0.009 ) , depression ( P = 0.02 ) , and relationships ( P = 0.004 ) . CONCLUSIONS Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation . It may , however , prevent the development of LV dilation , and it leads to improved quality of life OBJECTIVE --To determine whether recombinant human erythropoietin improves the quality of life and exercise capacity of anaemic patients receiving haemodialysis . DESIGN --A double blind , r and omised , placebo controlled study . SETTING --Eight Canadian university haemodialysis centres . PATIENTS --118 Patients receiving haemodialysis aged 18 - 75 with haemoglobin concentrations less than 90 g/l , no causes of anaemia other than erythropoietin deficiency , and no other serious diseases . INTERVENTIONS -- Patients were r and omised to three groups to receive placebo ( n = 40 ) , erythropoietin to achieve a haemoglobin concentration of 95 - 110 g/l ( n = 40 ) , or erythropoietin to achieve a haemoglobin concentration of 115 - 130 g/l ( n = 38 ) . Erythropoietin was given intravenously thrice weekly , initially at 100 units/kg/dose . The dose was subsequently adjusted to achieve the target haemoglobin concentration . All patients with a serum ferritin concentration less than 250 micrograms/l received oral or intravenous iron for one month before the study and as necessary throughout the trial . MAIN OUTCOME MEASURES --Scores obtained with kidney disease question naire , sickness impact profile , and time trade off technique ; and results of six minute walk test and modified Naughton stress test . RESULTS --The mean ( SD ) haemoglobin concentration at six months was 74 ( 12 ) g/l in patients given placebo , 102 ( 10 ) g/l in those in the low erythropoietin group , and 117 ( 17 ) g/l in those in the high erythropoietin group . Compared with the placebo group , patients treated with erythropoietin had a significant improvement in their scores for fatigue , physical symptoms , relationships , and depression on the kidney disease question naire and in the global and physical scores on the sickness impact profile . The distance walked in the stress test increased in the group treated with erythropoietin , but there was no improvement in the six minute walk test , psychosocial scores on the sickness impact profile , or time trade off scores . There was no significant difference in the improvement in quality of life or exercise capacity between the two groups taking erythropoietin . Patients taking erythropoietin had a significantly increased diastolic blood pressure despite an increase in either the dose or number of antihypertensive drugs used . Eleven of 78 patients treated with erythropoietin had their sites of access clotted compared with only one of 40 patients given placebo . CONCLUSIONS -- Patients receiving erythropoietin were appreciably less fatigued , complained of less severe physical symptoms , and had moderate improvements in exercise tolerance and depression compared with patients not receiving erythropoietin . At the doses used in this trial there was a higher incidence of hypertension and clotting of the vascular access in patients treated with erythropoietin It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation . In this r and omized , double-blind study , lower ( 9.5 to 11.5 g/dl ) and higher ( 13.5 to 14.5 g/dl ) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk . Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation . The primary outcome measure was left ventricular volume index ( LVVI ) . The study enrolled 596 patients . Mean age , duration of dialysis therapy , baseline predialysis hemoglobin , and LVVI were 50.8 yr , 0.8 yr , 11.0 g/dl , and 69 ml/m2 , respectively ; 18 % had diabetic nephropathy . Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl , respectively , at 24 wk . Percentage changes in LVVI between baseline and last value were similar ( 7.6 % in the higher and 8.3 % in the lower target group ) as were the changes in left ventricular mass index ( 16.8 versus 14.2 % ) . For the secondary outcomes , the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group ( 1.21 versus -2.31 ; P = 0.036 ) . Overall adverse event rates were similar in both target groups ; higher ( P < 0.05 ) rates of skeletal pain , surgery , and dizziness were seen in the lower target group , and headache and cerebrovascular events were seen in the higher target group . Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure , compared with partial correction This second interim report of the National Cooperative rHu Erythropoietin Study presents data from 324 patients new to recombinant human erythropoietin ( Epoetin alfa ) who completed at least 12 months of study participation . Mean hematocrit levels increased to approximately 30 % by month 3 in patients on hemodialysis ( n = 293 ) and stabilized for the remainder of the study whether Epoetin alfa was administered by the intravenous ( n = 250 ) or subcutaneous ( n = 42 ) route . The intravenous dosage level ranged between 106.9 and 121.6 U/kg/wk ; subcutaneous dosing ranged between 87.4 and 108.0 U/kg/wk ; dosing levels in patients on peritoneal dialysis ( n = 31 ) were similar , although there was a trend towards slightly higher hematocrit levels . Throughout the 12 months of the study , there was no relationship between blood pressure and either hematocrit level or Epoetin alfa dose . Approximately two thirds of the patients were receiving iron supplementation at any given time , and there was a trend towards the increased use of oral iron supplements . The incidence of adverse events in this cohort of patients was low throughout the study , and there was no relationship between the incidence of adverse events and either hematocrit level or Epoetin alfa dose . Based on an analysis of data from baseline to first follow-up , Epoetin alfa therapy result ed in improvement in several quality -of-life factors , most notable of which was vitality . Improvement occurred in all patient subgroups with some variability in the level and intensity of effect . Overall , these data demonstrate that Epoetin alfa therapy is safe and effective when used in a broad cross-section of patients on dialysis . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established . METHODS We r and omly assigned 603 patients with an estimated glomerular filtration rate ( GFR ) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia ( hemoglobin level , 11.0 to 12.5 g per deciliter ) to a target hemoglobin value in the normal range ( 13.0 to 15.0 g per deciliter , group 1 ) or the subnormal range ( 10.5 to 11.5 g per deciliter , group 2 ) . Subcutaneous erythropoietin ( epoetin beta ) was initiated at r and omization ( group 1 ) or only after the hemoglobin level fell below 10.5 g per deciliter ( group 2 ) . The primary end point was a composite of eight cardiovascular events ; secondary end points included left ventricular mass index , quality -of-life scores , and the progression of chronic kidney disease . RESULTS During the 3-year study , complete correction of anemia did not affect the likelihood of a first cardiovascular event ( 58 events in group 1 vs. 47 events in group 2 ; hazard ratio , 0.78 ; 95 % confidence interval , 0.53 to 1.14 ; P=0.20 ) . Left ventricular mass index remained stable in both groups . The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year , respectively ( P=0.40 ) . Dialysis was required in more patients in group 1 than in group 2 ( 127 vs. 111 , P=0.03 ) . General health and physical function improved significantly ( P=0.003 and P<0.001 , respectively , in group 1 , as compared with group 2 ) . There was no significant difference in the combined incidence of adverse events between the two groups , but hypertensive episodes and headaches were more prevalent in group 1 . CONCLUSIONS In patients with chronic kidney disease , early complete correction of anemia does not reduce the risk of cardiovascular events . ( Clinical Trials.gov number , NCT00321919 [ Clinical Trials.gov ] . ) |
11,363 | 15,674,899 | No significant differences were demonstrated in secondary outcome measures .
AUTHORS ' CONCLUSIONS There is insufficient evidence of efficacy of individual antioxidants , or antioxidants in general , in the treatment of people with amyotrophic lateral sclerosis . | BACKGROUND Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis ( or motor neuron disease ) .
A range of antioxidant medications are available , and have been studied .
OBJECTIVES To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis . | Background : While the incidence of amyotrophic lateral sclerosis ( ALS ) is similar across the world ( range , 1.0 to 2.5/100 000 ) , a latitude gradient from north to south has been observed . Objective : To determine the incidence of ALS in Puglia , a region of south eastern Italy , and to test the latitude gradient hypothesis comparing the present study with findings in studies conducted with the same design in a northern latitude . Methods : Puglia ( 4 086 613 residents in 2001 ) is the site of a multicentre-multi source prospect i ve population based registry established in 1997 . All incident ALS cases during the period 1998–99 were enrolled and followed up . Cases were classified using the first and the revised El Escorial criteria . Results : During the study period 130 cases were enrolled . The annual crude incidence for ALS in Puglia for the two year period 1998–99 was 1.6/100 000 ( 95 % confidence interval , 1.3 to 1.9 ) . The incidence was higher for men ( incidence rate ( IR ) = 2.1 ( 1.7 to 2.7 ) than for women ( IR = 1.2 ( 0.9 to 1.5 ) ) in all age groups , with a male to female ratio of 1.6 . For both men and women , the incidence increased through age 75 and declined rapidly afterwards . The mean annual incidence adjusted by age and sex to the 2001 Italian population was 1.7/100 000 ( 1.4 to 2.0 ) . Conclusions : ALS incidence is within a narrow range across countries , with a peak between 65 and 75 years and a higher incidence in men . A north to south latitude gradient of ALS incidence is not supported by the results of cohort studies The present study set out to define the possible effect of reduced glutathione ( GSH ) , the substrate of glutathione peroxidase ( GSH-Px ) , a free radical inactivating enzyme , in amyotrophic lateral sclerosis ( ALS ) . Thirty-two patients affected by definite ALS seen in our institution between August 1993 and July 1994 were admitted to the study . The effect of GSH was studied in an open , crossover , r and omized study . GSH was given at the dose of 600 mg each day intramuscularly for 12 weeks . The patients , taken sequentially , were r and omly assigned to two groups . The first group received the drug while the second received only symptomatic therapies for 12 weeks . After a week of wash-out , the second group received GSH and the first only symptomatic therapies for 12 weeks . The rate of progression of the diseases was compared in the two groups . Clinical evaluation included manual test for muscle strength , Norris scale , bulbar scale , and forced vital capacity ( FVC ) percent . No significant difference was found in the progression of ALS in the two periods , although a slight slowing of the disease progression rate was found during the period of treatment , probably related to the open design of the study . Our data do not show any significant effect of reduced glutathione in modifying the progression of ALS.SommarioLo scopo del lavoro è stato definire il possibile effetto del glutatione ridotto ( GSH ) , il substrato della glutatione perossidasi ( GSH-Px ) , un enzima inattivatore dei radicali liberi , nella sclerosi laterale amiotrofica ( SLA ) . Sono stati ammessi nello studio 32 pazienti affetti da SLA definita visitati nel nostro Istituto dall'agosto 1993 a luglio 1995 . L'effetto del GSH è stato studiato in uno studio in aperto , crossover , r and omizzato . Il GSH è stato somministrato alla dose di 600 mg per via intramuscolare per 12 settimane . I pazienti sono stati assegnati a caso , secondo l'ordine di visita , a due gruppi . Per le prime 12 settimane il primo gruppo ha ricevuto il farmaco e il secondo solo terapie sintomatiche . Dopo un wash-out di una settimana , il secondo gruppo ha ricevuto il GSH e il primo solo terapie sintomatiche per altre 12 settimane . È stata confrontata la velocità di progressione dei sintomi nei due gruppi . La valutazione clinica comprendeva test manuali per la forza muscolare , la scala di Norris , una scala bulbare e la capacità vitale forzata ( FVC ) . Non è stata trovata alcuna differenza significativa nella velocità di progressione della SLA nei due periodi , anche se è stato osservato un lieve rallentamento nella velocità di progressione durante il perrodo di trattamento , forse dovuto al disegno in aperto dello studio . I nostri dati non dimostrano alcun effetto significativo del glutatione ridotto nel modificare la progressione della SLA Nutritional etiology of amyotrophic lateral sclerosis ( ALS ) , and other motor neuron disorders , can not be ignored even though many trials of nutritional therapy have not , thus far , yielded any benefit to the sufferers . Possibly the nutrients available , or the dosages used , have not been adequate to the circumstances ; perhaps an as-yet-unknown nutrient is deficient , poorly absorbed or under-utilized Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease , we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis ( ALS ) to examine whether it might modify the progression of the disease . Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months . Patients with familial ALS , pure progressive bulbar palsy , primary lateral sclerosis or progressive muscle atrophy were excluded ; a total of 111 patients were recruited . Fifty-three patients were r and omly assigned to receive the drug ( selegiline 10 mg/day orally for 6 months ) and the remaining 58 were considered ALS controls . Mortality was similar in the two groups ( 4 and 5 patients respectively ) , though the difference was not statistically significant . Among the survivors , mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found . The results did not change when the data were related to age , duration and characteristics of onset of the disease . The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups . Our data do not show any significant effect of selegiline in modifying the progression of ALS In this paper we present results from a double blind cross over trial with deprenyl , a selective and irreversible monoamine oxidase-B ( MAO-B ) inhibitor , in 10 patients suffering from amyotrophic lateral sclerosis . The patients were r and omised in such a way that half of the patients started with the active drug and half with the placebo treatment . Each patient was given 10 mg deprenyl ( eldepryl , 10 mg tablets ) per day for 12 weeks and then placebo for the same length of time . There was a drug free period of 12 weeks between the courses . The neurological status of the patients were evaluated every six weeks by using Norris , spinal and bulbar scores and it was observed that all cases deteriorated in their clinical status during the 36 weeks of the controlled study . MAO-B activity in blood platelets was completely inhibited during treatment with deprenyl . In the preliminary analysis performed so far , no obvious retardation in the progress of the disease could be observed with deprenyl treatment BACKGROUND The cause of amyotrophic lateral sclerosis ( ALS ) is not known , and there is no effective treatment . Cell death may be caused by oxidative damage . Selegiline hydrochloride ( Eldepryl ) is a monoamine oxidase-B inhibitor with antioxidant properties . OBJECTIVE To determine if selegiline affects the clinical course of patients with ALS . DESIGN Six-month , double-blind , placebo-controlled study of 133 patients with classical ALS and symptoms for less than 3 years . The primary end point to indicate effectiveness was the rate of change of the Appel ALS total score , an index of disease severity that incorporates strength and function in limbs , respiratory function , and bulbar function . RESULTS Of the 133 patients , 67 were r and omized to receive selegiline and 66 to receive placebo . One hundred four patients ( 53 in the selegiline group and 51 in the placebo group ) completed the 6-month trial . Both groups were comparable for baseline characteristics and mean Appel ALS total score ( 70.5 points for the selegiline group and 70.6 for the placebo group ) . There was no difference in the rate of progression as measured by the Appel ALS total score , showing an average increase of 22 points in 6 months . The monthly rate of change was 3.4 for the selegiline group and 3.5 for the placebo group . There was 1 adverse reaction : worsening depression . Seven patients died during the study ( 4 in the selegiline group and 3 in the placebo group ) . CONCLUSION Selegiline treatment had no significant effect on the rate of clinical progression or outcome of ALS Oxidative stress may contribute to the pathogenesis of amyotrophic lateral sclerosis ( ALS ) . We therefore examined prospect ively whether individuals who regularly use supplements of the antioxidant vitamins E and C have a lower risk of ALS than nonusers . The study population comprised 957,740 individuals 30 years of age or older participating in the American Cancer Society 's Cancer Prevention Study II . Information on vitamin use was collected at time of recruitment in 1982 ; participants then were followed up for ALS deaths from 1989 through 1998 via linkage with the National Death Index . During the follow‐up , we documented 525 deaths from ALS . Regular use of vitamin E supplements was associated with a lower risk of dying of ALS . The age‐ and smoking‐adjusted relative risk was 0.99 ( 95 % confidence interval [ CI ] , 0.69–1.41 ) among occasional users , 0.59 ( 95 % CI , 0.36–0.96 ) in regular users for less than 10 years , and 0.38 ( 95 % CI , 0.16–0.92 ) in regular users for 10 years or more as compared with nonusers of vitamin E ( p for trend = 0.004 ) . In contrast , no significant associations were found for use of vitamin C or multivitamins . These results suggest that vitamin E supplementation could have a role in ALS prevention . Ann Neurol Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis ( ALS ) by an array of antioxidants and added other drugs to the regimen whenever a patient reported deterioration . Our customary prescription sequence was N-acetylcysteine ( NAC ) ; vitamins C and E ; N-acetylmethionine ( NAM ) ; and dithiothreitol ( DTT ) or its isomer dithioerythritol ( DTE ) . Patients with a history of heavy exposure to metal were also given meso 2,3-dimercaptosuccinic acid ( DMSA ) . NAC , NAM , DTT , and DTE were administered by subcutaneous injection or by mouth or by both routes , the other vitamins and DMSA by mouth alone . The hospital pharmacy supplied NAC and NAM injections fluid as 100 ml bottles of 5.0 and 5.85 % solutions , respectively . DTT was delivered in special double-walled capsules of 200 mg . DTT/DTE injection fluid was added to the NAC and NAM bottles , the final DTT/DTE concentrations never exceeding 0.5 % . DMSA was provided in 250 mg capsules . All of the 36 patients used NAC and DTT/DTE ; 29 also used vitamins C and E ; 21 also used NAM ; and 7 also used DMSA , DMSA , NAM , vitamins C and E were tolerated well . In many patients , DTT , DTE , NAC and NAM induced pain , redness and swelling at the injection sites in that order of decreasing frequency . DTT and DTE did often and NAC did sometimes cause gastric pain , nausea and other abdominal discomfort . Comparison of survival in the treated group and in a cohort of untreated historical controls , disclosed a median survival of 3.4 years ( 95 % confidence interval : 3.0 - 4.2 ) in the treated and of 2.8 ( 95 % confidence interval 2.2 - 3.1 ) years in the control patients . This difference may be explained by self- selection of our highly motivated treated group and by its initial survival of diagnosis for an average of 8.5 months before onset of treatment . We conclude that antioxidants neither seem to harm ALS patients , nor do they seem to prolong survival Summary .Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis ( ALS ) . The antioxidant vitamin E ( alpha-tocopherol ) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS . The current study , a double blind , placebo-controlled , r and omised , stratified , parallel-group clinical trial , was design ed to determine whether vitamin E ( 5000 mg per day ) may be efficacious in slowing down disease progression when added to riluzole . Methods . 160 patients in 6 German centres with either probable or definite ALS ( according to the El Escorial Criteria ) and a disease duration of less than 5 years , treated with riluzole , were included in this study and were r and omly assigned to receive either alpha-tocopherol ( 5000 mg per day ) or placebo for 18 months . The Primary outcome measure was survival , calculating time to death , tracheostomy or permanent assisted ventilation , according to the WFN- Criteria of clinical trials . Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales , manual muscle testing ( BMRC ) , spasticity scale , ventilatory function and the Sickness Impact Profile ( SIP ALS/19 ) . Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18 . Vitamin E sample s were taken for compliance check and Quality Control of the trial . For Safety , a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18 . Height and weight were recorded at baseline and weight alone at the follow-up visits . A neurological examination as well as vital signs ( heart rate and blood pressure ) , an ECG and VEP ’s were recorded at each visit . Furthermore , spontaneously reported adverse experiences and serious adverse events were documented and st and ard laboratory tests including liver function tests performed . For Statistical Analysis , the population to be considered for the primary outcome measure was an “ intent-to-treat ” ( ITT ) population which included all r and omised patients who had received at least one treatment dose ( n = 160 patients ) . For the secondary outcome measures , a two way analysis of variance was performed on a patient population that included all r and omised patients who had at least one assessment after inclusion . Results . Concerning the primary endpoint , no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test . The functional assessment s showed a marginal trend in favour of vitamin E , without reaching significance . Conclusion . Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol . Larger or longer studies might be needed . However , administration of this megadose does not seem to have any significant side effects in this patient population The aim of the study was to assess the effect of pimozide voltage-dependent calcium channel blocker on the progression of ALS patients as compared to the potentially neuroprotective drugs , selegiline and vitamin E. There were 44 patients ( 17 females and 27 males , aged from 30 to 80 years , mean age : 56.2 years ) diagnosed as either definite or possible ALS . The study design was open r and omised . Patients were treated 3 - 12 months ; the daily dose of pimozide was 1 mg . The disease progression index was calculated as a difference between scores of Norris scale before and after treatment . Statistical analysis showed a significant decrease of the index of progression of the disease in pimozide treated patients as compared to the others . This effect was neither related to the progression of the disease nor advance of the disease at the beginning of treatment BACKGROUND Free radicals may play a role in the pathogenesis of amyotrophic lateral sclerosis . OBJECTIVE To investigate the efficacy of the free radical scavenging agent acetylcysteine in patients with amyotrophic lateral sclerosis . DESIGN R and omized , double-blind , placebo-controlled clinical trial to assess the effect of treatment with acetylcysteine on survival and disease progression . SETTING A university hospital referral setting . PATIENTS One hundred ten consecutive patients who fulfilled the diagnostic criteria for amyotrophic lateral sclerosis , followed up at monthly intervals for 12 months . INTERVENTION Acetylcysteine or placebo in a dose of 50 mg/kg per day subcutaneously for 12 months . MAIN OUTCOME MEASURE Survival . RESULTS After 12 months , 35 patients ( 65 % ) treated with acetylcysteine and 30 ( 54 % ) given placebo were still alive ( hazard ratio , 0.74 in the acetylcysteine group relative to the placebo group ; 95 % confidence interval , 0.41 to 1.33 ; log-rank test , P = .31 ) . Rates of disease progression , as expressed by decline in muscle strength , pulmonary function , disability , and bulbar function were similar in both groups . In the subgroup of 81 patients with limb onset of the disease , 28 patients ( 74 % ) in the acetylcysteine group and 22 ( 51 % ) in the placebo group survived 12 months ( hazard ratio , 0.50 ; 95 % confidence interval , 0.24 to 1.04 ; P = .06 ) . In the bulbar subgroup of 29 patients , seven patients ( 44 % ) receiving acetylcysteine and eight ( 62 % ) receiving placebo were alive at the end of the study ( hazard ratio , 1.66 ; 95 % confidence interval , 0.56 to 4.99 ; P = .36 ) . CONCLUSION In this trial , treatment with the free radical scavenger acetylcysteine did not result in a major increase in 12-month survival or a reduction in disease progression in patients with amyotrophic lateral sclerosis The activity of glutathione peroxidase ( GSH-Px ) as well as the activities of other antioxidative enzymes : CuZn superoxide dismutase ( CuZn SOD ) , catalase ( CAT ) , glutathione reductase ( GR ) in erythrocytes , as well as the activity of plasma glutathione transferase ( GST ) , and the plasma content of vitamins E and C were evaluated in 35 sporadic amyotrophic lateral sclerosis ( sALS ) patients . The results revealed significantly decreased activity of both GSH-Px and CuZn SOD in sALS patients compared with the control . These data showed that a disturbed oxidative/antioxidative balance in sALS patients exists not only in motoneurons but also in the blood . The effect of exogenously administered selenium ( Se ) , antioxidants , amino acids , a Ca2 + channel blocker such as nimodipine , and their combination in Alsamin was evaluated by screening parameter levels after 9 weeks of treatment . Only the use of all components together enhanced the activity of GSH-Px and the amount of vitamin E in sALS patients . Judging by the results of clinical trials , this treatment slowed the course of the disease |
11,364 | 22,542,374 | (18)F-FDG PET has a significant value in assessing treatment response to imatinib or other drugs in GIST patients .
(18)F-FDG PET allows an early assessment of treatment response and is a strong predictor of clinical outcome | OBJECTIVE To systematic ally review the role of (18)F-fluorodeoxyglucose ( (18)F-FDG ) positron emission tomography ( PET ) in evaluating treatment response to imatinib or other drugs in gastrointestinal stromal tumors ( GIST ) . | UNLABELLED Gastrointestinal stromal tumors ( GISTs ) are gaining the interest of research ers because of impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate . Initial reports suggest an impressive role for (18)F-FDG PET in follow-up of therapy for these tumors . However , the role of (18)F-FDG PET versus that of CT has not been established . Therefore , we compared the roles of (18)F-FDG PET and CT in staging and evaluation of early response to imatinib mesylate therapy in recurrent or metastatic GIST . METHODS The study included 54 patients who underwent (18)F-FDG PET and CT scans within 3 wk before initiation of imatinib mesylate therapy . Forty-nine of these patients underwent repeat scans 2 mo after therapy . The numbers of sites or organs containing lesions on (18)F-FDG PET and CT scans were compared . Corresponding lesions on (18)F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on follow-up were considered true positives . Lesions seen on (18)F-FDG PET or CT scans but not seen or confirmed to be of benign appearance with other imaging modalities or on follow-up were considered false positives . Measurements of the maximum st and ard uptake value ( SUV ) on (18)F-FDG PET scans and tumor size on CT scans were used for quantitative evaluation of early tumor response to therapy . RESULTS A total of 122 and 114 sites and /or organs were involved on pretherapy (18)F-FDG PET and CT scans , respectively . The sensitivity and positive predictive values ( PPVs ) for CT were 93 % and 100 % ; whereas these values for (18)F-FDG PET were 86 % and 98 % . However , the differences between these values for CT and (18)F-FDG PET were not statistically significant ( P = 0.27 for sensitivity and 0.25 for PPV ) . This suggests comparable performance of (18)F-FDG PET and CT in staging GISTs . Repeat scans at 2 mo after therapy showed agreement between (18)F-FDG PET and CT scans in 71.4 % of patients ( 57.1 % having a good response to therapy and 14.3 % lacking a response ) . Discrepant results between (18)F-FDG PET and CT were recorded for 28.6 % of the patients . (18)F-FDG PET predicted response to therapy earlier than did CT in 22.5 % of patients during a longer follow-up interval ( 4 - 16 mo ) , whereas CT predicted lack of response to therapy earlier than (18)F-FDG PET in 4.1 % . One patient did not undergo long-term follow-up . These findings suggest that (18)F-FDG PET is superior to CT in predicting early response to therapy in recurrent or metastatic GIST patients . CONCLUSION The performances of (18)F-FDG PET and CT are comparable in staging GISTs before initiation of imatinib mesylate therapy . However , (18)F-FDG PET is superior to CT in predicting early response to therapy . Thus , (18)F-FDG PET is a better guide for imatinib mesylate therapy AIM The aim of this study was to evaluate the utility of positron emission tomography with 18F-fluorodeoxyglucose ( FDG-PET ) in monitoring response in refractory GIST . METHODS This multicenter study prospect ively evaluated 21 patients with locally advanced and /or metastatic GIST refractory to with high-dose imatinib ( 800 mg/day ) treated with doxorubicin 15 - 20 mg/m2/weekly for 4 cycles , followed by imatinib maintenance ( 400 mg/day ) . CT and FDG-PET were performed at baseline and after completion of therapy . RESULTS Mean baseline tumor size on CT was 5.9 cm . Median progression-free survival ( PFS ) was 219 days ( range 62 - 1108 ) . Three out of 21 patients ( 14 % ) had partial responses ( PR ) under RECIST criteria , 12 patients ( 57 % ) remained stable ( SD ) and 6 showed progression ( PD ) of the disease during treatment ( 29 % ) . Six patients had PR by FDG-PET , 15 showed SD ( n=9 ) or PD ( n=6 ) based on EORTC criteria . Patients with a PFS < 6 mo showed a significantly higher ∑SUVmax at baseline ( 26.04±13.4 ) than those with PFS≥6 mo ( 9.82±5.0 ) ( P<0.05 ) . A correlation was found between PET response and PFS : PR 14±6.1 mo , SD 5.5±0.8 mo and PD 3.5±4.1 mo ( P<0.05 ) . A residual SUVmax < 5 after treatment correlated with improved PFS ( 314±315 days vs 131±91 days ) ( P<0.01 ) . Survival curves showed a significant association between PET response and PFS ( P<0.05 ) . Patients with wild-type genotype KIT ( KIT-WT ) showed a significantly lower baseline SUVmax ( 5.36±1.4 ) than non-WT KIT ( 8.40±3.6 ) ( P<0.05 ) . CONCLUSION FDG-PET is useful in assessing response of GIST refractory to imatinib and correlates with the presence of KIT-WT . Baseline ∑SUVmax can predict response to treatment in this series Purpose This multicenter phase 2 study assessed the tolerability and efficacy of motesanib , an oral inhibitor of Kit , platelet-derived growth factor receptor ( PDGFR ) , and vascular endothelial growth factor receptors ( VEGFR ) , in patients with imatinib-resistant gastrointestinal stromal tumors ( GIST ) . Methods Patients with advanced GIST who failed imatinib mesylate after ≥8 weeks of treatment with ≥600 mg daily received motesanib 125 mg orally once daily continuously for 48 weeks or until unacceptable toxicity or disease progression occurred . The primary endpoint was confirmed objective tumor response per RECIST and independent review . Secondary endpoints included progression-free survival ( PFS ) , time to progression ( TTP ) ; objective response by 18FDG-PET and by changes in tumor size and /or density ( Choi criteria ) ; pharmacokinetics and safety . Results In the patients evaluable for response ( N = 102 ) , the objective response rate was 3 % ; 59 % of patients achieved stable disease , with 14 % achieving durable stable disease ≥24 weeks ; 38 % had disease progression . Higher objective response rates were observed per 18FDG-PET ( N = 91 ) ( 30 % ) and Choi criteria ( 41 % ) . The median PFS was 16 weeks ( 95 % CI = 14–24 weeks ) ; the median TTP was 17 weeks ( 95 % CI = 15–24 weeks ) . The most common motesanib treatment-related grade 3 adverse events included hypertension ( 23 % ) , fatigue ( 9 % ) , and diarrhea ( 5 % ) . Motesanib did not accumulate with daily dosing . Conclusions In this study of patients with imatinib-resistant GIST , motesanib treatment result ed in acceptable tolerability and modest tumor control as evident in the proportion of patients who achieved stable disease and durable stable disease Summary Objectives To determine the quantitative parameters of DCE-US for predicting early functional response of patients with metastatic gastrointestinal stromal tumors ( GIST ) . Material s and methods Phase II multicentre clinical trial in patients with metastatic GIST treated with masatinib mesylate ( 7.5 mg/kg daily by oral route ) Patients followed using three different imaging techniques : 1 ) DCE-US before treatment and on days 1 , 7 , 15 and after 1 , 2 , 4 , 6 months and every 3 months . 2 ) CT assessment s , using RECIST criteria , before treatment , after 2 , 4 , 6 months and then every 3 months . 3 ) FDG PET before treatment and after 1 month . Results Twenty patients included and followed-up for up to 36 months , with 269 DCE-US examinations performed . No significant changes in the 7 selected DCE-US variables on day 1 and 7 vs baseline . On day 15 , significant reductions in all the variables related to blood volume recorded : area under the curve ( AUC ) ( p = 0 . 004 ) , area under the wash-in ( AUWI ) ( p = 0.002 ) , area under the wash-out ( AUWO ) ( p = 0.002 ) and Peak Intensity ( p = 0.005 ) . Also slope of wash-in changed significantly ( p = 0.003 ) . An important reduction in St and ard Uptake Values ( SUV ) recorded in 7/11 patients ( PFS > 18 months ) . Decrease in DCE-US AUC , AUWI and AUWO values on day 7 were predictive of PET-CT results . Conclusions AUC AUWI , AUWO are the DCE-US parameters related to blood volume that at D 15 can predict the response of GISTs to treatment with masatinib . Additional studies are ongoing PURPOSE The aim of this study was to identify factors predicting initial and late resistance of GI stromal tumor ( GIST ) patients to imatinib and to document the dose-response relationship in the prognostic subgroups . This study is based on the European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group r and omized trial comparing two doses of imatinib in advanced disease . PATIENTS AND METHODS Initial resistance was defined as progression within 3 months of r and omization , and late resistance was defined as progression beyond 3 months . Investigated cofactors include imatinib dose , age , sex , performance status , original disease site , site and size of lesions at trial entry , and baseline hematologic and biologic parameters . RESULTS Initial resistance was recorded for 116 ( 12 % ) of 934 assessable patients and was independently predicted by the presence of lung and absence of liver metastases , low hemoglobin level , and high granulocyte count . Among 818 patients who were alive and progression free at 3 months , 347 subsequent progressions were recorded , and late resistance was independently predicted by high baseline granulocyte count , primary tumor outside of the stomach , large tumor size , and low initial imatinib dose . The impact of initial dose on late resistance was mainly significant in patients with a high baseline granulocyte count ( > 5.10(9)/L ) and in patients with tumors of GI origin outside of the stomach and small intestine . CONCLUSION Our study identifies patients for whom initial and /or long-term treatment needs to be improved and patients who require a high initial dose . Correlation of these results with immunohistochemistry and molecular parameters may further help to underst and the biologic mechanisms of resistance Background : Malignant gastrointestinal stromal tumours ( GISTs ) are a rare subset of aggressive mesenchymal tumours specific to the gastrointestinal system . They are both locally aggressive and can metastasize . The aim of this analysis was to report on our experience of the utility of coincidence positron emission tomography ( co-PET ) based on an 18F-FDG gamma camera in assessing treatment response to imatinib using CT as the comparator and the final clinical outcome as the end point . Methods : We compared the results of CT and PET scans as predictors of outcome in a consecutive series of patients treated at the Prince of Wales hospital . All patients had biopsy-proven malignant GIST and were on treatment with the targeted pharmacotherapeutic agent imatinib . The majority of the patients were receiving treatment as part of the r and omized trial of the European Organization for Research and Treatment of Cancer , the Australian Gastrointestinal Trials Group and the Italian Sarcoma Group , comparing 400 with 800 mg ( 400 mg b.i.d . ) . The monitoring of tumour response was achieved by serial CT measurements according to the RECIST criteria . Concurrent 18F-FDG co-PET studies were performed within a mean of 2.8 days from the CT scan and were interpreted by a consensus panel of 2 nuclear medicine physicians . Results : A total of 18 patients were recruited into the study , with a total of 74 lesions . There were 47 liver lesions , 31 of which were identified on the initial 18F-FDG co-PET scans ( 63 % ) . There were 10 primary lesions ( 4 stomach , 4 duodenal , 2 small bowel ) , 9 of which were demonstrated on initial 18F-FDG co-PET examinations ( 90 % ) . There were 17 extrahepatic metastatic sites , 15 of which were visualized on the initial 18F-FDG study ( 88 % ) . Of the 18 patients , 8 showed concordant improvement on both CT and 18F-FDG co-PET criteria . One patient showed concordant worsening and 1 was not FDG avid . Eight patients initially showed discordance . 18F-FDG co-PET studies demonstrated changes preceding CT findings in all 8 patients with subsequent concordant improvement . Conclusion : 18F-FDG co-PET is a useful modality to monitor treatment response to imatinib in patients with malignant GIST . Although there is a relatively reduced sensitivity when compared with CT for the detection of lesions especially in the liver , co-PET changes in several instances precede the changes on CT scanning . This modality has the potential to influence clinical decision making and should be considered as part of the st and ard care of patients on imatinib Purpose : To evaluate sunitinib activity and potential cellular and molecular correlates in gastrointestinal stromal tumor ( GIST ) patients after imatinib failure , in addition to assessing the safety and pharmacokinetics ( PK ) of different dose schedules . Experimental Design : In this open-label , dose-ranging , phase I/II study , 97 patients with metastatic imatinib-resistant/intolerant GIST received sunitinib at doses of 25 , 50 , or 75 mg/d on one of three schedules . Serial tumor imaging was done using computed tomography and [18F]fluoro-2-deoxy-d-glucose positron emission tomography scanning . PK and cell proliferation and KIT phosphorylation status in tumor biopsies were also analyzed . Results : Clinical benefit was observed in 52 patients ( 54 % : 7 objective partial responses , 45 stable disease ≥6 months ) . Decreased tumor glycolytic activity was shown in most patients within 7 days of starting sunitinib using [18F]fluoro-2-deoxy-d-glucose positron emission tomography . Sunitinib treatment was associated with reduced tumor cell proliferation by > 25 % in 52 % of cases analyzed and reduced levels of phospho-KIT in tumor biopsies ( indicating target modulation ) . The recommended dose schedule was 50 mg/d for 4 weeks followed by 2 weeks off treatment . On the 50-mg dose across all schedules , 79 % of PK-evaluable patients achieved total drug trough concentrations above the target concentration ( 50 ng/mL ) within 14 days of dosing . In addition , adverse events were generally mild to moderate in severity . Conclusion : Cellular and molecular analyses showed that sunitinib clinical activity is associated with inhibition of KIT in GIST following imatinib failure , illustrating the rational approach used to develop a therapy aim ed at the underlying oncogenic signaling pathway aberrancy . ( Clin Cancer Res 2009;15(18):5902–9 Purpose Gastrointestinal stromal tumours ( GIST ) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to st and ard sarcoma chemotherapy . Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography ( ceCT ) and positron emission tomography ( PET ) with 18F-fluorodeoxyglucose ( FDG ) . The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging . Methods All patients with GIST undergoing PET or PET/CT examinations were prospect ively included in this study , and the median overall survival , time to progression and treatment duration were documented . The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging . Data for 34 patients ( 19 male , 15 female , 21–76 years ) undergoing PET or PET/CT for staging or restaging were analysed . Results In 28 patients , PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate ( Gleevec ; Novartis , Basel , Switzerl and ) . Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity . In contrast , ceCT criteria provided insufficient prognostic power . However , more lesions were found on ceCT images than on PET images , and FDG uptake was sometimes very variable . PET/CT delineated active lesions better than did the combination of PET and ceCT imaging . Conclusion Both PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients . PET/CT precisely delineates lesions and thus allows for the correct planning of surgical interventions Gastrointestinal stromal tumor ( GIST ) is the most common sarcoma arising in the gastrointestinal ( GI ) tract . Imatinib mesylate ( imatinib ) is efficacious in treating advanced and metastatic GIST . Patients undergoing resection of GIST realize a highly variable median disease-free survival ( DFS ) . In the absence of prospect i ve data , we conducted a r and omized , phase II study to assess the safety and efficacy of preoperative and postoperative imatinib for the treatment of GIST . Nineteen GIST patients undergoing surgical resection were r and omized to receive 3 , 5 , or 7 days of preoperative imatinib ( 600 mg daily ) . Patients received postoperative imatinib for 2 years . Perioperative adverse events were compared with those in an imatinib-naïve historical control . The efficacy of imatinib was assessed by 18fluorodeoxyglucose positron emission tomography ( 18FDG-PET ) , dynamic computed tomography ( dCT ) , terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) assay , and DFS . Imatinib did not affect surgical morbidity as compared with an imatinib-naïve cohort ( p ≥ 0.1 ) . Most patients responded to preoperative imatinib by 18FDG-PET and dCT ( 69 % and 71 % , respectively ) . Tumor cell apoptosis increased by an average of 12 % ( range 0–33 % ) and correlated with the duration of preoperative imatinib ( p = 0.04 ) . Median DFS of patients treated with surgery and imatinib was 46 months ( range 10–46 months ) . Tumor size was a predictor of recurrence after postoperative imatinib ( p = 0.02 ) . Imatinib appears to be safe and may be considered for patients undergoing surgical resection of their GIST . Radiographic response and tumor cell apoptosis occur within the first week of imatinib therapy OBJECTIVE We correlated changes in tumor density on CT with changes in glucose metabolism , or the maximum st and ardized uptake value ( SUV(max ) ) , on FDG PET and sought to develop CT imaging criteria that can be used to objective ly evaluate tumor response in patients with metastatic gastrointestinal stromal tumors ( GISTs ) who undergo treatment with imatinib mesylate . MATERIAL S AND METHODS Using the criteria established by the Response Evaluation Criteria in Solid Tumors ( RECIST ) group , we selected 173 tumors ( in 36 patients ) for study . Tumor size and density were determined objective ly , and overall tumor response ( OTR ) was evaluated subjectively on CT images . The changes in these parameters before and after treatment were correlated with changes in SUV(max ) . RESULTS Significant decreases were seen in both tumor density ( mean , 12.3 H [ 16.5 % ] ; p < 0.0001 ) and SUV(max ) ( mean , 3.43 [ 64.9 % ] ; p < 0.0001 ) . OTR evaluated subjectively , correlated well with changes in SUV(max ) ( p < 0.0001 ) . No statistically significant association was found between changes in tumor density and changes in SUV(max ) ( p = 0.3088 ) , but 70 % ( 14/20 ) of the patients with tumors that showed response on FDG PET exhibited at least a partial response by a change in tumor density . Tumor size was found to have decreased significantly 2 months after treatment ( p = 0.0070 ) . However , in 75 % of the patients , the disease was stable according to the traditional tumor response criteria of RECIST . CONCLUSION FDG PET is sensitive and specific for evaluating tumor response but can not be used in patients whose baseline FDG PET results are negative for tumors . Although subjective evaluation was a better indicator of treatment response than was tumor density alone , the tumor density measurement is a good indicator and provides a reliable quantitative means of monitoring the tumor . RECIST , using only tumor size , was unreliable for monitoring GISTs during the early stage of imatinib mesylate treatment UNLABELLED This study was implemented to compare the value of PET , CT , and dual-modality PET/CT imaging for assessing gastrointestinal stromal tumor ( GIST ) response to imatinib therapy . METHODS Twenty patients with histologically proven GIST underwent (18)F-FDG PET/CT imaging before and 1 , 3 , and 6 mo after the start of imatinib therapy . Separate PET and CT data sets , side-by-side PET and CT data sets , and fused PET/CT images were evaluated according to World Health Organization , Response Evaluation Criteria in Solid Tumors , and European Organisation for Research and Treatment of Cancer criteria for therapy response . Hounsfield units ( HU ) were assessed on CT images . A mean follow-up period of 381 + /- 134 d served as the st and ard of reference . RESULTS The numbers of lesions detected in all patients were 135 with PET , 249 with CT , 279 on side-by-side evaluation , and 282 on fused PET/CT images . Tumor response was correctly characterized in 95 % of patients after 1 mo and 100 % after 3 and 6 mo with PET/CT . PET and CT images viewed side by side were correct in 90 % of patients at 1 mo and 100 % at 3 and 6 mo . PET accurately diagnosed tumor response in 85 % of patients at 1 mo and 100 % at 3 and 6 mo . CT was found to be accurate in 44 % of patients at 1 mo , 60 % at 3 mo , and 57 % at 6 mo . HU were found to decrease by at least 25 % in 12 of 14 responders after 1 mo . CONCLUSION Tumor response to imatinib should be assessed with a combination of morphologic and functional imaging . Image fusion with combined PET/CT can provide additional information in individual cases when compared with side-by-side PET and CT PURPOSE Gastrointestinal stromal tumors ( GISTs ) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha ( PDGFRA ) kinases , which are targets for imatinib . In clinical studies , 75 % to 90 % of patients with advanced GISTs experience clinical benefit from imatinib . However , imatinib resistance is an increasing clinical problem . PATIENTS AND METHODS One hundred forty-seven patients with advanced , unresectable GISTs were enrolled onto a r and omized , phase II clinical study of imatinib . Specimens from pretreatment and /or imatinib-resistant tumors were analyzed to identify molecular correlates of imatinib resistance . Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity . RESULTS Molecular studies were performed using specimens from 10 patients with primary and 33 patients with secondary resistance . Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs . Secondary kinase mutations were rare in GISTs with primary resistance but frequently found in GISTs with secondary resistance ( 10 % v 67 % ; P = .002 ) . Evidence for clonal evolution and /or polyclonal secondary kinase mutations was seen in three ( 18.8 % ) of 16 patients . Secondary kinase mutations were nonr and omly distributed and were associated with decreased imatinib sensitivity compared with typical KIT exon 11 mutations . Using RNAi technology , we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways . CONCLUSION Different molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs . These findings have implication s for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs OBJECTIVE To analyze the outcome of 200 patients with gastrointestinal stromal tumor ( GIST ) who were treated at a single institution and followed up prospect ively . SUMMARY BACKGROUND DATA A GIST is a visceral sarcoma that arises from the gastrointestinal tract . Surgical resection is the mainstay of treatment because adjuvant therapy is unproven . METHODS Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years . Patient , tumor , and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival . RESULTS Of the 200 patients , 46 % had primary disease without metastasis , 47 % had metastasis , and 7 % had isolated local recurrence . In patients with primary disease who underwent complete resection of gross disease ( n = 80 ) , the 5-year actuarial survival rate was 54 % , and survival was predicted by tumor size but not microscopic margins of resection . Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site , peritoneum , and liver . CONCLUSIONS GISTs are uncommon sarcomas . Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection . Tumor recurrence tends to be intraabdominal . Investigational protocol s are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST Background The new anti-cancer drug imatinib mesylate inhibits the tyrosine kinase growth factor receptor , c-KIT , and has shown spectacular activity in patients with gastrointestinal stromal tumours ( GISTs ) . Objective To assess whether fluorodeoxyglucose positron emission tomography ( FDG PET ) is suitable for response evaluation of this new type of tumour treatment . Methods Sixteen consecutive patients with irresectable or metastasized GIST or another c-KIT ( CD117 ) positive mesenchymal tumour underwent FDG PET before and 1 week after the start of treatment with imatinib mesylate ( Glivec ® ) . Visual findings and st and ard uptake values ( SUVs ) were compared with the overall response to treatment , based on clinical and radiological response . Results PET visualized all known and some unknown tumour locations . The separation by PET after 1 week of treatment in ‘ PET responders ’ ( 11/16 patients , mean SUV reduction 65 % ) versus ‘ PET non-responders ’ ( 5/16 patients , mean SUV increase 16 % ) appeared to match almost perfectly with overall treatment response and proved correct in 14/15 patients ( prediction sensitivity 93 % ) . FDG uptake changes after 1 week of treatment were of greater magnitude than tumour volume changes on computed tomography at 8 weeks . Progression-free survival was significantly better in patients with a PET response ( P=0.002 ) . PET response predicted treatment outcome better than the radiological response . Finally , PET was helpful during follow-up , in discriminating side effects from tumour progression . Conclusion FDG PET is a valuable tool in patients with gastrointestinal stromal tumours treated with imatinib mesylate . It improves staging , accurately separates responders from non-responders in an early phase , and is helpful during follow-up Imatinib mesylate ( Glivec , formerly STI571 ) is the first effective systemic treatment for gastrointestinal stromal tumours ( GISTs ) . Major changes in tumour volume , however , tend to occur late after the start of treatment . The aim of this study was to evaluate if [18F]-fluorodeoxyglucose-positron emission tomography ( FDG-PET ) can be used for the early evaluation of response to imatinib mesylate treatment in soft-tissue sarcomas ( STS ) . 21 patients ( 17 GIST , 4 other STS ) underwent FDG-PET imaging prior to and 8 days after the start of treatment . PET response ( European Organization for Research and Treatment ( EORTC ) guidelines ) was observed in 13 GISTs ( 11 Complete Responders , 2 partial responders . Subsequent computerised tomography ( CT ) response Response Evaluation Criteria in Solid Tumours ( RECIST ) was observed in 10 of these patients after a median follow up of 8 weeks . Stable or progressive disease was observed on PET in 8 patients and none of them achieved a response on CT . PET response was also associated with a longer progression-free survival ( PFS ) ( 92 % versus 12 % at 1 year , P=0.00107 ) . We conclude that FDG-PET is an early and sensitive method to evaluate an early response to imatinib treatment BACKGROUND Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors . Imatinib mesylate , a selective tyrosine kinase inhibitor , has been shown in pre clinical models and preliminary clinical studies to have activity against such tumors . METHODS We conducted an open-label , r and omized , multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor . We assessed antitumor response and the safety and tolerability of the drug . Pharmacokinetics were assessed in a subgroup of patients . RESULTS A total of 147 patients were r and omly assigned to receive 400 mg or 600 mg of imatinib daily . Overall , 79 patients ( 53.7 percent ) had a partial response , 41 patients ( 27.9 percent ) had stable disease , and for technical reasons , response could not be evaluated in 7 patients ( 4.8 percent ) . No patient had a complete response to the treatment . The median duration of response had not been reached after a median follow-up of 24 weeks after the onset of response . Early resistance to imatinib was noted in 20 patients ( 13.6 percent ) . Therapy was well tolerated , although mild-to-moderate edema , diarrhea , and fatigue were common . Gastrointestinal or intraabdominal hemorrhage occurred in approximately 5 percent of patients . There were no significant differences in toxic effects or response between the two doses . Imatinib was well absorbed , with pharmacokinetics similar to those reported in patients with chronic myeloid leukemia . CONCLUSIONS Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor . Inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinal stromal tumors , which resist conventional chemotherapy In KIT‐expressing Ewing sarcoma cell lines , the addition of doxorubicin to imatinib increases apoptosis , compared with imatinib or doxorubicin alone . On the basis of these in vitro data , the authors conducted a phase 1‐2 trial of doxorubicin with imatinib in patients with gastrointestinal sarcoma tumors refractory to high‐dose imatinib therapy PURPOSE Positron emission tomography with (18)F-fluorodeoxyglucose ( FDG-PET ) was used to evaluate treatment response in patients with gastrointestinal stromal tumors ( GIST ) after administration of sunitinib , a multitargeted tyrosine kinase inhibitor , after imatinib failure . PATIENTS AND METHODS Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy ( 4 weeks of 50 mg/d , 2 weeks off ) . Treatment response was expressed as the percent change in maximal st and ardized uptake values ( SUV ) . The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria . RESULTS Progression-free survival ( PFS ) was correlated with early FDG-PET metabolic response ( P < .0001 ) . Using -25 % and + 25 % thresholds for SUV variations from baseline , early FDG-PET response was stratified in metabolic partial response , metabolically stable disease , or metabolically progressive disease ; median PFS rates were 29 , 16 , and 4 weeks , respectively . Similarly , when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib , the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater ( P < .0001 ) . None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria . Multivariate analysis showed shorter PFS in patients who had higher residual SUVs ( P < .0001 ) , primary resistance to imatinib ( P = .024 ) , or nongastric GIST ( P = .002 ) , regardless of the mutational status of the KIT and PDGFRA genes . CONCLUSION Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome . Thus , it offers opportunities to individualize and optimize patient therapy |
11,365 | 20,727,819 | CIRT is an information and communication technology commonly used in healthcare setting s. Interventions promoting CIRT adoption by healthcare professionals have shown some success in improving search ing skills and use of electronic data bases . | PURPOSE This paper presents the evidence on the effectiveness of interventions promoting the use of clinical information retrieval technologies ( CIRTs ) by healthcare professionals . | BACKGROUND Physicians have difficulty keeping up with new evidence from medical research . METHODS We developed the McMaster Premium LiteratUre Service ( PLUS ) , an internet-based addition to an existing digital library , which delivered quality - and relevance -rated medical literature to physicians , matched to their clinical disciplines . We evaluated PLUS in a cluster-r and omized trial of 203 participating physicians in Northern Ontario , comparing a Full-Serve version ( that included alerts to new articles and a cumulative data base of alerts ) with a Self-Serve version ( that included a passive guide to evidence -based literature ) . Utilization of the service was the primary trial end-point . RESULTS Mean logins to the library rose by 0.77 logins/month/user ( 95 % CI 0.43 , 1.11 ) in the Full-Serve group compared with the Self-Serve group . The proportion of Full-Serve participants who utilized the service during each month of the study period showed a sustained increase during the intervention period , with a relative increase of 57 % ( 95 % CI 12 , 123 ) compared with the Self-Serve group . There were no differences in these proportions during the baseline period , and following the crossover of the Self-Serve group to Full-Serve , the Self-Serve group 's usage became indistinguishable from that of the Full-Serve group ( relative difference 4.4 ( 95 % CI -23.7 , 43.0 ) . Also during the intervention and crossover periods , measures of self-reported usefulness did not show a difference between the 2 groups . CONCLUSION A quality - and relevance -rated online literature service increased the utilization of evidence -based information from a digital library by practicing physicians Abstract OBJECTIVE : To determine if a simple educational intervention can increase resident physician literature search activity . DESIGN : R and omized controlled trial . SETTING : University hospital-based internal medicine training program . PATIENTS / PARTICIPANTS : Forty-eight medical residents rotating on the general internal medicine service . INTERVENTIONS : One-hour didactic session , the use of well-built clinical question cards , and practical sessions in clinical question building . MEASUREMENTS AND MAIN RESULTS : Objective data from the library information system that included the number of log-ons to MEDLINE , search ing volume , abstract s viewed , full-text articles viewed , and time spent search ing . Median search activity as measured per person per week ( control vs intervention ) : number of log-ons to MEDLINE ( 2.1 vs 4.4 , P<.001 ) ; total number of search sets ( 24.0 vs 74.2 , P<.001 ) ; abstract s viewed ( 5.8 vs 17.7 , P=.001 ) ; articles viewed ( 1.0 vs 2.6 , P=.005 ) ; and hours spent search ing ( 0.8 vs 2.4 , P<.001 ) . CONCLUSIONS : A simple educational intervention can markedly increase resident search ing activity PURPOSE The study assesses potential for improving residents ' evidence -based medicine search ing skills in MEDLINE through real-time librarian instruction . SUBJECTS Ten residents on a rotation in a neonatal intensive care unit participated . METHODOLOGY Residents were r and omized into an instruction and a non-instruction group . Residents generated questions from rounds and search ed MEDLINE for answers . Data were collected through observation , search strategy analysis , and surveys . Librarians observed search es and collected data on questions , search ing skills , search problems , and the test group 's instruction topics . Participants performed st and ardized search es before , after , and six-months after intervention and were scored using a search strategy analysis tool ( 1 representing highest score and 5 representing lowest score ) . Residents completed pre- and post-intervention surveys to measure opinions about MEDLINE and search satisfaction . RESULTS Post-intervention , the test group formulated better questions , used limits more effectively , and reported greater confidence in using MEDLINE . The control group expressed less satisfaction with retrieval and demonstrated more errors when limiting . The test and control groups had the following average search scores respectively : 3.0 and 3.5 ( pre-intervention ) , 3.3 and 3.4 ( post-intervention ) , and 2.0 and 3.8 ( six-month post-intervention ) . CONCLUSION Data suggest that measurable learning outcomes were achieved . Residents receiving instruction improved and retained search ing skills six-months after intervention BACKGROUND The " Just-in-time Information " ( JIT ) librarian consultation service was design ed to provide rapid information to answer primary care clinical questions during patient hours . This study evaluated whether information provided by librarians to answer clinical questions positively impacted time , decision-making , cost savings and satisfaction . METHODS AND FINDING A r and omized controlled trial ( RCT ) was conducted between October 2005 and April 2006 . A total of 1,889 questions were sent to the service by 88 participants . The object of the r and omization was a clinical question . Each participant had clinical questions r and omly allocated to both intervention ( librarian information ) and control ( no librarian information ) groups . Participants were trained to send clinical questions via a h and -held device . The impact of the information provided by the service ( or not provided by the service ) , additional re sources and time required for both groups was assessed using a survey sent 24 hours after a question was su bmi tted . The average time for JIT librarians to respond to all questions was 13.68 minutes/ question ( 95 % CI , 13.38 to 13.98 ) . The average time for participants to respond their control questions was 20.29 minutes/ question ( 95 % CI , 18.72 to 21.86 ) . Using an impact assessment scale rating cognitive impact , participants rated 62.9 % of information provided to intervention group questions as having a highly positive cognitive impact . They rated 14.8 % of their own answers to control question as having a highly positive cognitive impact , 44.9 % has having a negative cognitive impact , and 24.8 % with no cognitive impact at all . In an exit survey measuring satisfaction , 86 % ( 62/72 responses ) of participants scored the service as having a positive impact on care and 72 % ( 52/72 ) indicated that they would use the service frequently if it were continued . CONCLUSIONS In this study , providing timely information to clinical questions had a highly positive impact on decision-making and a high approval rating from participants . Using a librarian to respond to clinical questions may allow primary care professionals to have more time in their day , thus potentially increasing patient access to care . Such services may reduce costs through decreasing the need for referrals , further tests , and other courses of action . TRIAL REGISTRATION Controlled-Trials.com IS RCT N96823810 The effect of introducing user fees on the frequency and quality of MEDLINE search ing with GRATEFUL MED by physicians in clinical setting s was tested . After training and free use ( prior study ) , consenting participants were r and omly allocated to pay search ing costs ( pay group ) or continue without fees ( no pay group ) . Fifty-nine physicians participated . Among the prior study 's frequent search ers , the pay group search ed at less than one third of the rate of those assigned to no pay . For less frequent search ers in the prior study , only 48 % of those assigned to pay did any search es , compared with 85 % for the no pay group ( P = 0.006 ) , and for those who did search , their frequency was almost half . However , there was no significant difference in the quality of search es ; both groups demonstrated about equivalent recall ( P = 0.77 ) , but significantly lower precision ( P = 0.03 ) than for the librarian 's independent search es . Similarly , there was no difference in the proportion of search es affecting clinical decisions for the two groups . Thus , imposing user charges for online search ing in clinical setting s after a period of free use adversely affects search ing quantity , but not quality . MEDLINE providers should consider whether user fees will undermine its benefits OBJECTIVE To determine if a preceptor and individualized feedback improves the performance of physicians in search ing MEDLINE in clinical setting s. DESIGN R and omized controlled trial with 2 to 10 months follow-up . SETTING A 300-bed teaching hospital . PARTICIPANTS All 392 physicians and physicians-in-training from 6 major clinical departments were invited to participate if they made patient-care decisions during the study period ; 79.4 % agreed . INTERVENTIONS All participants were given 2 hours of basic training , then r and omized to a control group ( no further intervention ) or an intervention group in which each person chose a clinical preceptor experienced in MEDLINE search ing and received individualized feedback from a study librarian on each of their 1st 10 search es . MAIN OUTCOME MEASURES The number and proportion of relevant and irrelevant references retrieved for 1st , 4th , and 8th search es of participants were compared with independent librarian search es on the same topics . RESULTS Intervention group members did not search more often than controls ( 5.9 search es per month versus 4.7 , respectively ; P = 0.26 ) and there were no significant differences in the quality of search es . Rather , search performance for both groups improved , with the average number of relevant references retrieved per search increasing from 4.5 to 7.4 ( P < 0.01 ) . The librarian retrieved more relevant citations than participants for the 1st search ( P = 0.001 ) but not for the 4th ( P = 0.60 ) or 8th ( P = 0.76 ) search es . CONCLUSIONS A program of assigning preceptors and providing feedback on individual search es did not enhance the quantity or quality of search es . Soon after a basic introduction to search ing , however , clinicians in both groups improved their search performance A double-blind r and omised controlled trial was conducted on a group of Hong Kong hospital clinicians . The objective was to test if a three-hour educational workshop ( with supervised h and s-on practice ) is more effective ( than no training ) to improve clinical question formulation , information-seeking skills , knowledge , attitudes , and search outcomes . The design was a post-test-only control group ; recruitment by stratified r and omization ( by profession ) , blocked at 800 . End-user training was more effective than no training in improving clinical question formulation , in raising awareness , knowledge , confidence and use of data bases , but had made no impact on preference for secondary data bases . It changed the attitude of clinicians to become more positive towards the use of electronic information services ( EIS ) . Participants had higher search performance and outcomes ( satisfaction with information obtained ( NNT = 3 ) , EIS satisfaction ( NNT = 3 ) and success in problem solving ( NNT = 4 ) ) . The workshop improved knowledge and skills in evidence -based search ing , but this effect gradually eroded with time . Search logs confirmed that follow-up is required if effects are to be sustained . Longer effects on search behaviours appear to be positive . A r and omised controlled trial is valuable in identifying cause- and -effect relations and to quantify the magnitude of the effects for management decision-making Background To practice Evidence -Based Medicine ( EBM ) , physicians must quickly retrieve evidence to inform medical decisions . Internal Medicine ( IM ) residents receive little formal education in electronic data base search ing , and have identified poor search ing skills as a barrier to practicing EBM . Objective To design and implement a data base search ing tutorial for IM residents on inpatient rotations and to evaluate its impact on residents ’ skill and comfort search ing MEDLINE and filtered EBM re sources . Design R and omized controlled trial . Residents r and omized to the search ing tutorial met for up to 6 1-hour small group sessions to search for answers to questions about current hospitalized patients . Participants Second- and 3rd-year IM residents . Measurements Residents in both groups completed an Objective Structured Search ing Evaluation ( OSSE ) , search ing for primary evidence to answer 5 clinical questions . OSSE outcomes were the number of successful search es , search times , and techniques utilized . Participants also completed self- assessment surveys measuring frequency and comfort using EBM data bases . Results During the OSSE , residents who participated in the intervention utilized more search ing techniques overall ( p < .01 ) and used PubMed ’s Clinical Queries more often ( p < .001 ) than control residents . Search ing “ success ” and time per completed search did not differ between groups . Compared with controls , intervention residents reported greater comfort using MEDLINE ( p < .05 ) and the Cochrane Library ( p < .05 ) on post-intervention surveys . The groups did not differ in comfort using ACP Journal Club , or in self-reported frequency of use of any data bases . Conclusions An inpatient EBM search ing tutorial improved search ing techniques of IM residents and result ed in increased comfort with MEDLINE and the Cochrane Library , but did not impact overall search ing success Over the past decade , on-line data bases have become increasingly popular among health care professionals . As a group , these ' end-users ' report utilizing data bases to keep abreast of medical progress , to conduct research and to address specific patient care issues . Throughout the literature , medical professionals ( ' content experts ' ) have proved to be less effective search ers than librarians ( ' search experts ' ) . The potential implication s of this discrepancy are worrysome . For any given clinical scenario , for example , published reports may reach contradictory conclusions . A poorly skilled search er may not retrieve enough articles to appreciate this fact . Optimizing search ing skills is therefore a worthwhile goal . As a first step , many medical schools introduce students to on-line data bases , most notably MEDLINE . Residency is an ideal time to continue this training . A recognized obstacle to provide residents with formal MEDLINE instruction is time constraint . We therefore conducted this study to ascertain the impact an individual 1-hour tutorial session would have on MEDLINE utilization among obstetrics and gynecology residents training at an academic medical centre . Outcome measures included MEDLINE search frequency , duration , recall , precision and search er satisfaction . Search recall measures the search er 's ability to retrieve articles deemed relevant to the question at h and . Search precision gauges the search ers ' ability to eliminate irrelevant articles . Although the sessions were well received , we were unable to demonstrate an improvement in the outcome measures analysed . Further research is therefore indicated so that cost-effective educational strategies can be recommended for wide-scale use Introduction : Our underst and ing about the role of the Internet as a re source for physicians has improved in the past several years with reports of patterns for use and measures of impact on medical practice . The purpose of this study was to begin to shape a theory base for more fully describing physicians ' information‐seeking behaviors as they apply to Internet use and applications for continuing education providers to more effectively support learning . Methods : A survey about Internet use and physician information seeking was administered by facsimile transmission to a r and om sample of 3,347 physicians . Results : Almost all physicians have access to the Internet , and most believe it is important for patient care . The most frequent use is in accessing the latest research on specific topics , new information in a disease area , and information related to a specific patient problem . Critical to seeking clinical information is the credibility of the source , followed by relevance , unlimited access , speed , and ease of use . Electronic media are viewed as increasingly important sources for clinical information , with decreased use of journals and local continuing medical education ( CME ) . Barriers to finding needed information include too much information , lack of specific information , and navigation or search ing difficulties . Discussion : The Internet has become an important force in how physicians deliver care . Underst and ing more about physician information‐seeking needs , behaviors , and uses is critical to CME providers to support a self‐directed curriculum for each physician . A shift to increased use of electronic CME options points to new dem and s for users and providers . Specific information about how physicians create a question and search for re sources is an area that requires providers to develop new skills |
11,366 | 23,349,764 | Both of general and central obesity were positively associated with the risk of CRC in this meta- analysis | BACKGROUND Mounting evidence indicates that obesity may be associated with the risk of colorectal cancer ( CRC ) .
To conduct a systematic review of prospect i ve studies assessing the association of obesity with the risk of CRC using meta- analysis . | To investigate the relation of dietary intakes of sucrose , meat , and fat , and anthropometric , lifestyle , hormonal , and reproductive factors to colon cancer incidence , data were analyzed from a prospect i ve cohort study of 35,215 Iowa ( United States ) women , aged 55–69 years and without a history of cancer , who completed mailed dietary and other question naires in 1986 . Through 1990 , 212 incident cases of colon cancer were documented . Proportional hazards regression was used to adjust for age and other risk factors . Risk factors found to be associated significantly with colon cancer included : ( i ) sucrose-containing foods and beverages other than ice cream/milk ; relative risks ( RR ) across the quintiles=1.00 , 1.73 , 1.56 , 1.54 , and 2.00 ( 95 % confidence intervals [ CI ] for quintiles two and five exclude 1.0 ) ; ( ii ) sucrose ; RR across the quintiles=1.00 , 1.70 , 1.81 , 1.82 , and 1.45 ( CI for quintiles two through four exclude 1.0 ) ; ( iii ) height ; RR=1.23 for highest to lowest quintile ( P for trend-0.02 ) ; ( iv ) body mass index ; RR=1.41 for highest to lowest quintile ( P for trend=0.03 ) ; and ( v ) number of livebirths , RR=1.59 for having had one to two livebirths and 1.80 for having had three or more livebirths compared with having had none ( P for trend=0.04 ) . These data support hypotheses that sucrose intake or being tall or obese increases colon cancer risk ; run contrary to the hypothesis that increased parity decreases risk ; support previous findings of no association with demographic factors other than age , cigarette smoking , or use of oral contraceptives or estrogen replacement therapy ; and raise questions regarding previous associations with meat , fat , protein , and physical activity . Cancer Causes and Control 1994 , 5 , 38–52 Studies of colon cancer risk in males have reported strong positive associations with obesity , particularly with central adiposity . The association has been weaker and less consistent for women . In a prospect i ve cohort study of women , body measurements were taken directly ; fat mass and fat‐free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist‐to‐hip ratio ( WHR ) . Among 24,072 women followed on average for 10.4 years , 212 colon cancers were ascertained via the population cancer registry . We review ed medical records of all cases and classified them according to anatomic site and stage . The central adiposity measures of WHR ( hazard ratio per 0.1 unit increase = 1.31 , 95 % confidence interval ( CI ) 1.08–1.58 ) and waist circumference ( hazard ratio per 10 cm increase = 1.14 , 95 % CI 1.02–1.28 ) were positively associated with colon cancer risk . There was little or no association between other anthropometric measures and risk of colon cancer . There was some evidence that the associations were stronger for proximal tumors , but no evidence that risk differed by stage for any of the anthropometric measures . Central adiposity appears to be associated with colon cancer risk in women . © 2005 Wiley‐Liss , The authors chose to examine the association between body mass index ( BMI ) and incident colorectal cancer across the spectrum of BMI , including underweight persons , because detailed prospect i ve cohort data on this topic in Asians is scarce , as is data on underweight persons ( BMI , < 18.5 kg/m2 ) in any population BACKGROUND Several studies of male colon cancer have found positive associations with body size and composition . It is uncertain whether this relationship is due to non-adipose mass , adipose mass , distribution of adipose mass such as central adiposity , or all three . METHODS In a prospect i ve cohort study of men aged 27 - 75 at recruitment in 1990 - 1994 , body measurements were taken by interviewers . Fat mass and fat-free mass ( FFM ) were estimated from bioelectrical impedance analysis . Waist circumference and waist-to-hips ratio ( WHR ) estimated central adiposity . Incident colon cancers were ascertained via the population cancer registry . Altogether , 16,556 men contributed 145,433 person-years and 153 colon cancers . RESULTS Rate ratios ( RRs ) comparing men in the fourth quartile with those in the first quartile were as follows : FFM 2.3 [ 95 % confidence interval ( CI ) 1.4 - 3.7 ] ; height 1.9 ( 95 % CI 1.1 - 3.1 ) ; waist circumference 2.1 ( 95 % CI 1.3 - 3.5 ) ; WHR 2.1 ( 95 % CI 1.3 - 3.4 ) ; fat mass 1.8 ( 95 % CI 1.1 - 3.0 ) ; and body mass index 1.7 ( 95 % CI 1.1 - 2.8 ) . When continuous measures of FFM and WHR were modeled together , the RR for FFM per 10 kg was 1.37 ( 95 % CI 1.04 - 1.80 ) and the RR for WHR per 0.1 unit was 1.65 ( 95 % CI 1.28 - 2.13 ) . After adjustment for FFM and WHR , the RRs for fat mass and body mass index were no longer statistically significant . CONCLUSION Male colon cancer appears to be related to body size and composition by two different pathways , via central adiposity and via non-adipose mass In most studies , body mass index ( BMI ) has been associated with increased risk of colorectal or colon cancer in men , but the relation is weaker and less consistent for women , possibly because of interactions with age or hormone replacement therapy . The authors examined the relation between BMI and colorectal cancer incidence in a large , prospect i ve US cohort of 307,708 men and 209,436 women from the NIH-AARP Diet and Health Study . During follow-up of the cohort from 1995 to 2000 , 2,314 cases of colorectal cancer were observed in men and 1,029 in women . BMI was related to increased risk of incident colon cancer , but not rectal cancer , for both men and women . For men , relative risks of colon cancer for a BMI of 18.5-<23 , 23-<25 , 25-<27.5 , 27.5-<30 , 30-<32.5 , 32.5-<35 , 35-<40 , and > or = 40 kg/m(2 ) were 1.0 ( referent ) , 1.11 , 1.22 , 1.44 , 1.53 , 1.57 , 1.71 , and 2.39 , respectively ( 95 % confidence interval : 1.59 , 3.58 ; p-trend < 0.0005 ) . Corresponding relative risks for women were 1.0 , 1.20 , 1.29 , 1.31 , 1.28 , 1.13 , 1.46 , and 1.49 ( 95 % confidence interval : 0.98 , 2.25 ; p-trend = 0.02 ) . BMI was related to colon cancer risk for younger ( aged 50 - 66 years ) but not older ( aged 67 - 71 years ) women . The association was not modified by hormone replacement therapy in women or physical activity in men or women Abstract Objective : Epidemiologic data relating obesity to risk of colorectal cancer in women have been inconclusive . Two recent studies have suggested that the association may be modified by estrogen status ; BMI was positively associated with colorectal cancer risk among women with high estrogen exposures [ premenopausal women , and postmenopausal women who currently received postmenopausal hormone therapy ( PMH ) ] . We prospect ively investigated the role of BMI in colorectal cancer risk along with the modifying effects of estrogen in a large cohort from the Women 's Health Study . Methods : Among 39,876 apparently healthy women aged ≥45 years at baseline ( 54 % of them were postmenopausal ) , 37,671 were eligible for the present study . During an average of 8.7 years of follow-up , 202 women had a confirmed diagnosis of colorectal cancer . Baseline BMI was calculated by dividing self-reported weight in kilograms by height in meters squared . Results : The multivariate relative risks ( RRs ) and 95 % confidence interval ( CI ) of colorectal cancer were 1.72 ( 1.12–2.66 ) for 27–29.9 kg/m2 , and 1.67 ( 1.08–2.59 ) for ≥30 kg/m2 , as compared with BMI < 23 kg/m2(p for trend = 0.02 ) . This positive association was seen primarily in the proximal colon ( p for trend = 0.004 ) . When the association was further examined according to PMH use among postmenopausal women , we found that both current and never users with higher BMI were at a greater risk of colorectal cancer ( p for interaction between BMI and PMH use = 0.33 ) . As compared with BMI < 23 kg/m2 , the multivariate RRs and 95 % CI for 27–29.9 and ≥30 kg/m2 were 1.98 ( 0.98–3.99 ) and 1.41 ( 0.65–3.06 ) among current users , and 1.05 ( 0.42–2.65 ) and 2.91 ( 1.40–6.06 ) among never users . Conclusions : These data suggest that higher BMI was associated with an elevated risk of colorectal cancer , and the positive relationship was not altered by estrogen exposure among postmenopausal women Objective To examine the relation between body mass index ( kg/m2 ) and cancer incidence and mortality . Design Prospect i ve cohort study . Participants 1.2 million UK women recruited into the Million Women Study , aged 50 - 64 during 1996 - 2001 , and followed up , on average , for 5.4 years for cancer incidence and 7.0 years for cancer mortality . Main outcome measures Relative risks of incidence and mortality for all cancers , and for 17 specific types of cancer , according to body mass index , adjusted for age , geographical region , socioeconomic status , age at first birth , parity , smoking status , alcohol intake , physical activity , years since menopause , and use of hormone replacement therapy . Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period . Increasing body mass index was associated with an increased incidence of endometrial cancer ( trend in relative risk per 10 units=2.89 , 95 % confidence interval 2.62 to 3.18 ) , adenocarcinoma of the oesophagus ( 2.38 , 1.59 to 3.56 ) , kidney cancer ( 1.53 , 1.27 to 1.84 ) , leukaemia ( 1.50 , 1.23 to 1.83 ) , multiple myeloma ( 1.31 , 1.04 to 1.65 ) , pancreatic cancer ( 1.24 , 1.03 to 1.48 ) , non-Hodgkin 's lymphoma ( 1.17 , 1.03 to 1.34 ) , ovarian cancer ( 1.14 , 1.03 to 1.27 ) , all cancers combined ( 1.12 , 1.09 to 1.14 ) , breast cancer in postmenopausal women ( 1.40 , 1.31 to 1.49 ) and colorectal cancer in premenopausal women ( 1.61 , 1.05 to 2.48 ) . In general , the relation between body mass index and mortality was similar to that for incidence . For colorectal cancer , malignant melanoma , breast cancer , and endometrial cancer , the effect of body mass index on risk differed significantly according to menopausal status . Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined . Among postmenopausal women in the UK , 5 % of all cancers ( about 6000 annually ) are attributable to being overweight or obese . For endometrial cancer and adenocarcinoma of the oesophagus , body mass index represents a major modifiable risk factor ; about half of all cases in postmenopausal women are attributable to overweight or obesity BACKGROUND Several recent large prospect i ve cohort studies have failed to demonstrate the presumed protective effect of fruit , vegetable , and dietary fiber consumption on colorectal cancer risk . To further explore this issue , we have examined these associations in a population that consumes relatively low amounts of fruit and vegetables and high amounts of cereals . METHODS We examined data obtained from a food-frequency question naire used in a population -based prospect i ve mammography screening study of women in central Sweden . Women with colorectal cancer diagnosed through December 31 , 1998 , were identified by linkage to regional cancer registries . Cox proportional hazards models were used to estimate relative risks . All statistical tests were two-sided . RESULTS During an average 9.6 years of follow-up of 61 463 women , we observed 460 incident cases of colorectal cancer ( 291 colon cancers , 159 rectal cancers , and 10 cancers at both sites ) . In the entire study population , total fruit and vegetable consumption was inversely associated with colorectal cancer risk . Subanalyses showed that this association was due largely to fruit consumption . The association was stronger , however , and the dose-response effect was more evident among individuals who consumed the lowest amounts of fruit and vegetables . Individuals who consumed less than 1.5 servings of fruit and vegetables per day had a relative risk for developing colorectal cancer of 1.65 ( 95 % confidence interval = 1.23 to 2.20 ; P(trend ) = .001 ) compared with individuals who consumed more than 2.5 servings . We observed no association between colorectal cancer risk and the consumption of cereal fiber , even at amounts substantially greater than previously examined , or of non-cereal fiber . CONCLUSIONS Individuals who consume very low amounts of fruit and vegetables have the greatest risk of colorectal cancer . Relatively high consumption of cereal fiber does not appear to lower the risk of colorectal cancer The relation between relative body weight and colorectal cancer among women is unclear . In a large prospect i ve cohort study , we found a positive association only for distal cancers among younger women that became attenuated at older ages . These results support previous reports in which results were stratified by age or colorectal cancer site . © 2001 Cancer Research BACKGROUND Physical inactivity and high body mass index ( weight in kilograms divided by height in square meters ) have been linked to increased risk of colon cancer . However , none of the few prospect i ve studies in women has shown a statistically significant reduction in colon cancer incidence or mortality associated with increased leisure-time physical activity . PURPOSE In this prospect i ve study , we asked whether leisure-time physical activity , body mass index , or body fat distribution could significantly influence the risk of colon cancer in women . METHODS The participants in this study were enrolled in the Nurses ' Health Study , which began in 1976 . Every 2 years , the women provided additional personal information and information on medical risk factors and major medical events . The time spent per week at a variety of leisure-time physical activities was determined , and the time spent at each activity was multiplied by its typical energy expenditure , expressed in terms of metabolic equivalents or METs . The result ing values for each woman were added to yield an MET-hours-per-week score . Reported diagnoses of colon cancer were confirmed by review of hospital records and pathology reports . Relative risks and associated 95 % confidence intervals were calculated . RESULTS In multivariate analyses that included body mass index , women who expended more than 21 MET-hours per week on leisure-time physical activity had a relative risk of colon cancer of 0.54 ( 95 % confidence interval [ CI ] = 0.33 - 0.90 ) in comparison with women who expended less than 2 MET-hours per week . Women who had a body mass index greater than 29 kg/m2 had a relative risk of colon cancer of 1.45 ( 95 % CI = 1.02 - 2.07 ) in comparison with women who had a body mass index less than 21 kg/m2 . A tendency toward higher colon cancer risk was observed for increasing waist-to-hip ratio ( relative risk = 1.48 [ 95 % CI = 0.88 - 2.49 ] for comparison of the highest quintile ratio [ > 0.833 ] to the lowest [ < 0.728 ] ) . CONCLUSIONS AND IMPLICATION S The significant inverse association between leisure-time physical activity and incidence of colon cancer in women in this study is consistent with what has been found in men . Recommendations to increase physical activity and maintain lean body weight should receive greater emphasis as part of a feasible approach to the prevention of colon cancer Westernization or industrialization leads to an increase in rates of colon cancer , which is the second leading cause of malignant death in the United States [ 1 ] . Although the precise causes of colon cancer remain unclear , a diet high in red meat or animal fat and low in fruits and vegetables appears to increase the risk for this malignancy [ 2 , 3 ] . It is perhaps less well recognized that an inverse association between physical activity and risk for colon cancer has been seen in studies of occupational activity only [ 4 - 12 ] and of both job-related and recreational activity [ 13 - 23 ] . In addition , many studies have found an association between body mass and elevated risk for colon cancer in men ; this association is weaker in women [ 24 - 33 ] . The fact that the association is stronger in men suggests that the abdominal distribution of adiposity typical in men may be an important component of enhanced risk . More limited evidence suggests that height , which may be a proxy for a person 's net energy intake during childhood and adolescence , is related to a higher risk for colon cancer [ 33 - 35 ] . We examine the association between physical activity , obesity , and attained height in relation to risk for colon cancers and their precursory adenomas in a large cohort of male health professionals in the United States . Waist and hip circumferences were available for a subcohort of the study population . We address the hypotheses that physical inactivity , obesity , and height increase the risk for colon cancer and adenoma independently of each other and of diet , and that the abdominal pattern of obesity is an additional independent risk factor . Methods Study Population The Health Professionals Follow-up Study [ 36 ] was started in 1986 ; in that year , 51 529 male dentists , optometrists , osteopaths , podiatrists , pharmacists , and veterinarians in the United States between 40 and 75 years of age responded to a mailed question naire . They reported on their leisure-time physical activity ( described below ) ; current body weight ; weight at age 21 years ; height ; history of cancer and other medical conditions ; parental history of various diseases , including colorectal cancer ; and use of aspirin and other nonsteroidal anti-inflammatory medications . They also reported dietary and alcohol intake using a vali date d [ 37 , 38 ] , semi-quantitative food-frequency question naire . We mailed an optional question naire in 1987 to assess waist and hip circumferences . In 1988 , 1990 , and 1992 , we up date d exposure information and ascertained newly diagnosed medical conditions and history of colonoscopy or sigmoidoscopy , including the indications for endoscopy : bleeding in stool , positive results from tests for occult fecal blood , abdominal pain , diarrhea or constipation , family history of colorectal cancer , routine screening without symptoms , or follow-up [ 39 ] . Most of the deaths in the cohort were reported by family members or by the postal system in response to the follow-up question naires . We also used the National Death Index to identify deaths among nonrespondents [ 40 ] . Assessment of Physical Activity The 1986 question naire included a section about mainly recreational or leisure-time physical activity . The reliability and validity of question naires design ed to assess physical activity have been investigated [ 41 - 43 ] . A question naire such as the one used in our cohort was evaluated in a cohort of U.S. nurses and was found to provide useful information [ 44 ] , and similar results were found during a similar validation study done within the Health Professionals cohort ( Chasan-Taber S. Personal communication ) . Participants reported the average time per week spent doing each of eight moderate and vigorous activities , choosing from among 10 possible responses that ranged from 0 minutes to 11 or more hours per week . The specific activities listed were walking or hiking outdoors ( including walking during golf ) ; jogging ( slower than 10 minutes/mile ) ; running ( 10 minutes/mile or faster ) ; bicycling ( including that done on a stationary machine ) ; lap swimming ; tennis , squash , or racquetball ; and calisthenics or rowing . In addition , each respondent reported the number of flights of stairs he climbed daily and his usual walking pace . The reported time spent at each activity per week was multiplied by its typical energy expenditure requirements expressed in metabolic equivalents ( METs ) [ 45 ] to yield a MET-hour score . One MET , which is the energy expended by sitting quietly , is equivalent to 3.5 mL of oxygen uptake per kilogram of body weight per minute for a 70-kg adult . For example , 1 hour per week of running contributed 10.2 MET-hours , 1 hour of tennis contributed 6 MET-hours , and 1 hour of walking at a moderate pace contributed 3.2 MET-hours . Body weight was excluded from the derivation of energy expenditure from physical activity to avoid confounding the expenditure variable by body weight . If more than one published intensity level was available for a given activity , the moderate or general MET value was chosen . An average MET value was assigned to the categories that listed more than one activity , such as rowing or calisthenics , and squash or racquetball . Assessment of Anthropometric Variables Each man reported his current weight and height and his weight at age 21 years on the 1986 question naire . In 1987 , we mailed an optional question naire once to obtain additional exposure information , including body circumference measurements . We instructed each participant to measure ( to the nearest quarter inch ) his waist at the umbilicus and his hips at the largest circumference between the waist and thighs while st and ing and without measuring over bulky clothing [ 46 ] . We provided a tape measure and an illustration to help st and ardize the measurements . Sixty-five percent of the cohort responded . We used the Quetelet index ( kilograms/height in meters2 ) as a measure of total adiposity , waist-to-hip ratio to measure relative distribution of fat , and waist circumference to estimate total abdominal fat . Although the waist-to-hip ratio has been used more widely , waist circumference provides an estimate of absolute abdominal adiposity , the component most closely related to important metabolic abnormalities , including hyperinsulinemia , hypertension , and high triglyceride levels . To remove extraneous variation in the waist circumference because of height ( taller men tend to have larger waist circumferences due to their larger body size rather than to obesity ) , we adjusted waist for height using residual analysis [ 47 ] . We first regressed waist on height using multiple linear regression and then added the residual to the average waist size ( 37.4 inches ) for a man of average height ( 70 inches ) to convert this measure back to the initial scale . This conversion created for each man a st and ardized waist circumference unconfounded by height . We evaluated the precision of self-reported anthropometric measures among 123 cohort members who were part of a dietary validation study [ 46 ] . Trained technicians paid the sub study participants two visits , approximately 6 months apart , to measure current weight and waist and hip circumferences . The Pearson correlation between self-report and the average of the technicians ' two measurements was 0.97 for weight , 0.95 for waist circumference , 0.88 for hip circumference , and 0.69 for waist-to-hip ratio . The men 's self- measurements of their waist circumferences were 0.36 inches greater , their self- measurements of hip circumferences were 0.78 inches smaller , and their self- measurements of weight were 2.3 pounds less than the technician 's measurements . Identification of Patients with Colorectal Cancers In 1988 , 1990 , and 1992 , we asked each participant whether cancer had been diagnosed during the previous 2 years . The response rate to the follow-up question naires was 94 % through 31 January 1992 . When a participant ( or a decedent 's next-of-kin ) reported a diagnosis of cancer of the colon or rectum , we sought permission to obtain hospital records and pathology reports . A study physician , blinded to exposure information , review ed all medical records received and extracted data about histologic type , anatomic location , and stage of the cancer . Proximal colon cancers were defined as those from the cecum to and including the splenic flexure , and distal colon cancers were defined as those in the descending and sigmoid colon . We confirmed 249 new cases of colorectal adenocarcinoma ( excluding carcinoma in situ ) , 90 % by medical records and the remainder with corroborating information about diagnosis and treatment from the cohort member . Two hundred three cancers were in the colon and 46 were in the rectum . Identification of Patients with Colorectal Adenomas and Controls Because more than 90 % of the adenomas were diagnosed during endoscopic procedures for screening or for unrelated gastrointestinal conditions , we restricted the adenoma analysis to men who had had a colonoscopy or sigmoidoscopy . This was done to reduce the potential for detection bias . Most procedures were sigmoidoscopies ; thus , we analyzed only adenomas of the distal colorectum . Although we did not examine proximal colon adenomas , this should not have biased inferences for the distal colorectum . However , different causes for proximal adenomas may exist . A total of 12 879 men who did not meet any of the exclusion criteria ( see Data Analysis ) reported having had an endoscopy between 1986 and 1992 . In 1993 , we sent a mailing to a r and om sample of 200 controls ( men who reported negative results from an endoscopy ) to confirm that they did not have adenomas . After one mailing , 140 ( 70 % ) controls granted us permission to review the medical records of their endoscopic procedure ; none had an unreported , histologically confirmed adenoma . We were able to recontact 96 % of the men who reported a diagnosis of polyp , and we received medical records in response to more than 96 % of the requests sent to medical record departments , Obesity is a controversial risk factor for colorectal cancer ( CRC ) in older women . We evaluated associations between multiple body size parameters and incident CRC in the prospect i ve , population -based Iowa Women 's Health Study ( IWHS ) . IWHS participants , ages 55 to 69 years , provided data regarding height ; weight ; weight at ages 50 , 40 , 30 , 18 years ; hip circumference ; and waist circumference at baseline ( 1986 ) . Derived variables included body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , and “ overweight years ” ( OWY ; conceptually similar to cigarette pack-years ) . Incident CRC cases ( n = 1,464 ) were ascertained from the State Health Registry of Iowa , through 2005 . Multivariable Cox regression models were fit to estimate body size – associated CRC risks . Among 36,941 women ( 619,961 person-years ) , baseline height , weight , BMI , hip circumference , waist circumference , and WHR were all positively associated with incident CRC ( P trend ≤ 0.003 for each ) . Baseline BMI yielded the highest CRC risk estimates ( obese III versus normal , RR = 1.56 ; 95 % CI = 1.10–2.22 ; P trend < 0.001 ) and was more closely associated with distal than proximal tumors ( P trend < 0.001 versus 0.06 ) . Conversely , height was more closely associated with proximal than distal tumors ( P trend < 0.001 versus 0.04 ) . Other body size parameters were less predictive of incident CRC . These data strongly support a positive association between increased body size and CRC risk among older women . Further investigation of when increased body size has the greatest effect on CRC risk ( i.e. , early adulthood versus later adulthood ) might also be informative , particularly with respect to defining subsite-specific pathways of colorectal carcinogenesis . Cancer Prev Res ; 3(12 ) ; 1608–20 . © 2010 AACR In a 6-year prospect i ve study , the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study ( California , 1976 - 1982 ) who , at baseline , had no documented or reported history of cancer . The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates . The authors found a positive association with total meat intake ( risk ratio ( RR ) for > or = 1 time/week vs. no meat intake = 1.85 , 95 % confidence interval ( CI ) 1.19 - 2.87 ; p for trend = 0.01 ) and , among subjects who favored specific types of meat , positive associations with red meat intake ( RR for > or = 1 time/week vs. no red meat intake = 1.90 , 95 % CI 1.16 - 3.11 ; p for trend = 0.02 ) and white meat intake ( RR for > or = 1 time/week vs. no white meat intake = 3.29 , 95 % CI 1.60 - 6.75 ; p for trend = 0.006 ) . An inverse association with legume intake ( RR for > 2 times/week vs. < 1 time/week = 0.53 , 95 % CI 0.33 - 0.86 ; p for trend = 0.03 ) was observed . Among men , a positive association with body mass index was observed ( relative to the RR for tertile III ( > 25.6 kg/m2 ) vs. tertile I ( < 22.5 kg/m2 ) = 2.63 , 95 % CI 1.12 - 6.13 ; p for trend = 0.05 ) . A complex relation was identified whereby subjects exhibiting a high red meat intake , a low legume intake , and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables . This pattern of putative risk factors would likely contribute to increases in both insulin resistance ( high body mass , high red meat intake ) and glycemic load ( low legume intake ) , a synergism that , if causal , implicates hyperinsulinemic exposure in colon carcinogenesis . The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology Background Although body mass index has been shown to be associated with colon cancer , studies of rectal cancer risk have generally reported no association . The relationship between rectal cancer risk and central adiposity , overall fat mass , and fat-free mass is unknown . Methods In a prospect i ve cohort study of people aged 27–75 years , body measurements were taken directly ; fat mass and fat-free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist-to-hip ratio . Among 16,867 men and 24,247 women followed on average for 10.3 years , 229 rectal cancers were ascertained via the population cancer registry . Results When comparing the highest tertile with the lowest tertile , weight ( hazard ratio = 1.4 , 95 % confidence interval ( CI ) 1.1–2.0 ) , waist circumference ( hazard ratio = 1.4 , 95 % CI 1.0–1.9 ) , fat mass ( hazard ratio = 1.4 , 95 % CI 1.0–2.0 ) and percent fat ( hazard ratio = 1.4 , 95 % CI 1.0–2.0 ) were positively associated with rectal cancer risk . There was no evidence that risk differed by sex for any of the anthropometric measures . Conclusions Waist circumference and fat mass may be weakly related to risk of rectal cancer BACKGROUND While previous studies suggest that overweight , middle-aged men may face increased risk of colon cancer , it is unclear whether their weights as young adults influence this risk . It is also unknown whether their level of physical activity affects their risk of developing colon cancer . PURPOSE To determine the relationship between being overweight in middle-age or young adulthood and colon cancer risk , we prospect ively studied alumni of Harvard University . We also investigated whether being overweight influences risk differently for men with different levels of physical activity . METHODS In 1962 or 1966 ( 1962/1966 ) , alumni completed question naires on weight , height , other sociodemographic characteristics , and medical history . We obtained information on weight and height at college entry from university archives . Alumni ( n = 17,595 ) were followed from 1962/1966 to 1988 for colon cancer occurrence , ascertained from follow-up question naires in 1977 and 1988 and death certificates . RESULTS Between 1962/1966 and 1988 , 302 cases of colon cancer were diagnosed . Colon cancer risk increased with higher levels of Quetelet 's index ( weight [kg]/height [m]2 ) in 1962/1966 . Relative risk per unit increase , adjusted for age , physical activity , and parental history of cancer , was 1.08 ( 95 % confidence interval [ CI ] , 1.04 - 1.13 ) . Quetelet 's index at college entry did not predict risk as well ( adjusted relative risk per unit increase , 1.05 ; 95 % CI , 1.00 - 1.10 ) . The heaviest fifth of alumni during both college time and in 1962/1966 had almost two and one-half times the risk of the lightest fifth of alumni ( adjusted relative risk , 2.40 ; 95 % CI , 1.40 - 4.13 ) . When alumni were classified according to activity level in 1962/1966 , higher levels of Quetelet 's index were significantly associated with colon cancer risk only among those who were less active . CONCLUSIONS Overweight during middle-age or young adulthood is associated with higher colon cancer risk ; in overweight , physically active men , however , the risk of colon cancer may not be increased Predictors of colorectal cancer have been extensively studied with some evidence suggesting that risk factors vary by subsite . Using data from 2 prospect i ve cohort studies , we examined established risk factors to determine whether they were differentially associated with colon and rectal cancer . Our study population included 87,733 women from the Nurses ' Health Study ( NHS ) and 46,632 men from the Health Professionals Follow Up Study ( HPFS ) . Exposure information was collected via biennial question naires ( dietary variables were collected every 4 years ) . During the follow-up period ( NHS : 1980 to May 31 , 2000 ; HPFS : 1986 to January 31 , 2000 ) , we identified 1,139 cases of colon cancer and 339 cases of rectal cancer . We used pooled logistic regression to estimate multivariate relative risks for the 2 outcomes separately and then used polytomous logistic regression to compare these estimates . In the combined cohort , age , gender , family history of colon or rectal cancer , height , body mass index , physical activity , folate , intake of beef , pork or lamb as a main dish , intake of processed meat and alcohol were significantly associated with colon cancer risk . However , only age and sex were associated with rectal cancer . In a stepwise polytomous logistic regression procedure , family history and physical activity were associated with statistically significant different relative risks of colon and rectal cancer . Our findings support previous suggestions that family history and physical activity are not strong contributors to the etiology of rectal cancer . Future investigations of colon or rectal cancer should take into consideration risk factor differences by subsite Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer . Anthropometric measures ( height , weight , and body mass index ( weight (kg)/height (m)(2 ) ) and metabolic abnormalities associated with insulin resistance syndrome ( IRS ) ( abnormalities in measured blood pressure , high density lipoprotein ( HDL ) cholesterol , and total cholesterol ) were prospect ively evaluated for associations with incident colon ( n = 227 ) , rectal ( n = 183 ) , and colorectal ( n = 410 ) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study . Cox proportional hazards models were used to calculate hazard ratios and 95 % confidence intervals . In comparison with the lowest quintile , the highest quintile of body mass index was significantly associated with colorectal cancer ( hazard ratio ( HR ) = 1.70 , 95 % confidence interval ( CI ) : 1.01 , 2.85 ; p-trend = 0.01 ) , particularly colon cancer . Subjects with a cluster of three IRS-related conditions ( hypertension , body mass index > /=25 kg/m(2 ) , and HDL cholesterol level < 40 mg/dl ( < 1.55 mmol/liter ) ) , compared with those with fewer conditions , had a significantly increased risk of colorectal cancer ( HR = 1.40 , 95 % CI : 1.12 , 1.74 ) , particularly colon cancer ( HR = 1.58 , 95 % CI : 1.18 , 2.10 ) , but not rectal cancer . These results support the hypothesis that the significant association observed between IRS-defining metabolic abnormalities and colorectal cancer is determined primarily by adiposity Epidemiological studies are remarkably consistent , especially among men , in showing that overweight and obesity [ body mass index ( BMI ) > 25 ] are associated with increased risk of colon cancer . However , no prospect i ve studies address the influence of weight change in adulthood on subsequent colon cancer risk . In this study , we investigated whether weight change influences colon cancer risk utilizing prospect ively collected weight data . We included 46,349 men aged 40 - 75 participating in the Health Professionals Follow-Up Study . Question naires including items on weight were completed every second year during follow-up from 1986 to 2004 . Up date d weight change between consecutive question naires during follow-up and recalled weight gain since age 21 was evaluated . All eligible men were cancer-free at baseline . Proportional hazard and restricted spline regression models were implemented . Over an 18-year period , we documented 765 cases of colon cancer . Cumulative mean BMI > 22.5 was associated with significantly increased risk of colon cancer . The short-term weight change in the prior 2 to 4 years was positively and significantly associated with risk [ HR = 1.14 ( 95 % confidence interval , 1.00 - 1.29 ) for 4.54 kg ( 10 pounds ) increment , p = 0.04 for overall trend ] . Weight gain per 10 years since age 21 was associated with significantly increased risk [ HR = 1.33 ( 1.12 - 1.58 ) for 4.54 kg increase per 10 years , p = 0.001 ] . We estimated that 29.5 % of all colon cancer cases was attributable to BMI above 22.5 . Our results add support that overweight and obesity are modifiable risk factors for colon cancer among men and suggest that weight has an important influence on colon cancer risk even in later life Objective To investigate the association of body mass index ( BMI ) or body height with colorectal cancer incidence in a population -based prospect i ve study . Methods We identified 986 ( 626 men and 360 women ) newly diagnosed cases of colorectal cancer during the 9.4-year follow-up of a cohort consisting of 102,949 ( 49,158 male and 53,791 female ) middle-aged and elderly Japanese . Results Lower BMI groups ( lower than 23 ) were not associated with colorectal cancer compared with the 23–24.9 BMI group . Any categories of 25–26.9 , 27–29.9 , or 30 or more BMI were associated with an increased risk of colorectal cancer compared with the lower than 25 BMI ( RR , 1.2 for 25–26.9 , 1.4 for 27–29.9 , and 1.5 for 30 or more ; p for trend , 0.004 ) in men . These associations were more evident only in invasive-type cancer analysis . BMI was not associated with the risk of colorectal cancer in women . No significant association with height was obtained for either men or women . Conclusions The association of BMI with colorectal cancer was confirmed in a Japanese population as well as Western population s. Only invasive-cancer analysis suggested that BMI was important for tumor growth and proliferation . Approximately 6.7 % of colorectal cancer was attributable to a BMI of 25 or higher in middle-aged and elderly Japanese men Background : Several large studies of obesity and colorectal cancer risk have found no association among women but a reasonably consistent positive association among men . In women , a positive association that is stronger among , or limited to , those who are premenopausal has been suggested by studies that stratified analyses by age , although no previous study has examined the association by menopausal status . Methods : We used proportional hazards analyses to estimate hazard ratios relating obesity to colorectal cancer risk among 89 835 women aged 40–59 years at recruitment into the Canadian National Breast Screening Study , a multicentre r and omised controlled trial of mammography screening for breast cancer . During an average 10.6 years of follow up ( 936 433 person years ) , a total of 527 women were diagnosed with incident colorectal cancer ( 363 colon and 164 rectal ) . Results : We found that obesity ( body mass index ≥30 kg/m2 ) was associated with an approximately twofold increased risk of colorectal cancer among women who were premenopausal at baseline ( hazard ratio 1.88 , 95 % confidence interval 1.24–2.86 ) . There was no association among postmenopausal women ( p for interaction=0.01 ) , and there was only a weak positive association in the entire cohort . Conclusions : Our data suggest that obesity is associated with a twofold increased risk of colorectal cancer in premenopausal women but is not associated with altered risk in postmenopausal women . Effect modification by menopausal status may better explain the inconsistent or weak findings in previous studies than the presumed lack of an association among women Overexpression of fatty acid synthase ( FASN ) , a key enzyme for de novo lipogenesis , is observed in many cancers including colorectal cancer and is associated with poor clinical outcomes . Cellular FASN expression is physiologically upregulated in a state of energy excess . Obesity and excess energy balance have been known to be risk factors for colorectal cancer . High degree of microsatellite instability ( MSI-H ) is a distinct phenotype in colorectal cancer , associated with CpG isl and methylator phenotype ( CIMP ) . Previous data suggest that obesity or altered energy balance may potentially modify risks for MSI-H cancers and microsatellite stable ( MSS ) cancers differently . However , the relationship between MSI and FASN overexpression has not been investigated . Using 976 cases of population -based colorectal cancer sample s from 2 large prospect i ve cohort studies , we correlated FASN expression ( by immunohistochemistry ) with MSI , KRAS and BRAF mutations , p53 expression ( by immunohistochemistry ) , and CIMP status [ determined by MethyLight for 8 CIMP-specific gene promoters including CACNA1 G , CDKN2A ( p16 ) , CRABP1 , IGF2 , MLH1 , NEUROG1 , RUNX3 , and SOCS1 ] . Marked ( 2 + ) FASN overexpression was observed in 110 ( 11 % ) of the 976 tumors and was significantly more common in MSI-H tumors ( 21 % [ 28/135 ] ) than MSI-low ( 5.6 % [ 4/72 ] , P = .004 ) and MSS tumors ( 11 % [ 72/678 ] , P = .001 ) . The association between FASN overexpression and MSI-H persisted even after stratification by CIMP status . In contrast , FASN overexpression was not correlated with CIMP after stratification by MSI status . Fatty acid synthase overexpression was not significantly correlated with sex , tumor location , p53 , or KRAS/BRAF status . In conclusion , FASN overexpression in colorectal cancer is associated with MSI-H , independent of CIMP status We conducted a population -based prospect i ve cohort study in Japan to examine the relationship between body mass index ( BMI ) and the risk of incidence of any cancer and of cancer at individual sites . Body mass index was calculated from self-administered body weight and height at baseline . Relative risks ( RR ) and 95 % confidence intervals ( CI ) were calculated in multivariate proportional-hazards models . Among 27,539 persons ( 15,054 women and 12,485 men ) aged 40 years or older who were free of cancer at enrollment in 1984 , 1,672 ( 668 women and 1,004 men ) developed cancer during 9 years of follow-up . In women , after adjustment for potential confounders , the RR of all cancers associated with different BMI , relative to a BMI of 18.5 - 24.9 , were 1.04 ( 95 % CI = 0.85 - 1.27 ) for BMI = 25.0 - 27.4 , 1.29 ( 1.00 - 1.68 ) for BMI = 27.5 - 29.9 and 1.47 ( 1.06 - 2.05 ) for BMI > /=30.0 ( p for trend = 0.007 ) . Higher BMI was also significantly associated with higher risk of cancers of the colorectum , breast ( postmenopausal ) , endometrium and gallbladder in women . In men , we observed significantly increased all-cancer risk among only never-smokers . Overweight and obesity could account for 4.5 % ( all subjects ) or 6.2 % ( never-smokers ) of the risk of any cancer in women and -0.2 % ( all subjects ) or 3.7 % ( never-smokers ) in men . The value for women was within the range among women reported from Western population s ( 3.2%-8.8 % ) . Our data demonstrate that excess weight is a major cancer risk among Japanese women BACKGROUND Body weight and body mass index ( BMI ) are positively related to risk of colon cancer in men , whereas weak or no associations exist in women . This discrepancy may be related to differences in fat distribution between sexes or to the use of hormone replacement therapy ( HRT ) in women . METHODS We used multivariable adjusted Cox proportional hazards models to examine the association between anthropometric measures and risks of colon and rectal cancer among 368 277 men and women who were free of cancer at baseline from nine countries of the European Prospect i ve Investigation Into Cancer and Nutrition . All statistical tests were two-sided . RESULTS During 6.1 years of follow-up , we identified 984 and 586 patients with colon and rectal cancer , respectively . Body weight and BMI were statistically significantly associated with colon cancer risk in men ( highest versus lowest quintile of BMI , relative risk [ RR ] = 1.55 , 95 % confidence interval [ CI ] = 1.12 to 2.15 ; P(trend ) = .006 ) but not in women . In contrast , comparisons of the highest to the lowest quintile showed that several anthropometric measures , including waist circumference ( men , RR = 1.39 , 95 % CI = 1.01 to 1.93 ; P(trend ) = .001 ; women , RR = 1.48 , 95 % CI = 1.08 to 2.03 ; P(trend ) = .008 ) , waist-to-hip ratio ( WHR ; men , RR = 1.51 , 95 % CI = 1.06 to 2.15 ; P(trend ) = .006 ; women , RR = 1.52 , 95 % CI = 1.12 to 2.05 ; P(trend ) = .002 ) , and height ( men , RR = 1.40 , 95 % CI = 0.99 to 1.98 ; P(trend ) = .04 ; women , RR = 1.79 , 95 % CI = 1.30 to 2.46 ; P(trend)<.001 ) were related to colon cancer risk in both sexes . The estimated absolute risk of developing colon cancer within 5 years was 203 and 131 cases per 100,000 men and 129 and 86 cases per 100,000 women in the highest and lowest quintiles of WHR , respectively . Upon further stratification , no association of waist circumference and WHR with risk of colon cancer was observed among postmenopausal women who used HRT . None of the anthropometric measures was statistically significantly related to rectal cancer . CONCLUSIONS Waist circumference and WHR , indicators of abdominal obesity , were strongly associated with colon cancer risk in men and women in this population . The association of abdominal obesity with colon cancer risk may vary depending on HRT use in postmenopausal women ; however , these findings require confirmation in future studies |
11,367 | 16,235,382 | MAIN RESULTS The most rigorous ( intent-to-treat ) analysis found no significant differences between MST and usual services in restrictive out-of-home placements and arrests or convictions .
Pooled results that include studies with data of varying quality tend to favor MST , but these relative effects are not significantly different from zero .
The study sample size is small and effects are not consistent across studies ; hence , it is not clear whether MST has clinical ly significant advantages over other services .
There is inconclusive evidence of the effectiveness of MST compared with other interventions with youth .
There is no evidence that MST has harmful effects | BACKGROUND Multisystemic Therapy ( MST ) is an intensive , home-based intervention for families of youth with social , emotional , and behavioral problems .
Masters-level therapists engage family members in identifying and changing individual , family , and environmental factors thought to contribute to problem behavior .
Intervention may include efforts to improve communication , parenting skills , peer relations , school performance , and social networks .
Most MST trials were conducted by program developers in the USA ; results of one independent trial are available and others are in progress .
OBJECTIVES To provide unbiased estimates of the impacts of MST on restrictive out-of-home living arrangements , crime and delinquency , and other behavioral and psychosocial outcomes for youth and families . | The mechanisms through which multisystemic therapy ( MST ) decreased delinquent behavior were assessed in 2 sample s of juvenile offenders . Sample 1 included serious offenders who were predominantly rural , male , and African American . Sample 2 included substance-abusing offenders who were predominantly urban , male , and Caucasian . Therapist adherence to the MST protocol ( based on multiple respondents ) was associated with improved family relations ( family cohesion , family functioning , and parent monitoring ) and decreased delinquent peer affiliation , which , in turn , were associated with decreased delinquent behavior . Furthermore , changes in family relations and delinquent peer affiliation mediated the relationship between caregiver-rated adherence and reductions in delinquent behavior . The findings highlight the importance of identifying central change mechanisms in determining how complex treatments such as MST contribute to ultimate outcomes This article examined the long-term effects of multisystemic therapy ( MST ) vs. individual therapy ( IT ) on the prevention of criminal behavior and violent offending among 176 juvenile offenders at high risk for committing additional serious crimes . Results from multiagent , multi method assessment batteries conducted before and after treatment showed that MST was more effective than IT in improving key family correlates of antisocial behavior and in ameliorating adjustment problems in individual family members . Moreover , results from a 4-year follow-up of rearrest data showed that MST was more effective than IT in preventing future criminal behavior , including violent offending . The implication s of such findings for the design of violence prevention programs are discussed OBJECTIVE Although several treatments for adolescent substance abuse have been identified as promising by review ers and federal agencies , treatment effects extending beyond 12 months have not been demonstrated in r and omized clinical trials . The primary purpose of this report was to examine the 4-year outcomes of an evidence -based treatment of substance-abusing juvenile offenders . METHOD Eighty of 118 substance-abusing juvenile offenders participated in a follow-up 4 years after taking part in a r and omized clinical trial comparing multisystemic therapy ( MST ) with usual community services . A multi method ( self-report , biological , and archival measures ) assessment battery was used to measure the criminal behavior , illicit drug use , and psychiatric symptoms of the participating young adults . RESULTS Analyses demonstrated significant long-term treatment effects for aggressive criminal activity ( 0.15 versus 0.57 convictions per year ) but not for property crimes . Findings for illicit drug use were mixed , with biological measures indicating significantly higher rates of marijuana abstinence for MST participants ( 55 % versus 28 % of young adults ) . Long-term treatment effects were not observed for psychiatric symptoms . CONCLUSIONS Findings provide some support for the long-term effectiveness of an evidence d-based family-oriented treatment of substance-abusing juvenile offenders . The clinical , research , and policy implication s of these findings are noted Hospitalization and out-of-home placement data for 113 youth participating in a r and omized trial comparing home-based multisystemic therapy ( MST ; n = 57 ) with hospitalization(n = 56 ) for psychiatric crisis stabilization were analyzed following the completion of MST treatment — approximately 4 months post approval for emergency psychiatric hospitalization . Analyses showed that MST prevented any hospitalization for 57 % of the participants in the MST condition and reduced the overall number of days hospitalized by 72 % . Importantly , the reduction in use and length of hospitalization was not offset by increased use of other placement options , as MST reduced days in other out-of-home placements by 49 % . The cost implication s for the viability of MST as an alternative to hospitalization for youth presenting psychiatric emergencies are discussed OBJECTIVE The primary purpose of this study was to determine whether multisystemic therapy ( MST ) , modified for use with youths presenting psychiatric emergencies , can serve as a clinical ly viable alternative to inpatient psychiatric hospitalization . METHOD One hundred sixteen children and adolescents approved for emergency psychiatric hospitalization were r and omly assigned to home-based MST or inpatient hospitalization . Assessment s examining symptomatology , antisocial behavior , self-esteem , family relations , peer relations , school attendance , and consumer satisfaction were conducted at 3 times : within 24 hours of recruitment into the project , shortly after the hospitalized youth was released from the hospital ( 1 - 2 weeks after recruitment ) , and at the completion of MST home-based services ( average of 4 months postrecruitment ) . RESULTS MST was more effective than emergency hospitalization at decreasing youths ' externalizing symptoms and improving their family functioning and school attendance . Hospitalization was more effective than MST at improving youths ' self-esteem . Consumer satisfaction scores were higher in the MST condition . CONCLUSIONS The findings support the view that an intensive , well-specified , and empirically supported treatment model , with judicious access to placement , can effectively serve as a family- and community-based alternative to the emergency psychiatric hospitalization of children and adolescents OBJECTIVE This study presents findings from a 1-year follow-up to a r and omized clinical trial comparing multisystemic therapy ( MST ) , modified for use with youths presenting psychiatric emergencies , with inpatient psychiatric hospitalization . METHOD One hundred fifty-six children and adolescents approved for emergency psychiatric hospitalization were r and omly assigned to home-based MST or inpatient hospitalization followed by usual services . Assessment s examining mental health symptoms , out-of-home placement , school attendance , and family relations were conducted at five times : within 24 hours of recruitment , shortly after the hospitalized youth was released from the hospital ( 1 - 2 weeks after recruitment ) , at the completion of MST ( average of 4 months postrecruitment ) , and 10 and 16 months postrecruitment . RESULTS Based on placement and youth-report measures , MST was initially more effective than emergency hospitalization and usual services at decreasing youths ' symptoms and out-of-home placements and increasing school attendance and family structure , but these differences generally dissipated by 12 to 16 months postrecruitment . Hospitalization produced a rapid , but short-lived , decrease in externalizing symptoms based on caregiver reports . CONCLUSION Findings suggest that youths with serious emotional disturbance might benefit from continuous access to a continuum of evidence -based practice s titrated to clinical need The effectiveness and transportability of multisystemic therapy ( MST ) were examined in a study that included 118 juvenile offenders meeting DSM-III-R criteria for substance abuse or dependence and their families . Participants were r and omly assigned to receive MST versus usual community services . Outcome measures assessed drug use , criminal activity , and days in out-of-home placement at posttreatment ( T2 ) and at a 6-month posttreatment follow-up ( T3 ) ; also treatment adherence was examined from multiple perspectives ( i.e. , caregiver , youth , and therapist ) . MST reduced alcohol , marijuana , and other drug use at T2 and total days in out-of-home placement by 50 % at T3 . Reductions in criminal activity , however , were not as large as have been obtained previously for MST . Examination of treatment adherence measures suggests that the modest results of MST were due , at least in part , to difficulty in transporting this complex treatment model from the direct control of its developers . Increased emphasis on quality assurance mechanisms to enhance treatment fidelity may help overcome barriers to transportability The effects of multisystemic therapy ( MST ) in treating violent and chronic juvenile offenders and their families in the absence of ongoing treatment fidelity checks were examined . Across 2 public sector mental health sites , 155 youths and their families were r and omly assigned to MST versus usual juvenile justice services . Although MST improved adolescent symptomology at posttreatment and decreased incarceration by 47 % at a 1.7-year follow-up , findings for decreased criminal activity were not as favorable as observed on other recent trials of MST . Analyses of parent , adolescent , and therapist reports of MST treatment adherence , however , indicated that outcomes were substantially better in cases where treatment adherence ratings were high . These results highlight the importance of maintaining treatment fidelity when disseminating complex family-based services to community setting Multisystemic therapy ( MST ) delivered through a community mental health center was compared with usual services delivered by a Department of Youth Services in the treatment of 84 serious juvenile offenders and their multiproblem families . Offenders were assigned r and omly to treatment conditions . Pretreatment and posttreatment assessment batteries evaluating family relations , peer relations , symptomatology , social competence , and self-reported delinquency were completed by the youth and a parent , and archival records were search ed at 59 weeks postreferral to obtain data on rearrest and incarceration . In comparison with youths who received usual services , youths who received MST had fewer arrests and self-reported offenses and spent an average of 10 fewer weeks incarcerated . In addition , families in the MST condition reported increased family cohesion and decreased youth aggression in peer relations . The relative effectiveness of MST was neither moderated by demographic characteristics nor mediated by psychosocial variables OBJECTIVE This study examined the effects of an innovative treatment model that was design ed to reduce treatment dropout among substance abusing or dependent juvenile offenders . METHOD One hundred eighteen delinquents who met diagnostic criteria for substance abuse or dependence were r and omly assigned to receive either home-based multisystemic therapy ( N=58 ) or treatment that was provided by the usual community services ( N=60 ) . RESULTS In the multisystemic therapy condition , 98 % ( N=57 ) of the families completed a full course of treatment , which lasted an average of 130 days . In contrast , 78 % ( N=47 ) of the families assigned to treatment through the usual community services received no mental health or substance abuse treatment in the 5 months after referral . CONCLUSIONS The serious and long-st and ing problem of high dropout rates in the substance abuse field can be greatly attenuated by services that increase accessibility and place greater responsibility for engagement on service providers The development and validation of family-based alternatives to out-of-home placements for children is an important goal in the mental health services field . The rigorous evaluation of such alternatives , however , can be difficult to accomplish . The purpose of this article is to describe initial barriers experienced during the pilot study of a r and omized trial , funded by the National Institute of Mental Health , conducted in a field setting , and the strategies that were used to overcome these barriers . The r and omized trial is examining home-based multisystemic therapy as an alternative to the psychiatric hospitalization of youths presenting psychiatric emergencies . The pilot study illuminated the interface of treatment and services research issues , prompting significant changes in the project 's clinical procedures , organization , and supervisory processes , as well as in the project 's interface with existing community re sources for serving youths with serious emotional disturbances BACKGROUND MST is an intensive home- and community-based intervention for youths with serious antisocial behaviour and other serious clinical problems , which has been effective at reducing out-of-home placements and producing favourable long-term clinical outcomes in the US . The aims of the study were to determine the degree to which these outcomes would be replicated in Norway for youths with serious behaviour problems and to conduct a r and omised trial of MST by an independent team of investigators . METHOD Participants were 100 seriously antisocial youths in Norway who were r and omly assigned to Multisystemic Therapy ( MST ) or usual Child Welfare Services ( CS ) treatment conditions . Data were gathered from youths , parents , and teachers pre- and post-treatment . RESULTS MST was more effective than CS at reducing youth internalising and externalising behaviours and out-of-home placements , as well as increasing youth social competence and family satisfaction with treatment . DISCUSSION This is the first study of MST outside of the US and one of the first not conducted by the developers of MST . The findings replicate those obtained by MST 's developers and demonstrate the generalisability of short-term MST effects beyond the US Two important theoretical assumptions of family therapy were examined : ( a ) Child behavior problems are associated with cross-generational coalitions , and ( b ) treatment of these coalitions using family therapy leads to decreases in individual symptomatology . Ss were 45 delinquent adolescents assigned to multisystemic therapy ( MST ) or individual therapy and 16 well-adjusted adolescents . Pretreatment and posttreatment assessment s included measures of observed family relations and self-reported symptoms . Cross-generational coalitions were more evident in families of delinquents vs. families of well-adjusted adolescents . In addition , changes in adolescent and paternal symptoms in the MST group were linked with changes in marital relations . Implication s for systemic conceptualizations of symptom maintenance and change are highlighted |
11,368 | 23,349,621 | Interventions for other conditions showed suggestive benefits in some cases , but the results were not consistent .
No evidence of publication bias was demonstrated on visual or statistical examination of the funnel plots for either disease management or health behaviours .
Text messaging interventions increased adherence to ART and smoking cessation and should be considered for inclusion in services . | BACKGROUND Mobile technologies could be a powerful media for providing individual level support to health care consumers .
We conducted a systematic review to assess the effectiveness of mobile technology interventions delivered to health care consumers . | Objective : To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic , economically disadvantaged HIV-positive population . Design : A two-group r and omized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach . Methods : Current smokers from a large , inner city HIV/AIDS care center were recruited and r and omized to receive either usual care or a cellular telephone intervention . The usual care group received brief physician advice to quit smoking , targeted self-help written material s and nicotine replacement therapy . The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components . Smoking-related outcomes were assessed at a 3-month follow-up . Results : The trial had 95 participants and 77 ( 81.0 % ) completed the 3-month follow-up assessment . Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3 % for the usual care group and 36.8 % for the cellular telephone group ; participants who received the cellular telephone intervention were 3.6 times ( 95 % confidence interval , 1.3 - 9.9 ) more likely to quit smoking compared with participants who received usual care ( P = 0.0059 ) . Conclusions : These results suggest that individuals living with HIV/AIDS are receptive to , and can be helped by , smoking cessation treatment . In addition , smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS , such as counseling delivered by cellular telephone , can significantly increase smoking abstinence rates over that achieved by usual care Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones . This social cognitive theory-based intervention ( called “ STUB IT ” ) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques . Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation . Methods A r and omized controlled trial was conducted with 6-month follow-up . Participants had to be 16 years of age or over , be current daily smokers , be ready to quit , and have a video message-capable phone . Recruitment targeted younger adults predominantly through radio and online advertising . Registration and data collection were completed online , prompted by text messages . The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date , role model , and timing of messages . Extra messages were available on dem and to beat cravings and address lapses . The control group also set a quit date and received a general health video message sent to their phone every 2 weeks . Results The target sample size was not achieved due to difficulty recruiting young adult quitters . Of the 226 r and omized participants , 47 % ( 107/226 ) were female and 24 % ( 54/226 ) were Maori ( indigenous population of New Zeal and ) . Their mean age was 27 years ( SD 8.7 ) , and there was a high level of nicotine addiction . Continuous abstinence at 6 months was 26.4 % ( 29/110 ) in the intervention group and 27.6 % ( 32/116 ) in the control group ( P = .8 ) . Feedback from participants indicated that the support provided by the video role models was important and appreciated . Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone . However , there was sufficient positive feedback about the ease of use of this novel intervention , and the support obtained by observing the role model video messages , to warrant further investigation . Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12606000476538 ; http://www.anzctr.org.au/trial_view.aspx?ID=81688 ( Archived by WebCite at http://www.webcitation.org/5umMU4sZi AIMS To assess Sweet Talk , a text-messaging support system design ed to enhance self-efficacy , facilitate uptake of intensive insulin therapy and improve glycaemic control in paediatric patients with Type 1 diabetes . METHODS One hundred and twenty-six patients fulfilled the eligibility criteria ; Type 1 diabetes for > 1 year , on conventional insulin therapy , aged 8 - 18 years . Ninety-two patients were r and omized to conventional insulin therapy ( n = 28 ) , conventional therapy and Sweet Talk ( n = 33 ) or intensive insulin therapy and Sweet Talk ( n = 31 ) . Goal - setting at clinic visits was reinforced by daily text-messages from the Sweet Talk software system , containing personalized goal -specific prompts and messages tailored to patients ' age , sex and insulin regimen . RESULTS HbA(1c ) did not change in patients on conventional therapy without or with Sweet Talk ( 10.3 + /- 1.7 vs. 10.1 + /- 1.7 % ) , but improved in patients r and omized to intensive therapy and Sweet Talk ( 9.2 + /- 2.2 % , 95 % CI -1.9 , -0.5 , P < 0.001 ) . Sweet Talk was associated with improvement in diabetes self-efficacy ( conventional therapy 56.0 + /- 13.7 , conventional therapy plus Sweet Talk 62.1 + /- 6.6 , 95 % CI + 2.6 , + 7.5 , P = 0.003 ) and self-reported adherence ( conventional therapy 70.4 + /- 20.0 , conventional therapy plus Sweet Talk 77.2 + /- 16.1 , 95 % CI + 0.4 , + 17.4 , P = 0.042 ) . When surveyed , 82 % of patients felt that Sweet Talk had improved their diabetes self-management and 90 % wanted to continue receiving messages . CONCLUSIONS Sweet Talk was associated with improved self-efficacy and adherence ; engaging a classically difficult to reach group of young people . While Sweet Talk alone did not improve glycaemic control , it may have had a role in supporting the introduction of intensive insulin therapy . Scheduled , tailored text messaging offers an innovative means of supporting adolescents with diabetes and could be adapted for other health-care setting s and chronic diseases Background Prevention of the onset of depression in adolescence may prevent social dysfunction , teenage pregnancy , substance abuse , suicide , and mental health conditions in adulthood . New technologies allow delivery of prevention programs scalable to large and disparate population s. Objective To develop and test the novel mobile phone delivery of a depression prevention intervention for adolescents . We describe the development of the intervention and the results of participants ’ self-reported satisfaction with the intervention . Methods The intervention was developed from 15 key messages derived from cognitive behavioral therapy ( CBT ) . The program was fully automated and delivered in 2 mobile phone messages/day for 9 weeks , with a mixture of text , video , and cartoon messages and a mobile website . Delivery modalities were guided by social cognitive theory and marketing principles . The intervention was compared with an attention control program of the same number and types of messages on different topics . A double-blind r and omized controlled trial was undertaken in high schools in Auckl and , New Zeal and , from June 2009 to April 2011 . Results A total of 1348 students ( 13–17 years of age ) volunteered to participate at group sessions in schools , and 855 were eventually r and omly assigned to groups . Of these , 835 ( 97.7 % ) self-completed follow-up question naires at postprogram interviews on satisfaction , perceived usefulness , and adherence to the intervention . Over three-quarters of participants viewed at least half of the messages and 90.7 % ( 379/418 ) in the intervention group reported they would refer the program to a friend . Intervention group participants said the intervention helped them to be more positive ( 279/418 , 66.7 % ) and to get rid of negative thoughts ( 210/418 , 50.2%)—significantly higher than proportions in the control group . Conclusions Key messages from CBT can be delivered by mobile phone , and young people report that these are helpful . Change in clinician-rated depression symptom scores from baseline to 12 months , yet to be completed , will provide evidence on the effectiveness of the intervention . If proven effective , this form of delivery may be useful in many countries lacking widespread mental health services but with extensive mobile phone coverage . Clinical Trial Australia New Zeal and Clinical Trials Registry ( ACTRN ) : 12609000405213 ; http://www.anzctr.org.au/trial_view.aspx?ID=83667 ( Archived by WebCite at http://www.webcitation.org/64aueRqOb INTRODUCTION Substantial evidence indicates that cigarette smoking among people living with HIV/AIDS ( PLWHA ) represents a significant public health concern . However , few efforts to assess smoking cessation interventions targeting this population have been reported . In this brief report , 3-month outcomes from an ongoing treatment trial for PLWHA who smoke are described . METHODS Study participants were recruited from a large HIV care center serving a diverse population of PLWHA . A two-group r and omized design was used to compare the efficacy of usual-care ( UC ) smoking cessation treatment versus a cell phone intervention ( CPI ) . Follow-ups were conducted at the HIV clinic 3 months postenrollment . Using an intent-to-treat approach , a series of multiple regression models were used to compare smoking outcomes in the 2 groups . RESULTS Four hundred and seventy-four participants were enrolled and r and omized , UC ( n = 238 ) and CPI ( n = 236 ) . Mean age in the sample was 44.8 ( SD = 8.1 ) years , and the majority were male ( 70.0 % ) , Black ( 76.6 % ) , and had an education level of high school or less ( 77.5 % ) . At follow-up , participants in the CPI group were 4.3 ( 95 % CI = 1.9 , 9.8 ) times more likely to be abstinent ( 7 day ) compared with those in the UC group . Similarly , significant point estimates were observed for the other smoking outcomes of interest . CONCLUSIONS Findings from this preliminary report indicate that a smoking cessation intervention for PLWHA consisting of cell phone-delivered proactive counseling results in significantly higher abstinence rates compared with a st and ard care approach . Evaluation of the long-term ( 6-month and 12-month ) efficacy of the CPI approach is ongoing Adherence to antiretroviral therapy ( ART ) represents one of the strongest predictors of progression to AIDS , yet it is difficult for most patients to sustain high levels of adherence . This study compares the efficacy of a personalized cell phone reminder system ( ARemind ) in enhancing adherence to ART versus a beeper . Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85 % were r and omized to a cellular phone ( CP ) or beeper ( BP ) . CP subjects received personalized text messages daily ; in contrast , BP subjects received a reminder beep at the time of dosing . Interviews were scheduled at weeks 3 and 6 . Adherence to ART was measured by self-report ( SR , 7-day recall ) , pill count ( PC , past 30 days at baseline , then past 3 weeks ) , Medication Event Monitoring System ( MEMS ; cumulatively at 3 and 6 weeks ) , and via a composite adherence score constructed by combining MEMS , pill count , and self report . A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks . Nineteen subjects completed all visits , 10 men and 9 females . The mean age was 42.7 ± 6.5 years , 37 % of subjects were Caucasian and 89 % acquired HIV heterosexually . The average adherence to ART was 79 % by SR and 65 % by PC at baseline in both arms ; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence . A larger and longer prospect i ve study is needed to confirm these findings and to better underst and optimal reminder messages and user fatigue This paper describes the results of a controlled multicenter study on the effect of the computer assistance in the intensive insulin therapy . The patient collective consisted of 50 diabetics , r and omly divided in two groups with 25 patients per group . The Multiple Subcutaneous Injection ( MSI ) group was treated with the usually intensive regimen . The treatment in the Computer Assisted Meal Related Insulin Therapy ( CAMIT ) group was performed with the aid of a specialized pocket computer . Only in the CAMIT group during the study we observed a significant decrease : in the mean blood glucose ( BG ) with 1.6+/-0.4 mmol/l ( P<0.05 ) , in the BG amplitudes by 1.0+/-0.3 mmol/l ( P<0.05 ) , and in the hypoglycemia frequency-from 2.0+/-0.4 to 1.2+/-0.3 ( P<0.01 ) hypoglycemic episodes weekly . The HbA(1 ) values fell in the MSI group by 3.7+/-3.7 % and in the CAMIT group significantly by 15.6+/-2.2 % ( P<0.05 ) . Consequently , the computer-assisted intensive insulin therapy result ed in an improved metabolic control New technologies have influenced communication and interaction among people , enabling them to overcome face-to-face limitations and eliminating the need for persons in a communicative relationship to be in the same place at the same time . This project aim ed to test the effectiveness of mobile phone usage applied to emotion induction . The authors wanted to check whether or not mobile narratives supported by multimedia mobile phones can enhance relaxation and reduce anxiety in a sample of commuters . The project sample consisted of 120 commuters , college students aged 20 to 25 years . The sample was r and omly assigned into four conditions : the Vidnar group experienced the mobile narrative on a mobile phone during their daily train trip ; the Nonar group experienced only video content proposed on a mobile phone ; the MP3 group experienced only the audio content proposed on an MP3 player ; and the Control group provided a no-intervention condition . The study measured participants ' emotional state ( State-Trait Anxiety Inventory [ STAI ] State question naire ) , trait ( STAI Trait question naire , Generalized Self-Efficacy Scale ) , and sense of presence ( Slater-Usoh-Steed Question naire [ UCL-SUS ] and the International Test Commission-Sense of Presence Inventory [ ITC-SOPI ] ) before and after the experience . The main results showed a significant decrease in anxiety level ( p < 0.05 , assessed by STAI State question naire ) and an increase in relaxation level ( p < 0.001 ) assessed by the Visual Analog Scale ( VAS ) . No significant differences were found in other conditions OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year BACKGROUND Portable h and -held information technology offers much promise not only in assessing dietary intake in the real world , but also in providing dietary feedback to individuals . However , stringent research design s have not been employed to examine whether it can be effective in modifying dietary behaviors . The purpose of this pilot study was to evaluate the efficacy of a h and -held computer ( i.e. , personal digital assistant [ PDA ] ) for increasing vegetable and whole-grain intake over 8 weeks in mid-life and older adults , using a r and omized study design . METHODS Twenty-seven healthy adults aged > or = 50 were r and omized and completed the 8-week study . Intervention participants received an instructional session and a PDA programmed to monitor their vegetable and whole-grain intake levels twice per day and to provide daily individualized feedback , goal - setting , and support . Controls received st and ard , age-appropriate , written nutritional education material s. Dietary intake was assessed via the Block Food Frequency Question naire at baseline and 8 weeks . RESULTS Relative to controls , intervention participants reported significantly greater increases in vegetable servings ( 1.5 - 2.5 servings/day ; p=0.02 ) , as well as a trend toward greater intake of dietary fiber from grains ( 3.7 - 4.5 servings/day ; p=0.10 ) . CONCLUSIONS This study 's findings provide preliminary evidence that using portable h and -held technology to provide daily individualized feedback on dietary behavior in the real world can increase the dietary intake of healthy food groups Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 ) OBJECTIVE To improve quality and efficiency of care for elderly patients with type 2 diabetes , we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare ( u-healthcare ) service , which is an individualized health management system using advanced medical information technology . RESEARCH DESIGN AND METHODS We conducted a 6-month r and omized , controlled clinical trial involving 144 patients aged > 60 years . Participants were r and omly assigned to receive routine care ( control , n = 48 ) , to the self-monitored blood glucose ( SMBG , n = 47 ) group , or to the u-healthcare group ( n = 49 ) . The primary end point was the proportion of patients achieving A1C < 7 % without hypoglycemia at 6 months . U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient ’s mobile phone . Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server . Once the data are transferred to the server , an automated system , the CDSS rule engine , generates and sends patient-specific messages by mobile phone . RESULTS After 6 months of follow-up , the mean A1C level was significantly decreased from 7.8 ± 1.3 % to 7.4 ± 1.0 % ( P < 0.001 ) in the u-healthcare group and from 7.9 ± 1.0 % to 7.7 ± 1.0 % ( P = 0.020 ) in the SMBG group , compared with 7.9 ± 0.8 % to 7.8 ± 1.0 % ( P = 0.274 ) in the control group . The proportion of patients with A1C < 7 % without hypoglycemia was 30.6 % in the u-healthcare group , 23.4 % in the SMBG group ( 23.4 % ) , and 14.0 % in the control group ( P < 0.05 ) . CONCLUSIONS The CDSS-based u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients Objective : Byst and er cardiopulmonary resuscitation ( CPR ) significantly improves survival of cardiac arrest victims . Dispatch assistance increases byst and er CPR , but the quality of dispatcher-assisted CPR remains unsatisfactory . This study was conducted to assess the effect of adding interactive video communication to dispatch instruction on the quality of byst and er chest compressions in simulated cardiac arrests . Design : A r and omized controlled study with a scenario developed to simulate cardiac arrest in a public place . Setting : The victim was simulated by a mannequin and the cell phone for dispatch assistance was a video cell phone with both voice and video modes . Chest compression-only CPR instruction was used in the dispatch protocol . Subjects : Ninety-six adults without CPR training within 5 years were recruited . Interventions : The subjects were r and omized to receive dispatch assistance on chest compression with either voice instruction alone ( voice group , n = 53 ) or interactive voice and video demonstration and feedback ( video group , n = 43 ) via a video cell phone . Measurements and Main Results : Performance of chest compression-only CPR throughout the scenario was videotaped . The quality of CPR was evaluated by review ing the videos and mannequin reports . Chest compressions among the video group were faster ( median rate 95.5 vs. 63.0 min−1 , p < 0.01 ) , deeper ( median depth 36.0 vs. 25.0 mm , p < 0.01 ) , and of more appropriate depth ( 20.0 % vs. 0 % , p < 0.01 ) . The video group had more “ h and s-off ” time ( 5.0 vs. 0 second , p < 0.01 ) , longer time to first chest compression ( 145.0 vs. 116.0 seconds , p < 0.01 ) and total instruction time ( 150.0 vs. 121.0 seconds , p < 0.01 ) . Conclusion : The addition of interactive video communication to dispatcher-assisted chest compression-only CPR initially delayed the commencement of chest compressions , but subsequently improved the depth and rate of compressions . The benefit was achieved mainly through real-time feedback Generalized anxiety disorder ( GAD ) is a common anxiety disorder characterized by 6 months of " excessive anxiety and worry " about a variety of events and situations . Anxiety and worry are often accompanied by additional symptoms like restlessness , being easily fatigued , difficulty concentrating , irritability , muscle tension and disturbed sleep . GAD is usually treated with medications and /or psychotherapy . In particular , the two most promising treatments seem to be cognitive therapy and applied relaxation . In this study we integrated these approaches through the use of a biofeedback enhanced virtual reality ( VR ) system used both for relaxation and controlled exposure . Moreover , this experience is strengthened by the use of a mobile phone that allows patients to perform the virtual experience even in an outpatient setting . This paper describe the results of a controlled trial ( NCT00602212 ) involving 20 GAD patients r and omly assigned to the following groups : ( 1 ) the VR and Mobile group ( VRMB ) including biofeedback ; ( 2 ) the VR and Mobile group ( VRM ) without biofeedback ; ( 3 ) the waiting list ( WL ) group . The clinical data underlined that ( a ) VR can be used also in the treatment of GAD ; ( b ) in a VR treatment , patients take advantage of a mobile device that delivers in an outpatient setting guided experiences , similar to the one experienced in VR Background Postnatal women ( < 12 months postpartum ) are at increased risk of physical inactivity . Purpose To evaluate the efficacy and feasibility of a theory-based physical activity ( PA ) intervention delivered to postnatal women primarily via mobile telephone short message service ( SMS ) . Methods Eighty-eight women were r and omized to the intervention ( n = 45 ) or minimal contact control ( n = 43 ) condition . The 12-week intervention consisted of a face-to-face PA goal - setting consultation , a goal - setting magnet , three to five personally tailored SMS/week and a nominated support person who received two SMS per week . SMS content targeted constructs of social cognitive theory . Frequency ( days/week ) and duration ( min/week ) of PA participation and walking for exercise were assessed via self-report at baseline , 6 and 13 weeks . Results Intervention participants increased PA frequency by 1.82 days/week ( SE ± 0.18 ) by 13 weeks ( F(2,85 ) = 4.46 , p = 0.038 ) and walking for exercise frequency by 1.08 days/week ( SE ± 0.24 ) by 13 weeks ( F(2,85 ) = 5.38 , p = 0.02 ) . Positive trends were observed for duration ( min/week ) of PA and walking for exercise . Conclusions Intervention exposure result ed in increased frequency of PA and walking for exercise in postnatal women OBJECTIVE To analyze the effect of an intervention to provide information with mobile phone text messages to patients with hypertension on compliance with therapy for hypertension . DESIGN Comparative , controlled , multicenter , r and omized cluster study . SETTING 26 primary care health centers in Spain . PARTICIPANTS 26 research ers were r and omized to a control group or an intervention group ( 52 patients each , for a total of 104 patients ) . All patients were receiving monotherapy for uncontrolled hypertension . INTERVENTION Patients in the control group received their physician 's usual interventions . Patients in the intervention group received messages and reminders sent to their mobile phones 2 days per week during 4 months . MAIN OUTCOME MEASURES Tablets were counted and blood pressure was measured at the start of the study and 1 , 3 , and 6 months later . The percentage of compliers , mean percentage of compliance and degree of control of hypertension were compared . The reduction in absolute and relative risk was calculated , as was the number of individuals needed to treat to avoid noncompliance . RESULTS The results were evaluated for a total of 67 individuals ( 34 in the intervention group and 33 in the control group ) . The rate of compliance was 85.1 % ( CI , 74.9%-95.3 % ) overall , 85.7 % ( CI , 70.5%-100.9 % ) in the control group and 84.4 % in the intervention group ( CI , 70.7%-95.3 % ) ( P = NS ) . Mean percentage compliance was 90.2%+/-16.3 % overall , 88.1%+/-20.8 % in the control group and 91.9%+/-11.6 % in the intervention group ( P = NS ) . The percentage of patients whose hypertension was controlled at the end of the study was 51.5 % ( CI , 34.4%-68.6 % ) in the control group and 64.7 % ( CI , 48.6%-80.8 % ) in the intervention group ( P = NS ) . CONCLUSIONS The telephone messaging intervention with alerts and reminders sent to mobile phones did not improve compliance with therapy in patients with hypertension Background Asthma is a common medical condition caused by chronic inflammation of the airways . Characteristic symptoms of the illness include attacks of shortness of breath , wheezing , tightness in the chest , and cough . Asthma is commonly treated by inhaled corticosteroids , which help to suppress inflammation of the airways and reduce the frequency of severe symptoms and attacks . This medication in the form of inhalers is known as preventer or controller medication and many patients also take short-acting bronchodilators to control acute symptoms ( reliever medication ) . In order to provide therapeutic benefit , preventer medication needs to be taken regularly on a daily basis . However , non-adherence to preventer medication is a common problem in patients diagnosed with asthma and these results in the overuse of reliever medication , increased asthma symptoms , more frequent asthma attacks , and hospital admissions ( Stern et al. , 2006 ) . Optimal adherence to inhaled corticosteroids requires patients to take their preventer medication on 80 % or more occasions , as this is associated with greatest asthma control ( Lasmar et al. , 2009 ) . Objective While effective preventative medication is readily available for asthma , adherence is a major problem due to patients ’ beliefs about their illness and medication . We investigated whether a text message programme targeted at changing patients ’ illness and medication beliefs would improve adherence in young adult asthma patients . Methods Two hundred and sixteen patients aged between 16 and 45 on asthma preventer medication were recruited from pamphlets dispensed with medication and e-mails sent to members of a targeted marketing website . Participants were r and omized to receive individually tailored text messages based on their illness and medication beliefs over 18 weeks or no text messages . Illness and medication beliefs were assessed at baseline and at 18 weeks . Adherence rates were assessed by phone calls to participants at 6 , 12 , and 18 weeks and at 6 and 9 months . Results At 18 weeks , the intervention group had increased their perceived necessity of preventer medication , increased their belief in the long-term nature of their asthma , and their perceived control over their asthma relative to control group ( all p<0.05 ) . The intervention group also significantly improved adherence over the follow-up period compared to the control group with a relative average increase in adherence over the follow-up period of 10 % ( p<0.001 ) . The percentage taking over 80 % of prescribed inhaler doses was 23.9 % in the control group compared to 37.7 % in the intervention group ( p<0.05 ) . Conclusion A targeted text message programme increases adherence to asthma preventer inhaler and may be useful for other illnesses where adherence is a major issue BACKGROUND Self-monitoring for weight loss has traditionally been performed with paper diaries . Technologic advances could reduce the burden of self-monitoring and provide feedback to enhance adherence . PURPOSE To determine if self-monitoring diet using a PDA only or the PDA with daily tailored feedback ( PDA+feedback [ FB ] ) , was superior to using a paper diary on weight loss and maintenance . DESIGN The Self-Monitoring and Recording Using Technology ( SMART ) Trial was a 24-month r and omized clinical trial ; participants were r and omly assigned to one of three self-monitoring groups . SETTING / PARTICIPANTS From 2006 to 2008 , a total of 210 overweight/obese adults ( 84.8 % female , 78.1 % white ) were recruited from the community . Data were analyzed in 2011 . INTERVENTION Participants received st and ard behavioral treatment for weight loss that included dietary and physical activity goals , encouraged the use of self-monitoring , and was delivered in group sessions . MAIN OUTCOME MEASURES Percentage weight change at 24 months , adherence to self-monitoring over time . RESULTS Study retention was 85.6 % . The mean percentage weight loss at 24 months was not different among groups ( paper diary : -1.94 % , 95 % CI = -3.88 , 0.01 ; PDA : -1.38 % , 95 % CI= -3.38 , 0.62 ; PDA+FB : -2.32 % , 95 % CI= -4.29 , -0.35 ) ; only the PDA+FB group ( p=0.02 ) demonstrated a significant loss . For adherence to self-monitoring , there was a time-by-treatment group interaction between the combined PDA groups and the paper diary group ( p=0.03 ) but no difference between PDA and PDA+FB groups ( p=0.49 ) . Across all groups , weight loss was greater for those who were adherent ≥60 % versus < 30 % of the time ( p<0.001 ) . CONCLUSIONS PDA+FB use result ed in a small weight loss at 24 months ; PDA use result ed in greater adherence to dietary self-monitoring over time . However , for sustained weight loss , adherence to self-monitoring is more important than the method used to self-monitor . A daily feedback message delivered remotely enhanced adherence and improved weight loss , which suggests that technology can play a role in improving weight loss . TRIAL REGISTRATION This study is registered at clinical trials.gov NCT00277771 AIM To compare the effectiveness of two methods of follow-up : short message service and telephone follow-up on type 2 diabetes adherence for three months . BACKGROUND Using telemedicine approaches may preserve appropriate blood glucose levels and may improve adherence to diabetes control recommendations in diabetic patients . DESIGN A quasi-experimental , two-group , pretest and post-test design was used in this study to evaluate the effectiveness of nurse 's follow-up via cellular phones and telephones . METHODS The sample consisted of 77 patients with type 2 diabetes that r and omly were assigned to two groups : telephone follow-up ( n = 39 ) and short message service ( n = 38 ) . Telephone interventions were applied by a research er for three months ; twice a week for the first month and every week for the second and third month . For three successive months , the short message service group that received messages about adherence to therapeutic regimen was examined . The data gathering instrument included data sheets - to record glycosylated haemoglobin - and the question naire related to adherence therapeutic regimen . Data gathering was carried out at the beginning of the study and after three and six months . The data were analysed using descriptive and inferential statistic methods with SPSS version 11.5 . RESULTS Results showed that both interventions had significant mean changes in glycosylated haemoglobin . For the telephone group ( p < 0.001 ) , a mean change of -0.93 and for the short message service group ( p < 0.001 ) , a mean change of -1.01 . There was no significant difference in diet adherence ( p = 0.000 ) , physical exercise ( p = 0.000 ) and medication taking ( p = 0.000 ) adherence in either groups . CONCLUSION Intervention using short message services of cellular phones and nurse-led-telephone follow-up improved HbA1c levels and adherence to diabetes therapeutic regimen for three months in type 2 diabetic patients . RELEVANCE TO CLINICAL PRACTICE Both of follow-up intervention uses in this study can decrease HbA1c levels and escalate adherence to diabetes control recommendations in people with type 2 diabetes for three months Background Telemonitoring of patients with chronic heart failure ( CHF ) is an emerging concept to detect early warning signs of impending acute decompensation in order to prevent hospitalization . Objective The goal of the MOBIle TELemonitoring in Heart Failure Patients Study ( MOBITEL ) was to evaluate the impact of home-based telemonitoring using Internet and mobile phone technology on the outcome of heart failure patients after an episode of acute decompensation . Methods Patients were r and omly allocated to pharmacological treatment ( control group ) or to pharmacological treatment with telemedical surveillance for 6 months ( tele group ) . Patients r and omized into the tele group were equipped with mobile phone – based patient terminals for data acquisition and data transmission to the monitoring center . Study physicians had continuous access to the data via a secure Web portal . If transmitted values went outside individually adjustable borders , study physicians were sent an email alert . Primary endpoint was hospitalization for worsening CHF or death from cardiovascular cause . Results The study was stopped after r and omization of 120 patients ( 85 male , 35 female ) ; median age was 66 years ( IQR 62 - 72 ) . The control group comprised 54 patients ( 39 male , 15 female ) with a median age of 67 years ( IQR 61 - 72 ) , and the tele group included 54 patients ( 40 male , 14 female ) with a median age of 65 years ( IQR 62 - 72 ) . There was no significant difference between groups with regard to baseline characteristics . Twelve tele group patients were unable to begin data transmission due to the inability of these patients to properly operate the mobile phone ( “ never beginners ” ) . Four patients did not finish the study due to personal reasons . Intention-to-treat analysis at study end indicated that 18 control group patients ( 33 % ) reached the primary endpoint ( 1 death , 17 hospitalizations ) , compared with 11 tele group patients ( 17 % , 0 deaths , 11 hospitalizations ; relative risk reduction 50 % , 95 % CI 3 - 74 % , P = .06 ) . Per- protocol analysis revealed that 15 % of tele group patients ( 0 deaths , 8 hospitalizations ) reached the primary endpoint ( relative risk reduction 54 % , 95 % CI 7 - 79 % , P= .04 ) . NYHA class improved by one class in tele group patients only ( P < .001 ) . Tele group patients who were hospitalized for worsening heart failure during the study had a significantly shorter length of stay ( median 6.5 days , IQR 5.5 - 8.3 ) compared with control group patients ( median 10.0 days , IQR 7.0 - 13.0 ; P= .04 ) . The event rate of never beginners was not higher than the event rate of control group patients . Conclusions Telemonitoring using mobile phones as patient terminals has the potential to reduce frequency and duration of heart failure hospitalizations . Providing elderly patients with an adequate user interface for daily data acquisition remains a challenging component of such a concept OBJECTIVE : To estimate whether women receiving daily text-message reminders have increased oral contraceptive pill adherence compared with women not receiving reminders . METHODS : This r and omized controlled trial estimated whether there was an effect of daily text-message reminders on oral contraceptive pill adherence of new oral contraceptive pill users . Pill-taking was tracked for 3 months by an electronic monitoring device with wireless data collection . During the study period , participants assigned the intervention received a daily reminder text message . Eighty-two women were assigned r and omly to detect a 1.6±2.0 pill difference ( 90 % power , 5 % & agr ; , 15 % dropout ) . RESULTS : Participants were 79 % white , non-Hispanic , 99 % high school graduates , and 99 % nulliparous with a mean age of 22 years . Most reported condom use with past coital activity , and more than half reported prior emergency contraception use . The mean number of missed pills per cycle did not differ significantly between the groups : 4.9±3.0 for the text-message group and 4.6±3.5 for the control group ( P=.60 ) . The number of missed pills per cycle increased over the course of the study , but this pattern did not increase differentially between the groups . Adherence recorded by the electronic monitoring device indicated much poorer adherence than that recorded by patient diaries . Despite poor pill-taking , there were no pregnancies . CONCLUSION : Daily text-message reminders did not improve oral contraceptive pill adherence . Although the lack of benefit may be attributed to the frequent use of alternative reminder systems in the control group , the rate of missed pills when measured objective ly was still very high in both groups . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00733707 . LEVEL OF EVIDENCE : OBJECTIVE : To estimate whether daily educational text messages affect oral contraceptive pill ( OCP ) continuation at 6 months . METHODS : We r and omized young women electing OCPs at an urban family planning health center to either routine care or routine care plus 180 days of daily educational text messages . Investigators masked to treatment allocation r and omized participants who were not masked to treatment . The primary outcome measure was self-reported OCP continuation through a telephone call at 6 months ( contacts between 5 and 8 months ) . RESULTS : We enrolled 962 participants ( 480 intervention and 482 routine care ) and obtained continuation data on 683 ( 346 and 337 , respectively ) . At the follow-up , 64 % of participants r and omized to the intervention were still OCP users compared with 54 % of the routine care group ( P=.005 ) . Continuation was highest in the intervention group if the interview took place while the intervention was ongoing ( 75 % compared with 54 % , P=.003 ) ; the effect of the intervention on continuation was less after the intervention ended ( 60 % compared with 54 % , P=.16 ) . Participants receiving the intervention were more likely to continue oral contraception than control participants at 6 months ( odds ratio 1.44 , 95 % confidence interval 1.03–2.00 ) in analyses adjusted for age , race or ethnicity , age at coitarche , pregnancy history , and OCP experience . CONCLUSION : The use of daily educational text messages improves OCP continuation at 6 months over routine care alone . Ten women would need to receive this simple intervention to improve continuation in one . This effect is strongest in the women whose follow-up took place while the text intervention was ongoing . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . Clinical Trials.gov , NCT00677703 . LEVEL OF EVIDENCE : Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837 Diaries are frequently used to evaluate therapy . Forgetfulness , however , can lead to missed entries . With paper diaries , these missing entries can be backfilled , compromising the reasons for using a diary . Electronic diaries are a potential means of mitigating this limitation . The pilot study was conducted to evaluate use of a mobile phone diary . Twelve subjects with mild persistent asthma were r and omly assigned to mobile or paper diary for 2 weeks and then crossed over to use the other diary type for next 2 weeks . Of the 12 subjects , 7 preferred the mobile diary . However , the mean prevalence of missing data was greater when using the mobile ( 18 % ± 9 % ) compared to paper diary ( 9 % ± 4 % ; P = 0.05 ) . In conclusion , the mobile diary was preferred by slightly more subjects . The greater prevalence of missing data when using this diary most likely results from the inability to backfill missing entries . Trial Registration : Clintrials.gov NCT00367263 ( http:// clinical trials.gov/ct2/show/NCT00367263 ) BACKGROUND Conscripts are a vulnerable population group for HIV infection . Their serostatus has been monitored in Thail and as part of the national sentinel surveillance since 1997 . Given the nature of the military environment , an innovative program is needed to promote safe sex to reduce the rate of sexually transmitted infections ( STIs ) and HIV . OBJECTIVE The present study proposed to evaluate the program of " Squad Leader Mentors through Short Message Services on Mobile Phones " in improving the required knowledge , attitudes , and the safe sex practice among conscript groups . MATERIAL AND METHOD A quasi-experimental design was applied in separate areas . The subjects were recruited by multistage sampling techniques . One hundred forty eight conscripts from the Lop Buri Military District were r and omly selected to be the study group , and 114 conscripts from the Sara Buri Military District were the control group . The study and control groups were matched for background characteristics . The changes in knowledge , attitudes , and safe sex practice were measured by pre- and post-test question naires over a six-month period . RESULTS There were significant changes in overall scores of knowledge of safe sex and STIs . Benefits of using SMS and squad leaders that acted as mentors in the study groups ( p-value < 0.001 * * ) were observed . The safe sex practice s in the study group showed significant increase in condom use with risky partners such as sex workers and other men ( p-value < 0.001 * * ) . Therefore , it is believe that conscripts can be mentors in promoting safe sex ( p-value = 0.006 * ) . CONCLUSION The presented program can genuinely increase knowledge and practice of safe sex among conscripts in the study group When undergo ambulatory surgical operations , the majority of patients experience high level of anxiety . Different experimental studies have shown that distraction techniques are effective in reducing pain and related anxiety . Since Virtual reality ( VR ) has been demonstrated a good distraction technique , it has been repeatedly used in hospital context s for reducing pain in burned patients , but it has never been used during surgical operations . With the present r and omized controlled study we intended to verify the effectiveness of VR in reducing anxiety in patients undergoing ambulatory operations under local or regional anaesthesia . In particular , we measured the degree to which anxiety associated with surgical intervention was reduced by distracting patients with immersive VR provided through a cell phone connected to an HMD compared to a no-distraction control condition . A significant reduction of anxiety was obtained after 45 minutes of operation in the VR group , but not in the control group and , after 90 minutes , the reduction was larger in the experimental group than in other one . In conclusion , this study presents an innovative promising technique to reduce anxiety during surgical interventions , even if more studies are necessary to investigate its effectiveness in other kinds of operations and in larger numbers of patients Abstract Objective : To assess the effect of a multifaceted intervention directed at general practitioners on six year mortality , morbidity , and risk factors of patients with newly diagnosed type 2 diabetes . Design : Pragmatic , open , controlled trial with r and omisation of practice s to structured personal care or routine care ; analysis after 6 years . Setting : 311 Danish practice s with 474 general practitioners ( 243 in intervention group and 231 in comparison group ) . Participants : 874 ( 90.1 % ) of 970 patients aged ≥40 years who had diabetes diagnosed in 1989 - 91 and survived until six year follow up . Intervention : Regular follow up and individualised goal setting supported by prompting of doctors , clinical guidelines , feedback , and continuing medical education . Main outcome measures : Predefined clinical non-fatal outcomes , overall mortality , risk factors , and weight . Results : Predefined non-fatal outcomes and mortality were the same in both groups . The following risk factor levels were lower for intervention patients than for comparison patients ( median values ) : fasting plasma glucose concentration ( 7.9 v 8.7 mmol/l , P=0.0007 ) , glycated haemoglobin ( 8.5 % v 9.0 % , P<0.0001 ; reference range 5.4 - 7.4 % ) , systolic blood pressure ( 145 v 150 mm Hg , P=0.0004 ) , and cholesterol concentration ( 6.0 v 6.1 mmol/l , P=0.029 , adjusted for baseline concentration ) . Both groups had lost weight since diagnosis ( 2.6 v 2.0 kg ) . Metformin was the only drug used more frequently in the intervention group ( 24 % ( 110/459 ) v 15 % (61/415)).Intervention doctors arranged more follow up consultations , referred fewer patients to diabetes clinics , and set more optimistic goals . Conclusions : In primary care , individualised goals with educational and surveillance support may for at least six years bring risk factors of patients with type 2 diabetes to a level that has been shown to reduce diabetic complications but without weight gain . What is already known on this topic Evidence is increasing that control of hyperglycaemia , hypertension , and dyslipidaemia may postpone the development of diabetic complications in patients with type 2 diabetes Maintaining good control over a long period can be difficult What this study adds Structured individualised personal care with educational and surveillance support for general practitioners reduced levels of risk factors in type 2 diabetic patients after six years Risk factors were reduced to a level that has been shown to have a beneficial effect on diabetic complications Participants also showed modest weight OBJECTIVE To compare the effect of two different types of short text message service ( SMS-text ) reminders on the uptake of screening mammogram . METHODS A r and omized controlled trial was conducted in 2010 among females aged between 40 and 75 , benefiting from the Health Insurance Plan at the American University of Beirut , whose cell phone numbers were available in their electronic medical records , and who did not do a mammogram in the past 2 years . The sample ( n=385 ) was r and omly divided into two subgroups . The first subgroup ( n1=192 ) received a general SMS-text inviting its members to do a mammogram while the second subgroup ( n2=193 ) received an additional informative SMS-text informing them about the benefits of mammogram screening . RESULTS 30.7 % ( 59 ) of subgroup 1 and 31.6 % ( 61 ) of subgroup 2 underwent a mammogram screening test during the 6 months follow up interval post-intervention ( Chi-square test , p-value ≥ 0.05 ) . There was no difference between the response rates in the two subgroups . CONCLUSION A brief invitation SMS-text message for screening mammogram was found to be as effective as a detailed informative one Background To our knowledge , no studies have evaluated whether weight loss can be promoted in overweight adults through the use of an intervention that is largely based on daily SMS ( Short Message Service : text ) and MMS ( Multimedia Message Service : small picture ) messages transmitted via mobile phones . Objective This paper describes the development and evaluation of a text message – based intervention design ed to help individuals lose or maintain weight over 4 months . Methods The study was a r and omized controlled trial , with participants being exposed to one of the following two conditions , lasting 16 weeks : ( 1 ) receipt of monthly printed material s about weight control ; ( 2 ) an intervention that included personalized SMS and MMS messages sent two to five times daily , printed material s , and brief monthly phone calls from a health counselor . The primary outcome was weight at the end of the intervention . A mixed-model repeated- measures analysis compared the effect of the intervention group to the comparison group on weight status over the 4-month intervention period . Analysis of covariance ( ANCOVA ) models examined weight change between baseline and 4 months after adjusting for baseline weight , sex , and age . Results A total of 75 overweight men and women were r and omized into one of the two groups , and 65 signed the consent form , completed the baseline question naire , and were included in the analysis . At the end of 4 months , the intervention group ( n = 33 ) lost more weight than the comparison group ( −1.97 kg difference , 95 % CI −0.34 to −3.60 kg , P = .02 ) after adjusting for sex and age . Intervention participants ’ adjusted average weight loss was 2.88 kg ( 3.16 % ) . At the end of the study , 22 of 24 ( 92 % ) intervention participants stated that they would recommend the intervention for weight control to friends and family . Conclusions Text messages might prove to be a productive channel of communication to promote behaviors that support weight loss in overweight adults . Trial Registration Clinical trials.gov NCT00415870 ; http:// clinical trials.gov/ct2/show/NCT00415870 ( Archived by WebCite at http://www.webcitation.org/5dnolbkFt Objectives : To determine the effectiveness of a mobile phone text messaging smoking cessation programme . Design : R and omised controlled trial Setting : New Zeal and Participants : 1705 smokers from throughout New Zeal and who wanted to quit , were aged over 15 years , and owned a mobile phone were r and omised to an intervention group that received regular , personalised text messages providing smoking cessation advice , support , and distraction , or to a control group . All participants received a free month of text messaging ; starting for the intervention group on their quit day to assist with quitting , and starting for the control group at six months to encourage follow up . Follow up data were available for 1624 ( 95 % ) at six weeks and 1265 ( 74 % ) at six months . Main outcome measures : The main trial outcome was current non-smoking ( that is , not smoking in the past week ) six weeks after r and omisation . Secondary outcomes included current non-smoking at 12 and 26 weeks . Results : More participants had quit at six weeks in the intervention compared to the control group : 239 ( 28 % ) v 109 ( 13 % ) , relative risk 2.20 ( 95 % confidence interval 1.79 to 2.70 ) , p < 0.0001 . This treatment effect was consistent across subgroups defined by age , sex , income level , or geographic location ( p homogeneity > 0.2 ) . The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests . Reported quit rates remained high at six months , but there was some uncertainty about between group differences because of incomplete follow up . Conclusions : This programme offers potential for a new way to help young smokers to quit , being affordable , personalised , age appropriate , and not location dependent . Future research should test these findings in different setting s , and provide further assessment of long term quit rates Background Malaria chemoprophylaxis compliance is suboptimal among French soldiers despite the availability of free malaria chemoprophylaxis and repeated health education before , during and after deployment to malaria endemic areas . Methods In 2007 , a r and omized controlled study was performed among a cohort of French soldiers returning from Côte d'Ivoire to assess the feasibility and acceptability of sending a daily short message service ( SMS ) reminder message via mobile device to remind soldiers to take their malaria chemoprophylaxis , and to assess the impact of the daily reminder SMS on chemoprophylaxis compliance . Malaria chemoprophylaxis consisted of a daily dose of 100 mg doxycycline monohydrate , which began upon arrival in Côte d'Ivoire and was to be continued for 28 days following return to France . Feasibility and acceptability were assessed by question naire . Cohort members were followed for a 28 day period , with compliance assessed by use of an electronic medication monitoring device , from which several indicators were developed : daily proportion of compliant individuals , average number of pills taken , and early discontinuation . Results Among 424 volunteers r and omized to the study , 47.6 % were assigned to the SMS group and 52.3 % to the control group . Approximately 90 % of subjects assigned to the SMS group received a daily SMS at midday during the study . Persons of the SMS group agreed more frequently that SMS reminders were very useful and that the device was not annoying . Compliance did not vary significantly between groups across the compliance indicators . ConclusionS MS did not increase malaria chemoprophylaxis compliance above baseline , likely because the persons did not benefit from holidays after the return and stayed together . So the reminder by SMS was noted by all subjects of the study . Another study should be done to confirm these results on soldiers going on holidays from employment after return or with individual travellers Affordable and effective antiretroviral therapy ( ART ) adherence interventions are needed for many patients to promote positive treatment outcomes and prevent viral resistance . We conducted a two-arm r and omized trial ( n = 40 men and women receiving and less than 95 % adherent to ART ) to test a single office session followed by four biweekly cell phone counseling sessions that were grounded in behavioral self-management model of medication adherence using data from phone-based unannounced pill counts to provide feedback-guided adherence strategies . The control condition received usual care and matched office and cell phone/pill count contacts . Participants were baseline assessed and followed with biweekly unannounced pill counts and 4-month from baseline computerized interviews ( 39/40 retained ) . Results showed that the self-regulation counseling delivered by cell phone demonstrated significant improvements in adherence compared to the control condition ; adherence improved from 87 % of pills taken at baseline to 94 % adherence 4 months after baseline , p < 0.01 . The observed effect sizes ranged from moderate ( d = 0.45 ) to large ( d = 0.80 ) . Gains in adherence were paralleled with increased self-efficacy ( p < 0.05 ) and use of behavioral strategies for ART adherence ( p < 0.05 ) . We conclude that the outcomes from this test of concept trial warrant further research on cell phone-delivered self-regulation counseling in a larger and more rigorous trial Objective : There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy ( ART ) . This study tested the efficacy of short message service ( SMS ) reminders on adherence to ART among patients attending a rural clinic in Kenya . Design : A r and omized controlled trial of four SMS reminder interventions with 48 weeks of follow-up . Methods : Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and r and omly assigned to a control group or one of the four intervention groups . Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency . Adherence was measured using the medication event monitoring system . The primary outcome was whether adherence exceeded 90 % during each 12-week period of analysis and the 48-week study period . The secondary outcome was whether there were treatment interruptions lasting at least 48 h. Results : In intention-to-treat analysis , 53 % of participants receiving weekly SMS reminders achieved adherence of at least 90 % during the 48 weeks of the study , compared with 40 % of participants in the control group ( P = 0.03 ) . Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group ( 81 vs. 90 % , P = 0.03 ) . Conclusion : These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in re source -limited setting 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 OBJECTIVE South Africa has one of the highest human immunodeficiency virus ( HIV ) prevalence rates in the world , but despite the well-established benefits of HIV counseling and testing ( HCT ) , there is low uptake of HCT . The study aim ed to investigate the effectiveness of using short message services ( SMSs ) to encourage HCT while interrogating the impact of altering SMS content and dosage ( the number of SMSs ) . MATERIAL S AND METHODS About 2,533 participants were recruited via an SMS sent to 24,000 mobiles r and omly sample d from a pre-existing data base . Recruits were r and omly allocated to four intervention groups that received 3 or 10 informational ( INFO ) or motivational ( MOTI ) SMSs , and a control group . After the intervention , participants were prompted to go for HCT , and postintervention assessment was done after 3 weeks . RESULTS In comparison with the control , receipt of 10 MOTI messages had the most impact on uptake of HCT with a 1.7-fold increased odds of testing ( confidence interval 95 % ; p=0.0036 ) . The lack of efficacy of three SMSs indicates a threshold effect , that is , a minimum number of MOTI SMSs is required . INFO SMSs , whether 3 or 10 were sent , did not have a statistically significant effect . The cost can be calculated for the marginal effect of the SMSs , that is , the cost to get people to test over and above those who were likely to test without the intervention . Use of 10 MOTI SMSs yielded a cost-per-tester of $ 2.41 . CONCLUSIONS While there are method ological issues apparent in our study , the results demonstrate the potential of SMSs to influence the uptake of HCT , the importance of appropriate content , and the need to determine a threshold for SMS-based interventions . These results indicate a potential for SMSs to be used more generally for interventions encouraging people to take health-related actions , and the need for further research in this field . The reasonable cost-per-tester is promising for the scale-up of such an intervention The evaluation in real-life setting s of services for the follow-up and control of hypertensive patients is a complex intervention , which still needs analysis of the roles , tasks , and re sources involved in the basic items : patient , healthcare professional , and the interaction between the two . To evaluate the impact of patient-general practitioner ( GP ) short-messages-based interaction , isolated from other items , on the degree of hypertension control in the follow-up of medium-to-low-risk patients in primary care , a r and omized controlled trial has been performed : 38 GPs enrolled 285 hypertensive patients who recorded the results of self-blood-pressure ( BP ) monitoring , heart rate , and body weight , and completed an optional question naire in an identical manner over a six-month period . The telemedicine group ( TmG ) sent the data to a telemedicine-based system that enabled patient-GP interaction ; the control group ( CG ) recorded the data on paper and could only deliver it to their GP personally in the routine visits . In the TmG , the results were better , but not significantly so , for : 1 ) degree of hypertension control , in terms of the percentage of uncontrolled hypertensives at the final visit ( TmG versus CG : 31.7 % versus 35.6 % ; p = 0.47 ) ; 2 ) reduction in hypertension during follow-up , comparing measurements ( performed by a professional ) at the initial and final visits of systolic BP ( 15.5 versus 11.9 ; p = 0.13 ) and diastolic BP ( 9.6 versus 4.4 ; p = 0.40 ) ; and 3 ) adherence to the protocol within compliance levels of interest in a real-life follow-up service : Gt50 % ( 84.8 % versus 73.3 % ) and Gt25 % ( 92.4.8 % versus 75.4 % ) ( p = 0.053 ) . Other factors such as average values of self-measured systolic BP , diastolic BP and heart rate , acceptability of the protocol , and median number of consultations and hospital admissions were similar in both groups . Outcomes show that , taken alone , the patient-GP short-messages-based interaction has very little impact on the degree of hypertension control in patients with this profile . In complex interventions , to discriminate the impact of each of its components in isolation will enable us to design an efficient follow-up service , little dem and ing in terms of healthcare professional dedication , and optimized in other basic aspects The more consistently someone records their food intake the more likely they are to lose weight . We hypothesized that subjects who kept track via their preferred method would demonstrate higher adherence and therefore improved outcomes compared to those who used a non-preferred method . Participants were r and omly assigned to use a paper , PDA , or Web-based diary and classified as " Preferred " if they used their preferred method and " Non-Preferred " if they did not . Days adherent to diary use were collected for 12 weeks . Weight , % body fat , waist circumference , and self-efficacy scores were measured at baseline , 6 and 12 weeks . Thirty nine participants completed the 12 week study . Fifty nine percent were male . The mean age was 35 and mean baseline BMI was 33 kg/m(2 ) ( + /-3.5 ) . Forty four % ( n=17 ) used their " Preferred " diary method and 56 % ( n=22 ) did not . Participants who used their preferred diary were more adherent to recording both food intake ( 64.2 % vs. 43.4 % , p=.015 ) and exercise ( 60.6 % vs. 31.2 % , p=.001 ) . Though no difference was seen between groups on weight management outcomes , these results suggest that diary preference affects adherence to diary use OBJECTIVES To investigate the acceptability and feasibility of using short message services ( SMS ) via cell phones to ensure adherence to management prescriptions by diabetic patients . METHODS Type 2 diabetic patients with 5 or more years of diabetes and having HbA1c between 7.0 % to 10 % were r and omized to the control arm ( n = 105 ) to receive st and ard care and to the intervention arm ( SMS , n = 110 ) . Messages in English on principles of diabetes management were sent once in 3 days , the contents and frequencies varied as per the patients ' preferences . The study duration was 1 year . All participants were advised to report for quarterly clinic visits . A comparative assessment of the clinical , biochemical and anthropometric outcomes was made among the groups at the annual visit . RESULTS Annual review was possible in 71 % of intervention group and 63 % of control group . SMS was acceptable to the patients and the median number requested was 2 per week . HbA1c and plasma lipids improved significantly in the SMS group . CONCLUSIONS The pilot study showed that frequent communication via SMS was acceptable to diabetic patients and it helped to improve the health outcomes A robust , h and -held , patient-oriented insulin regimen optimizer ( POIRO ) has been developed . Relevant information is entered by selecting appropriate items from choices displayed on a touch-sensitive screen rather than a conventional keyboard . All data items are recorded , together with their time and date of entry , and may be recalled at any time with glucose values displayed graphically to provide an overview of glycaemic control . When requested , an integral , hybrid , statistical and rule-based expert system program uses all available data to suggest an optimum insulin dose within physician determined , pre-set limits . POIRO has been formally evaluated in a r and omized crossover pilot trial , comparing two 3 week periods with and without decision support , in six patients with type 1 diabetes . Mean ( SE ) pre-pr and ial blood glucose levels were significantly lower during the period when decision support was available ( 7.5 ( 0.4 ) versus 8.9 ( 0.4 ) mmol/l , p = 0.015 ) with no increase in the frequency or severity of hypoglycaemia . The device , which was well received by the patients , may offer a relatively inexpensive method of providing expert diabetic advice at a distance . The persistence of improved glycaemic control , even after decision support was switched off , suggests the device could be used intermittently by patients and may have educational value Technology may improve self-monitoring adherence and dietary changes in weight loss treatment . Our study aim ed to investigate whether using a personal digital assistant ( PDA ) with dietary and exercise software , with and without a feedback message , compared to using a paper diary/record ( PR ) , results in greater weight loss and improved self-monitoring adherence . Healthy adults ( N = 210 ) with a mean BMI of 34.01 kg/m(2 ) were r and omized to one of three self-monitoring approaches : PR ( n = 72 ) , PDA with self-monitoring software ( n = 68 ) , or PDA with self-monitoring software and daily feedback messages ( PDA+FB , n = 70 ) . All participants received st and ard behavioral treatment . Self-monitoring adherence and change in body weight , waist circumference , and diet were assessed at 6 months ; retention was 91 % . All participants had a significant weight loss ( P < 0.01 ) but weight loss did not differ among groups . A higher proportion of PDA+FB participants ( 63 % ) achieved ≥ 5 % weight loss in comparison to the PR group ( 46 % ) ( P < 0.05 ) and PDA group ( 49 % ) ( P = 0.09 ) . Median percent self-monitoring adherence over the 6 months was higher in the PDA groups ( PDA 80 % ; PDA+FB 90 % ) than in the PR group ( 55 % ) ( P < 0.01 ) . Waist circumference decreased more in the PDA groups than the PR group ( P = 0.02 ) . Similarly , the PDA groups reduced energy and saturated fat intake more than the PR group ( P < 0.05 ) . Self-monitoring adherence was greater in the PDA groups with the greatest weight change observed in the PDA+FB group Summary Background Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term . We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence , which was biochemically verified at 6 months . Methods In this single-blind , r and omised trial , undertaken in the UK , smokers willing to make a quit attempt were r and omly allocated , using an independent telephone r and omisation system , to a mobile phone text messaging smoking cessation programme ( txt2stop ) , comprising motivational messages and behavioural-change support , or to a control group that received text messages unrelated to quitting . The system automatically generated intervention or control group texts according to the allocation . Outcome assessors were masked to treatment allocation . The primary outcome was self-reported continuous smoking abstinence , biochemically verified at 6 months . All analyses were by intention to treat . This study is registered , number IS RCT N 80978588 . Findings We assessed 11 914 participants for eligibility . 5800 participants were r and omised , of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group ; eight were excluded because they were r and omised more than once . Primary outcome data were available for 5524 ( 95 % ) participants . Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group ( 10·7 % txt2stop vs 4·9 % control , relative risk [ RR ] 2·20 , 95 % CI 1·80–2·68 ; p<0·0001 ) . Similar results were obtained when participants that were lost to follow-up were treated as smokers ( 268 [ 9 % ] of 2911 txt2stop vs 124 [ 4 % ] of 2881 control [ RR 2·14 , 95 % CI 1·74–2·63 ; p<0·0001 ] ) , and when they were excluded ( 268 [ 10 % ] of 2735 txt2stop vs 124 [ 4 % ] of 2789 control [ 2·20 , 1·79–2·71 ; p<0·0001 ] ) . No significant heterogeneity was shown in any of the prespecified subgroups . Interpretation The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services . Funding UK Medical Research Council , Primary Care Research Networks Background Previous trials of telemonitoring for heart failure management have reported inconsistent results , largely due to diverse intervention and study design s. Mobile phones are becoming ubiquitous and economical , but the feasibility and efficacy of a mobile phone-based telemonitoring system have not been determined . Objective The objective of this trial was to investigate the effects of a mobile phone-based telemonitoring system on heart failure management and outcomes . Methods One hundred patients were recruited from a heart function clinic and r and omized into telemonitoring and control groups . The telemonitoring group ( N = 50 ) took daily weight and blood pressure readings and weekly single-lead ECGs , and answered daily symptom questions on a mobile phone over 6 months . Readings were automatically transmitted wirelessly to the mobile phone and then to data servers . Instructions were sent to the patients ’ mobile phones and alerts to a cardiologist ’s mobile phone as required . Results Baseline question naires were completed and returned by 94 patients , and 84 patients returned post- study question naires . About 70 % of telemonitoring patients completed at least 80 % of their possible daily readings . The change in quality of life from baseline to post- study , as measured with the Minnesota Living with Heart Failure Question naire , was significantly greater for the telemonitoring group compared to the control group ( P = .05 ) . A between-group analysis also found greater post- study self-care maintenance ( measured with the Self-Care of Heart Failure Index ) for the telemonitoring group ( P = .03 ) . Brain natriuretic peptide ( BNP ) levels , self-care management , and left ventricular ejection fraction ( LVEF ) improved significantly for both groups from baseline to post- study , but did not show a between-group difference . However , a subgroup within-group analysis using the data from the 63 patients who had attended the heart function clinic for more than 6 months revealed the telemonitoring group had significant improvements from baseline to post- study in BNP ( decreased by 150 pg/mL , P = .02 ) , LVEF ( increased by 7.4 % , P = .005 ) and self-care maintenance ( increased by 7 points , P = .05 ) and management ( increased by 14 points , P = .03 ) , while the control group did not . No differences were found between the telemonitoring and control groups in terms of hospitalization , mortality , or emergency department visits , but the trial was underpowered to detect differences in these metrics . Conclusions Our findings provide evidence of improved quality of life through improved self-care and clinical management from a mobile phone-based telemonitoring system . The use of the mobile phone-based system had high adherence and was feasible for patients , including the elderly and those with no experience with mobile phones . Trial Registration Clinical Trials.gov The self-management of asthma can improve clinical outcomes . Recently , mobile telephones have been widely used as an efficient , instant personal communication tool . This study investigated whether a self-care system will achieve better asthma control through a mobile telephone-based interactive programme . This was a prospect i ve , controlled study in outpatient clinics . From 120 consecutive patients with moderate-to-severe persistent asthma , 89 were eventually recruited for the study , with 43 in the mobile telephone group ( with a mobile telephone-based interactive asthma self-care system ) . In the mobile telephone group , mean±sem peak expiratory flow rate significantly increased at 4 ( 378.2±9.3 L·min−1 ; n = 43 ; p = 0.020 ) , 5 ( 378.2±9.2 L·min−1 ; n = 43 ; p = 0.008 ) and 6 months ( 382.7±8.6 L·min−1 ; n = 43 ; p = 0.001 ) compared to the control group . Mean±sem forced expiratory volume in 1 s significantly increased at 6 months ( 65.2±3.2 % predicted ; n = 43 ; p<0.05 ) . Patients in the mobile telephone group had better quality of life after 3 months , as determined using the Short Form-12 ® physical component score , and fewer episodes of exacerbation and unscheduled visits than the control group . Patients in the mobile telephone group significantly increased their mean daily dose of either systemic or inhaled corticosteroids compared with the control group . The mobile telephone-based interactive self-care system provides a convenient and practical self-monitoring and -management of asthma , and improves asthma control OBJECTIVE To investigate the short- and long-term effectiveness and the predictors of weight loss in a mobile phone weight-loss programme among healthy overweight adults . DESIGN One hundred and twenty-five healthy , overweight ( BMI = 26 - 36 kg/m2 ) , 25 - 44-year-old , screened volunteers were r and omized to an experimental group ( n 62 ) to use a mobile phone-operated weight-loss programme or to a control group ( n 63 ) with no intervention . Via text messaging , the programme instructed a staggered reduction of food intake and daily weight reporting with immediate tailored feedback . Assessment s were at 0 , 3 , 6 , 9 and 12 months for the experimental group ; at 0 and 12 months for the control group . Main outcome variables were changes in body weight and waist circumference . RESULTS By 12 months the experimental group had lost significantly more weight than the control group ( 4.5 ( sd 5.0 ) v. 1.1 ( sd 5.8 ) kg ; F(1,80 ) = 8.0 , P = 0.006 ) and had a greater reduction in waist circumference ( 6.3 ( sd 5.3 ) v. 2.4 ( sd 5.4 ) cm ; F(1,80 ) = 55.2 , P = 0.0001 ) . Early weight loss , self-efficacy , contact frequency , attitudes towards the medium , changes in work and family life and changes made in dietary habits were the strongest predictors of weight loss . CONCLUSIONS This mobile phone weight-loss programme was effective in short- and long-term weight loss . As a minimum-advice , maximal-contact programme , it offers ideas for future weight-loss programmes OBJECTIVE To test the efficacy in promoting brisk walking of two theory-based interventions that incorporate implementation intentions and text message ( Short Message Service ; SMS ) reminders directed at one 's walking-related plans or goals . DESIGN Participants ( N = 149 ) were r and omized to one of three conditions ( implementation intention + SMS plan reminder , implementation intention + SMS goal reminder , control ) before completing measures at baseline and follow-up 4 weeks later . At follow-up , the experimental groups were given a surprise recall task concerning their plans . All participants completed an equivalent goal recall task . MAIN OUTCOME MEASURES Vali date d self-report measures of physical activity and measures of implementation intention and goal recall , weight , and waist-to-hip ratio . RESULTS Both intervention groups increased their brisk walking relative to the control group , without reducing other physical activity . The goal reminder group lost the most weight . The SMS plan reminder group recalled more of their plans than the SMS goal reminder group , but the latter were more successful in goal recall . CONCLUSION Both interventions can promote brisk walking in sedentary population s. Text messages aid the recall of , and could enhance interventions that target , implementation intentions and goals CONTEXT Influenza infection results in substantial costs , morbidity , and mortality . Vaccination against influenza is particularly important in children and adolescents who are a significant source of transmission to other high-risk population s , yet pediatric and adolescent vaccine coverage remains low . Traditional vaccine reminders have had a limited effect on low-income population s ; however , text messaging is a novel , scalable approach to promote influenza vaccination . OBJECTIVE To evaluate targeted text message reminders for low-income , urban parents to promote receipt of influenza vaccination among children and adolescents . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 9213 children and adolescents aged 6 months to 18 years receiving care at 4 community-based clinics in the United States during the 2010 - 2011 influenza season . Of the 9213 children and adolescents , 7574 had not received influenza vaccine prior to the intervention start date and were included in the primary analysis . INTERVENTION Parents of children assigned to the intervention received up to 5 weekly immunization registry-linked text messages providing educational information and instructions regarding Saturday clinics . Both the intervention and usual care groups received the usual care , an automated telephone reminder , and access to informational flyers posted at the study sites . MAIN OUTCOME MEASURES Receipt of an influenza vaccine dose recorded in the immunization registry via an electronic health record by March 31 , 2011 . Receipt was secondarily assessed at an earlier fall review date prior to typical widespread influenza activity . RESULTS Study children and adolescents were primarily minority , 88 % were publicly insured , and 58 % were from Spanish-speaking families . As of March 31 , 2011 , a higher proportion of children and adolescents in the intervention group ( 43.6 % ; n = 1653 ) compared with the usual care group ( 39.9 % ; n = 1509 ) had received influenza vaccine ( difference , 3.7 % [ 95 % CI , 1.5%-5.9 % ] ; relative rate ratio [ RRR ] , 1.09 [ 95 % CI , 1.04 - 1.15 ] ; P = .001 ) . At the fall review date , 27.1 % ( n = 1026 ) of the intervention group compared with 22.8 % ( n = 864 ) of the usual care group had received influenza vaccine ( difference , 4.3 % [ 95 % CI , 2.3%-6.3 % ] ; RRR , 1.19 [ 95 % CI , 1.10 - 1.28 ] ; P < .001 ) . CONCLUSIONS Among children and adolescents in a low-income , urban population , a text messaging intervention compared with usual care was associated with an increased rate of influenza vaccination . However , the overall influenza vaccination rate remained low . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01146912 Test-taking anxiety or stress is very common among university students . It can be very distressing and sometimes debilitating . Exam anxiety involves physical components and emotional components that may be taken into account for managing and reducing anxiety . An approach to control exam anxiety is to learn how to regulate emotions . To help students in managing exam stress we developed a specific protocol based on mobile narratives -- multimedia narratives experienced on UMTS/3 G phones . 30 female university students ( M=23.48 ; sd=1.24 ) who were going to perform an exam within a week were included in the trial . They were r and omly divided in five groups according to the type and mobility of the medium used : ( 1 ) audio only narrative ( CD at home ) ; ( 2 ) audio only narrative ( portable MP3 ) ; ( 3 ) audio and video narrative ( DVD at home ) ; ( 4 ) audio and video narrative ( UMTS based ) ; ( 5 ) control group . Audio/video narratives induced a reduction in exam anxiety in more than 80 % of the sample vs 50 % of the MP3 sample and 0 % of the CD sample . Further , all the users who experienced mobile narratives on UMTS phones were able to relax before the exam , against 50 % of DVD users and 33 % of audio-only users . The trial showed a better efficacy of mobile narratives experienced on UMTS phones in reducing the level of exam stress and in helping the student to relax . These results suggest that for the specific sample considered -- Italian university students -- the media used for providing an anti-stress protocol has a clear impact on its efficacy OBJECTIVE To assess whether pedometers and text messaging increase physical activity in adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS A 12-week r and omized controlled trial was conducted . A total of 78 subjects participated in the trial ( mean ± SD age 14.4 ± 2.37 years , 36 [ 47 % ] male ) . Intervention participants wore an open pedometer and received regular motivational text messages . Control participants received usual care . Primary outcomes were daily step count ( 4-day closed pedometer ) and physical activity question naire . RESULTS Baseline median step count was 11,063 steps/day ( range 1,541–20,158 ) . At 12 weeks , mean daily step count reduced by 840 ( 95 % CI −1,947 to 266 ) in the control group and by 22 ( −1,407 to 1,364 ) in the intervention group ( P = 0.4 ) . Mean self-reported moderate or vigorous physical activity increased by 38.5 min/week in the control group and by 48.4 in the intervention group ( P = 0.9 ) . CONCLUSIONS A 12-week intervention using pedometers and text messaging as motivational tools in adolescents with type 1 diabetes did not increase physical activity OBJECTIVE To assess whether a warning system based on mobile SMS messages increases the adherence of HIV-infected Brazilian women to antiretroviral drug-based treatment regimens and their impressions and satisfaction with respect to incoming messages . DESIGN A r and omized controlled trial was conducted from May 2009 to April 2010 with HIV-infected Brazilian women . All participants ( n=21 ) had a monthly multidisciplinary attendance ; each participant was followed over a 4-month period , when adherence measures were obtained . Participants in the intervention group ( n=8 ) received SMS messages 30 min before their last scheduled time for a dose of medicine during the day . The messages were sent every Saturday and Sunday and on alternate days during the working week . Participants in the control group ( n=13 ) did not receive messages . MEASUREMENTS Self-reported adherence , pill counting , microelectronic monitors ( MEMS ) and an interview about the impressions and satisfaction with respect to incoming messages . RESULTS The HIV Alert System ( HIVAS ) was developed over 7 months during 2008 and 2009 . After the study period , self-reported adherence indicated that 11 participants ( 84.62 % ) remained compliant in the control group ( adherence exceeding 95 % ) , whereas all 8 participants in the intervention group ( 100.00 % ) remained compliant . In contrast , the counting pills method indicated that the number of compliant participants was 5 ( 38.46 % ) for the control group and 4 ( 50.00 % ) for the intervention group . Microelectronic monitoring indicated that 6 participants in the control group ( 46.15 % ) were adherent during the entire 4-month period compared to 6 participants in the intervention group ( 75.00 % ) . According to the feedback of the 8 participants who completed the research in the intervention group , along with the feedback of 3 patients who received SMS for less than 4 months , that is , did not complete the study , 9 ( 81.81 % ) believed that the SMS messages aided them in treatment adherence , and 10 ( 90.90 % ) responded that they would like to continue receiving SMS messages . CONCLUSION SMS messaging can help Brazilian women living with HIV/AIDS to adhere to antiretroviral therapy for a period of at least 4 months . In general , the results are encouraging because the SMS messages stimulated more participants in the intervention group to be adherent to their treatment , and the patients were satisfied with the messages received , which were seen as reminders , incentives and signs of affection by the health clinic for a marginalized population BACKGROUND Mobile ( cell ) phone communication has been suggested as a method to improve delivery of health services . However , data on the effects of mobile health technology on patient outcomes in re source -limited setting s are limited . We aim ed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load . METHODS WelTel Kenya1 was a multisite r and omised clinical trial of HIV-infected adults initiating antiretroviral therapy ( ART ) in three clinics in Kenya . Patients were r and omised ( 1:1 ) by simple r and omisation with a r and om number generating program to a mobile phone short message service ( SMS ) intervention or st and ard care . Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. R and omisation , laboratory assays , and analyses were done by investigators masked to treatment allocation ; however , study participants and clinic staff were not masked to treatment . Primary outcomes were self-reported ART adherence ( > 95 % of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits ) and plasma HIV-1 viral RNA load suppression ( < 400 copies per mL ) at 12 months . The primary analysis was by intention to treat . This trial is registered with Clinical Trials.gov , NCT00830622 . FINDINGS Between May , 2007 , and October , 2008 , we r and omly assigned 538 participants to the SMS intervention ( n=273 ) or to st and ard care ( n=265 ) . Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group ( relative risk [ RR ] for non-adherence 0·81 , 95 % CI 0·69 - 0·94 ; p=0·006 ) . Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group , ( RR for virologic failure 0·84 , 95 % CI 0·71 - 0·99 ; p=0·04 ) . The number needed to treat ( NNT ) to achieve greater than 95 % adherence was nine ( 95 % CI 5·0 - 29·5 ) and the NNT to achieve viral load suppression was 11 ( 5·8 - 227·3 ) . INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals . Mobile phones might be effective tools to improve patient outcome in re source -limited setting s. FUNDING US President 's Emergency Plan for AIDS Relief BACKGROUND Although early shock with an automated external defibrillator ( AED ) is one of the several key elements to save out-of-hospital cardiac arrest ( OHCA ) victims , it is not always easy to find and retrieve a nearby AED in emergency setting s. We developed a cell phone web system , the Mobile AED Map , displaying nearby AEDs located anywhere . The simulation trial in the present study aims to compare the time and travel distance required to access an AED and retrieve it with and without the Mobile AED Map . METHODS DESIGN R and omised controlled trial . SETTING Two fields where it was estimated to take 2min ( 120 - 170 m ) to access the nearest AED . Participants were r and omly assigned to either the Mobile AED Map group or the control group . We provided each participant in both groups with an OHCA scenario , and measured the time and travel distance to find and retrieve a nearby AED . RESULTS Forty-three volunteers were enrolled and completed the protocol . The time to access and retrieve an AED was not significantly different between the Mobile AED Map group ( 400±238s ) and the control group ( 407±256s , p=0.92 ) . The travel distance was significantly shorter in the Mobile AED Map group ( 606 m vs. 891 m , p=0.019 ) . Trial field conditions affected the results differently . CONCLUSIONS Although the new Mobile AED Map reduced the travel distance to access and retrieve the AED , it failed to shorten the time . Further technological improvements of the system are needed to increase its usefulness in emergency setting s ( UMIN000002043 ) Background Forming specific health plans can help translate good intentions into action . Mobile text reminders can further enhance the effects of planning on behavior . Objective Our aim was to explore the combined impact of a Web-based , fully automated planning tool and mobile text reminders on intention to change saturated fat intake , self-reported saturated fat intake , and portion size changes over 4 weeks . Methods Of 1013 men and women recruited online , 858 were r and omly allocated to 1 of 3 conditions : a planning tool ( PT ) , combined planning tool and text reminders ( PTT ) , and a control group . All outcome measures were assessed by online self-reports . Analysis of covariance was used to analyze the data . Results Participants allocated to the PT ( meansat urated fat 3.6 , meancopingplanning 3 ) and PTT ( meansaturatedfat 3.5 , meancopingplanning 3.1 ) reported a lower consumption of high-fat foods ( F 2,571 = 4.74 , P = .009 ) and higher levels of coping planning ( F 2,571 = 7.22 , P < .001 ) than the control group ( meansat urated f at 3.9 , meancopingplanning 2.8 ) . Participants in the PTT condition also reported smaller portion sizes of high-fat foods ( mean 2.8 ; F 2 , 569 = 4.12 , P = .0 ) than the control group ( meanportions 3.1 ) . The reduction in portion size was driven primarily by the male participants in the PTT ( P = .003 ) . We found no significant group differences in terms of percentage saturated fat intake , intentions , action planning , self-efficacy , or feedback on the intervention . Conclusions These findings support the use of Web-based tools and mobile technologies to change dietary behavior . The combination of a fully automated Web-based planning tool with mobile text reminders led to lower self-reported consumption of high-fat foods and greater reductions in portion sizes than in a control condition . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 61819220 ; http://www.controlled-trials.com/IS RCT N61819220 ( Archived by WebCite at http://www.webcitation.org/63YiSy6R8 A single-blind within-subjects trial was used to test the efficacy of sending SMS text messages to patients with a traumatic brain injury as a means of improving their recall of rehabilitation goals . Eleven participants were recruited from two community-based rehabilitation centres and were sent text messages relating to three r and omly selected goals from a selection of six current goals three times per day for 14 days . Participants ’ recall of their rehabilitation goals was assessed at baseline , seven days , and 14 days via free recall and cued recall procedures . Results showed that goals in the “ text ” condition were recalled better than goals in the “ no text ” condition . Practical applications and extensions are discussed Implementation intentions planning in advance the situation in which one will act , have been proposed to be an effective self-regulatory technique for changing health behaviour . Encouraging people to receive text message reminders of their implementation intentions should enhance their strength and , thus , it was predicted that this combined approach would be particularly effective in increasing exercise . Participants ( N = 155 ) were r and omly allocated to one of five conditions ( implementation intentions and SMS , implementation intention , SMS or one of two control groups ) then completed self-report measures of exercise behaviour and motivation . Four weeks later , they responded to similar items . Results suggested that the combined intervention increased exercise frequency significantly more than the other strategies including the implementation intention group . It is proposed , therefore , that implementation intention effects can be enhanced via plan reminders BACKGROUND AND AIMS Many people with schizophrenia have severe cognitive impairments that hamper their activities . The effect of pharmacological and behavioural interventions on cognitive functioning has been demonstrated , but even after successful intervention considerable impairments can remain . Therefore , we sought for alternative ways to help patients cope with the effects of their cognitive impairments . In the present study , we have evaluated the efficacy of short message service ( SMS ) text messages to compensate for the effects of cognitive impairments in schizophrenia in daily life . DESIGN A waiting list controlled trial was conducted : patients were quasi-r and omly assigned to an A-B-A ( baseline-intervention-follow-up ) condition or an A-A-B-A condition that included an additional 7-week waiting list . The waiting list was included to control for the effect of time on relevant outcome . METHOD Sixty-two people with schizophrenia or related psychotic disorders were included in the study . All patients showed impaired goal -directed behaviour in daily life-situations . Patients were prompted with SMS text messages to improve their everyday functioning . The primary outcome measure was the percentage of goals achieved . RESULTS The overall percentage of goals achieved increased with prompting , while performance dropped to baseline level after withdrawing the prompts . Keeping appointments with mental health workers and carrying out leisure activities increased with prompting , while medication adherence and attendance at training sessions remained unchanged . A majority of the patients enjoyed receiving the SMS text messages . DISCUSSION Prompting can significantly improve achievement of a number of relevant goals . For other goals , combining prompting with interventions that enhance motivation seems indicated A mobile phone with a glucometer integrated into the battery pack ( the ‘ Diabetes Phone ’ ) was launched in Korea in 2003 . We compared its effect on management of type 2 diabetes to the Internet-based glucose monitoring system ( IBGMS ) , which had been studied previously . We conducted a r and omized trial involving 69 patients for three months . Participants were assigned to an Internet group or a phone group . The phone group communicated with medical staff through the mobile phone only . Their glucose-monitoring data were automatically transferred to individual , web-based charts and they received medical recommendations by short message service . The Internet group used the IBGMS . There were no significant differences between the groups at baseline . After three months ' intervention , HbA1c levels of both groups had decreased significantly , from 7.6 % to 6.9 % for the Internet group and from 8.3 % to 7.1 % for the phone group ( P < 0.01 ) . Levels of patient satisfaction and adherence to medical advice were similar . Mobile , bidirectional communication between doctors and patients using the diabetes phone was as effective for glucose control as the previously-studied Internet-based monitoring system and it was good for patient satisfaction and adherence AIMS The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide . To improve the quality and efficiency of chronic disease care , we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care ( UCDC ) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension . METHODS We conducted a r and omized , controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre . RESULTS After 12 weeks , there were significant improvements in HbA(1c ) in the intervention group ( 7.6 + /- 0.9 % to 7.1 + /- 0.8 % , P < 0.001 ) compared with the control group ( 7.4 + /- 0.9 % to 7.6 + /- 1.0 % , P = 0.03 ) . Furthermore , we observed a significant reduction in systolic and diastolic blood pressure , as well as improvements in total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels in the intervention group . Furthermore , there was a significant increase in adiponectin levels in the intervention group compared with the control group , although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group . CONCLUSIONS The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension OBJECTIVE The purpose of this trial was to investigate the feasibility and short-term outcomes of a tailored intervention , delivered via text messages to wireless h and held computers , to reduce alcohol-related consequences among college students . METHOD Forty college students were r and omly assigned to one of two study groups . In the control group , participants used h and held computers to complete daily surveys about their drinking behavior and related variables . In the treatment group , participants used the h and held computers to complete daily surveys and to receive individually tailored messages on the units . The tailored messages addressed consequences of alcohol use and were tailored to respondents ' reported behavior , self-efficacy , and outcome expectancies regarding alcohol-related consequences . RESULTS All treatment group participants reported receiving messages on their h and held computers ; most students were sent messages on 12 - 14 days . Controlling for baseline differences , participants in the treatment group reported drinking significantly fewer drinks per drinking day than participants in the control group during the study period . At follow-up , participants in the treatment group had lower expectancies that they would get in trouble as a result of alcohol consumption than did control group participants . Participants provided both positive and negative feedback about the messages . CONCLUSIONS This study demonstrated the feasibility of delivering tailored messages via wireless h and held computers . Tailored messages about avoiding negative consequences of alcohol use delivered via h and held computers had small but positive effects on alcohol-related attitudes and behaviors . Future research should replicate these findings with a larger , more diverse sample , during a longer period , and with other audiences BACKGROUND As obesity rates rise , new weight-loss methods are needed . Little is known about the use of podcasting ( audio files for a portable music player or computer ) to promote weight loss , despite its growing popularity . DESIGN A 12-week RCT was conducted . SETTING / PARTICIPANTS The study sample comprised overweight men and women ( BMI = 25 - 40 kg/m(2 ) ; n=78 ) in the Raleigh-Durham NC area . INTERVENTION In 2008 , participants were r and omly assigned to receive 24 episodes of a currently available weight-loss podcast ( control podcast ) or a weight-loss podcast based on social cognitive theory ( SCT ) design ed by the research ers ( enhanced podcast ) for 12 weeks . MAIN OUTCOME MEASURES Weight was measured on a digital scale at baseline and follow-up . Both groups also completed question naires assessing demographic information , food intake , physical activity , and SCT constructs at the introductory and 12-week meetings . Additional question naires at the 12-week meeting assessed perceptions of the intervention . RESULTS Data collection and analysis occurred in 2008 and intention-to-treat was used . Enhanced group participants ( n=41 ) had a greater decrease in weight ( -2.9+/-3.5 kg enhanced group vs -0.3+/-2.1 control group ; p<0.001 between groups ) and BMI ( -1.0+/-1.2 kg/m(2 ) enhanced group vs -0.1+/-0.7 kg/m(2 ) control group ; p<0.001 between groups ) than the control group ( n=37 ) and had greater weight-loss-related knowledge ( p<0.05 ) , elaboration ( p<0.001 ) , and user control ( p<0.001 ) and less cognitive load ( p<0.001 ) . CONCLUSIONS The results of this study suggest that the use of behavioral , theory-based podcasting may be an effective way to promote weight loss . TRIAL REGISTRATION NCT00771095 BACKGROUND Brief interventions have the potential to reduce heavy drinking in young adults who present to the emergency department ( ED ) , but require time and re sources rarely available . Text-messaging ( TM ) may provide an effective way to collect drinking data from young adults after ED discharge as well as to provide immediate feedback and ongoing support for behavior change . The feasibility of screening young adults in the ED , recruiting them for a TM-based interventional trial , collecting weekly drinking data through TM , and the variance in drinking outcomes remains unknown . METHODS Young adults in 3 urban EDs ( n = 45 ; aged 18 to 24 years , 54 % women ) identified as hazardous drinkers by the Alcohol Use Disorders Identification Test-Consumption score were r and omly assigned to weekly TM-based feedback with goal setting ( Intervention ) , weekly TM-based drinking assessment s without feedback ( Assessment ) , or control . Participants in the Intervention group who reported ≥5 ( for men ) and ≥4 ( for women ) maximum drinks during any one 24-hour period were asked whether they would set a goal to reduce their drinking the following week . We describe the interaction with TM and goal setting . We also describe the heavy drinking days ( HDDs ) , drinks per drinking day ( DPDD ) using timeline follow-back procedure at baseline and 3 months . RESULTS We screened 109 young adults over 157 hours across 24 unique days and 52 ( 48 % ; 95 % CI 38 to 50 ) screened positive for hazardous drinking . Of these , 45 ( 87 % ; 95 % CI 74 to 94 ) met inclusion criteria , were enrolled and r and omized , and 6 ( 13 % ; 95 % CI 5 to 27 ) did not complete 3-month web-based follow-up ; 88 % ( 95 % CI 84 to 91 ) of weekly TM-based drinking assessment s were answered , with 77 % ( 95 % CI 58 to 90 ) of participants responding to all 12 weeks . Agreeing to set a goal was associated with a repeat HDD 36 % ( 95 % CI 17 to 55 ) of the time compared with 63 % ( 95 % CI 44 to 81 ) when not willing to set a goal . At 3 months , participants that were exposed to the TM-based intervention had 3.4 ( SD 5.4 ) fewer HDDs in the last month and 2.1 ( SD 1.5 ) fewer DPDD when compared to baseline . CONCLUSIONS TM can be used to assess drinking in young adults and can deliver brief interventions to young adults discharged from the ED . TM-based interventions have the potential to reduce heavy drinking among young adults but larger studies are needed to establish efficacy One of the best strategies for dealing with stress is learning how to relax . However , relaxing is difficult to achieve in typical real world situations . For this study , we developed a specific protocol based on mobile narratives - multimedia narratives experienced on UMTS/3 G phones - to help workers in reducing commuting stress . In a controlled trial 33 commuters were r and omly divided between three conditions : Mobile narratives ( MN ) ; New age music and videos ( NA ) ; no treatment ( CT ) . In two consecutive days the MN and NA sample s experienced during their commute trip 2 x 2 6-minute multimedia experiences on a Motorola A925 3 G phone provided by the " TRE " Italian UMTS carrier : the MN sample experienced a mobile narrative based on the exploration of a desert beach ; the NA sample experienced a commercial new age video with similar visual contents . The trials showed the efficacy of mobile narratives in reducing the level of stress experienced during a commute trip . No effects were found in the other groups . These results suggest that 3 G mobile h and sets may be used as relaxation tool if backed by a specific therapeutic protocol and meaningful narratives OBJECTIVE The objective of this study is to compare the skill retention of two groups of lay persons , six months after their last CPR training . The intervention group was provided with animation-assisted CPRII ( AA-CPRII ) instruction on their cellular phones , and the control group had nothing but what they learned from their previous training . METHODS This study was a single blind r and omized controlled trial . The participants ' last CPR trainings were held at least six months ago . We revised our CPR animation for on-site CPR instruction content emphasizing importance of chest compression . Participants were r and omized into two groups , the AA-CPRII group ( n=42 ) and the control group ( n=38 ) . Both groups performed three cycles of CPR and their performances were video recorded . These video clips were assessed by three evaluators using a checklist . The psychomotor skills were evaluated using the ResusciAnne SkillReporter . RESULTS Using the 30-point scoring checklist , the AA-CPRII group had a significantly better score compared to the control group ( p<0.001 ) . Psychomotor skills evaluated with the AA-CPRII group demonstrated better performance in h and positioning ( p=0.025 ) , compression depth ( p=0.035 ) and compression rate ( p<0.001 ) than the control group . CONCLUSION The AA-CPRII group result ed in better checklist scores , including chest compression rate , depth and h and positioning . Animation-assisted CPR could be used as a reminder tool in achieving effective one-person-CPR performance . By installing the CPR instruction on cellular phones and having taught them CPR with it during the training enabled participants to perform better CPR Introduction In this paper , we evaluated the feasibility of a telemedical ( TM ) support program and its effect on glycemic control in adolescents with type 1 diabetes mellitus ( T1DM ) . Thirty-six adolescents ( m=20 , median age at the start of the study : 15.3 years ( range : 10.7–19.3 years ) , median age at diagnosis : 9.3 years ( 2.1–13.8 years ) , median duration of disease : 6.4 years ( 1.0–12.8 years ) , HbA1c>8 % , all on intensified insulin therapy ) were r and omized in a crossover trial over 6 months ( 3 months with TM , 3 months with conventional support and paper diary ( PD ) ) . During the TM phase , the patients sent their data ( date , time , blood glucose , carbohydrate intake , insulin dosage ) via mobile phone , at least daily , to our server and diabetologists sent back their advice via short message service ( SMS ) once a week . Results Glycemic control improved during the TM phase , while it deteriorated during the PD phase : TM-PD group HbA1c ( % , median ( range ) ) : 9.05 ( 8–11.3 ) ( at 0 months ) , 8.9 ( 6.9–11.3 ) ( at 3 months ) , and 9.2 ( 7.4–12.6 ) ( at 6 months ) , and PD-TM group : 8.9 ( 8.3–11.6 ) , 9.9 ( 8.1–11 ) , and 8.85 ( 7.3–11.7 ) ( p<0.05 ) . Patients rated the TM support program to be a good idea . Technical problems with General Packet Radio Service ( GPRS ) data transmission led to data loss and decreased patient satisfaction . Conclusion Our telemedical support program , VIE-DIAB , proved to be feasible in adolescents and helped to improve glycemic control BACKGROUND Cell phone text messaging , via the Short Messaging Service ( SMS ) , offers the promise of a highly portable , well-accepted , and inexpensive modality for engaging youth and young adults in the management of their diabetes . This pilot and feasibility study compared two-way SMS cell phone messaging with e-mail reminders that were directed at encouraging blood glucose ( BG ) monitoring . METHODS Forty insulin-treated adolescents and young adults with diabetes were r and omized to receive electronic reminders to check their BG levels via cell phone text messaging or e-mail reminders for a 3-month pilot study . Electronic messages were automatically generated , and participant replies with BG results were processed by the locally developed Computerized Automated Reminder Diabetes System ( CARDS ) . Participants set their schedule for reminders on the secure CARDS website where they could also enter and review BG data . RESULTS Of the 40 participants , 22 were r and omized to receive cell phone text message reminders and 18 to receive e-mail reminders ; 18 in the cell phone group and 11 in the e-mail group used the system . Compared to the e-mail group , users in the cell phone group received more reminders ( 180.4 vs. 106.6 per user ) and responded with BG results significantly more often ( 30.0 vs. 6.9 per user , P = 0.04 ) . During the first month cell phone users su bmi tted twice as many BGs as e-mail users ( 27.2 vs. 13.8 per user ) ; by month 3 , usage waned . CONCLUSIONS Cell phone text messaging to promote BG monitoring is a viable and acceptable option in adolescents and young adults with diabetes . However , maintaining interest levels for prolonged intervals remains a challenge Thail and 's implementation of the Directly Observed Treatment , Short course ( DOTS ) strategy to increase tuberculosis ( TB ) control program efficacy has not achieved the World Health Organization ( WHO ) TB key targets . We defined two TB control models in the study . Patients in Model 1 were treated with a conventional DOTS strategy and in Model 2 , patients were treated the same as Model method 1 but were given a phone call reminder to take their medication . Multi-drug resistant tuberculosis ( MDR-TB ) and non-MDR-TB patients were r and omized into either Model 1 or 2 . Treatment outcomes were given as cure rates , completion rates , failure rates or success rates at 18 months in the MDR-TB group and 6 months in the non-MDR-TB group . The sputum conversion rate at 1 month were evaluated for both groups . In the MDR-TB group , the sputum conversion rate was 20 % ( 95 % CI 8 - 45 ) in Model 1 and 90 % ( 95 % CI 73 - 98 ) in Model 2 ( p < 0.001 ) . In the non-MDR-TB group , the sputum conversion rate was 52 % ( 95 % CI 36 - 70 ) in Model 1 and 37 % ( 95 % CI 22 - 56 ) in Model 2 although the difference was not significant ( p = 0.221 ) . The Model 2 success rates were significantly higher ( 73.7 % , 96.7 % ) in both the MDR-TB and non-MDR-TB groups ( p < 0.001 , p = 0.047 ) . The MDR-TB rate in northern Thail and decreased from 4.1 % during April-September 2008 to 1.8 % during April-September 2009 . Further study of the association between implementation of Model 2 and MDR-TB incidence reduction needs to be carried out Background : This study examined whether mobile phone-based , one-way video messages about diabetes self-care improve hemoglobin A1c ( A1C ) and self-monitoring of blood glucose ( SMBG ) . Methods : This was a 1-year prospect i ve r and omized trial with two groups . The active intervention lasted 6 months . The study enrolled 65 people with A1C > 8.0 % who were established ( > 6 months ) patients in the endocrinology clinics of the Walter Reed Health Care System . Participants were r and omized to receive “ usual care ” or self-care video messages from their diabetes nurse practitioner . Video messages were sent daily to cell phones of study participants . Hemoglobin A1c and SMBG data were collected at 0 , 3 , 6 , 9 , and 12 months . Results : Participants who received the messages had a larger rate of decline in A1C than people who received usual care ( 0.2 % difference over 12 months , adjusting for covariates ; p = .002 and p = .004 for the interaction between time and group and for the quadratic effect of time by group , respectively ) . Hemoglobin A1c decline was greatest among participants who received video messages and viewed > 10 a month ( 0.6 % difference over 12 months , adjusting for covariates ; p < .001 for the interaction between time and group and the quadratic effect ) . Self-monitoring of blood glucose metrics were not related to the intervention . Conclusions : A one-way intervention using mobile phone-based video messages about diabetes self-care can improve A1C . Engagement with the technology is an important predictor of its success . This intervention is simple to implement and sustain AIM Conventional follow-up of type 1 diabetic patients treated with continuous subcutaneous insulin infusion ( CSII ) was compared with intensive coaching using the Web and the cellular phone network for retrospective data transmission and short message service ( SMS ) . METHODS Thirty poorly controlled patients ( HbA1c 7.5 - 10 % ) were enrolled in a bicenter , open-label , r and omized , 12-month , two-period , crossover study . After a 1-month run-in period , 15 patients were r and omly assigned to receive weekly medical support through SMS based upon weekly review of glucose values , while 15 patients continued to download self-monitored blood glucose ( SMBG ) values on a weekly basis without receiving SMS . After 6 months , patients crossed over to the alternate sequence for 6 additional months . Visits at the clinic were maintained every 3 months . RESULTS Patients with long-st and ing inadequately controlled diabetes ( 24 + /- 13 years ) were included . A non-significant trend to reduction in HbA(1c ) ( -0.25+/-0.94 % , P<0.10 ) and mean glucose values ( -9.2+/-25 mg/dl , P=0.06 ) during the 6-month SMS sequence was observed as compared with the no-SMS period . No safety issue ( hypoglycemia , glucose variability ) was reported . Adherence to SMBG was not affected by the trial . Quality of life analysis suggests a significant improvement in DQOL global score , as well as the DQOL satisfaction with life subscale , during the SMS sequence . CONCLUSIONS Long-term telemedical follow-up of insulin pump-treated patients using a cellular phone- , SMS- and Web-based platform is feasible , safe , does not alter quality of life and associated with a trend toward improved metabolic control OBJECTIVES The present study evaluates a new CPR feedback application for the iPhone ( iCPR ) design ed to improve chest compression performance tested in a cardiac arrest simulation to evaluate performance and acceptance by healthcare professionals and lay people . METHODS We built an application specifically dedicated to self-directed CPR training through a tutorial that includes a simple feedback module to guide training in order to improve the quality of chest compressions . We tested it in a sample of 50 users to evaluate the effect of iCPR on performance and it is acceptance . The participants were r and omly assigned to one of the study groups and were asked to perform a trial of 2 min of chest compressions ( CC ) , to answer a predefined set of questions and then to perform two more minutes of CC . The first group performing the sequence of CC with iCPR - questions - CC without feedback , and the second the sequence CC without feedback - questions CC with iCPR . RESULTS The mean compression rate was 101±2.8 min(-1 ) when CC were performed with iCPR and 107.8±20.5 min(-1 ) when performed without iCPR ( p<0.01 ) . Overall , the participants considered iCPR useful to maintain CC at the desired rate of 100 compressions per minute . CONCLUSIONS The iCPR feedback tool was able to significantly improve the performance of chest compressions in terms of the compression rate in a simulated cardiac arrest scenario . The participants also believed that iCPR helped them to achieve the correct chest compression rate and most users found this device easy to use BACKGROUND Efforts to achieve population -wide increases in walking and similar moderate-intensity physical activities potentially can be enhanced through relevant applications of state-of-the-art interactive communication technologies . Yet few systematic efforts to evaluate the efficacy of h and -held computers and similar devices for enhancing physical activity levels have occurred . The purpose of this first-generation study was to evaluate the efficacy of a h and -held computer ( i.e. , personal digital assistant [ PDA ] ) for increasing moderate intensity or more vigorous ( MOD+ ) physical activity levels over 8 weeks in mid-life and older adults relative to a st and ard information control arm . DESIGN R and omized , controlled 8-week experiment . Data were collected in 2005 and analyzed in 2006 - 2007 . SETTING / PARTICIPANTS Community-based study of 37 healthy , initially underactive adults aged 50 years and older who were r and omized and completed the 8-week study ( intervention=19 , control=18 ) . INTERVENTION Participants received an instructional session and a PDA programmed to monitor their physical activity levels twice per day and provide daily and weekly individualized feedback , goal setting , and support . Controls received st and ard , age-appropriate written physical activity educational material s. MAIN OUTCOME MEASURE Physical activity was assessed via the Community Healthy Activities Model Program for Seniors ( CHAMPS ) question naire at baseline and 8 weeks . RESULTS Relative to controls , intervention participants reported significantly greater 8-week mean estimated caloric expenditure levels and minutes per week in MOD+ activity ( p<0.04 ) . Satisfaction with the PDA was reasonably high in this largely PDA-naive sample . CONCLUSIONS Results from this first-generation study indicate that h and -held computers may be effective tools for increasing initial physical activity levels among underactive adults Adolescent mothers in Washington , DC have a high rate of subsequent teen pregnancies , often within 24 months . Children of teen mothers are at risk for adverse psychosocial outcomes . When adolescents are strongly attached to parents , schools , and positive peers , they may be less likely to repeat a pregnancy . This study tested the efficacy of a counseling intervention delivered by cell phone and focused on postponing subsequent teen pregnancies by strengthening healthy relationships , reproductive practice s , and positive youth assets . The objective of this study was to compare time to a repeat pregnancy between the intervention and usual care groups , and , secondarily , to determine whether treatment intensity influenced time to subsequent conception . Primiparous pregnant teens ages 15–19 , were recruited in Washington , DC . Of 849 teens screened , 29.3 % ( n = 249 ) met inclusion criteria , consented to participate , and completed baseline measures . They were then r and omized to the intervention ( N = 124 ) or to usual care ( N = 125 ) . Intervention group teens received cell phones for 18 months of counseling sessions , and quarterly group sessions . Follow-up measures assessed subsequent pregnancy through 24 months post-delivery . A survival analysis compared time to subsequent conception in the two treatment groups . Additional models examined the effect of treatment intensity . By 24 months , 31 % of the intervention and 36 % of usual care group teens had a subsequent pregnancy . Group differences were not statistically significant in intent-to-treat analysis . Because there was variability in the degree of exposure of teens to the curriculum , a survival analysis accounting for treatment intensity was performed and a significant interaction with age was detected . Participants who were aged 15–17 years at delivery showed a significant reduction in subsequent pregnancy with increased levels of intervention exposure ( P < 0.01 ) , but not those ≥18 years . Adolescents ≥18 years faced considerable challenges to treatment success . Individual , social , and context ual factors are all important to consider in the prevention of repeat teen pregnancy . Cell phone-based approaches to counseling may not be the most ideal for addressing complex , socially-mediated behaviors such as this , except for selective subgroups . A lack of re sources within the community for older teens may interfere with program success Abstract Objective : To assess the hazards associated with long term use of tobacco . Design : Prospect i ve study of mortality in relation to smoking habits assessed in 1951 and again from20time to time thereafter , with causes sought of deaths20over 40 years ( to 1991 ) . Continuation of a study that was last reported after 20 years ' follow up ( 1951 - 71 ) . Subjects : 34 439 British male doctors who replied20to a postal question naire in 1951 , of whom 10 000 had died during the first 20 years and another 10 000 have died during the second 20 years . Results - Excess mortality associated with20smoking was about twice as extreme during the second half of the study as it had been during the first half . The death rate ratios during 1971 - 91 ( comparing continuing cigarette smokers with lifelong20non-smokers ) were approximately threefold at ages 45 - 64 and twofold at ages 65 - 84 . The excess mortality was chiefly from diseases that can be caused by smoking . Positive associations with smoking were confirmed for death from cancers of the mouth , oesophagus , pharynx , larynx , lung , pancreas , and bladder ; from chronic obstructive pulmonary disease and other respiratory diseases ; from vascular diseases ; from peptic ulcer ; and ( perhaps because of confounding by personality and alcohol use ) from cirrhosis , suicide , and poisoning . A negative association was confirmed with death20from Parkinson 's disease . Those who stopped20smoking before middle age subsequently avoided almost all of the excess risk that they would otherwise have suffered , but even those who stopped smoking in middle age were subsequently at substantially less risk than those who continued to smoke . Conclusion : Results from the first 20 years of this study , and of other studies at that time , substantially20underestimated the hazards of long term use of tobacco . It now seems that about half of all regular cigarette smokers will eventually be killed by their habit We have evaluated the feasibility of using the mobile phone short message service ( SMS ) for symptom monitoring in patients with asthma . All consecutive patients admitted to hospital for asthma during an 11-month period were considered for enrolment ( n = 497 ) . Those meeting the inclusion criteria were r and omized into a control ( n = 60 ) and intervention group ( n = 60 ) . Patients in the intervention group received SMS messages according to a structured workflow , while patients in the control group had no SMS support . In the intervention group , the mean response rate to the messages was 82 % . There was an improvement in the Asthma Control Test ( ACT ) scores in 36 subjects in the intervention group compared to 28 subjects in the control group . There were reductions in the number of nebulizations in 54 subjects in the control group compared to 50 subjects in the intervention group , and reductions in emergency department visits in 57 subjects in the control group compared to 51 subjects in the intervention group . However , none of these differences were significant . There was no reduction in admission rates in either group ( P = 0.5 ) . The service was accepted by most patients , but its long-term effectiveness on the management of asthma remains to be determined This paper reports on a research trial design ed to evaluate the benefits of a health mentoring programme supported with a web and mobile phone based self-monitoring application for enhancing self-efficacy for self-management skills and quality of life for people with CF . This r and omised , single-blind controlled trial evaluated two strategies design ed to improve self-management behaviour and quality of life . Task-specific self-efficacy was fostered through mentorship and self-monitoring via a mobile phone application . Trial participants were r and omised into one of three groups : Control , Mentor-only and Mentor plus mobile phone . Analysis and discussion focus on the experiences of participants through a methodology utilising descriptive statistics and semi-structured interviews . The results highlight the challenges of stimulating self-management behaviours particularly in adolescents and in the evaluation of the role of mobile applications in supporting them OBJECTIVE The present study attempts to develop and pilot the feasibility and efficacy of a novel intervention using affective messages as a strategy to increase physical activity ( PA ) levels in adolescents . Design An exploratory pilot r and omized control trial was used to compare behaviour change over 2 weeks . A modified form of the International Physical Activity Question naire was used to assess PA behaviour . A total of 120 adolescents ( 16 - 19 years ) from 4 sixth forms in West Yorkshire completed the field-based study . METHOD Participants were r and omly assigned to one of three experimental conditions , or the control condition ( N=28 ) . Participants in experimental conditions received 1 short messaging service ( SMS ) text message per day over the 2 weeks , which included manipulations of either affective beliefs ( enjoyable/unenjoyable ; N=31 ) , instrumental beliefs ( beneficial/harmful ; N=30 ) , or a combination of these ( N=31 ) . Control participants received one SMS text message per week . Outcomes were measured at baseline and at the end of the 2 week intervention . RESULTS PA levels increased by the equivalent of 31.5 minutes of moderate ( four metabolic equivalent ) activity per week during the study . Main effects of condition ( p=.049 ) , and current physical activity level ( p=.002 ) were identified , along with a significant interaction between condition and current activity level ( p=.006 ) . However , when the sample was split at baseline into active and inactive participants , a main effect of condition remained for inactive participants only ( p=.001 ) . Post hoc analysis revealed that inactive participants who received messages targeting affective beliefs increased their activity levels significantly more than the instrumental ( p=.012 ) , combined ( p=.002 ) , and control groups ( p=.018 ) . CONCLUSION Strategies based on affective associations may be more effective for increasing PA levels in inactive individuals RATIONALE , AIMS AND OBJECTIVES Utilizing information technology , such as Internet and cellphones , holds great promise in enhancing diabetic care . Yet few studies have examined the impact of cellphone technology on type 2 diabetics ' self-care . The primary aim of the study is to examine the feasibility of utilizing this technology to assist with diabetes self-care in a clinic population as well as its impact on clinical outcomes . METHODS Thirty patients with a diagnosis of type 2 diabetes at two Community Health Centers were r and omized to intervention or control . Intervention patients participated in a brief intervention and received tailored daily messages via cellphone prompting them to enhance their diabetic self-care behaviour . Patients at the control site continued with their st and ard diabetes self-management . RESULTS A mean improvement in HbA1c levels was apparent ( -0.1 , SD = 0.3 % ; P = 0.1534 ) in the intervention group , compared with a mean deterioration in the control ( 0.3 , SD = 1.0 % ; P = 0.3813 ) , yet without statistical significance . Self-efficacy scores improved significantly in the intervention group ( -0.5 , SD = 0.6 ; P = 0.0080 ) compared with no improvement in the control ( 0.0 , SD = 1.0 ; P = 0.9060 ) . Participants encountered numerous technological barriers when attempting to adhere to the intervention protocol . CONCLUSION The results indicate the intervention had a positive impact on some clinical outcome and self-efficacy . Although the technology appears feasible in a clinical setting technology must be made more user-friendly before a larger phase II trial is conducted Abstract We investigated the effectiveness of a workplace intervention program that utilized self-monitoring of daily salt excretion by an electronic salt sensor and sent personalized e-mail advice via cellular phone . Forty-one hypertensive male workers were assigned to intervention and control groups , then counseled together . Intervention group members were asked to measure daily salt excretion and received e-mail advice . After 4 weeks , a greater decrease of blood pressure ( BP ) was observed in the intervention group , with significant reductions to daily salt excretion and home BP . The new intervention program is considered useful for BP control among hypertensive workers BACKGROUND When performed effectively , cardiopulmonary resuscitation ( CPR ) by byst and ers reduces mortality due to sudden cardiac arrest . Telemedicine applications offer a means by which byst and ers can get specific instructions for h and ling the emergency situation . M-AID , a first aid application for mobile phones , uses an intelligent algorithm of ' yes ' or ' no ' questions to judge the ongoing situation and give the user detailed instructions . The aim of this study was to evaluate the benefit of this mobile phone application in a scenario of sudden cardiac arrest . METHODS One hundred and nineteen volunteers were assigned at r and om either to the test or the control group . All participants were confronted with the same scenario of acute coronary syndrome leading to cardiac arrest . The participants were either equipped with a mobile phone running the software ( test group ) or had to h and le the situation without support ( control group ) . The participants received a certain amount of credits for each action taken according to a pre-defined protocol and these credits were added to a score and compared between the groups . Participants were divided into subgroups according to their medical and technical experience . RESULTS The test group generally achieved a slightly higher average score that was not statistically significant ( 21.11 versus 19.97 ; p=0.302 ) . In contrast , the performance of the individuals in the control group was significantly faster ( 2.41 min versus 4.24 min ; p<0.001 ) . Use of the mobile phone software did not enhance the chance of survival . Subgroup analysis showed that experienced mobile phone users performed significantly better than non-experienced individuals , but not as well as participants with advanced first aid knowledge . CONCLUSIONS Experience in the use of mobile phones is a prerequisite for the efficient use of the tested M-AID version . This application can not replace skills acquisition by practical training . In a subgroup with experience in mobile phone use and basic knowledge in CPR , the device improved performance of CPR Please cite this paper as : Lund S , Hemed M , Nielsen B , Said A , Said K , Makungu M , Rasch V. Mobile phones as a health communication tool to improve skilled attendance at delivery in Zanzibar : a cluster‐r and omised controlled trial . BJOG 2012;119:1256–1264 Objective To carry out a r and omised controlled trial on the effect of a new method of health promotion — email and mobile phone text messages ( short messaging service (SMS))—on young people 's sexual health . Methods 994 people aged 16–29 were recruited at a music festival to a non-blinded r and omised controlled trial . Participants were r and omised to either receive sexual health promotion messages ( n=507 ) or the control group ( n=487 ) . The 12-month intervention included SMS ( catchy sexually transmissible infections prevention slogans ) and emails . Participants completed question naires at the festival at baseline and online after 3 , 6 and 12 months . Outcomes were differences between the control and intervention groups in health-seeking behaviour , condom use with risky partners ( new or casual partners or two or more partners within 12 months ) and STI knowledge . Results 337 ( 34 % ) completed all three follow-up question naires and 387 ( 39 % ) completed the final question naire . At 12 months , STI knowledge was higher in the intervention group for both male ( OR=3.19 95 % CI 1.52 to 6.69 ) and female subjects ( OR=2.36 95 % CI 1.27 to 4.37 ) . Women ( but not men ) in the intervention group were more likely to have had an STI test ( OR=2.51 , 95 % CI 1.11 to 5.69 ) , or discuss sexual health with a clinician ( OR=2.92 , 95 % CI 1.66 to 5.15 ) than their control counterparts . There was no significant impact on condom use . Opinions of the messages were favourable . Conclusion This simple intervention improved STI knowledge in both sexes and STI testing in women , but had no impact on condom use . SMS and email are low cost , popular and convenient , and have considerable potential for health promotion . Clinical trial registration number Australian Clinical Trials Registry - ACTRN12605000760673 Background Previous interventions have shown promising results using theory-based podcasts to deliver a behavioral weight-loss intervention . Objective The objective of our study was to examine whether a combination of podcasting , mobile support communication , and mobile diet monitoring can assist people in weight loss . Methods In this 6-month , minimal contact intervention , overweight ( n = 96 , body mass index 32.6 kg/m2 ) adults were recruited through television advertisements and email listservs and r and omly assigned to Podcast-only or Podcast+Mobile groups . Both groups received 2 podcasts per week for 3 months and 2 minipodcasts per week for months 3–6 . In addition to the podcasts , the Podcast+Mobile group was also instructed to use a diet and physical activity monitoring application ( app ) on their mobile device and to interact with study counselors and other participants on Twitter . Results Weight loss did not differ by group at 6 months : mean –2.7 % ( SD 5.6 % ) Podcast+Mobile , n = 47 ; mean –2.7 % ( SD 5.1 % ) Podcast , n = 49 ; P = .98 . Days/week of reported diet monitoring did not differ between Podcast+Mobile ( mean 2.3 , SD 1.9 days/week ) and Podcast groups ( mean 1.9 , SD 1.7 days/week ; P = .28 ) but method of monitoring did differ . Podcast+Mobile participants were 3.5 times more likely than the Podcast group to use an app to monitor diet ( P = .01 ) , whereas the majority of Podcast participants reported using the Web ( 14/41 , 34 % ) or paper ( 12/41 , 29 % ) . There were more downloads per episode in the Podcast+Mobile group ( 1.4/person ) than in the Podcast group ( 1.1/person ; P < .001 ) . The number of podcasts participants reported downloading over the 6-month period was significantly moderately correlated with weight loss in both the Podcast+Mobile ( r = –.46 , P = .001 ) and the Podcast ( r = –.53 , P < .001 ) groups . Podcast+Mobile participants felt more user control at 3 months ( P = .02 ) , but not at 6 months , and there was a trend ( P = .06 ) toward greater elaboration among Podcast+Mobile participants . There were significant differences in reported source of social support between groups . More Podcast participants relied on friends ( 11/40 , 28 % vs 4/40 , 10 % ; P = .045 ) whereas Podcast+Mobile participants relied on online sources ( 10/40 , 25 % vs 0/40 ; P = .001 ) . Conclusions Results confirm and extend previous findings showing a minimally intensive weight-loss intervention can be delivered via podcast , but prompting and mobile communication via Twitter and monitoring app without feedback did not enhance weight loss . Trial Registration Clinical trials.gov NCT01139255 ; http:// clinical trials.gov/ct2/show/NCT01139255 ( Archived by WebCite at http://www.webcitation.org/625OjhiDy Background : Low-income African-American adolescents suffer a disproportionate burden of asthma morbidity . Purpose : To evaluate the ability of our intervention , the Adolescents ’ Disease Empowerment and Persistency Technology ( ADEPT ) for asthma , to increase asthma knowledge in our target population . Methods : This was a 14-week ( 2-week run-in and 12-week treatment ) r and omized , double-blind , placebo-controlled pilot study in which 28 inner-city African-American adolescents with asthma , between 10 and 18 years of age , were r and omized to receive ( 1 ) celebrity asthma messages ( experimental group ) , or ( 2 ) general health messages ( control group ) between music tracks on an MP3 player . The asthma messages were recorded by famous athletes , musicians , and other celebrities popular among this group of teenagers . Asthma knowledge , assessed by the ZAP Asthma Knowledge instrament , was collected pre- and post-intervention . Results : Mean improvement in ZAP score was significantly higher in the experimental group ( 8.1 % , SD 7.2 % ) than the control group ( 0.4 % , SD 7.2 % ) ( p = 0.05 ) . Conclusion : These findings suggest that this may be an innovative and promising new approach to improving asthma outcomes in this difficult-to-reach population Home peak expiratory flow ( PEF ) measurement is recommended by asthma guidelines . In a 16-week r and omized controlled study on 16 subjects with asthma ( 24.6 6.5 years old , asthma duration small ze , Cyrillic 6 months ) , we examined Global System for Mobile Communications ( GSM ) mobile telephone short-message service ( SMS ) as a novel means of telemedicine in PEF monitoring . All subjects received asthma education , self-management plan , and st and ard treatment . All measured PEF three times daily and kept a symptom diary . In the study group , therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients . There was no significant difference between the groups in absolute PEF , but PEF variability was significantly smaller in the study group ( 16.12 + /- 6.93 % vs. 27.24 + /- 10.01 % , p = 0.049 ) . forced expiratory flow in 1 second ( FEV1 ; % predicted ) in the study group was slightly but significantly increased ( 81.25 + /- 17.31 vs. 77.63 + /- 14.80 , p = 0.014 ) and in the control group , unchanged ( 78.25 + /- 21.09 vs. 78.88 + /- 22.02 , p = 0.497 ) . Mean FEV1 was similar in the two groups both before and after the study . Controls had significantly higher scores for cough ( 1.85 + /- 0.43 vs. 1.42 + /- 0.28 , p < 0.05 ) and night symptoms ( 1.22 + /- 0.23 vs. 0.85 + /- 0.32 , p < 0.05 ) . There was no significant difference between the groups in daily consumption of inhaled medicine , forced vital capacity , or compliance . Per patient , per week , the additional cost of follow-up by SMS was Euros 1.67 ( equivalent to approximately $ 1.30 per 1 Euro ) , and SMS transmission required 11.5 minutes . Although a study group of 40 patients is needed for the follow-up study to achieve the power of 80 % within the 95 % confidence interval , we conclude that SMS is a convenient , reliable , affordable , and secure means of telemedicine that may improve asthma control when added to a written action plan and st and ard follow-up We compared the effectiveness of two media ( text messages and pamphlets ) in imparting health education to mothers of preschool children . Mothers and their children were r and omized into two groups . There were 72 mothers and their children in the pamphlet group and 71 in the text message group . The mothers were given health education by one of the two modes for four weeks . Knowledge , attitude and practice s of the mothers were assessed by a question naire pre- and post-intervention . Visible plaque scores of their children were also recorded pre- and post-intervention . There were significant improvements in knowledge ( P < 0.001 ) , attitude ( P < 0.001 ) and practice s ( P < 0.001 ) in both groups . There was also a significant reduction in visible plaque scores ( P < 0.001 ) in both groups . Text messaging was more effective than pamphlets in improving knowledge , attitude and practice s of mothers , but the comparative reduction in plaque score between groups was not significant . Text messaging appears to be an effective means of imparting oral health education INTRODUCTION The objective of this study was to test the feasibility and acceptance of an intervention using text messaging ( short message service [ SMS ] ) for continuous individual support of smoking cessation in young adults . Additionally , the optimal feedback intensity was investigated , and short-term efficacy of the intervention was explored . METHODS In a cafeteria of the University of Greifswald , 575 visitors were screened for smoking status and usage of text messaging . From these , 194 persons who fulfilled the inclusion criteria of daily smoking and weekly usage of SMS were invited for participation in an SMS-based intervention . From these , 174 ( 90 % ) consented to participate . The participants were r and omly allocated to one of three study groups : ( a ) control condition without intervention , ( b ) intervention with one weekly SMS feedback ( 1SMS ) , or ( c ) intervention with three weekly SMS feedbacks ( 3SMS ) . In study groups ( b ) and ( c ) , individualized SMS feedbacks were sent to the participants weekly , based on data from the baseline assessment and a weekly SMS assessment of the stages of change according to the transtheoretical model . Program use and acceptance were compared between the two intervention groups differing in support intensity . An exploration of the short-term efficacy of the program was conducted by comparing the three study groups at the end of the 3-month intervention program on smoking variables . RESULTS The median number of replies to the weekly SMS assessment s was 12.5 in the 1SMS group and 13.0 in the 3SMS group ( not significant ) . The acceptance of the program did not differ between the intervention groups . At post assessment , no significant differences between the three study groups emerged on the examined smoking variables . DISCUSSION The high participation and retention rates suggest that SMS-based smoking cessation interventions are attractive for young adults . Support intensity did not affect the acceptance of the program . Longer follow-up periods and larger sample s are required to obtain conclusive results about the efficacy of this intervention approach BACKGROUND Video games have received widespread application in health care for distraction and behavior modification therapy . Studies on the effect of cognitive distraction during the preoperative period are lacking . We evaluated the efficacy of an interactive distraction , a h and -held video game ( VG ) in reducing preoperative anxiety in children . METHODS In a r and omized , prospect i ve study of 112 children aged 4 - 12 years undergoing outpatient surgery , anxiety was assessed after admission and again at mask induction of anesthesia , using the modified Yale Preoperative Anxiety Scale ( mYPAS ) . Postoperative behavior changes were assessed with the Posthospital Behavior Question naire ( PHBQ ) . Patients were r and omly assigned to three groups : parent presence ( PP ) , PP+a h and -held VG , and PP+0.5 mg.kg-1 oral midazolam ( M ) given>20 min prior to entering the operating room . RESULTS There was a statistically significant increase in anxiety ( P<0.01 ) in groups M and PP at induction of anesthesia compared with baseline , but not in VG group . VG patients demonstrated a decrease in anxiety from baseline ( median change in mYPAS -3 ) , the difference compared with PP ( + 11.8 ) was significant ( P=0.04 ) . The change in anxiety in the M group ( + 7.3 ) was not statistically different from other groups . Sixty-three percent of patients in VG group had no change or decrease in anxiety after treatment , compared with 26 % in M group and 28 % in PP group ( P=0.01 ) . There was no difference in anxiety changes between female and male patients . CONCLUSIONS A h and -held VG can be offered to most children as a low cost , easy to implement , portable , and effective method to reduce anxiety in the preoperative area and during induction of anesthesia . Distraction in a pleasurable and familiar activity provides anxiety relief , probably through cognitive and motor absorption Treatment of severe haemophilia with factor concentrates is by self-infusion in the home . Adherence to record keeping on paper diaries is poor . A r and omized-controlled trial compared adherence with record keeping of paper diaries with h and -held computers . Forty-one individuals with severe haemophilia , were r and omized to h and -held computers ( n = 22 ) or paper diaries ( n = 19 ) and followed for 6 months . About 86.2 % ( 679 of 788 ) of infusions by patients in the computer group were in compliance with the data su bmi ssion schedule compared with only 48.3 % ( 358 of 741 ) of infusions by patients using paper diaries ( P < 0.0001 ) . The time intervals between infusions and the receipt of data were shorter in the computer group ( median 0.25 vs. 25 days respectively , P < 0.0001 ) . Reminder phone calls by the clinic were made less frequently to users of h and -held computers than to users of paper diaries ( median one vs. five times , P < 0.0001 ) . Accuracy of data was similar for both methods . Compliance with h and -held computers was superior to paper diaries . The clinic received data from h and -held computers mostly on the same day , and nurses could thereby provide clinical advice more effectively . Although h and -held computers did not result in increased accuracy , errors could be detected and corrected more rapidly . Electronic data can more easily be verified , analysed and summarized than that from paper diaries OBJECTIVE The main objective was to compare the satisfaction levels of antenatal care between healthy pregnant women who received short message service ( SMS ) via mobile phone for prenatal support , and those who did not . The second objective was to compare the confidence , anxiety levels and also pregnancy outcomes . DESIGN A r and omized controlled trial . MATERIAL AND METHOD 68 healthy pregnant women who attended the antenatal clinic and delivered at Siriraj Hospital , who met the inclusion criteria s between May 2007 and October 2007 , were enrolled and r and omly allocated into two r and om groups . The study group received two SMS messages per week from 28 weeks of gestation until giving birth . The other group was pregnant women who did not receive SMS . Both groups had the same antenatal and perinatal care . The satisfaction , confidence and anxiety scores were evaluated using a question naire at the postpartum ward . The pregnancy outcomes were also compared in these two groups . RESULTS The satisfaction levels of the women who received prenatal support in SMS messages , were significantly higher than those of who did not receive the messages both in the antenatal period ( 9.25 vs. 8.00 , p < 0.001 ) and during labor ( 9.09 vs. 7.90 , p = 0.007 ) . In the SMS using group , the confidence level was'higher ( 8.91 vs. 7.79 , p = 0.001 ) and the anxiety level was lower ( 2.78 vs. 4.93 , p = 0.002 ) than the control group n the antenatal period , however no diference in pregnancy outcomes were found . CONCLUSION The present study shows the higher satisfaction level of pregnant women who received SMS via mobile phone during their antenatal service when compared with the general antenatal care group . The study also show the higher confidence level and lower anxiety level in the antenatal period but no difference in pregnancy outcomes PURPOSE To assess the efficacy of a pharmacist-led , primary care-based , disease management program to improve cardiovascular risk factors and glycated hemoglobin ( A(1C ) ) levels in vulnerable patients with poorly controlled diabetes . METHODS A r and omized controlled trial of 217 patients with type 2 diabetes and poor glycemic control ( A(1C ) level > or=8.0 % ) was conducted at an academic general medicine practice from February 2001 to April 2003 . Intervention patients received intensive management from clinical pharmacists , as well as from a diabetes care coordinator who provided diabetes education , applied algorithms for managing glucose control and decreasing cardiovascular risk factors , and addressed barriers to care . Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider . Outcomes were recorded at baseline and at 6 and 12 months . Primary outcomes included blood pressure , A(1C ) level , cholesterol level , and aspirin use . Secondary outcomes included diabetes knowledge , satisfaction , use of clinical services , and adverse events . RESULTS For the 194 patients ( 89 % ) with 12-month data , the intervention group had significantly greater improvement than did the control group for systolic blood pressure ( -9 mm Hg ; 95 % confidence interval [ CI ] : -16 to -3 mm Hg ) and A(1C ) level ( -0.8 % ; 95 % CI : -1.7 % to 0 % ) . Change in total cholesterol level was not significant . At 12 months , aspirin use was 91 % in the intervention group versus 58 % among controls ( P < 0.0001 ) . Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients . There were no significant differences in use of clinical services or adverse events . CONCLUSION Our comprehensive disease management program reduced cardiovascular risk factors and A(1C ) levels among vulnerable patients with type 2 diabetes and poor glycemic control BACKGROUND We have developed a winter forecasting service to predict when patients with COPD are at higher risk of an exacerbation and alert them via an automated telephone call . AIMS To assess the effect of the service and its ability to predict periods of increased risk . METHODS A 4-month prospect i ve r and omised controlled trial using clinical criteria and the EXACT PRO question naire to identify exacerbations . Patients were r and omly allocated to receive alert calls . All patients completed a diary including the EXACT PRO question naire on a BlackBerry Smartphone each day . They were contacted and assessed if they appeared to be exacerbating . RESULTS 79 patients participated , 40 received alert calls . The exacerbation frequency per patient per week was significantly greater during periods of predicted high risk ( 0.086 ± 0.010 v 0.055 ± 0.010 ) . The exacerbation frequency ( ± st and ard error of the mean , SEM ) in patients receiving alert calls was lower ( 0.95 ± 0.27 v 1.17 ± 0.29 ) but this was not statistically significant . Fewer patients receiving alert calls had one or more EXACT event compared to the controls ( 34 % v 53 % , p=0.11 ) , their duration was shorter ( 8.2 ± 2.0 v10.1 ± 1.9 days , p=0.481 ) and they were less severe ( AUC 65 ± 21 v 115 ± 22 , p=0.118 ) . There were no significant differences in the mean change ( ± SEM ) in SGRQ scores between the groups . CONCLUSIONS The ability of the forecast to predict high risk periods was confirmed unequivocally . Alert calls appeared to reduce the frequency and severity of exacerbations but these effects did not reach statistical significance , perhaps because of the number of participants , lower than expected exacerbation rates , and the fact that there was contact with patients in both groups whenever they appeared to be exacerbating OBJECTIVE Lifestyle programs can reduce the level of overweight in children ; however , maintenance results and adherence to treatment are difficult to achieve . New technologies , such as the Short Message Service ( SMS ) , might be a promising tool for enhancing interventions . The effect of an SMS approach aim ed at improving treatment results and reducing dropout rates in a pediatric lifestyle intervention , is explored . METHOD Overweight and obese children ( N = 141 ; age 7 - 12 years ) participating in a lifestyle program were r and omly assigned to an intervention group receiving an SMS Maintenance Treatment ( SMSMT ) for 38 weeks ( n = 73 ) or to a control group receiving no SMSMT ( n = 68 ) . Children were asked to send weekly self-monitoring data on exercise , eating behavior , and emotional well-being . In return , they received tailored feedback messages . A differential decrease in BMI was analyzed with repeated measures ANOVA and dropout with logistic regression analysis . RESULTS We found no significant difference in BMI decrease between the two groups after 12 months ; however , we showed that the SMSMT group had 3.25 times less probability of dropping out after 1 year ( p = .01 ) than controls . In the first 3 months of SMSMT , the SMSMT completers sent 0.80 SMSs per week , which reduced to 0.50 SMSs in the final 3 months . Younger children sent more SMSs ( p = .03 ) . CONCLUSIONS These results indicate that SMSMT is effective in reducing dropout rates from a pediatric lifestyle intervention . Future research should examine the effectiveness of SMSMT on weight management and related psychosocial variables OBJECTIVE To determine the effectiveness of cell phone wireless text messaging for improving adherence to a healthy behaviour . DESIGN A r and omised , unblinded , controlled trial was conducted with 102 subjects , 18 years or older , each having a cell phone and willing to take 1 vitamin C pill per day for 1 month for preventive reasons . Intervention group participants received text messaging reminders and were asked to acknowledge receiving their messages after taking the vitamins , whereas control group subjects had no text messaging activity . MEASUREMENTS Self-reported adherence and the number of participant text messages acknowledging vitamins taken . RESULTS Both groups reported an increased adherence after the trial : by 246 % for the intervention group and by 131 % for the control group . There was a non-significant difference between the two groups at endpoint : an average difference of 0.8 between the number of pills missed in the last week of the trial ( 2.5 out of 7 in the intervention and 3.3 out of 7 in the control group ) with a power of 0.54 . The study revealed a significant correlation ( coefficient=-0.352 , sig.=0.01 ) between the average number of text messaging acknowledgements sent by the intervention group participants and the number of pills they reported missed during the last week of the trial . CONCLUSION This was a small r and omised controlled trial with inconclusive but encouraging results . It suggests a new approach in addressing insufficient adherence in outpatient conditions and shows that the use of information technology tools for compliance warrants further research Objective : To evaluate the capability of DietMatePro , a PDA-based dietary assessment program , to monitor dietary intake and to improve adherence to a dietary regimen . Design : R and omized controlled trial . Subjects . Overweight and obese ( Body Mass Index ( BMI ) 25–40 ) participants without dietary restrictions . Intervention : Participants ( n = 174 ) were r and omized to record usual dietary intake using either DietMatePro or a paper food diary for one week to compare concordance with 24-hr recall . At the week 1 visit , participants were individually counseled to follow the diet recommendations of the Ornish Prevention Diet for three weeks and continue monitoring food intake using the assigned method to estimate adherence to the intervention by monitoring condition . Outcome Measures : Spearman correlations between week 1 24-hr recall and the assigned recording method were compared to assess validity . Mean pre-post changes in intake measured by 24-hr recall were compared according to monitoring condition to measure adherence to the Ornish diet . Results : Correlations of energy and nutrient values reported on the food label ranged from 0.41 to 0.71 for the DietMatePro condition versus 0.63 to 0.83 for the paper-based diary . Diet adherence was higher among DietMatePro ( 43 % ) compared to the paper diary ( 28 % ) group ( p = 0.039 ) . Conclusions /Applications : DietMatePro does not appear to produce more valid data than paper-based approaches . DietMatePro may improve adherence to dietary regimens compared to paper-based methods BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant Aim : To conduct a pilot r and omised controlled trial of mobile phone-based smoking cessation support intervention for the UK population . Design : R and omised controlled trial ( txt2stop ) . Setting : Community . Participants : 200 participants responding to radio , poster and leaflet-based promotions regarding the trial . Main outcome measures : The response rate for the outcome measures planned for the main trial . Participants ’ qualitative responses to open-ended questions about the intervention content . Secondary outcomes were the outcomes planned for the main trial including the point prevalence of self-reported smoking at 4 weeks and pooled effect estimate for the short-term results for the STOMP and txt2stop trials . Results : The response rate at 4 weeks was 96 % and at 6 months was 92 % . The results at 4 weeks show a doubling of self-reported quitting relative risk ( RR ) 2.08 ( 95 % CI 1.11 to 3.89 ) , 26 % vs 12 % . The pooled effect estimate combining txt2stop and a previous New Zeal and trial in the short term is RR 2.18 ( 95 % CI 1.79 to 2.65 ) . Conclusions : Mobile phone-based smoking cessation is an innovative means of delivering smoking cessation support , which doubles the self-reported quit rate in the short term . It could represent an important , but as yet largely unused , medium to deliver age-appropriate public health measures . The long-term effect of this mobile phone-based smoking cessation support will be established by a large r and omised controlled trial currently in recruitment BACKGROUND Poor adherence to asthma treatment is a well-recognised challenge and is associated with increased morbidity , mortality and consumption of health care re sources . This study examined the impact of receiving a daily text message reminder on one 's cell phone on adherence to asthma treatment . METHODS A total of 26 subjects aged 18 - 45 years , with a clinical history of asthma and a positive methacholine challenge test ( PD(20)<or=4micromol ) were r and omised to receive , or to not receive , a daily short message service ( SMS ) reminder on their cell phone to take their anti-asthmatic medication . Inhaled corticosteroids to last for eight weeks and a prescription for four additional weeks were given to the subjects . The primary outcome was adherence to asthma treatment . Secondary outcomes were reimbursement of asthma medication , and change in exhaled nitric oxide levels , lung function , and airway responsiveness . RESULTS The absolute difference in mean adherence rate between the two groups after 12 weeks was 17.8 % , 95 % CI ( 3.2 - 32.3 % ) , p=0.019 . No significant differences were observed between the two r and omisation groups for the secondary outcomes . CONCLUSION Daily text message reminders are already after a short period of observation associated with increased adherence to anti-asthmatic medication INTRODUCTION Study aims were to assess the feasibility and acceptability of a tailored self-help smoking cessation intervention for pregnant smokers ( MiQuit ) . Secondary aims were to assess whether MiQuit affected cognitive determinants of quitting and to provide a range of potential effect sizes of the intervention effect on smoking abstinence . METHODS A r and omized controlled trial was undertaken in which pregnant smokers were allocated to either receive MiQuit , a tailored self-help leaflet followed by an 11-week program of tailored text messages , or to a control group , receiving a nontailored self-help leaflet . Participants were 207 pregnant smokers identified by community midwives across 7 NHS Trusts ( United Kingdom ) . At 3-month follow-up , intervention acceptability , cognitive determinants of quitting , and smoking outcomes ( self-reported and cotinine-vali date d 7-day point prevalence abstinence ) were assessed . RESULTS Feasibility : 94 % ( 95 % CI 89%-99 % ) of MiQuit participants reported receiving both intervention components . Acceptability : 9 % ( 95 % CI 4%-15 % ) of MiQuit participants opted to discontinue the text messages . Mechanism : compared with controls , MiQuit participants were more likely to set a quit date ( p = .049 ) and reported higher levels of self-efficacy ( p = .024 ) , harm beliefs ( p = .052 ) , and determination to quit ( p = .019 ) . Potential efficacy : self-reported abstinence-MiQuit 22.9 % , control 19.6 % ; odds ratio ( OR ) = 1.22 , 95 % CI 0.62 - 2.41 ; cotinine-vali date d abstinence-MiQuit 12.5 % , control 7.8 % ; OR = 1.68 , 95 % CI 0.66 - 4.31 . CONCLUSIONS Delivering tailored smoking cessation support to pregnant smokers via leaflet and text message is feasible and acceptable . The positive effects of MiQuit on cognitive determinants and the likelihood of setting a quit date are encouraging . A larger efficacy trial is warranted STUDY OBJECTIVE Given the ubiquitous presence of cellular telephones , we seek to evaluate the extent to which prerecorded audio cardiopulmonary resuscitation ( CPR ) instructions delivered by a cell telephone will improve the quality of CPR provided by untrained and trained lay rescuers . METHODS We r and omly assigned both previously CPR trained and untrained volunteers to perform CPR on a manikin for 3 minutes with or without audio assistance from a cell telephone programmed to provide CPR instructions . We measured CPR quality metrics-pauses ( ie , no flow time ) , compression rate ( minute ) , depth ( millimeters ) , and h and placement ( percentage correct)-across the 4 groups defined by being either CPR trained or untrained and receiving or not receiving cell telephone CPR instructions . RESULTS There was no difference in CPR measures for participants who had or had not received previous CPR training . Participants using the cell telephone aid performed better compression rate ( 100/minute [ 95 % confidence interval ( CI ) 97 to 103/minute ] versus 44/minute [ 95 % CI 38 to 50/minute ] ) , compression depth ( 41 mm [ 95 % CI 38 to 44 mm ] versus 31 mm [ 95 % CI 28 to 34 mm ] ) , h and placement ( 97 % [ 95 % CI 94 % to 100 % ] versus 75 % [ 95 % CI 68 % to 83 % ] correct ) , and fewer pauses ( 74 seconds [ 95 % CI 72 to 76 seconds ] versus 89 seconds [ 95 % CI 80 to 98 seconds ] ) compared with participants without the cell telephone aid . CONCLUSION A simple audio program that can be made available for cell telephones increases the quality of byst and er CPR in a manikin simulation PURPOSE : Efficient ways are needed to implement the secondary prevention ( SP ) of coronary heart disease . Because few studies have investigated Web-based SP programs , our aim was to determine the usefulness of a new Web-based telemonitoring system , connecting patients provided with self-measurement devices and care managers via mobile phone text messages , as a tool for SP . METHODS : A single-blind , r and omized controlled , clinical trial of 203 acute coronary syndrome ( ACS ) survivors , was conducted at a hospital in Madrid , Spain . All patients received lifestyle counseling and usual-care treatment . Patients in the telemonitoring group ( TMG ) sent , through mobile phones , weight , heart rate , and blood pressure ( BP ) weekly , and capillary plasma lipid profile and glucose monthly . A cardiologist accessed these data through a Web interface and sent recommendations via short message service . Main outcome measures were BP , body mass index ( BMI ) , smoking status , low-density lipoprotein-cholesterol ( LDL-c ) , and glycated hemoglobin A1c ( HbA1c ) . RESULTS : At 12-month followup , TMG patients were more likely ( RR = 1.4 ; 95 % CI = 1.1−1.7 ) to experience improvement in cardiovascular risk factors profile than control patients ( 69.6 % vs 50.5 % , P = .010 ) . More TMG patients achieved treatment goals for BP ( 62.1 % vs 42.9 % , P = .012 ) and HbA1c ( 86.4 % vs 54.2 % , P = .018 ) , with no differences in smoking cessation or LDL-c . Body mass index was significantly lower in TMG ( −0.77 kg/m2 vs + 0.29 kg/m2 , P = .005 ) . CONCLUSIONS : A telemonitoring program , via mobile phone messages , appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention , especially for overweight patients OBJECTIVE To examine acceptability , attrition , adherence , and preliminary efficacy of mobile phone short message service ( SMS ; text messaging ) for monitoring healthful behaviors in children . DESIGN All r and omized children received a brief psychoeducational intervention . They then either monitored target behaviors via SMS with feedback or via paper diaries ( PD ) or participated in a no-monitoring control ( C ) for 8 weeks . SETTING University of North Carolina at Chapel Hill . PARTICIPANTS Fifty-eight children ( age 5 - 13 ) and parents participated ; 31 completed ( SMS : 13/18 , PD : 7/18 , C : 11/22 ) . INTERVENTION Children and parents participated in a total of 3 group education sessions ( 1 session weekly for 3 weeks ) to encourage increasing physical activity and decreasing screen time and sugar-sweetened beverage consumption . MAIN OUTCOME MEASURES Treatment acceptability , attrition , and adherence to self-monitoring . ANALYSIS Descriptive statistics and nonparametric tests were used to analyze differences across time and group . RESULTS Children in SMS had somewhat lower attrition ( 28 % ) than both PD ( 61 % ) and C ( 50 % ) , and significantly greater adherence to self-monitoring than PD ( 43 % vs 19 % , P < .02 ) . CONCLUSIONS AND IMPLICATION S Short message service may be a useful tool for self-monitoring healthful behaviors in children , although the efficacy of this approach needs further study . Implication s suggest that novel technologies may play a role in improving health We conducted a r and omized controlled trial using mobile health technology in an ethnically diverse sample of 137 patients with complicated diabetes . Patients in the intervention group ( n = 72 ) were trained to measure their blood glucose with a sensor which transmitted the readings to a mobile phone via a Bluetooth wireless link . Clinicians were then able to examine and respond to the readings which were viewed with a web-based application . Patients in the control arm of the study ( n = 65 ) did not transmit their readings and received care with their usual doctor in the outpatient and /or primary care setting . The mean follow-up period was 9 months in each group . The default rate was higher in the patients in the intervention arm due to technical problems . In an intention-to-treat analysis there were no differences in HbA1c between the intervention and control groups . In a sub-group analysis of the patients who completed the study , the telemonitoring group had a lower HbA1c than those in the control group : 7.76 % and 8.40 % , respectively ( P = 0.06 ) INTRODUCTION We developed a cardiopulmonary resuscitation ( CPR ) instruction programme using motion capture animation integrated into cellular phones . We compared the effectiveness of animation-assisted CPR instruction with dispatcher-assisted instruction in participants with no previous CPR training . METHODS This study was a single blind cluster r and omized trial . Participants were allocated to either animation-assisted CPR ( AA-CPR ; 8 clusters , 44 participants ) group or dispatcher-assisted CPR ( DA-CPR ; 8 clusters , 41 participants ) . The overall performance and time of each step of CPR cycle were recorded on a checklist by 3 assessors . The objective performances were evaluated using the Resusci Anne SkillReporter Manikin . Differences between the groups were compared using an independent t-test adjusted for the effect of clustering . RESULTS The AA-CPR group had a significantly better checklist score ( p<0.001 ) and time to completion of 1 CPR cycle ( p<0.001 ) than the DA-CPR group . In an objective assessment of psychomotor skill , the AA-CPR group demonstrated more accurate h and positioning ( 68.8+/-3.6 % , p=0.033 ) and compression rate ( 72.4+/-3.7 % , p=0.015 ) than DA-CPR group . However , the accuracy of compression depth ( p=0.400 ) , ventilation volume ( p=0.977 ) and flow rate ( p=0.627 ) were below 30 % in both groups . CONCLUSION Audiovisual animated CPR instruction through a cellular phone result ed in better scores in checklist assessment and time interval compliance in participants without CPR skill compared to those who received CPR instructions from a dispatcher ; however , the accuracy of important psychomotor skill measures was unsatisfactory in both groups OBJECTIVE Byst and er cardiopulmonary resuscitation ( CPR ) has shown to significantly improve the survival of cardiac-arrest victims . Dispatcher assistance increases the number of byst and ers who perform CPR , but the quality of CPR remains unsatisfactory . This study was conducted to assess the effect of video coaching on the performance of CPR by untrained volunteers when compared with traditional audio instruction in simulated cardiac arrests . METHODS Adult volunteers were r and omised to receive audio-assisted instructions ( audio group=39 ) , or video-demonstrated instructions ( video group=39 ) via cellular phones on how to perform chest compressions on mannequins . Then , the volunteers ' performances were video-recorded . The quality of CPR was evaluated by review ing the videos and mannequin reports . RESULTS For the video group , the chest compression rate was more optimal ( 99.5min(-1 ) vs. 77.4min(-1 ) , P<0.01 ) and the time from the initial phone call to the first compressions was shorter ( 184s vs. 211s , P<0.01 ) . The depth of compressions was deeper in the audio group ( 31.3 mm vs. 27.5 mm , P=0.21 ) , but neither group performed the recommended depth of compression . The h and positions for compression were more appropriate in the video group ( 71.8 % vs. 43.6 % , P=0.01 ) . As many as 71.8 % of the video group had no ' h and s-off ' events when performing compression ( vs. 46.2 % for the audio group , P=0.02 ) . CONCLUSIONS Instructions from the dispatcher , along with a video demonstration of CPR , improved the time to initiate compression , the compression rate and the correct h and positioning . It also reduced the ' h and s-off ' events during CPR . However , emphasised instructions by video may be needed to increase the depth of compressions |
11,369 | 29,435,331 | Conclusions Indirect comparison of alternative azacitidine dosing regimens in MDS and AML shows a benefit for the 7-day regimen in attaining ORR . | Background 5-Azacitidine administered as a 7-day dosing regimen ( 7–0 - 0 ) is approved in high risk IPSS myelodysplastic syndrome ( MDS ) patients .
Alternative regimens such as a 5-day ( 5–0 - 0 ) or 7-day with a weekend break ( 5–2 - 2 ) are commonly used .
No r and omized controlled trial has been done directly comparing all three dosing regimens .
The objective of this study was to compare the efficacies of the 5–0 - 0 , 5–2 - 2 , and 7–0 - 0 regimens in MDS and AML . | Background To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of r and omized trials , we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery . Methods Using a cost-effectiveness approach from a clinical perspective ( i.e. risk benefit analysis ) we compared thromboprophylaxis with warfarin , low molecular weight heparin , unfractionated heparin , fondaparinux or ximelagatran in patients undergoing major orthopedic surgery , with sub-analyses according to surgery type . Proportions and variances of events defining risk ( major bleeding ) and benefit ( thrombosis averted ) were obtained through a meta- analysis and used to define beta distributions . Monte Carlo simulations were conducted and used to calculate incremental risks , benefits , and risk-benefit ratios . Finally , net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds , with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding . Results The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery , since ximelagatran was superior in total knee replacement but not in total hip replacement . Conclusions Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of r and omized trials with multiple arms by determining the option with the best risk-benefit profile . It can be helpful in clinical decision making since it incorporates risk , benefit , and personal risk acceptance PURPOSE Within the last two decades , a new underst and ing of the biology of myelodysplastic syndrome ( MDS ) has developed . With this underst and ing , new classification systems , such as the WHO diagnostic criteria , and the International Prognostic Scoring System and response criteria guidelines reported by the International Working Group ( IWG ) have been developed . We report the combined results of three previously reported clinical trials ( n = 309 ) with azacitidine using the WHO classification system for MDS and acute myeloid leukemia ( AML ) and IWG criteria for response . PATIENTS AND METHODS Data from three sequential Cancer and Leukemia Group B trials with azacitidine were recollected and reanalyzed as part of the New Drug Application process . The trials were conducted with either intravenous or subcutaneous azacitidine ( 75 mg/m2/d for 7 days every 28 days ) . RESULTS Complete remissions were seen in 10 % to 17 % of azacitidine-treated patients ; partial remissions were rare ; 23 % to 36 % of patients had hematologic improvement ( HI ) . The median number of cycles to first response was three , and 90 % of responses were seen by cycle 6 . Using current WHO criteria , 103 patients had AML at baseline ; 35 % to 48 % had HI or better responses . The median survival time for the 27 AML patients r and omly assigned to azacitidine was 19.3 months compared with 12.9 months for the 25 patients assigned to observation . Furthermore , azacitidine did not increase the rate of infection or bleeding above the rate caused by underlying disease . CONCLUSION Azacitidine provides important clinical benefits for patients with high-risk MDS Acute myeloid leukemia ( AML ) patients aged ≥60 years tolerate st and ard induction chemotherapy poorly . Therapy with azacitidine at a dose of 75 mg/m2/day for 7 days appears to be better tolerated , and is approved by the Food and Drug Administration ( FDA ) for the treatment of elderly AML patients with bone marrow ( BM ) blast counts of 20–30 % . Here , we report the results of a prospect i ve , phase 2 , open‐label study that evaluated the tolerability and efficacy of a 5‐day regimen of single‐agent subcutaneous azacitidine 100 mg/m2/day administered every 28 days in 15 elderly patients with newly diagnosed AML , 14 of whom had BM blast counts > 30 % . The overall response rate was 47 % . Complete remission , partial remission , and hematologic improvement were achieved by 20 , 13 , and 13 % of patients , respectively . Median overall survival was 355 days for the entire cohort , and 532 days for responders . Median time to best response was 95 days , and median treatment duration was 198 days ( range = 13–724 days ) . Grade 3–4 hematologic toxicities comprised predominantly febrile neutropenia ( 40 % ) and thrombocytopenia ( 20 % ) . Febrile neutropenia was the most common cause of hospitalization . Nonhematologic toxicities , consisting of injection‐site skin reactions and fatigue ( Grade s 1–2 ) , occurred in 73 % ( n = 11 ) of patients . No treatment‐related deaths occurred during the study . The dose and schedule of therapy remained constant in all but four patients . The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m2/day for 5 days every 28 days is a feasible , well‐tolerated , and effective alternative to st and ard induction chemotherapy in elderly patients with AML Abstract This phase II trial treated elderly or frail patients with acute myeloid leukemia ( AML ) with single-agent subcutaneous azacytidine at 100 mg/m2 , on 5 of 28 days for up to six cycles . Treatment was stopped for lack of response , or continued to progression in responders . The primary endpoint was response within 6 months . A response rate ≥ 34 % was considered a positive trial outcome . From September 2008 to April 2010 , 45 patients from 10 centers ( median age 74 [ 55–86 ] years ) were accrued . Patients received four ( 1–21 ) cycles . Best response was complete response/complete response with incomplete recovery of neutrophils and /or platelets ( CR/CRi ) in eight ( 18 % ; 95 % confidence interval [ CI ] : 8–32 % . ) , 0 ( 0 % ) partial response ( PR ) , seven ( 16 % ) hematologic improvement , 17 ( 38 % ) stable disease . Three non-responding patients stopped treatment after six cycles , 31 patients stopped early and 11 patients continued treatment for 8–21 cycles . Adverse events ( grade ≥ III ) were infections ( n = 13 ) , febrile neutropenia ( n = 8) , thrombocytopenia ( n = 7 ) , dyspnea ( p = 6 ) , bleeding ( n = 5 ) and anemia ( n = 4 ) . Median overall survival was 6 months . Peripheral blood blast counts , grouped at 30 % , had a borderline significant association with response ( p = 0.07 ) . This modified azacytidine schedule is feasible for elderly or frail patients with AML in an outpatient setting with moderate , mainly hematologic , toxicity and response in a proportion of patients , although the primary objective was not reached The myelodysplastic syndromes ( MDSs ) are heterogeneous with respect to clinical characteristics , pathologic features , and cytogenetic abnormalities . This heterogeneity is a challenge for evaluating response to treatment . Therapeutic trials in MDS have used various criteria to assess results , making cross- study comparisons problematic . In 2000 , an International Working Group ( IWG ) proposed st and ardized response criteria for evaluating clinical ly significant responses in MDS . These criteria included measures of alteration in the natural history of disease , hematologic improvement , cytogenetic response , and improvement in health-related quality of life . The relevance of the response criteria has now been vali date d prospect ively in MDS clinical trials , and they have gained acceptance in research studies and in clinical practice . Because limitations of the IWG criteria have surfaced , based on practical and reported experience , some modifications were warranted . In this report , we present recommendations for revisions of some of the initial criteria Azacitidine 's efficacy in therapy-related myeloid neoplasms ( t-MN ) has not been well-studied . In our retrospective review of 84 t-MN patients treated with azacitidine , median overall survival ( OS ) was 14.5 months and overall response rate was 43 % , including 11 % complete remission , 4 % marrow complete remission , and 11 % partial remission . In patients who underwent allogeneic transplant ( 25 % ) , median OS was 19.2 versus 12.8 months ( P=0.023 ) for those who did not . Response rates were comparable to those reported for de novo myelodysplastic syndrome . When we analyzed outcomes according to five scoring systems , only the Global MD And erson Risk Model predicted survival with statistical significance The phase III AZA-001 study established that azacitidine significantly improves overall survival compared with conventional care regimens ( hazard ratio 0.58 [ 95 % confidence interval 0.43–0.77 ] , P<0.001 ) . This analysis was conducted to investigate the relationship between treatment response and overall survival . AZA-001 data were analyzed in a multivariate Cox regression analysis with response as a time-varying covariate . Response categories were “ Overall Response ” ( defined as complete remission , partial remission , or any hematologic improvement ) and “ Stable Disease ” ( no complete or partial remission , hematologic improvement , or progression ) or “ Other ” ( e.g. disease progression ) . Achieving an Overall Response with azacitidine reduced risk of death by 95 % compared with achieving an Overall Response with the conventional care regimens ( hazard ratio 0.05 [ 95%CI : 0.01–0.43 ] , P=0.006 ) . Sensitivity analyses indicated that significantly improved overall survival remained manifest for patients with a hematologic improvement who had never achieved complete or partial remission ( hazard ratio 0.19 [ 95%CI : 0.08–0.46 ] , P<0.001 ) . Stable Disease in both azacitidine-treated and conventional care-treated patients was also associated with a significantly reduced risk of death ( hazard ratio 0.09 , [ 95%CI : 0.06–0.15 ] ; P<0.001 ) . These results demonstrate azacitidine benefit on overall survival compared with conventional care regimens in patients with higher-risk myelodysplastic syndromes who achieve hematologic response but never attain complete or partial remission , in addition to the survival advantage conferred by achievement of complete or partial remission . This study was registered with clinical trials.gov ( NCT00071799 ) This prospect i ve phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin ( Epo ) in transfusion-dependent patients with lower-risk myelodysplastic syndrome ( MDS ) . Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for > 8 weeks and a transfusion need of ⩾4 units over 8 weeks were included . Aza 75 mg m−2 d−1 , 5/28 days , was given for six cycles ; non-responding patients received another three cycles combined with Epo 60 000 units per week . Primary end point was transfusion independence ( TI ) . All patients underwent targeted mutational screen for 42 c and i date genes . Thirty enrolled patients received ⩾one cycle of Aza . Ten patients discontinued the study early , 7 due to adverse events including 2 deaths . Thirty-eight serious adverse events were reported , the most common being infection . Five patients achieved TI after six cycles and one after Aza+Epo , giving a total response rate of 20 % . Mutational screening revealed a high frequency of recurrent mutations . Although no single mutation predicted for response , SF3A1 ( n=3 ) and DNMT3A ( n=4 ) were only observed in non-responders . We conclude that Aza can induce TI in severely anemic MDS patients , but efficacy is limited , toxicity substantial and most responses of short duration . This treatment can not be generally recommended in lower-risk MDS . Mutational screening revealed a high frequency of mutations Hypomethylating agents , such as 5-azacitidine ( 5-AZA ) and 5-aza-2’-deoxycytidine ( decitabine ) , have recently been approved for the treatment of myelodysplastic syndromes ( MDS ) . Several r and omized trials have shown favorable results concerning response rate , survival , transformation to acute leukemia , and quality of life . In these trials , treatment was administered continuously until progression . In the retrospective study presented here , we evaluated the outcome of patients with higher risk MDS or secondary acute myeloid leukemia ( sAML ) treated with a limited number of 5-AZA cycles . A total of 32 patients received 5-AZA alone ( n = 30 ) or in combination with valproic acid and all-trans retinoic acid ( n = 2 ) . 5-AZA was administered subcutaneously at a fixed dose of 75 mg/m2 daily for 7 days and repeated every 28 days . 5-AZA was given for a median of four courses . Treatment was continued for two more cycles as consolidation in patients who had achieved complete remission ( CR ) , marrow CR , or stable disease with hematologic improvement . The overall response rate was 50 % according to the modified International Working Group criteria . Complete remissions were achieved in 15.6 % and stable disease in 34.4 % of patients . Peripheral blood counts normalized in 6.3 % of patients while hematologic improvement was achieved in 25 % . The median time to AML in responding patients was 45 weeks , while AML occurred after a median of 14 weeks in non-responding patients ( P = .038 ) . The median survival of all patients was 60 weeks ; the median survival of responders was 74 weeks compared with 26 weeks in non-responders ( P = .047 ) . In this retrospective analysis , 5-AZA was associated with a survival advantage in responding patients with higher risk MDS or sAML . These favorable results suggest that patients may benefit even from a limited number of courses of 5-AZA . A r and omized controlled clinical trial is required to prospect ively vali date these findings PURPOSE Azacitidine ( AZA ) is effective treatment for myelodysplastic syndromes ( MDS ) at a dosing schedule of 75 mg/m(2)/d subcutaneously for 7 days every 4 weeks . The initial phase of this ongoing multicenter , community-based , open-label study evaluated three alternative AZA dosing schedules without weekend dosing . PATIENTS AND METHODS MDS patients were r and omly assigned to one of three regimens every 4 weeks for six cycles : AZA 5 - 2 - 2 ( 75 mg/m(2)/d subcutaneously for 5 days , followed by 2 days no treatment , then 75 mg/m(2)/d for 2 days ) ; AZA 5 - 2 - 5 ( 50 mg/m(2)/d subcutaneously for 5 days , followed by 2 days no treatment , then 50 mg/m(2)/d for 5 days ) ; or AZA 5 ( 75 mg/m(2)/d subcutaneously for 5 days ) . RESULTS Of patients r and omly assigned to AZA 5 - 2 - 2 ( n = 50 ) , AZA 5 - 2 - 5 ( n = 51 ) , or AZA 5 ( n = 50 ) , most were French-American-British ( FAB ) lower risk ( refractory anemia [RA]/RA with ringed sideroblasts/chronic myelomonocytic leukemia with < 5 % bone marrow blasts , 63 % ) or RA with excess blasts ( 30 % ) , and 79 ( 52 % ) completed > or = six treatment cycles . Hematologic improvement ( HI ) was achieved by 44 % ( 22 of 50 ) , 45 % ( 23 of 51 ) , and 56 % ( 28 of 50 ) of AZA 5 - 2 - 2 , AZA 5 - 2 - 5 , and AZA 5 arms , respectively . Proportions of RBC transfusion-dependent patients who achieved transfusion independence were 50 % ( 12 of 24 ) , 55 % ( 12 of 22 ) , and 64 % ( 16 of 25 ) , and of FAB lower-risk transfusion-dependent patients were 53 % ( nine of 17 ) , 50 % ( six of 12 ) , and 61 % ( 11 of 18 ) , respectively . In the AZA 5 - 2 - 2 , AZA 5 - 2 - 5 , and AZA 5 groups , 84 % , 77 % , and 58 % , respectively , experienced > or = 1 grade 3 to 4 adverse events . CONCLUSION All three alternative dosing regimens produced HI , RBC transfusion independence , and safety responses consistent with the currently approved AZA regimen . These results support AZA benefits in transfusion-dependent lower-risk MDS patients Epidemiologic studies of disease often produce inconclusive or contradictory results due to small sample sizes or regional variations in the disease incidence or the exposures . To clarify these issues , research ers occasionally pool and reanalyse original data from several large studies . In this paper we explore the use of a two-stage r and om-effects model for analysing pooled case-control studies and undertake a thorough examination of bias in the pooled estimator under various conditions . The two-stage model analyses each study using the model appropriate to the design with study -specific confounders , and combines the individual study -specific adjusted log-odds ratios using a linear mixed-effects model ; it is computationally simple and can incorporate study -level covariates and r and om effects . Simulations indicate that when the individual studies are large , two-stage methods produce nearly unbiased exposure estimates and st and ard errors of the exposure estimates from a generalized linear mixed model . By contrast , joint fixed-effects logistic regression produces attenuated exposure estimates and underestimates the st and ard error when heterogeneity is present . While bias in the pooled regression coefficient increases with inter study heterogeneity for both models , it is much smaller using the two-stage model . In pooled analyses , where covariates may not be uniformly defined and coded across studies , and occasionally not measured in all studies , a joint model is often not feasible . The two-stage method is shown to be a simple , valid and practical method for the analysis of pooled binary data . The results are applied to a study of reproductive history and cutaneous melanoma risk in women using data from ten large case-control studies Abstract The safety and efficacy of azacitidine ( 5-day schedule ) were assessed in a multicenter study in 40 patients ( median age 72 years ) with acute myeloid leukemia ( AML ) medically unfit for ( n = 20 ) or resistant to chemotherapy ( n = 20 ) from April to October 2008 . Median marrow blasts were 42 % . After a median follow-up of 13 months , response ( complete remission [CR]/partial remission [PR]/hematologic improvement [ HI ] ) was 50 % and 10 % in newly diagnosed and relapsed/refractory patients , respectively ( p = 0.008 ) . Median time-to-response was 2.5 months with a median duration of 5.9 months . Median survival was not reached for responders versus 3.8 months for 15 ( 38 % ) patients with stable disease ( p < 0.045 ) . High-risk cytogenetics was associated with inferior survival ( p = 0.05 ) . Lower marrow blasts on day 15 of cycle 1 , irrespective of pretreatment count , predicted subsequent response ( p = 0.01 ) . Azacitidine is active and well tolerated in elderly patients with newly diagnosed AML BACKGROUND Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage . In this trial , we aim ed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens . METHODS In a phase III , international , multicentre , controlled , parallel-group , open-label trial , patients with higher-risk myelodysplastic syndromes were r and omly assigned one-to-one to receive azacitidine ( 75 mg/m(2 ) per day for 7 days every 28 days ) or conventional care ( best supportive care , low-dose cytarabine , or intensive chemotherapy as selected by investigators before r and omisation ) . Patients were stratified by French-American-British and international prognostic scoring system classifications ; r and omisation was done with a block size of four . The primary endpoint was overall survival . Efficacy analyses were by intention to treat for all patients assigned to receive treatment . This study is registered with Clinical Trials.gov , number NCT00071799 . FINDINGS Between Feb 13 , 2004 , and Aug 7 , 2006 , 358 patients were r and omly assigned to receive azacitidine ( n=179 ) or conventional care regimens ( n=179 ) . Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis . After a median follow-up of 21.1 months ( IQR 15.1 - 26.9 ) , median overall survival was 24.5 months ( 9.9-not reached ) for the azacitidine group versus 15.0 months ( 5.6 - 24.1 ) for the conventional care group ( hazard ratio 0.58 ; 95 % CI 0.43 - 0.77 ; stratified log-rank p=0.0001 ) . At last follow-up , 82 patients in the azacitidine group had died compared with 113 in the conventional care group . At 2 years , on the basis of Kaplan-Meier estimates , 50.8 % ( 95 % CI 42.1 - 58.8 ) of patients in the azacitidine group were alive compared with 26.2 % ( 18.7 - 34.3 ) in the conventional care group ( p<0.0001 ) . Peripheral cytopenias were the most common grade 3 - 4 adverse events for all treatments . INTERPRETATION Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care This study analyzed the outcomes of myelodysplastic syndrome patients treated with azacitidine . Between August 2006 and June 2008 , a total of 126 patients were treated with azacitidine at a dose of 75 mg/m2/day subcutaneously for 7 days , which was repeated every 28 days . The median age of the patients was 64 ( range , 20–82 ) years . Forty-three patients ( 33.4 % ) were classified as intermediate-2 and high risk according to International Prognostic Scoring System ( IPSS ) , while 61 patients ( 47.3 % ) were classified as high and very high risk according to WHO Prognostic Scoring System ( WPSS ) . Sixty patients ( 47.6 % ) exhibited a response at the median of 3 ( range , 1–5 ) cycles . A complete response was observed in 21 patients ( 16.7 % ) , a partial response in six patients ( 4.8 % ) , and total hematologic improvement in 61 patients ( 48.4 % ) . For the IPSS risk group , the median survival for the patients with intermediate-1 was 20.0 months , for intermediate-2 was 14.9 months , and for high risk was 6.3 months ( p = 0.008 ) . For the WPSS risk group , the median survival duration was 21.3 months for the very low and low risk patients , 16.5 months for intermediate risk patients , and 14.9 months for the high and very high risk patients ( p = 0.003 ) . The patients with higher than normal lactate dehydrogenase ( LDH ) levels at the time of diagnosis showed a poor survival ( p = 0.003 ) . The median survival duration for the patients with high LDH levels was 13.9 months , while that for the patients with normal LDH levels was 20.6 months . The multivariate analyses revealed that high LDH levels [ hazard ratio ( HR ) 4.384 , p < 0.001 ] and high and very high WPSS risk group ( HR 3.855 , p = 0.014 ) were significantly associated with a worse survival , whereas a response to azacitidine was identified as a good prognostic factor for survival ( HR 0.224 , p = 0.019 ) . In conclusion , while the pretreatment risk group and initial LDH levels were both confirmed as important prognostic factors to predict the outcomes for patients treated with azacitidine , more effective therapies are still needed to prevent disease progression The approved 7‐day schedule of subcutaneous azacitidine for myelodysplastic syndrome is associated with injection site reactions and bruising and may be inconvenient because of the need for weekend doses . Although pharmacokinetic data with IV azacitidine suggests equivalence , there are no efficacy data published . Patients with all myelodysplastic syndromes ( MDS ) FAB subtypes were enrolled and received 75 mg/m2/d of azacitidine by 20‐min intravenous infusion for 5 days in every 28 days . Global methylation studies were performed at baseline and prior to Cycle 3 . Twenty‐five patients were enrolled and 22 were evaluable . Median age was 69.5 years ; 9 ( 41 % ) patients had lower‐risk disease ( IPSS Low or Int‐1 ) and 13 ( 59 % ) had higher‐risk disease ( IPSS Int‐2 or High ) . Twenty‐seven percent of patients responded ( 5 CRs and 1 PR ) . The median time to response was 108 days . The median PFS was 339 days ( 11.3 months ) , the median OS was 444 days ( 14.8 months ) and the median duration of response ( DOR ) was 450 days ( 15.0 months ) . Global methylation studies suggest a greater degree of demethylation in responders . This regimen appeared to offer a PR + CR rate and median DOR somewhat similar to what has been reported with the 7‐day subcutaneous regimen ; however , OS was shorter . Am . J. Hematol . 2009 . © 2009 Wiley‐Liss , Myelodysplastic syndrome ( MDS ) patients with renal impairment ( RI ) were not assessed in the approval trials of 5-azacytidine , thus the optimal use of 5-azacytidine in such patients is currently undefined . We retrospectively analyzed 42 IPSS intermediate-2 and high-risk patients with moderate , mild or no RI undergoing 5-azacytidine therapy in a non-trial setting . We demonstrate that patients in all three groups achieved comparable responses and had similar overall and event-free survival . Likewise , both treatment toxicity and dose adjustments were not significantly influenced by renal function status . A transient but reversible decline in glomerular filtration rate was observed in patients either with or without RI , without affecting the therapeutic schedule . Our results provide the first evidence that 5-azacytidine is effective and well-tolerated in patients with mild and moderate RI and , if confirmed by prospect i ve r and omized studies , advocate that such patients can be managed in an analogous fashion to patients with normal renal function PURPOSE Patients with high-risk myelodysplastic syndrome ( MDS ) have high mortality from bone marrow failure or transformation to acute leukemia . Supportive care is st and ard therapy . We previously reported that azacitidine ( Aza C ) was active in patients with high-risk MDS . PATIENTS AND METHODS A r and omized controlled trial was undertaken in 191 patients with MDS to compare Aza C ( 75 mg/m(2)/d subcutaneously for 7 days every 28 days ) with supportive care . MDS was defined by French-American-British criteria . New rigorous response criteria were applied . Both arms received transfusions and antibiotics as required . Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C. RESULTS Responses occurred in 60 % of patients on the Aza C arm ( 7 % complete response , 16 % partial response , 37 % improved ) compared with 5 % ( improved ) receiving supportive care ( P < .001 ) . Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care ( P = .007 ) . Transformation to acute myelogenous leukemia occurred as the first event in 15 % of patients on the Aza C arm and in 38 % receiving supportive care ( P = .001 ) . Eliminating the confounding effect of early cross-over to Aza C , a l and mark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care ( P = .03 ) . Quality -of-life assessment found significant major advantages in physical function , symptoms , and psychological state for patients initially r and omized to Aza C. CONCLUSION Aza C treatment results in significantly higher response rates , improved quality of life , reduced risk of leukemic transformation , and improved survival compared with supportive care . Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine ( AZA ) remain largely unknown . Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate , patient-named program . Diagnosis was RA/RARS/RCMD in 4 % , RAEB-1 in 20 % , RAEB-2 in 54 % , and RAEB-t ( AML with 21%-30 % marrow blasts ) in 22 % . Cytogenetic risk was good in 31 % , intermediate in 17 % , and poor in 47 % . Patients received AZA for a median of 6 cycles ( 1 - 52 ) . Previous low-dose cytosine arabinoside treatment ( P = .009 ) , bone marrow blasts > 15 % ( P = .004 ) , and abnormal karyotype ( P = .03 ) independently predicted lower response rates . Complex karyotype predicted shorter responses ( P = .0003 ) . Performance status ≥ 2 , intermediate- and poor-risk cytogenetics , presence of circulating blasts , and red blood cell transfusion dependency ≥ 4 units/8 weeks ( all P < 10(-4 ) ) independently predicted poorer overall survival ( OS ) . A prognostic score based on those factors discriminated 3 risk groups with median OS not reached , 15.0 and 6.1 months , respectively ( P < 10(-4 ) ) . This prognostic score was vali date d in an independent set of patients receiving AZA in the AZA-001 trial ( P = .003 ) . Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS ( P < 10(-4 ) ) . In conclusion , routine tests can identify subgroups of patients with distinct prognosis with AZA treatment |
11,370 | 17,253,564 | Pemetrexed disodium in combination with cisplatin and with folic acid and vitamin B(12 ) supplementation may improve survival when used in combination with cisplatin in good performance status patients . | BACKGROUND Malignant pleural mesothelioma ( MPM ) is a highly aggressive malignancy whose incidence is expected to increase in the United Kingdom , Western Europe , and Australia over the next 20 years as a result of occupational exposure to asbestos fibres .
Surgery is feasible in only a small proportion of cases , and radiotherapy and cytotoxic chemotherapy are used in palliation .
Pemetrexed is the first and only chemotherapy agent that has been granted a marketing approval for use in combination with cisplatin for the treatment of chemo-naïve patients with unresectable MPM .
OBJECTIVES To examine evidence on the clinical effectiveness of pemetrexed disodium used in combination with cisplatin for the treatment of unresectable malignant pleural mesothelioma in chemotherapy naïve patients compared with other cytotoxic agents used alone or in combination , or supportive care . | Background : The incidence of mesothelioma is rising rapidly in the UK . There is no generally accepted st and ard treatment . The BTS recommends active symptom control ( ASC ) . It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity . Palliation as recorded by patients has been fully reported for only two regimens : mitomycin , vinblastine , and cisplatin ( MVP ) , and vinorelbine ( N ) . The BTS and collaborators planned to conduct a phase III r and omised trial comparing ASC only , ASC+MVP , and ASC+N in 840 patients with survival as the primary outcome measure . The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two st and ard quality of life ( QL ) question naires for mesothelioma . Methods : Collaborating centres registered all new patients with mesothelioma . Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL question naires and were r and omised between all three or any two of ( 1 ) ASC only , ( 2 ) ASC+4 cycles of MVP , and ( 3 ) ASC+12 weekly doses of N. Results : During 1 year , 242 patients were registered of whom 109 ( 45 % ) were r and omised ( 55 % of the 197 eligible patients ) . Fifty two patients from 20 centres were r and omised to an option including ASC only . This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial . The EORTC QL question naire was superior to FACT-L in terms of completeness of data and patient preference . Clinical ly relevant palliation was achieved with ASC . Conclusion : The planned phase III trial is feasible BACKGROUND With the rising incidence of malignant mesothelioma ( MM ) , it is important to optimise treatment to control symptoms , maintain quality of life and , if possible , prolong life . We have analysed prospect ively collected data to evaluate a frequently used palliative chemotherapy regimen . PATIENTS AND METHODS Between October 1986 and May 2002 all patients with inoperable pleural mesothelioma were considered for treatment with MVP ( mitomycin C 8 mg/m2 every 6 weeks , vinblastine 6 mg/m2 every 3 weeks and cisplatin 50 mg/m2 every 3 weeks ) chemotherapy . Symptoms were assessed by physician assessment at baseline and after each cycle of chemotherapy . RESULTS One hundred and fifty patients were treated with MVP for mesothelioma . Forty-three per cent had a performance status ( PS ) 2 or worse . The response rate was 15.3 % , with 68.6 % having stable disease . Sixty-nine per cent reported an improvement in symptoms ; in particular there were good responses for pain ( 71 % ) , cough ( 62 % ) and dyspnoea ( 50 % ) . The most common grade 3/4 toxicity was neutropenia ( 22 % ) . Median overall survival was 7 months , with 1-year survival 31 % and 2-year survival 11 % . Median survival for patients with PS 0/1 was 10 months , and was 6 months for patients with PS 2/3 . Poor prognostic factors in univariate analysis included poor PS , weight loss , mixed or sarcomatoid histology , low haemoglobin and high white blood cell count . Excluding pathological subtype , the prognostic significance of poor PS and weight loss were retained in multivariate analysis . CONCLUSIONS Palliation of symptoms in MM is achievable with current cisplatin-based treatments PURPOSE To evaluate the therapeutic impact of a simple combination chemotherapy regimen on symptoms related to malignant mesothelioma . MATERIAL S AND METHODS Between October 1986 and June 1997 , 39 patients with advanced inoperable malignant mesothelioma were treated with palliative MVP ( mitomycin-C 8 mg/m2 q. six weeks , vinblastine 6 mg/m2 q. three weeks and cisplatin 50 mg/m2 q. three weeks ) chemotherapy and assessed for objective response and relief of symptoms . RESULTS Eight of 39 patients ( 20 % ) achieved an objective partial response with a median duration of nine months : only five patients had progression of disease during chemotherapy . Twenty-four of 39 ( 62 % ) had an overall improvement in their symptomology with particularly good responses for pain ( 79 % ) . These benefits were independent of performance status . Resolution of symptoms was achieved in all responding patients within two treatment cycles . There was no statistically significant difference in duration and incidence of symptom response in those patients achieving radiological PR compared with those with no change and more than 60 % of patients with radiological no change obtained useful symptom control . The treatment was well tolerated with only four patients developing grade 3 leucopenia and three with grade 3 nausea . CONCLUSIONS MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic benefit . These results should be the basis for further trials of MVP in the management of mesothelioma with symptom control as a principal endpoint PURPOSE To examine the individual and joint effect of various pretreatment clinical characteristics on the survival of patients with mesothelioma treated by the Cancer and Leukemia Group B ( CALGB ) . PATIENTS AND METHODS Between June 1984 and September 1994 , 337 patients with malignant mesothelioma and no prior chemotherapy were accrued to seven phase II studies conducted by the CALGB which screened the efficacy of 10 treatment regimens or dose levels . The eligibility criteria for all studies were virtually identical . Patient characteristics include the following : age older than 60 years ( 63 % ) ; male ( 83 % ) ; performance status ( PS ) of 0 or 1 ( 81 % ) ; chest pain ( 60 % ) ; definite asbestos exposure ( 62 % ) ; > 5 % weight loss ( 41 % ) ; and pleural involvement ( 94 % ) . Median survival time ( MST ) for the 10 treatment regimens ranged from 3.9 to 9.8 months ( overall=7.2 ; 95 % confidence interval [ CI ] , 6.5 to 8.3 ) , with 1-year survival between 14 % and 50 % ( overall=27 % ; 95 % CI , 23 to 33 % ) . RESULTS Cox survival models and exponential regression trees were used to examine the prognostic importance of pretreatment patient characteristics . Univariate analyses show that patients with poor Eastern Cooperative Oncology Group PS , chest pain , dyspnea , platelet count ( PLT ) > 400,000/microL , weight loss , serum lactate dehydrogenase ( LDH ) level > 500 IU/L , pleural involvement , low hemoglobin ( HGB ) level , high WBC count , and increasing age over 75 years have a worse prognosis . With decreasing risk ratio , multivariate Cox analyses showed that pleural involvement , LDH > 500 IU/L , poor PS , chest pain , PLT > 400,000/microL , nonepithelial histology , and increasing age older than 75 years jointly predict poor survival . PS was the most important prognostic split in the regression tree . Terminal nodes were amalgamated to form six distinct prognostic subgroups with MST ( 2-year survival ) of 13.9 ( 38 % ) in 36 patients , 9.5 ( 21 % ) in 36 patients , 9.2 ( 10 % ) in 146 patients , 6.5 ( 3 % ) in 33 patients , 4.4 ( 0 % ) in 73 patients , and 1.4 ( 0 % ) in 13 patients ( p<0.0001 ) . CONCLUSIONS The subgroup with the best survival ( MST=13.9 months ) included patients with PS=0 and age younger than 49 years , and patients with PS=0 , age of 49 years or older , and HGB > or = 14.6 . The worst survival ( MST= 1.4 months ) occurred for patients with PS= 1/2 and WBC > or = PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy . Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time PURPOSE This report describes the data and analysis leading to the approval of pemetrexed ( LY 231514 , MTA , Alimta , Eli Lilly and Co. , Indianapolis , IN ) by the U.S. Food and Drug Administration ( FDA ) of a New Drug Application for the treatment of malignant pleural mesothelioma ( MPM ) . EXPERIMENTAL DESIGN The FDA review of the efficacy and safety of pemetrexed assessed in a r and omized clinical trial of 448 patients with unresectable MPM comparing pemetrexed plus cisplatin with cisplatin alone , as well as pre clinical pharmacology and chemistry data , are described . The basis for marketing approval is discussed . RESULTS In one r and omized , single-blind , multicenter international trial , 226 patients were r and omized to the pemetrexed and cisplatin arm and 222 patients were r and omized to cisplatin alone . Median survival times were 12.1 months for pemetrexed and cisplatin and 9.3 months for cisplatin ( P = 0.021 ; hazard ratio , 0.766 ; 95 % confidence interval , 0.61 - 0.96 ) . Myelosuppression , predominantly neutropenia , was the most common toxicity of pemetrexed plus cisplatin . Other common adverse events were fatigue , leucopenia , nausea , dyspnea , vomiting , chest pain , anemia , thrombocytopenia , and anorexia . CONCLUSIONS Pemetrexed in combination with cisplatin was approved by the FDA on February 4 , 2004 for the treatment of patients with MPM whose disease is either unresectable or who are otherwise not c and i date s for curative surgery . The recommended dose of pemetrexed is 500 mg/m(2 ) intra venous infusion over 10 minutes on day 1 of each 21-day cycle in combination with 75 mg/m(2 ) cisplatin infused over 2 hours beginning 30 minutes after the pemetrexed infusion . Patients must receive oral folic acid and vitamin B(12 ) injections before the start and during therapy to reduce severe toxicities . Patients should also receive corticosteroids with the chemotherapy to decrease the incidence of skin rash . Approval was based on a demonstration of survival improvement in a single r and omized trial . Response rates and time to tumor progression were not included in product labeling because of inconsistencies in assessment s among the investigators , independent radiologic review ers , and the FDA , reflecting the difficulty of radiographic assessment s in malignant mesothelioma . Complete prescribing information is available on the FDA Web site at http://www . fda .gov/cder/approval/index.htm PURPOSE Multitargeted antifolate ( MTA ; LY231514 ) has broad pre clinical antitumor activity and inhibits a variety of intracellular enzymes involved in the folate pathways . This study was design ed to ( 1 ) determine the maximum-tolerated dose ( MTD ) , dose-limiting toxicities ( DLT ) , and pharmacokinetics of MTA combined with cisplatin ; ( 2 ) determine a recommended dose for phase II studies ; and ( 3 ) collect anecdotal information on the antitumor activity of MTA combined with cisplatin . PATIENTS AND METHODS Patients with solid tumors received MTA intravenously over 10 minutes and cisplatin over 2 hours once every 21 days . In cohort 1 , both agents were administered on day 1 starting with MTA 300 mg/m(2 ) and cisplatin 60 mg/m(2 ) . In cohort 2 , MTA ( 500 or 600 mg/m(2 ) ) was administered on day 1 , followed by cisplatin ( 75 mg/m(2 ) ) on day 2 . RESULTS In cohort 1 , 40 assessable patients received 159 courses of treatment . The MTD was MTA 600 mg/m(2)/cisplatin 100 mg/m(2 ) . DLTs were reversible leukopenia/neutropenia and delayed fatigue . Hydration before cisplatin therapy did not influence MTA pharmacokinetics . Eleven objective remissions included one complete response in a patient with relapsed squamous cell head and neck carcinoma , and partial responses in four of ten patients with epithelial pleural mesothelioma . In cohort 2 , 11 assessable patients received 23 courses of treatment . The MTD was MTA 600 mg/m(2 ) and cisplatin 75 mg/m(2 ) . DLTs were neutropenic sepsis , diarrhea , and skin toxicity . Two patients died of treatment-related complications during the study . Two patients had objective remissions ( one mesothelioma patient , one colon cancer patient ) . CONCLUSION The combination of MTA and cisplatin is clinical ly active , and administering both agents on day 1 is superior to a split schedule . Further development of this combination for mesothelioma is warranted PURPOSE To evaluate the response rate and impact on quality of life of vinorelbine given as cycles of 30 mg/m(2 ) weekly for 6 weeks to patients with malignant pleural mesothelioma . PATIENTS AND METHODS Twenty-nine patients with histologically proven malignant pleural mesothelioma were enrolled ( 26 male patients and three female patients ; median age , 58 years [ range , 29 to 77 years ] ) . Seventeen patients had epithelioid tumors , two had sarcomatoid tumors , and 10 had biphasic tumors . The International Mesothelioma Interest Group staging system was used : one patient had stage Ib disease , 10 had stage II disease , eight had stage III disease , and 10 had stage IV disease . Patients were treated with weekly injections of vinorelbine 30 mg/m(2 ) . A cycle consisted of six weekly injections . The new guidelines to evaluate the response to treatment in solid tumors were used . Responses were measured by spiral computed tomography scan . RESULTS All twenty-nine patients had measurable disease and were assessed for response . There were seven partial responses ( 24 % [ 95 % confidence interval , 10 % to 44 % ] ) , 16 patients had stable disease ( 55 % ) , and six patients had disease progression on therapy ( 21 % ) . The median number of vinorelbine injections was 12 ( range , 2 to 30 ) . Quality -of-life analyses showed a benefit for vinorelbine therapy . CONCLUSION Vinorelbine shows promise in the palliation of patients with malignant pleural mesothelioma . The relatively low toxicity of the drug suggests that trials of vinorelbine in combination with other agents should be feasible PURPOSE This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Patients with a histologically proven diagnosis of MPM , chemotherapy-naive measurable lesions , and adequate organ function received pemetrexed ( 500 mg/m2 ) intravenously over 10 minutes every 3 weeks . After a protocol change , most patients also received folic acid and vitamin B12 supplementation to improve safety . RESULTS A total of 64 patients were enrolled . Nine ( 14.1 % ) of the 64 patients had a partial response . The Kaplan-Meier estimate for median overall survival was 10.7 months . Forty-three patients received vitamin supplementation for all courses of therapy , and 21 patients did not . Seven of the nine responders were vitamin supplemented . The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients . Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients ( median , six v two cycles , respectively ) . Grade 3/4 neutropenia ( 23.4 % ) and grade 3/4 leukopenia ( 18.8 % ) were the most common laboratory toxicities . Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events ( grade 3 , 6.3 % ; grade 4 , 0.0 % each ) . The incidence of these toxicities was generally lower in the supplemented patients . CONCLUSION Single-agent pemetrexed for MPM result ed in a moderate response rate ( 14.1 % ) and median overall survival of 10.7 months . Patients supplemented with folic acid and vitamin B12 tolerated treatment better ( less toxicity and more cycles of treatment ) and had a 5-month greater median overall survival than nonsupplemented patients . These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation PURPOSE Multitargeted antifolate ( MTA ) is an investigational agent that , like gemcitabine , exhibits broad activity in solid tumors . A phase I trial of MTA and gemcitabine was undertaken , based on the demonstration of pre clinical cytotoxic synergy . PATIENTS AND METHODS Thirty-five patients ( group I ) received 164 courses ( median , four ; range , one to 14 courses ) of treatment of gemcitabine at doses of 1,000 and 1,250 mg/m(2 ) on days 1 and 8 and MTA at doses of 200 , 300 , 400 , 500 , and 600 mg/m(2 ) , given 90 minutes after gemcitabine on day 1 . Courses were repeated every 3 weeks . Because the day 8 dose of gemcitabine was reduced or omitted in 57 % of courses due to neutropenia , 21 patients ( group II ) were treated on an alternate schedule , with MTA administered on day 8 rather than day 1 . This group received 85 treatment courses ( median , four ; range , one to 10 courses ) . RESULTS The most common and dose-limiting toxicity was neutropenia . Other toxicities included nausea , fatigue , rash , and elevated hepatic transaminases . The maximum-tolerated dose was gemcitabine/MTA 1,000/500 mg/m(2 ) for group I and 1,250/500 mg/m(2 ) for group II . Thirteen objective responses were documented ( colorectal cancer , n = 3 ; non-small-cell lung cancer , n = 3 ; cholangiocarcinoma , n = 2 ; ovarian carcinoma , n = 2 ; mesothelioma , n = 1 ; breast cancer , n = 1 ; and adenocarcinoma of unknown primary site , n = 1 ) . Gemcitabine had no effect on the disposition of MTA . CONCLUSION The gemcitabine/MTA combination is broadly active and warrants further evaluation . The sequence of gemcitabine administered on days 1 and 8 with MTA administered on day 8 is better tolerated and is recommended for further study at doses of gemcitabine/MTA 1,250/500 mg/m(2 ) |
11,371 | 10,796,703 | There is insufficient evidence to justify is its routine use in cystic fibrosis | BACKGROUND Cystic fibrosis-related liver disease peaks in adolescence with up to 20 % of patients developing chronic liver disease .
Early changes in the liver may ultimately result in end stage liver disease with patients needing transplantation .
One therapeutic option currently used is ursodeoxycholic acid .
OBJECTIVES To assess the effectiveness of ursodeoxycholic acid in cystic fibrosis liver disease . | Increased circulating levels of hepatotoxic bile acids may contribute to the cholestasis characteristic of cystic fibrosis-related liver disease . The aims of this study were to compare serum bile acid profiles in patients with cystic fibrosis with and without liver disease , and to evaluate the effect of treatment with ursodeoxycholic acid , a non-hepatotoxic bile acid , on liver biochemistry and serum bile acids in patients with cystic fibrosis-related liver disease . Fasting and postpr and ial serum bile acid levels were analysed in 15 patients ( nine males ; median age 18 years ) with cystic fibrosis-related liver disease and compared with serum bile acid levels in 18 cystic fibrosis patients ( 12 males ; median age 22 years ) without liver disease and 10 control subjects . Fasting and postpr and ial serum levels of primary and secondary serum bile acids were analysed using high-performance liquid chromatography . Liver biochemistry and serum bile acids were measured in six cystic fibrosis patients with liver disease before and 6 months after treatment with ursodeoxycholic acid 20 mg/kg/day and compared with six control patients with cystic fibrosis-related liver disease . Total fasting and postpr and ial serum bile acid levels were significantly ( P < 0.01 ) elevated in patients with liver disease compared to those without liver disease and controls . The fasting glycine conjugates of cholic acid , chenodeoxycholic acid and deoxycholic acid , and the fasting and postpr and ial taurine conjugates of cholic acid and chenodeoxycholic acid were significantly ( P < 0.05 ) elevated in liver disease patients compared to patients without liver disease and controls . After 6 months ' treatment with ursodeoxycholic acid , although the serum was significantly saturated with ursodeoxycholic acid and significant improvements in liver biochemistry were observed in the treatment group , there was no significant reduction in the levels of individual serum bile acids . Although circulating levels of potentially hepatotoxic serum bile acids are elevated in patients with cystic fibrosis-related liver disease , improvements in liver biochemistry associated with ursodeoxycholic acid treatment can not be attributed solely to alterations in levels of endogenous bile acids Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis ( CF ) . Preliminary data suggest that ursodeoxycholic acid ( UDCA ) may be beneficial for treatment of this manifestation . We performed a double-blind , multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides st and ard liver function tests . We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA . From June to December 1990 , we enrolled in 12 centers 55 CF patients with liver disease ( 39 male subjects ; median age , 13.8 years ) . They were r and omly assigned to receive for 1 year one of the following treatments : UDCA ( 15 mg/kg body weight daily ) plus taurine ( 30 mg/kg body weight daily ) , UDCA plus placebo , placebo plus taurine , or double placebo . Clinical and laboratory evaluations were performed every 3 months . After 1 year , deterioration of overall clinical conditions , as indicated by the Shwachman-Kulczycki score ( SKS ) , occurred in patients who received placebo but not in those who received UDCA ( P = .025 ) . Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase ( GGT ) ( P = .004 ) and 5'-nucleotidase ( P = .006 ) levels . Treatment with taurine was followed by a significant increase in serum prealbumin levels ( P = .053 ) , a trend toward a reduction in fat malabsorption , and no effect on the biochemical profile . No severe side effects occurred with any treatment . Thus , we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease . Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and , in an uncontrolled study , also in young adults with cystic fibrosis ( CF ) and chronic cholestasis . As an improvement in nutritional status was also observed in these young adult patients , we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease . The study included 51 patients ( 27 male patients and 24 female patients ; age range , 8–32 years ; median , 14 ) with body mass percentiles < 90 % . Patients were r and omly assigned to receive either ursodeoxycholic acid ( 10–12 mg/kg/day ) alone or with taurine ( 18–22 mg/kg/day ) . Patients were followed in a crossover fashion within each group ; 6 months of treatment was r and omly alternated with 6 months of placebo . Nine patients dropped out before concluding the study . Liver function tests , nutritional status , and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment . Nutritional status and fat absorption were not significantly modified by either treatment . Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease . Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid , either alone or with taurine , does not improve the nutritional status of young malnourished CF patients . Higher doses given for longer periods might be worth investigating BACKGROUND Ursodeoxycholic acid ( UDCA ) is beneficial in cholestasis related to cystic fibrosis ( CF ) . High-dose treatment has been recommended to compensate for bile salt malabsorption . We compared the results of low-dose ( 10 mg/kg/day ) and high-dose ( 20 mg/kg/day ) UDCA treatment on liver biochemistry after 3 and 12 months ' treatment . METHODS Thirty CF patients ( age > 5 years ) with biochemical cholestasis and compensated liver disease were r and omized for low-dose ( n = 17 ) or high-dose ( n = 13 ) UDCA . Baseline clinical variables were comparable . RESULTS After 1 year one patient had died of liver failure ( low dose ) , and three had dropped out because of pruritus ( one in each group ) or personal choice ( low dose ) . In the high-dose group improvement in gamma-glutamyl transferase values was more pronounced after 3 months and 1 year ( P < 0.004 ) , and improvement of alanine aminotransferase was better after 1 yer ( P < 0.02 ) . Improvement of alkaline phosphatase and aspartate aminotransferase was comparable . Complete normalization of liver enzymes and bilirubin occurred more often in the high-dose group . CONCLUSION High-dose UDCA induces a better response of liver biochemistry values than low-dose UDCA in CF patients with cholestatic liver disease The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospect i ve , r and omized , double-blind , placebo-controlled trial . Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern , liver histological appearance and endoscopic retro grade cholangiography were included in the trial . Six patients received ursodeoxycholic acid ( 13 to 15 mg/kg body wt/day ) , and eight patients received placebo . Two patients had to be withdrawn from the study , one because of UDCA-related diarrhea and the other because of worsening of the disease during placebo treatment . Patients in the ursodeoxycholic acid group improved significantly during 1 yr of treatment with respect to serum levels of bilirubin ( median = -50 % ) , alkaline phosphatase ( median = -67 % ) , gamma-glutamyltransferase ( median = -53 % ) , AST ( median = -54 % ) and ALT ( median = -36 % ) compared with the placebo group , but not with respect to serum levels of hydrophobic bile acids . During ursodeoxycholic acid treatment , histopathological features also improved significantly , as evaluated by multiparametric score . Expression of human leukocyte antigen class I molecules appeared to be markedly reduced on liver cells after ursodeoxycholic acid treatment . We conclude that ursodeoxycholic acid is beneficial in reducing disease activity in patients with primary sclerosing cholangitis Previous studies from our groups have demonstrated improvements in biochemical markers of liver function when cystic fibrosis patients with associated liver disease were administered oral ursodeoxycholic acid . The magnitude of the response was somewhat less than that found when comparable doses ( 10 to 15 mg/kg body wt/day ) of ursodeoxycholic acid are given to other liver disease patients ; this may be explained by the bile acid malabsorption that is characteristic of the disease . For this reason a dose-response study was carried out in nine cystic fibrosis patients with liver disease to establish whether improved efficacy could be obtained with higher doses . Ursodeoxycholic acid in doses of 5 , 10 and 15 mg/kg body wt/day was given orally for consecutive 2-mo periods in a replicated Latin-square design . After this , all patients received 20 mg/kg body wt/day . Liver function , individual serum bile acids and biliary bile acid composition were determined at entry and at the end of each treatment period . Our data demonstrate that the magnitude of the biochemical improvement in serum liver enzymes was significantly greater with higher doses of ursodeoxycholic acid ; at 20 mg/kg body wt/day it was similar to that reported for patients with other liver diseases administered lower doses . Biliary ursodeoxycholic acid enrichment increased with increasing doses , attaining 42 % + /- 6 % of the total biliary bile acids with the highest dose . Fasting serum ursodeoxycholic acid concentrations increased during ursodeoxycholic acid administration but were variable and correlated poorly with the dose of ursodeoxycholic acid administered , whereas no correlation was found between serum ursodeoxycholic acid concentration and the proportion of ursodeoxycholic acid in bile . ( ABSTRACT TRUNCATED AT 250 WORDS Cholesterol gallstones are dissolved in man by chenodeoxycholic acid ( CDCA ) and ursodeoxycholic acid ( UDCA ) . To test the comparative efficacy of these two cholelitholytic bile acids , 223 gallstones patients were r and omly treated with either UDCA or CDCA at two different doses : 7 to 8 mg per kg per day and 14 to 15 mg per kg per day . Efficacy and factors influencing dissolution ( dose , size of the stones , and time ) were evaluated after 3 , 6 , and 12 months of treatment . UDCA was significantly more efficacious than was CDCA after 3 and 6 months of treatment , whereas after 12 months , no significant differences were observed . UDCA was equally effective at high and low doses , both on small and large stones . CDCA was significantly more effective at high doses and on small stones . Seventy-four per cent of the total dissolutions with UDCA and 42 % with CDCA occurred within the first 6 months of treatment . Diarrhea and hypertransaminasemia occurred only in the CDCA-treated patients . We conclude that UDCA seems to be the bile acid of choice in dissolving cholesterol gallstones This was a prospect i ve open study that examined the quantitative and qualitative analysis of hepatobiliary scintigraphy ( DISIDA ) in detecting liver involvement in cystic fibrosis ( CF ) . Forty-four adult and pediatric patients ( median age , 12.1 years ; range , 1.1 - 36.3 years ) were divided into three groups : group 1 , no evidence of liver involvement ( n = 8) ; group 2 , biochemical evidence of liver involvement on two or more occasions ( n = 26 ) ; and group 3 , clinical evidence of liver disease ( n = 10 ) . In groups 1 and 2 , the most common qualitative scintigraphic finding was focal intrahepatic retention of tracer ( 26/34 patients , 12 of whom had normal findings on ultrasonography ) . This finding corresponds to focal cholestasis and may warrant treatment with the choleretic agent ursodeoxycholic acid ( UDCA ) . In the group 3 patients , the abnormal qualitative scintigraphic appearances ( heterogeneous uptake of tracer and nodular liver outline ) added little to the findings on ultrasonography ; however , these patients had a prolonged mean hepatic clearance time compared with those in groups 1 and 2 ( one-way ANOVA ; P < .015 ) . It is proposed that scintigraphy with DISIDA has a role in the detection of early liver involvement in cystic fibrosis BACKGROUND In primary biliary cirrhosis the hepatic lesions may result , at least in part , from the intracellular accumulation of potentially toxic endogenous bile acids . Preliminary work suggests that the administration of ursodiol ( also called ursodeoxycholic acid ) , a hydrophilic bile acid without hepatotoxicity , leads to improvement in the condition of patients with primary biliary cirrhosis . METHODS We conducted a two-year , multicenter , double-blind trial to compare the efficacy of ursodiol with that of placebo . Patients with biopsy-proved primary biliary cirrhosis were r and omly assigned to receive either ursodiol ( 13 to 15 mg per kilogram of body weight per day ) ( n = 73 ) or placebo ( n = 73 ) . Treatment failure was defined as a doubling of bilirubin levels to more than 70 mumol per liter or the occurrence of a severe complication ( ascites or variceal bleeding ) or an adverse reaction . RESULTS Treatment failed in 6 patients in the ursodiol group , as compared with 13 in the placebo group ( P less than 0.01 by Cox regression model ) . A single patient in each group withdrew because of minor adverse effects . After two years of treatment , the proportion of patients with clinical ly overt disease decreased only in the ursodiol group ( P less than 0.02 ) . The patients treated with ursodiol had significant improvements in serum levels of bilirubin , alkaline phosphatase , alanine aminotransferase , aspartate aminotransferase , gamma-glutamyltransferase , cholesterol , and IgM ( all P less than 0.001 ) ; the antimitochondrial-antibody titer ( P less than 0.01 ) ; and the Mayo risk score ( P less than 0.001 ) . Follow-up analysis of 95 liver-biopsy specimens showed a significant improvement in the mean histologic score ( P less than 0.002 ) and in all the characteristic histologic features except fibrosis only in the group given ursodiol . CONCLUSIONS Ursodiol is a safe and effective treatment for primary biliary cirrhosis |
11,372 | 30,051,331 | Studies engaged patients at multiple levels of the health care system and suggested that in-person deliberation with health system leadership was most effective .
Studies involving patient engagement in research focused on increasing study participation .
Discussion PFACs engage communities through individual projects but evidence of their impact on outcomes is lacking . | Background Patient-centeredness is a characteristic of high- quality medical care and requires engaging community members in health systems ’ decision-making .
One key patient engagement strategy is patient , family , and community advisory boards/councils ( PFACs ) , yet the evidence to guide PFACs is lacking .
Systematic review s on patient engagement may benefit from patient input , but feasibility is unclear .
Methods A team of physicians , research ers , and a PFAC member conducted a systematic review to examine the impact of PFACs on health systems and describe optimal strategies for PFAC conduct . | 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 Recent studies have suggested that there is a positive impact of patient-centered care ( PCC ) on both the patient-physician relationship and subsequent patient health-related behaviors . One recent prospect i ve study reported a significant relationship between the degree of PCC experienced by patients during their hospitalization for acute myocardial infa rct ion ( AMI ) and their postdischarge cardiac symptoms . A limitation of this study , however , was a lack of information regarding the technical quality of the AMI care , which might have explained at least part of the differences in outcomes . The present study was undertaken to test the influence of both PCC and technical care quality on outcomes among AMI patients . METHODS We analyzed data from a national sample of 1,858 veterans hospitalized for an initial AMI in a Department of Veterans Affairs medical center during fiscal years 2003 and 2004 for whom data had been compiled on evidence -based treatment and who had also completed a Picker question naire assessing perceptions of PCC . Cox proportional hazards models were used to estimate the relationship between PCC and survival 1-year postdischarge , controlling for technical quality of care , patient clinical condition and history , admission process characteristics , and patient sociodemographic characteristics . We hypothesized that better PCC would be associated with a lower probability of death 1-year postdischarge , even after controlling for patient characteristics and the technical quality of care . RESULTS Better PCC was associated with a significantly but modestly lower hazard of death over the 1-year study period ( hazard ratio 0.992 , 95 percent confidence interval 0.986 - 0.999 ) . CONCLUSIONS Providing PCC may result in important clinical benefits , in addition to meeting patient needs and expectations Progress towards the Millennium Development Goals ( MDGs ) has been uneven . Inequalities in child health are large and effective interventions rarely reach the most in need . Little is known about how to reduce these inequalities . We describe and explain the equity impact of a women ’s group intervention in India that strongly reduced the neonatal mortality rate ( NMR ) in a cluster-r and omised trial . We conducted secondary analyses of the trial data , obtained through prospect i ve surveillance of a population of 228 186 . The intervention effects were estimated separately , through r and om effects logistic regression , for the most and less socio-economically marginalised groups . Among the most marginalised , the NMR was 59 % lower in intervention than in control clusters in years 2 and 3 ( 70 % , year 3 ) ; among the less marginalised , the NMR was 36 % lower ( 35 % , year 3 ) . The intervention effect was stronger among the most than among the less marginalised ( P-value for difference = 0.028 , years 2 - 3 ; P-value for difference = 0.009 , year 3 ) . The stronger effect was concentrated in winter , particularly for early NMR . There was no effect on the use of health-care services in either group , and improvements in home care were comparable . Participatory community interventions can substantially reduce socio-economic inequalities in neonatal mortality and contribute to an equitable achievement of the unfinished MDG agenda 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 ) Objective The objective of this study was to describe the involvement of patients or their representatives in quality management ( QM ) functions and to assess associations between levels of involvement and the implementation of patient-centred care strategies . Design A cross-sectional , multilevel study design that surveyed quality managers and department heads and data from an organizational audit . Setting R and omly selected hospitals ( n = 74 ) from seven European countries ( The Czech Republic , France , Germany , Pol and , Portugal , Spain and Turkey ) . Participants Hospital quality managers ( n = 74 ) and heads of clinical departments ( n = 262 ) in charge of four patient pathways ( acute myocardial infa rct ion , stroke , hip fracture and deliveries ) participated in the data collection between May 2011 and February 2012 . Main Outcome Measures Four items reflecting essential patient-centred care strategies based on an on-site hospital visit : ( 1 ) formal survey seeking views of patients and carers , ( 2 ) written policies on patients ' rights , ( 3 ) patient information literature including guidelines and ( 4 ) fact sheets for post-discharge care . The main predictors were patient involvement in QM at the ( i ) hospital level and ( ii ) pathway level . Results Current levels of involving patients and their representatives in QM functions in European hospitals are low at hospital level ( mean score 1.6 on a scale of 0 to 5 , SD 0.7 ) , but even lower at departmental level ( mean 0.6 , SD 0.7 ) . We did not detect associations between levels of involving patients and their representatives in QM functions and the implementation of patient-centred care strategies ; however , the smallest hospitals were more likely to have implemented patient-centred care strategies . Conclusions There is insufficient evidence that involving patients and their representatives in QM leads to establishing or implementing strategies and procedures that facilitate patient-centred care ; however , lack of evidence should not be interpreted as evidence of no effect BACKGROUND We design ed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization . METHODS We selected 39 family physicians at r and om , and 315 of their patients participated . Office visits were audiotaped and scored for patient-centered communication . In addition , patients were asked for their perceptions of the patient-centeredness of the visit . The outcomes were : ( 1 ) patients ' health , assessed by a visual analogue scale on symptom discomfort and concern ; ( 2 ) self-report of health , using the Medical Outcomes Study Short Form-36 ; and ( 3 ) medical care utilization variables of diagnostic tests , referrals , and visits to the family physician , assessed by chart review . The 2 measures of patient-centeredness were correlated with the outcomes of visits , adjusting for the clustering of patients by physician and controlling for confounding variables . RESULTS Patient-centered communication was correlated with the patients ' perceptions of finding common ground . In addition , positive perceptions ( both the total score and the subscore on finding common ground ) were associated with better recovery from their discomfort and concern , better emotional health 2 months later , and fewer diagnostic tests and referrals . CONCLUSIONS Patient-centered communication influences patients ' health through perceptions that their visit was patient centered , and especially through perceptions that common ground was achieved with the physician . Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals PURPOSE / OBJECTIVES To describe community-based participatory processes used to develop promotore training on cancer research , and to assess the feasibility of training promotores from rural communities to disseminate cancer research information . DESIGN Prospect i ve , cohort design . SETTING Rural communities in the state of Kansas . SAMPLE 34 Spanish-speaking promotores attended an information session ; 27 enrolled and 22 completed training . METHODS With input from a community advisory board , the authors developed a leadership and cancer curriculum and trained Spanish-speaking promotores to disseminate information on cancer research . Promotores completed pretraining and post-training surveys in Spanish to assess demographic characteristics and changes in knowledge of cancer , cancer treatment and cancer research studies , and intent to participate in cancer research . MAIN RESEARCH VARIABLES Cancer knowledge , awareness of cancer clinical trials , interest in participating in cancer clinical research studies . FINDINGS Compared to pretraining , after training , promotores were more likely to correctly define cancer , identify biopsies , describe cancer stages , and report ever having heard of cancer research studies . CONCLUSIONS Completion rates of the training and willingness to participate in cancer research were high , supporting the feasibility of training promotores to deliver community-based education to promote cancer research participation . IMPLICATION S FOR NURSING Nursing professionals and research ers can collaborate with promotores to disseminate cancer education and research among underserved rural Latino communities in Kansas and elsewhere . Members of these communities appear willing and interested in improving their knowledge of cancer and cancer clinical trials Purpose : This article uses an interactional analysis instrument to characterize patient-centered care in the primary care setting and to examine its relationship with health care utilization . Methods : Five hundred nine new adult patients were r and omized to care by family physicians and general internists . An adaption of the Davis Observation Code was used to measure a patient-centered practice style . The main outcome measures were their use of medical services and related charges monitored over 1 year . Results : Controlling for patient sex , age , education , income , self-reported health status , and health risk behaviors ( obesity , alcohol abuse , and smoking ) , a higher average amount of patient-centered care recorded in visits throughout the 1-year study period was related to a significantly decreased annual number of visits for specialty care ( P = .0209 ) , less frequent hospitalizations ( P = .0033 ) , and fewer laboratory and diagnostic tests ( P = .0027 ) . Total medical charges for the 1-year study were also significantly reduced ( P = .0002 ) , as were charges for specialty care clinic visits ( P = .0005 ) , for all patients who had a greater average amount of patient-centered visits during that same time period . For female patients , the regression equation predicted 15.47 % of the variation in total annual medical charges compared with male patients , for whom 31.18 % of the variation was explained by the average percent of patient-centered care , controlling for sociodemographic variables , health status , and health risk behaviors . Conclusions : Patient-centered care was associated with decreased utilization of health care services and lower total annual charges . Reduced annual medical care charges may be an important outcome of medical visits that are patient-centered Background Patients are increasingly seen as active partners in healthcare . While patient involvement in individual clinical decisions has been extensively studied , no trial has assessed how patients can effectively be involved in collective healthcare decisions affecting the population . The goal of this study was to test the impact of involving patients in setting healthcare improvement priorities for chronic care at the community level . Methods Design : Cluster r and omized controlled trial . Local communities were r and omized in intervention ( priority setting with patient involvement ) and control sites ( no patient involvement ) . Setting : Communities in a canadian region were required to set priorities for improving chronic disease management in primary care , from a list of 37 vali date d quality indicators . Intervention : Patients were consulted in writing , before participating in face-to-face deliberation with professionals . Control : Professionals established priorities among themselves , without patient involvement . Participants : A total of 172 individuals from six communities participated in the study , including 83 chronic disease patients , and 89 health professionals . Outcomes : The primary outcome was the level of agreement between patients ’ and professionals ’ priorities . Secondary outcomes included professionals ’ intention to use the selected quality indicators , and the costs of patient involvement . Results Priorities established with patients were more aligned with core generic components of the Medical Home and Chronic Care Model , including : access to primary care , self-care support , patient participation in clinical decisions , and partnership with community organizations ( p < 0.01 ) . Priorities established by professionals alone placed more emphasis on the technical quality of single disease management . The involvement intervention fostered mutual influence between patients and professionals , which result ed in a 41 % increase in agreement on common priorities ( 95%CI : + 12 % to + 58 % , p < 0.01 ) . Professionals ’ intention to use the selected quality indicators was similar in intervention and control sites . Patient involvement increased the costs of the prioritization process by 17 % , and required 10 % more time to reach consensus on common priorities . Conclusions Patient involvement can change priorities driving healthcare improvement at the population level . Future research should test the generalizability of these findings to other context s , and assess its impact on patient care . Trial registration The Netherl and s National Trial Register # NTR2496 |
11,373 | 27,290,677 | Our meta- analysis suggests a significantly higher risk of TVMI with BRS compared with conventional stents and no significant differences in the rates of occurrence of the other outcomes during one-year follow-up . | AIMS Several studies have suggested good procedural and similar clinical outcomes between everolimus-eluting Absorb bioresorbable stents ( BRS ) versus conventional drug-eluting stents ( DES ) , but the evidence is not definitive .
Our aim was to perform a systematic review and meta- analysis to investigate the effects of BRS versus conventional drug-eluting and bare metallic stents on the cardiovascular endpoints and all-cause mortality . | AIMS We evaluated the feasibility and the acute performance of the everolimus-eluting bioresorbable vascular scaffolds ( BVS ) for the treatment of patients presenting with ST-segment elevation myocardial infa rct ion ( STEMI ) . METHODS AND RESULTS The present investigation is a prospect i ve , single-arm , single-centre study , reporting data after the BVS implantation in STEMI patients . Quantitative coronary angiography and optical coherence tomography ( OCT ) data were evaluated . Clinical outcomes are reported at the 30-day follow-up . The intent-to-treat population comprises a total of 49 patients . The procedural success was 97.9 % . Pre-procedure TIMI-flow was 0 in 50.0 % of the patients ; after the BVS implantation , a TIMI-flow III was achieved in 91.7 % of patients and the post-procedure percentage diameter stenosis was 14.7 ± 8.2 % . No patients had angiographically visible residual thrombus at the end of the procedure . Optical coherence tomography analysis performed in 31 patients showed that the post-procedure mean lumen area was 8.02 ± 1.92 mm(2 ) , minimum lumen area 5.95 ± 1.61 mm(2 ) , mean incomplete scaffold apposition area 0.118 ± 0.162 mm(2 ) , mean intraluminal defect area 0.013 ± 0.017 mm(2 ) , and mean percentage malapposed struts per patient 2.80 ± 3.90 % . Scaffolds with > 5 % malapposed struts were 7 . At the 30-day follow-up , target-lesion failure rate was 0 % . Non-target-vessel revascularization and target-vessel myocardial infa rct ion ( MI ) were reported . A non-target-vessel non-Q-wave MI occurred . No cases of cardiac death or scaffold thrombosis were observed . CONCLUSION In the present series , the BVS implantation in patients presenting with acute MI appeared feasible , with high rate of final TIMI-flow III and good scaffold apposition . Larger studies are currently needed to confirm these preliminary data Objective of this study was to assess the clinical performance of bioresorbable vascular scaffold ( BVS ) compared to everolimus-eluting stent ( EES ) in subjects with ST-segment elevation myocardial infa rct ion ( STEMI ) . We included all consecutive patients with STEMI who underwent percutaneous coronary intervention ( PCI ) with BVS implantation in centers participating to the Italian ABSORB Prospect i ve Registry ( BVS-RAI ) and PCI with EES in the same centers during the same period . The 2 groups were compared . The primary end point was patient-oriented composite end point ( POCE ) including cardiac death , myocardial infa rct ion , and target lesion revascularization ( TLR ) at the longest available follow-up . BVS or EES thrombosis at follow-up was also evaluated . Of the 563 patients with STEMI included , 122 received BVS and 441 EES . Procedural success was obtained in 549 ( 97.5 % ) cases without significant differences between the 2 groups ( BVS 99.3 % vs EES 97.0 % , p = 0.2 ) . At a median of 220-day ( interquartile range 178 to 369 ) follow-up , no significant differences were observed in terms of POCE ( BVS 4.9 % vs EES 7.0 % , p = 0.4 ) ; death ( BVS 0.8 % , EES 2.0 % , p = 0.4 ) , MI ( BVS 4.1 % , EES 2.0 % , p = 0.2 ) , TLR ( BVS 4.1 % , EES 4.5 % , p = 0.8 ) , device thrombosis ( BVS 2.5 % , EES 1.4 % , p = 0.4 ) . All TLR cases were successfully managed with re-PCI in both groups . A propensity matching of the study population s showed no significant differences regarding POCE at the longest available follow-up ( odds ratio 0.53 , 0.1 to 4.3 ) . In conclusion , in this direct prospect i ve comparison , BVS was associated with similar clinical results compared to EES in the STEMI setting . Larger and adequately powered r and omized trials are needed to fully assess the potential clinical benefit of BVS versus the current st and ard of care in patients with STEMI BACKGROUND In patients with coronary artery disease who receive metallic drug-eluting coronary stents , adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall . Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes . METHODS In this large , multicenter , r and omized trial , 2008 patients with stable or unstable angina were r and omly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular ( Absorb ) scaffold ( 1322 patients ) or an everolimus-eluting cobalt-chromium ( Xience ) stent ( 686 patients ) . The primary end point , which was tested for both noninferiority ( margin , 4.5 percentage points for the risk difference ) and superiority , was target-lesion failure ( cardiac death , target-vessel myocardial infa rct ion , or ischemia-driven target-lesion revascularization ) at 1 year . RESULTS Target-lesion failure at 1 year occurred in 7.8 % of patients in the Absorb group and in 6.1 % of patients in the Xience group ( difference , 1.7 percentage points ; 95 % confidence interval , -0.5 to 3.9 ; P=0.007 for noninferiority and P=0.16 for superiority ) . There was no significant difference between the Absorb group and the Xience group in rates of cardiac death ( 0.6 % and 0.1 % , respectively ; P=0.29 ) , target-vessel myocardial infa rct ion ( 6.0 % and 4.6 % , respectively ; P=0.18 ) , or ischemia-driven target-lesion revascularization ( 3.0 % and 2.5 % , respectively ; P=0.50 ) . Device thrombosis within 1 year occurred in 1.5 % of patients in the Absorb group and in 0.7 % of patients in the Xience group ( P=0.13 ) . CONCLUSIONS In this large-scale , r and omized trial , treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold , as compared with an everolimus-eluting cobalt-chromium stent , was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year . ( Funded by Abbott Vascular ; ABSORB III Clinical Trials.gov number , NCT01751906 . ) BACKGROUND The first CE-approved bioresorbable vascular scaffold ( BVS ) is effective at treating simple lesions and stable coronary artery disease , but it has yet to be assessed versus the best-in-class drug-eluting stents ( DES ) . OBJECTIVES This study sought to compare the performance of a BVS with that of everolimus-eluting stents ( EES ) and biolimus-eluting stents ( BES ) in all-comer patients . METHODS The EVERBIO II ( Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents II ) trial was a single-center , assessor-blinded study of 240 patients r and omly assigned in a 1:1:1 ratio to EES , BES , or BVS . The only exclusion criterion was a reference vessel diameter > 4.0 mm , which precluded treatment with BVS . The primary endpoint was angiographic late lumen loss ( LLL ) at 9 months . Secondary endpoints included patient-oriented major acute coronary events ( MACE ) ( death , myocardial infa rct ion [ MI ] , and any revascularization ) , device-oriented MACE ( cardiac death , MI , and target lesion revascularization ) , and stent thrombosis at the 9-month clinical follow-up . RESULTS Follow-up angiography was performed in 216 patients ( 90.7 % ) at 9 months . In-stent LLL was similar between patients treated with BVS ( 0.28 ± 0.39 mm ) and those treated with EES/BES ( 0.25 ± 0.36 mm ; p = 0.30 ) . Clinical outcomes were similar at 9 months : the patient-oriented MACE rate was 27 % in BVS and 26 % in the EES/BES group ( p = 0.83 ) and the device-oriented MACE rate was 12 % in BVS and 9 % in the EES/BES group ( p = 0.6 ) . CONCLUSIONS New-generation metallic DES ( EES/BES ) were not superior to BVS in terms of angiographic LLL and clinical outcomes . ( Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents [ EVERBIO II ] ; NCT01711931 ) OBJECTIVES This study sought to perform clinical and imaging assessment s of the DESolve Bioresorbable Coronary Scaffold ( BCS ) . BACKGROUND BCS , which is drug eluting , may have potential advantages compared with conventional metallic drug-eluting stents . The DESolve system , design ed to provide vessel support and neointimal suppression , combines a poly-l-lactic acid-based scaffold with the antiproliferative myolimus . METHODS The DESolve First-in-Man ( a non-r and omized , consecutive enrollment evaluation of the DESolve myolimus eluting bioresorbable coronary stent in the treatment of patients with de novo native coronary artery lesions ) trial was a prospect i ve multicenter study enrolling 16 patients eligible for treatment . The principal safety endpoint was a composite of cardiac death , myocardial infa rct ion , and clinical ly indicated target lesion revascularization . The principal imaging endpoint was in-scaffold late lumen loss ( LLL ) assessed by quantitative coronary angiography ( QCA ) at 6 months . Intravascular ultrasound ( IVUS ) and optical coherence tomography ( OCT ) imaging was performed at baseline and 6 months ; multislice computed tomography ( MSCT ) was performed at 12 months . RESULTS Acute procedural success was achieved in 15 of 15 patients receiving a study scaffold . At 12 months , there was no scaffold thrombosis and no major adverse cardiac events directly attributable to the scaffold . At 6 months , in-scaffold LLL ( by QCA ) was 0.19 ± 0.19 mm ; neointimal volume ( by IVUS ) was 7.19 ± 3.56 % , with no evidence of scaffold recoil or late malapposition . Findings were confirmed with OCT and showed uniform , thin neointimal coverage ( 0.12 ± 0.04 mm ) . At 12 months , MSCT demonstrated excellent vessel patency . CONCLUSIONS This study demonstrated the feasibility and efficacy of the DESolve BCS . Results showing low in-scaffold LLL , low % neointimal volume at 6 months , no chronic recoil , and maintenance of lumen patency at 12 months prompt further study . ( DESolve First-in-Man ; EudraCT number 2011 - 000027 - 32 ) |
11,374 | 30,548,734 | Analyses including ROI-based studies revealed differences between phobics and healthy subjects in several regions of the limbic circuit .
However , when focusing on whole-brain analysis , only the anterior midcingulate cortex differentiated SP from controls .
The inclusion of ROI-based results artificially inflates group differences in fMRI meta-analyses . | About 90 % of fMRI findings on specific phobias ( SP ) include analysis of region of interest ( ROI ) .
This approach characterized by higher sensitivity may produce inflated results , particularly when findings are aggregated in meta-analytic maps .
Here , we conducted a systematic review and activation likelihood estimation ( ALE ) meta- analysis on SP , testing the impact of the inclusion of ROI-based studies . | Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders . The present study aim ed to identify changes in brain activation following cognitive-behavioral therapy ( CBT ) in subjects suffering from specific phobia . Using functional magnetic resonance imaging ( fMRI ) , brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects . Phobics were r and omly assigned to a therapy-group ( TG ) and a waiting-list control group ( WG ) . Both groups of phobics were scanned twice . Between scanning sessions , CBT was given to the TG . Before therapy , brain activation did not differ between both groups of phobics . As compared to control subjects , phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex ( ACC ) . CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged . In the second scanning session , a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG . These results propose that increased activation in the insula and ACC is associated with specific phobia , whereas an attenuation of these brain responses correlates with successful therapeutic intervention Significance Functional MRI ( fMRI ) is 25 years old , yet surprisingly its most common statistical methods have not been vali date d using real data . Here , we used resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses . Using this null data with different experimental design s , we estimate the incidence of significant results . In theory , we should find 5 % false positives ( for a significance threshold of 5 % ) , but instead we found that the most common software packages for fMRI analysis ( SPM , FSL , AFNI ) can result in false-positive rates of up to 70 % . These results question the validity of a number of fMRI studies and may have a large impact on the interpretation of weakly significant neuroimaging results . The most widely used task functional magnetic resonance imaging ( fMRI ) analyses use parametric statistical methods that depend on a variety of assumptions . In this work , we use real resting-state data and a total of 3 million r and om task group analyses to compute empirical familywise error rates for the fMRI software packages SPM , FSL , and AFNI , as well as a nonparametric permutation method . For a nominal familywise error rate of 5 % , the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference . Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape . By comparison , the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference . These findings speak to the need of validating the statistical methods being used in the field of neuroimaging Neurofunctional mechanisms underlying cognitive behavior therapy ( CBT ) are still not clearly understood . This functional magnetic resonance imaging ( fMRI ) study focused on changes in brain activation as a result of one-session CBT in patients suffering from spider phobia . Twenty-six female spider phobics and 25 non-phobic subjects were presented with spider pictures , generally disgust-inducing , generally fear-inducing and affectively neutral scenes in an initial fMRI session . Afterwards , the patients were r and omly assigned to either a therapy group ( TG ) or a waiting list group ( WG ) . The scans were repeated one week after the treatment or after a one-week waiting period . Relative to the non-phobic participants , the patients displayed increased activation in the amygdala and the fusiform gyrus as well as decreased activation in the medial orbitofrontal cortex ( OFC ) during the first exposure . The therapy effect consisted of increased medial OFC activity in the TG relative to the WG . Further , therapy-related reductions in experienced somatic anxiety symptoms were positively correlated with activation decreases in the amygdala and the insula . We conclude that successful treatment of spider phobia is primarily accompanied by functional changes of the medial OFC . This brain region is crucial for the self-regulation of emotions and the relearning of stimulus-reinforcement associations BACKGROUND The study aim ed to identify brain activation during direct and automatic processing of phobogenic stimuli in specific phobia . METHODS Responses to phobia-related and neutral pictures ( spiders and mushrooms ) were measured by means of event-related functional magnetic resonance imaging during two different tasks . In the identification task , subjects were asked to identify the object ( spider or mushroom ) . In a dem and ing distraction task , subjects had to match geometric figures displayed in the foreground of the pictures . RESULTS Phobics showed greater responses to spiders versus mushrooms in the left amygdala , left insula , left anterior cingulate gyrus ( ACC ) , and left dorsomedial prefrontal cortex ( DMPFC ) during the identification task and in the left and right amygdala during the distraction task . All of these activations were also significantly increased compared to control subjects who did not show stronger brain activation to spiders versus mushrooms under any task condition . CONCLUSIONS Our findings propose specific neural correlates of automatic versus direct evaluation of phobia-relevant threat . While the amygdala , especially the right amygdala , seems to be crucially involved in automatic stimuli processing , activation of areas such as the insula , ACC and DMPFC is rather associated with direct threat evaluation and requires sufficient attentional re sources BACKGROUND Neurocircuitry models of anxiety disorders suggest dysregulated mechanisms encompassing both automatic and elaborate threat processing . However , the extent to which these processes might be differentially modified by psychotherapy and the neural basis of such changes are unknown . We examined the effects of cognitive-behavioral therapy ( CBT ) in patients with anxiety disorder on brain responses to subliminal and supraliminal threat . METHODS 3-Tesla functional magnetic resonance imaging was used to assess neural responses to disorder-related stimuli , presented during two backward-masking conditions employed to manipulate stimulus awareness . In 28 spider-phobic patients r and omly assigned to a therapy group or a waiting-list control group scanning was performed before and after completing CBT or a waiting period . Scanning was performed one time in 16 healthy control subjects . Self-report and behavioral measures were used to relate CBT-mediated brain activation changes with symptom improvement . RESULTS Untreated patients demonstrated abnormal hyperactivation in the amygdala , fusiform gyrus , insula , anterior cingulate cortex , and dorsomedial prefrontal cortex . Successful CBT was reflected in an overall downregulation in these fear circuitry structures , especially in the right amygdala and anterior cingulate cortex , with reductions in amygdala responsiveness associated with self-reported symptom improvement . However , subliminal threat induced a pattern of right-lateralized hyperactivation in the amygdala and fusiform gyrus that was subject to intersession habituation across groups without showing significant sensitivity to CBT . CONCLUSIONS These results challenge prevailing models that emphasize a role for amygdala automaticity in the maintenance of anxiety . Our results suggest CBT-related changes in neural activation associated with fear responses to consciously perceived threat Anxiety disorder patients were repeatedly found to overestimate the association between disorder-relevant stimuli and aversive outcomes despite r and om contingencies . Such an illusory correlation ( IC ) might play an important role in the return of fear after extinction learning ; yet , little is known about how this cognitive bias emerges in the brain . In a functional magnetic resonance imaging study , 18 female patients with spider phobia and 18 healthy controls were exposed to pictures of spiders , mushrooms and puppies followed r and omly by either a painful electrical shock or nothing . In advance , both patients and healthy controls expected more shocks after spider pictures . Importantly , only patients with spider phobia continued to overestimate this association after the experiment . The strength of this IC was predicted by increased outcome aversiveness ratings and primary sensory motor cortex activity in response to the shock after spider pictures . Moreover , increased activation of the left dorsolateral prefrontal cortex ( dlPFC ) to spider pictures predicted the IC . These results support the theory that phobia-relevant stimuli amplify unpleasantness and sensory motor representations of aversive stimuli , which in turn may promote their overestimation . Hyper-activity in dlPFC possibly reflects a pre-occupation of executive re sources with phobia-relevant stimuli , thus complicating the accurate monitoring of objective contingencies and the unlearning of fear Behavioural studies suggest that phobic subjects are hypersensitive in the processing of phobia-related linguistic stimuli . We used functional magnetic resonance imaging ( fMRI ) to investigate blood oxygen level dependent ( BOLD ) brain activation to phobia-relevant words in spider phobic and non-phobic subjects . Phobia-related versus phobia-unrelated words elicited increased activation in prefrontal cortex , insula , and posterior cingulate cortex in spider phobics , while these effects were absent in controls . Furthermore , between-group comparisons confirmed that differential activations within these brain regions were specifically due to increased responses to phobia-related stimuli in phobics . Our results provide first insights into brain activation patterns when phobics are confronted with phobia-specific linguistic information und suggest a neural network for the processing of these threatening stimuli BACKGROUND The amygdala is implicated as a key brain structure in fear processing . Studies exploring this process using the paradigm of fear conditioning have implicated the amygdala in fear acquisition and in generating behavioral fear responses . As such , fear extinction could be expected to induce a reduction in amygdala activity . However , exposure in specific phobia has never been shown persistently to reduce amygdala activity . METHODS By means of event-related functional magnetic resonance imaging , responses to phobia-related , general threat , and neutral pictures were measured before and 2 weeks after an intensive exposure session in 20 subjects with specific phobia for spiders and compared with healthy control subjects . RESULTS Phobic subjects showed increased amygdala activity at baseline . This hyperactivity was significantly reduced 2 weeks after exposure therapy . Furthermore , a significant reduction of hyperactivity in anterior cingulate cortex and insula was found postexposure . CONCLUSIONS To our knowledge , this is the first study demonstrating the effect of exposure on the amygdala in specific phobia . Our findings suggest that exposure therapy can have an effect on subcortical structures Visiting the dentist is often accompanied by apprehension or anxiety . People , who suffer from specific dental phobia ( a disproportional fear of dental ) procedures show psychological and physiological symptoms which make dental treatments difficult or impossible . For such purpose s , hypnosis is often used in dental practice as an alternative for a number of treatments adjuvant or instead of sedation or general anaesthetics , as medication is often associated with risks and side effects . This is the first study to address the effects of a brief dental hypnosis on the fear processing structures of the brain in dental phobics using functional magnetic resonance imaging ( fMRI ) . 12 dental phobics ( DP ; mean 34.9years ) and 12 healthy controls ( CO ; mean 33.2years ) were scanned with a 3 T MRI whole body-scanner observing brain activity changes after a brief hypnotic invervention . An fMRI event-related design symptom provocation task applying animated audio-visual pseudor and omized strong phobic stimuli was presented in order to maximize the fearful reactions during scanning . Control videos showed the use of familiar electronic household equipment . In DP group , main effects of fear condition were found in the left amygdala and bilaterally in the anterior cingulate cortex ( ACC ) , insula and hippocampu ( R < L ) . During hypnosis DP showed a significantly reduced activation in all of these areas . Reduced neural activity patterns were also found in the control group . No amygdala activation was detected in healthy subjects in the two experimental conditions . Compared to DP , CO showed less bilateral activation in the insula and ACC in the awake condition . Findings show that anxiety-provoking stimuli such as undergoing dental surgery , endodontic treatments or insufficient anaesthetics , can be effectively reduced under hypnosis . The present study gives scientific evidence that hypnosis is a powerful and successful method for inhibiting the reaction of the fear circuitry structures |
11,375 | 23,912,477 | Reduced gamete exposure time may be associated with beneficial outcomes . | BACKGROUND Conflicting results have been reported regarding the technique of brief insemination used in IVF .
The aim of this meta- analysis was to determine if better clinical outcomes of IVF are associated with a brief co-incubation of gametes than with a st and ard overnight co-incubation . | A prospect i ve , r and omized study of 158 patients undergoing in-vitro fertilization ( IVF ) and embryo transfer was conducted to evaluate whether a shortened exposure of oocytes to spermatozoa enhances oocyte development , and subsequently influences the IVF outcome . A comparison was made between conventional treatment time and shorter exposure of retrieved oocytes to spermatozoa . Fertilization and cleavage rates , embryo quality , implantation and pregnancy rates in the study group ( short exposure ) versus controls ( st and ard IVF procedure ) were evaluated . Fertilization ( 56 versus 61 % ) and cleavage rates ( 96 versus 92 % ) were similar in the two groups respectively . However , embryo quality was significantly higher in the study group ( P < 0.05 ) . Moreover , the pregnancy and implantation rates were significantly increased ( 42.4 versus 26 % per embryo transfer , and 16 versus 10 % respectively ; P < 0.05 ) . Our results demonstrated that shorter exposure of oocytes to spermatozoa is superior to the st and ard time in IVF and may have a favourable effect on implantation rates by improving embryo quality OBJECTIVE To confirm whether brief exposure of human oocytes to spermatozoa in vitro results in equivalent fertilization rates and possibly better quality embryos than overnight coincubation and to determine if there was a difference in outcome with regard to the type of culture medium used . DESIGN Prospect i ve distribution of gametes between treatments in sequential patients . SETTING Assisted reproductive technology program in private hospital . PATIENT(S ) Consecutively treated subfertile couples entering an infertility program . INTERVENTION(S ) Assisted reproductive technology treatment for infertility involving oocyte retrieval and in vitro fertilization . MAIN OUTCOME MEASURE(S ) When possible , the outcome of fertilization and embryo quality were compared when gametes were coincubated for 1 hour or overnight . Two different formulations of human tubal fluid were compared in some cases . RESULT ( S ) There was no statistically significant difference in fertilization rates between a brief or overnight coincubation of gametes or between the two treatment groups with regard to the type of culture medium used . The quality of the embryos was significantly better in the 1-hour exposure group . The embryos in Basal XI human tubal fluid medium were of significantly better morphological quality than their siblings in D3 + human tubal fluid medium . CONCLUSION ( S ) Coincubation of oocytes and spermatozoa for a shorter period produced embryos of superior morphological quality than the generally accepted overnight protocol . A simple glucose and phosphate-free human tubal fluid medium result ed in early cleavage embryos of better morphological quality than a medium supplemented with glucose , taurine , and glutathione Human oocyte development was evaluated after a reduced time exposure to spermatozoa in vitro . A total of 119 patients were assigned to two study groups in a r and omized prospect i ve study in which each patient 's oocytes were exposed to spermatozoa for either 1 h ( group 1 - 58 patients ) or the st and ard 16 h incubation period ( group 2 - 61 patients ) . The fertilization rate obtained in group 1 was higher than in group 2 ( 285/393 , 73 % , and 272/410 , 66 % respectively ) , suggesting that the spermatozoa-oocyte interaction occurs within 1 h. This was confirmed in a study in vitro using fluorescently labelled spermatozoa and normal oocyte-cumulus complexes . Spermatozoa enter the cumulus complex within 15 min , traverse the cumulus layer within 3 h , and first appear in the oocyte cortex at 4 h post-insemination . The incidence of polyspermy was higher in oocytes exposed to spermatozoa for 16 h ( 3 % ) than for 1 h ( 1 % ) . There was no difference in the cleavage rate or morphological characteristics of embryos from both study groups . However , when evaluating the timing of embryo development , group 1 generated a significantly higher percentage of four to five cell embryos when compared to group 2 ( 55 versus 39 % ; P < 0.001 ) , documented at 40 h post-insemination . The implantation and pregnancy rates for group 1 were 11 and 28 % , while the corresponding rates for group 2 were 8 and 15 % . This suggests that a reduced exposure of oocyte to spermatozoa favours embryo viability , possibly due to a decrease in potential damage from sperm metabolic waste products Purpose : Recent studies showed a beneficial effect of reducing the time of sperm – oocyte interaction on fertilization , division , and implantation rates of the oocytes obtained from r and omized patients . In the present study , the effects of reduced insemination time on fertilization and embryo development were evaluated by using sibling oocytes from the same patient . Methods : A total of 464 oocytes from 36 patients was r and omly allocated to be inseminated for either 1 hr ( reduced ) or 18 hr ( regular ) . Results : Fertilization rates were not significantly different between reduced ( 135/229 ; 59 % ) and regular ( 150/235 ; 64 % ) groups . Cleavage rates and embryo quality were similar in both groups . A total of 135 embryos ( 73 from the reduced and 62 from the regular group ) was transferred to 36 patients . Thirty-four embryos implanted in 18 patients ( 25.2 % implantation and 50.0 % pregnancy rates ) . Conclusions : Fertilization , cleavage , and embryo development from 1-hr insemination is comparable , not superior , to those from an 18-hr insemination time , which is commonly used in in vitro fertilization programs . These data suggest that reduced insemination time can be used during in vitro fertilization to avoid unnecessarily longer exposure to spermatozoa BACKGROUND Traditionally oocytes have been exposed to sperm overnight , for 16 - 20 h. This long period of co-incubation , however , has been shown to create problems with high levels of reactive oxygen species ( ROS ) , which may affect embryo viability and cause hardening of the zona pellucida . Recently , a positive effect of reducing the co-incubation time to 90 - 120 min was reported . The objective of this study was to evaluate whether a further reduction of the co-incubation period could benefit the outcome of IVF . METHODS In this prospect i ve study , 777 sibling oocytes from 81 women undergoing IVF were divided via alternate allocation to co-incubation for either 30 s ( ultrashort co-incubation ) ( group A ) or for 90 min ( st and ard co-incubation ) ( group B ) . Endpoints were normal fertilization ( two-pronuclear , 2PN ) , polyspermy ( > 2PN ) , embryo quality ( EQ ) , clinical pregnancy ( CP ) and implantation ( IR ) . RESULTS The normal fertilization rates of the two groups were comparable : group A 58.6 % versus group B 58.0 % . Significantly lower rates of polyspermy were seen in group A compared to group B ( 2.8 versus 7.2 % , P = 0.008 ) . No statistically significant differences in EQ , CP or IR were seen . CONCLUSION This is the first study demonstrating the achievement of good fertilization rates in IVF with ultrashort co-incubation . Significantly lower rates of polyspermy were seen in the group with ultrashort compared to the st and ard co-incubation group . Further studies are , however , needed in order to evaluate whether ultrashort co-incubation has any effect on the outcome of IVF Comparisons were made among techniques used to treat male factor infertility . Patients with semen quality below that recognized by World Health Organization criteria as normal had a better success rate when treated by gamete intrafallopian transfer than by in vitro fertilization ( 25 % v. 7 % pregnancy rate per patient ) . When < 2 x 10(6 ) motile sperm were recovered , the fertilization rate and embryo cleavage rate were higher for microdrop insemination than for conventional insemination . When 7000 - 370,000 motile sperm were recovered , microdrop insemination result ed in a higher fertilization rate ( 46 % ) and a higher incidence of pregnancies ( 23 % of patients treated ) than subzonal sperm microinjection ( SUSM ) . However , for patients with 5000 - 50,000 motile sperm , the immediate transfer of SUSM oocytes to the Fallopian tube increased pregnancy rates for this technique to 24 % of patients treated . Direct microinjection of epididymal sperm from azoospermic men into the cytoplasm of oocytes result ed in pronuclear formation in 27 % of oocytes ; in comparison , pronuclear formation occurred in 5 % of SUSM oocytes . These data led to formulation of a logical treatment programme for male factor infertility Altering the coincubation time for spermatozoa and oocytes in vitro leads to varying results . Some authors suggest that longer exposure of spermatozoa to oocytes through coincubation is detrimental to fertilization and /or embryo development , possibly because of reactive oxygen species produced by the spermatozoa ( 1–5 ) . Other studies indicate that a decreased exposure time does not alter fertilization rates ( 3,6–9 ) and may even improve such rates ( 10–13 ) . In this report , we describe the results of our r and omized study on the effects of two coincubation times on in vitro fertilization ( IVF ) rates and embryo quality OBJECTIVE To examine the benefits of short coincubation of gametes compared to prolonged incubation in in vitro fertilization ( IVF ) . DESIGN Prospect i ve r and omized controlled study . SETTING Hospital-based fertility center . PATIENT(S ) One hundred thirty patients ( group 1 ) and 129 patients ( group 2 ) . INTERVENTION(S ) Oocytes from group 1 were exposed to spermatozoa for 2 hours , and oocytes from group 2 were exposed to spermatozoa for 20 hours . MAIN OUTCOME MEASURE(S ) Fertilization and cleavage rates , embryo quality , and pregnancy and implantation rates were evaluated . Estradiol ( E(2 ) ) and progesterone ( P(4 ) ) levels were measured in the wells of culture dishes after 2-hour exposure of oocytes/zygotes to spermatozoa in group 1 and after 20-hour exposure in both the groups . RESULT ( S ) There was no difference between the two groups in the fertilization rate and the number of embryos obtained . However , the proportion of grade 1 embryos was significantly higher among group 1 compared to group 2 patients . Clinical pregnancy and implantation rates were significantly higher among group 1 compared to group 2 . The significantly higher levels of E(2 ) and P(4 ) in the 20-hour cultures compared with the 2-hour cultures may have been detrimental to embryo quality , pregnancy , and implantation rates . CONCLUSION ( S ) Coincubation of gametes for 2 hours with st and ard or high insemination concentrations of spermatozoa significantly improved embryo quality and the pregnancy and implantation rates compared with overnight incubation of gametes Purpose Evaluate the effect of short gamete incubation on fertilization rate and embryo quality . Methods A prospect i ve study has been performed . Two thous and five hundred and forty seven sibling oocytes from 240 couples undergoing IVF attempts were allocated to a short ( 1 h ) or a st and ard ( 18 h ) insemination procedure . Diploid fertilization rate ( two pronuclei , 2PN ) , polyspermy ( > 2PN ) and embryo quality were compared . Results The fertilization rate was statistically lower in the short insemination group compared to the st and ard insemination one ( 64.9 % and 70.1 % ; P = 0.039 ) , with a similar polyspermy rate observed between the two groups . A slight , but non significant , increase was observed concerning good embryo quality rate in the short insemination group when compared to the st and ard insemination , both at day 2 ( 60.1 vs. 58.1 % ; P = 0.06 ) and day 3 ( 53.2 vs. 48.5 % ; P = 0.22 ) . Conclusion This new study highlights that a 1 h gamete exposure decreases the fertilization rate and does not improve embryo quality compared with a st and ard 18 h insemination procedure Abstract Purpose : To investigate whether very short exposure ofmature oocytes to sperm in vitro may affect the fertilizationrates , embryo cleavage rates , and embryo quality betweensibling oocytes in the same patient . Methods : Sibling oocytes of the same patient from 23 oocyte collection cycles were r and omly allocated to the study group , with a 1-hr or 3-hr sperm — oocyte incubation , or the controlgroup with the st and ard overnight gamete co-incubation . The fertilization rates , cleavage rates , and subsequentembryo quality were evaluated . Results : Our results showed no statistically significant differencesin fertilization rates , embryo cleavage rates , and quality of the embryos between the study group and thecontrol group . Conclusions : Since the present study showed that long exposureof the oocyte to sperm has no advantage over shortexposure , we prefer shortening the oocyte — sperm incubationperiod for reducing the negative effect induced bynonphysiologically high concentrations of spermatozoa OBJECTIVE To evaluate the results of a novel protocol that allows to rescue IVF unfertilized oocytes by intracytoplasmic sperm injection ( ICSI ) . DESIGN Prospect i ve clinical trial . SETTING Private reproductive medical center . PATIENT(S ) Thirty patients undergoing IVF . INTERVENTION(S ) Controlled ovarian stimulation ( COS ) , conventional IVF , rescue ICSI , embryo culture , and embryo transfer . MAIN OUTCOME MEASURE(S ) Identification of unfertilized IVF oocytes 6 hours after insemination and fertilization , and developmental rates of those oocytes after rescue microinjection , as well implantation and pregnancy rates ( PR ) . RESULT ( S ) All oocytes ( 392 ) from 30 patients were inseminated with st and ard IVF 3 hours after ovum pick-up . Polar body ( PB ) status was checked at decumulation and rechecked 3 hours later . Eighty-two oocytes were fertilized after IVF alone and 184 nonactivated oocytes ( failed fertilization ) were rescue microinjected and 166 of them fertilized ( 20 patients ) . Cleavage stage on day 2 was significantly more advanced and embryo grade was higher after st and ard IVF fertilization than after rescue ICSI . Eight of the 30 embryos transferred were implanted in the IVF-only patients ( 27 % ) and 8 of 68 embryos in the rescue ICSI patients ( 12 % ) . CONCLUSION ( S ) Rescue ICSI of unfertilized IVF oocytes 6 hours after insemination ( 9 hours after egg retrieval ) can provide normal fertilization , embryo development , and pregnancy ; however , corresponding outcome parameters tend to be impaired in comparison to the st and ard IVF fertilization results Although the average fertilization rate in most in-vitro fertilization ( IVF ) centres is approximately 60 - 70 % , there are cases of complete or virtually complete fertilization failures . The aim of our work was to study the fertilization and the subsequent cleavage characteristics of 1-day-old human oocytes treated by intracytoplasmic single sperm injection ( ICSI ) after failing to fertilize during the st and ard IVF procedure . A total of 115 metaphase II 1-day-old unfertilized oocytes were collected from 23 patients . No additional treatment was applied to the oocytes or to the semen sample . A single spermatozoon from the patient 's husb and was injected into the cytoplasm of each of these oocytes 21 - 33 h after ovum retrieval . Injected oocytes were observed at 16 - 18 h and again 42 - 44 h after the ICSI procedure . Of the injected oocytes , 92 % ( n = 106 ) were intact after ICSI , 38 % ( n = 44 ) had two distinct pronuclei and there was no difference in the fertilization rate of oocytes when and rological and non- and rological patients were compared . Similarly , there was no difference in the fertilization rate after ICSI where patients with acceptable or good ( > 15 % ) fertilization after st and ard IVF were compared to patients who had poor ( < or = 15 % ) fertilization after IVF . There was no significant difference in the sperm concentration or in the progressive forward motility ( a + b motility ) in these groups except where a + b motility of and rological and non- and rological patients was compared . The majority ( 84 % ) of the normally fertilized oocytes cleaved and most ( 77 % ) of these embryos showed < 20 % fragmentation 2 days after the ICSI procedure . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this prospect i ve r and omized work was to study the value of co-culturing human pronucleate oocytes with their cumulus cells . A total of 550 fertilized oocytes from 95 in-vitro fertilization patients were r and omly divided into two groups on the day after insemination . Group A oocytes ( n = 260 ) were left undisturbed with their attached cumulus cells and group B oocytes ( n = 290 ) were dissected from their cumulus cells . Both groups were incubated and examined daily for 3 days . In group A , 78 % ( 202/260 ) reached the 4-cell stage 48 h after retrieval compared to 69 % ( 200/290 ) in group B. At 72 h after retrieval , 70 % ( 141/202 ) had reached the 8-cell stage in group A compared to 56 % ( 112/200 ) in group B. The percentages of grade 1 embryos at 48 and 72 h after retrieval were 70 % ( 141/202 ) and 76 % ( 107/141 ) in group A compared to 50 % ( 100/200 ) and 43 % ( 48/112 ) in group B respectively . We concluded that co-culture of human oocytes with their cumulus cells significantly decreased their fragmentation and increased the number of embryos that reached the 4-cell and 8-cell stages with regular blastomeres . The technique is simple and avoids the use of heterogeneous cells Reports concerning the benefit of reducing the co-incubation time of gametes in connection with IVF have been conflicting . The present r and omized study was undertaken to determine whether a reduced co-incubation time would improve the embryo development and consequently the pregnancy and implantation rates . Oocytes from 87 patients were collected and half the oocytes from each patient ( n = 488 , group A ) were r and omized to 2 h incubation and the other half ( n = 504 , group B ) to overnight incubation . The oocytes were then cultured according to our st and ard procedure . Significant difference ( P = 0.02 ) was observed between the two groups regarding fertilization rate and polyspermy ( group A 72.5 % , 3 % and group B 80.5 % , 6 % respectively ) . However , no difference was observed in further development and morphology of the embryos . The two embryos with the best morphological score were selected for transfer . No significant difference was found between the different transfer groups regarding positive serum HCG and implantation rate . CONCLUSION : The present results and results from previously published studies indicate that the most important factor in connection with the culture method currently used is the amount of sperm added for co-incubation . This should be optimized to reduce the concentration of harmful sperm waste products and create optimal culture conditions A prospect i ve , r and omized study was conducted to evaluate the thickness of zona pellucida ( ZP ) after brief or st and ard exposure of human oocytes to spermatozoa , and to determine the correlation between ZP thickness , fertilization rate and embryo quality . The mean ZP thickness 48 h after insemination was found to be significantly less in fertilized oocytes than in non-fertilized oocytes in all treated groups ( 13.72 ± 3.0 µm and 15.08 ± 2.5 µm , respectively ; p < 0.007 ) . Zona pellucida thickness correlated positively with embryo quality . Brief exposure of gametes was found to influence ZP thickness . The ZP was significantly thinner after brief and intracytoplasmic sperm injection ( ICSI ) exposure of oocytes to spermatozoa than after st and ard in vitro fertilization ( IVF ) . The mean ZP thickness 24 and 48 h after fertilization was significantly greater in st and ard IVF ( 16.43 ± 2.8 µm and 15.22 ± 2.7 µm , respectively ) than in either the brief exposure or ICSI groups ( 12.78 ± 2.4 µm and 13.01 ± 3.5 µm vs. 13.46 ± 2.2 µm and 13.16 ± 2.4 µm ; p < 0.0001 ) A reduced time interval of oocyte exposure to spermatozoa was investigated to assess whether it could enhance oocyte development and improve embryo viability , especially in cases of male factor infertility . A total of 167 patients were included in a prospect i ve r and omized study . They were r and omly allocated to two major study groups , A ( n = 85 ) and B ( control group ; n = 82 ) . The oocytes from group A patients were exposed to spermatozoa for only 1 h ; those from group B were exposed for 16 h. The two study groups were then subdivided according to semen quality for further analysis of the results . Significantly higher percentages were obtained in group A than in group B in terms of the fertilization rate ( 74 versus 68 % , P < 0.025 ) , cleavage rate ( 53 versus 41 % , P < 0.005 ) , pregnancy rate ( 27 versus 12 % , P < 0.05 ) and implantation rate ( 11 versus 6 % , P < 0.05 ) . In addition , an increased fertilization rate was achieved in oocytes exposed to male factor spermatozoa for only 1 h compared with the conventional incubation period ( 78 versus 65 % , P < 0.01 ) . Advanced cellular stages ( 55 versus 41 % , P < 0.02 ) and higher implantation rates ( 13 versus 4 % , P < 0.05 ) were attained in the subgroup whose oocytes were exposed to normal spermatozoa for 1 h compared with the male factor spermatozoa with the st and ard culture interval . The higher fertilization rates , enhanced embryo development and viability achieved in group A indicate that prolonged exposure of oocytes to high concentrations of spermatozoa is detrimental , decreasing sperm-oocyte interaction and subsequent embryo implantation , particularly in male factor patients |
11,376 | 19,254,967 | A range of training , management , funding and organizational barriers existed in the implementation of these lay educator programmes .
Conclusions .
Peer-to-peer support and education programmes in diabetes have been considered useful in New Zeal and . | BACKGROUND Peer-to-peer support has the potential to assist people with diabetes , or at risk of diabetes .
OBJECTIVE To review the development of diabetes peer support initiatives in New Zeal and . | AIM To determine prevalence of known diabetes in those more than 20 years of age in Chennai city . METHODOLOGY Urban population was selected for the survey . Assuming the prevalence of known diabetes as 5.0 % in those aged > 20 years , the cluster sample size calculated to estimate it with 95 % CI and + /- 10 % precision , was 25800 individuals of all ages . This population obtained from 200 households in each of 30 r and omly selected corporation divisions of the city , was surveyed by social workers by house to house enquiry . General information and health status of every member of the household were recorded on prescribed forms . This survey was conducted during January-July , 1998 . RESULTS Among 26,066 individuals of all ages 779 had known diabetes and 99.4 % of them had type 2 diabetes . The prevalence of known diabetes was 2.9 % for all ages and both sexes combined . Crude and age-st and ardized prevalence was 4.9 % ( 95 % CI 4.6 - 5.2 ) for those aged > 20 years . The st and ardized prevalence was 10.5 % ( 95 % CI 9.8 - 11.2 ) in those aged > or = 40 years . The prevalence was significantly high ( P < 0.05 ) in females . CONCLUSION The prevalence of known diabetes was low in total population but increased in those aged > 20 and further increased in those aged > or = 40 years . The causes for high prevalence in > or = 40 year age group needs to be explored in this population AIMS To compare the impact on weight and exercise of a 2-year church-based diabetes risk reduction programme in four churches in South Auckl and , New Zeal and . METHODS A prospect i ve non-r and omized controlled study of a modular lifestyle and diabetes awareness intervention programme applying community development principles . The study involved four complete church congregations , two Samoan and two Tongan , with 516 participants at commencement . Risk of Type 2 diabetes is high among both ethnic groups . RESULTS Overall , 285 subjects were available for their second assessment . In one intervention church , weight gain was controlled ( vs. control 0 + /- 4.8 vs. + 3.1 + /- 9.8 kg , respectively ; P=0.05 ) , diabetes knowledge ( + 46 + /- 26 % vs. + 4 + /- 17 % ; P<0.001 ) and regular exercise ( at least 3 days per week : + 22 % vs. -8 % ; P=0.032 ) increased and readiness to change weight ( P=0.007 ) shifted towards maintenance ( e.g. maintenance + 41 % vs. + 8 % , respectively ) . The other intervention church increased diabetes knowledge ( + 19 + /- 24 vs. + 8 + /- 25 ; P<0.024 ) , but no other significant personal changes occurred . Attendance and perceived utility of the programme were greater in the first intervention church . CONCLUSIONS A moderate intensity , community-based , structured diabetes awareness and lifestyle programme can reduce diabetes risk , but increasing diabetes knowledge alone is not necessarily associated with healthier lifestyle choices . Continuous and detailed monitoring of penetration of interventions may be essential to help guide the timing of interventions and identify the need for additional strategies to increase participation and motivation AIMS To evaluate the acceptability and impact of a pilot diabetes awareness and exercise programme in a mainly Polynesian workforce . METHOD Comparison of change in question naire and anthropometric measurements in two hospital ancillary workforces . One group ( n = 108 ) received one community diabetes educator presentation , one video presentation and a 4 month exercise programme . The other group ( n = 99 ) served as controls . RESULTS Baseline diabetes knowledge was poor ( total score 26 ( SD 13 % ) ) and subjects were largely unfit with a high body mass index ( 31.5 ( 7.1 ) kg/m2 ) . The exercise sessions were well attended , although attendance declined over the 4 months . Increased diabetes knowledge was retained in the intervention group after 6 months when compared with controls ( total score 35(14)% vs 26(12)% respectively , p < 0.001 ) . One month after the termination of the programme , the proportion reporting regular exercise activity ( at least 30 minutes for 3 days per week ) had increased by 2 % in the intervention group but declined by 9 % in the control group ( p < 0.05 ) . CONCLUSIONS Diabetes knowledge and exercise can be increased in unfit subjects by the combination of culturally tailored exercise techniques and community diabetes educator/video presentations |
11,377 | 27,354,969 | Evidence to date suggests few sex differences in FEP in schizophrenia ; both men and women across the schizophrenia spectrum have deficits in FEP | AIM To review the literature on sex differences in facial emotion perception ( FEP ) across the schizophrenia spectrum . | Rationale Impaired emotion processing in schizophrenia predicts broader social dysfunction and has been related to negative symptom severity and amygdala dysfunction . Pharmacological modulation of emotion-processing deficits and related neural abnormalities may provide useful phenotypes for pathophysiological investigation . Objectives We used an acute benzodiazepine challenge to identify and modulate potential emotion-processing abnormalities in 20 unaffected first-degree relatives of individuals with schizophrenia , compared to 25 control subjects without a family history of psychosis . Methods An oral 1 mg dose of the short-acting anxiolytic benzodiazepine alprazolam was administered in a balanced crossover placebo-controlled double-blind design , preceding identical 3 T fMRI sessions approximately 1 week apart . Primary outcomes included fMRI activity in amygdala and related regions during two facial emotion-processing tasks : emotion identification and emotion memory . Results Family members exhibited abnormally strong alprazolam-induced reduction in amygdala and hippocampus activation during emotion identification , compared to equal reduction in both groups for the emotion memory task . Conclusions GABAergic modulation with alprazolam produced differential responses in family members vs. controls , perhaps by unmasking underlying amygdalar and /or GABAergic abnormalities . Such pharmacological fMRI paradigms could prove useful for developing drugs targeting specific neural circuits to treat or prevent schizophrenia PURPOSE Social cognition captures affect recognition , social cue perception , " theory of mind , " empathy , and attributional style . The aim of our study was to assess social cognition in schizophrenia in patients being treated with first-generation antipsychotic drugs ( FGAs ) , n=28 ( perphenazine and haloperidol , FGAs ) or with second-generation antipsychotic drugs ( SGAs ) , n=56 ( olanzapine and clozapine , SGAs ) . SUBJECTS AND METHODS Eighty-four patients completed the Facial Expression Recognition Test , the Voice Emotion Recognition Test , the Short Recognition Memory Test for Faces , and the Reading the Mind in the Eyes Test . Patients also completed the Visual Object and Space Perception Test ( VOSP ) as a control task , which would not engage social cognition . The patients were compared with fifty healthy controls matched for age and gender . RESULTS There were no significant differences on social cognitive performance between the FGA- and SGA-treatment groups . Nor was olanzapine superior to clozapine , FGAs or both . However , patients treated with FGAs performed significantly worse on VOSP compared to both groups treated with SGAs , a 10 % difference . CONCLUSIONS We can not conclude that SGAs were associated with better social cognition than FGAs . However , there were small but significant advantages for SGAs in non-social visual processing function , as evaluated with the VOSP |
11,378 | 23,757,486 | These results indicate that compression garments are effective in enhancing recovery from muscle damage | The purpose of the study was to determine the effects of compression garments on recovery following damaging exercise . | OBJECTIVES The purpose of this study was to investigate the physiological and psychological effects of massage on delayed onset muscle soreness ( DOMS ) . METHODS Eighteen volunteers were r and omly assigned to either a massage or control group . DOMS was induced with six sets of eight maximal eccentric contractions of the right hamstring , which were followed 2 h later by 20 min of massage or sham massage ( control ) . Peak torque and mood were assessed at 2 , 6 , 24 , and 48 h postexercise . Range of motion ( ROM ) and intensity and unpleasantness of soreness were assessed at 6 , 24 , and 48 h postexercise . Neutrophil count was assessed at 6 and 24 h postexercise . RESULTS A two factor ANOVA ( treatment v time ) with repeated measures on the second factor showed no significant treatment differences for peak torque , ROM , neutrophils , unpleasantness of soreness , and mood ( p > 0.05 ) . The intensity of soreness , however , was significantly lower in the massage group relative to the control group at 48 h postexercise ( p < 0.05 ) . CONCLUSIONS Massage administered 2 h after exercise induced muscle injury did not improve hamstring function but did reduce the intensity of soreness 48 h after muscle insult Abstract The aim of this study was to examine the effect of wearing graduated compression stockings on physiological and perceptual variables during and after intermittent ( Experiment 1 ) and continuous ( Experiment 2 ) running exercise . Fourteen recreational runners performed two multi-stage intermittent shuttle running tests with 1 h recovery between tests ( Experiment 1 ) . A further 14 participants performed a fast-paced continuous 10-km road run ( Experiment 2 ) . Participants wore commercially available knee-length graduated compression stockings ( pressure at ankle 18 – 22 mmHg ) beneath ankle-length sports socks ( experimental trials ) or just the latter ( control trials ) in a r and omized counterbalanced design ( for both experiments ) . No performance or physiological differences were observed between conditions during intermittent shuttle running . During the 10-km trials , there was a reduction in delayed-onset muscle soreness 24 h after exercise when wearing graduated compression stockings ( P < 0.05 ) . There was a marked difference in the frequency and location of soreness : two participants in the stockings trial but 13 participants in the control trial indicated soreness in the lower legs . Wearing graduated compression stockings during a 10-km road run appears to reduce delayed-onset muscle soreness after exercise in recreationally active men The aim of this investigation was to eluci date the efficacy of repeated cold water immersions ( CWI ) in the recovery of exercise induced muscle damage . A r and omised group consisting of eighteen males , mean ± s age , height and body mass were 24 ± 5 years , 1.82 ± 0.06 m and 85.7 ± 16.6 kg respectively , completed a bout of 100 drop jumps . Following the bout of damaging exercise , participants were r and omly but equally assigned to either a 12 min CWI ( 15 ± 1 ° C ; n = 9 ) group who experienced immersions immediately post-exercise and every 24 h thereafter for the following 3 days , or a control group ( no treatment ; n = 9 ) . Maximal voluntary contraction ( MVC ) of the knee extensors , creatine kinase activity ( CK ) , muscle soreness ( DOMS ) , range of motion ( ROM ) and limb girth were measured pre-exercise and then for the following 96 h at 24 h increments . In addition MVC was also recorded immediately post-exercise . Significant time effects were seen for MVC , CK , DOMS and limb girth ( p < 0.05 ) indicating muscle damage was evident , however there was no group effect or interaction observed showing that CWI did not attenuate any of the dependent variables ( p > 0.05 ) . These results suggest that repeated CWI do not enhance recovery from a bout of damaging eccentric contractions . Key pointsCryotherapy , particularly cold water immersions are one of the most common interventions used in order to enhance recovery post-exercise . There is little empirical evidence demonstrating benefits from cold water immersions . Research evidence is equivocal , probably due to method ological inconsistencies . Our results show that the cryotherapy administered did not attenuate any markers of EIMD or enhance the recovery of function . We conclude that repeated cold water immersions are ineffective in the recovery from heavy plyometric exercise and suggest athletes and coaches should use caution before using this intervention as a recovery strategy PURPOSE Venous hemodynamics evaluated during walking better reflect changes that occur under active physiologic conditions than do conventional static modes of exercise such as tip-toe exercise , knee bending , or dorsiflexion . We prospect ively studied the efficacy of air-plethysmography ( APG ) in monitoring venous hemodynamics during ambulation , and with this method we determined the hemodynamic effects of graduated elastic compression stockings on the lower limb during walking at various speeds . METHODS The residual volume fraction ( RVF% ) during treadmill walking was monitored with APG in 10 limbs with primary chronic venous insufficiency (CVI)(CEAP(2 - 4 ) ) at four speeds ( 1.0 , 1.5 , 2.0 and 2.5 km/h consecutively ) , with and without elastic compression ( 21 mm Hg at the ankle ) . The method was vali date d in comparison with st and ard APG , which is based on tip-toe exercise . RVF obtained during treadmill walking at 1.5 km/h was correlated with RVF measured with st and ard APG in 30 subjects : 12 healthy volunteers , 11 patients with primary CVI , and 7 postthrombotic limbs . Data were analyzed with nonparametric statistics . RESULTS RVF measurements during walking were reproduced with an intra-day coefficient of variation of 5.1 % to 16.5 % . RVF during walking correlated well with RVF during st and ard APG ( tip-toe ) ( r = 0.5 , P = .004 ) . At each of the investigated walking speeds , stockings improved venous hemodynamics by decreasing RVF , from a median of 50.5 % without stockings to 40.5 % with stockings at 1.0 km/h ( 19.8 % decrease ) , from 49 % to 39.5 % at 1.5 km/h ( 19.4 % decrease ) , from 50.5 % to 41 % at 2.0 km/h ( 18.8 % decrease ) , and from 53 % to 45.5 % at 2.5 km/h ( 14.2 % decrease ) ( all speeds , P < .02 ) . Efficacy of the stockings in decreasing RVF ( percent change in RVF ) was similar across the spectrum of examined speeds ( P = .47 ) . During walking with elastic stockings , nominal RVF values were also similar across the spectrum of walking speeds , except at 2.5 km/h ( P = .012 ) . During walking without stockings , RVF did not change with treadmill speed , nor did it differ from that obtained with conventional APG ( tip-toe ) ( P = .46 ) . The percentage decrease in RVF generated with elastic stockings correlated with the venous filling index ( r = 0.73 , P = .017 ) at 1.0 km/h . CONCLUSIONS APG is a reproducible and valid method for monitoring venous hemodynamics during walking . Graduated elastic compression stockings significantly improved venous hemodynamics by reducing RVF in limbs with primary CVI at all examined walking speeds ( 1.0 to 2.5 km/h ) . The effect was linearly correlated with the amount of reflux ( 1.0 km/h ) . The modified application of APG during walking offers a new noninvasive method for assessment of venous hemodynamics in limbs with CVI , enabling quantification of the actual effect of elastic compression therapy during ambulation PURPOSE The aim of this study was to determine whether compression garments improve intermittent-sprint performance and aid performance or self-reported recovery from high-intensity efforts on consecutive days . METHODS Following familiarization , 14 male rugby players performed two r and omized testing conditions ( with or without garments ) involving consecutive days of a simulated team sport exercise protocol , separated by 24 h of recovery within each condition and 2 weeks between conditions . Each day involved an 80-min high-intensity exercise circuit , with exercise performance determined by repeated 20-m sprints and peak power on a cart dynamometer ( single-man scrum machine ) . Measures of nude mass , heart rate , skin and tympanic temperature , and blood lactate ( La- ) were recorded throughout each day ; also , creatine kinase ( CK ) and muscle soreness were recorded each day and 48 h following exercise . RESULTS No differences ( P=.20 to 0.40 ) were present between conditions on either day of the exercise protocol for repeated 20-m sprint efforts or peak power on a cart dynamometer . Heart rate , tympanic temperature , and body mass did not significantly differ between conditions ; however , skin temperature was higher under the compression garments . Although no differences ( P=.50 ) in La- or CK were present , participants felt reduced levels of perceived muscle soreness in the ensuing 48 h postexercise when wearing the garments ( 2.5+/-1.7 vs 3.5+/-2.1 for garment and control ; P=.01 ) . CONCLUSIONS The use of compression garments did not improve or hamper simulated team-sport activity on consecutive days . Despite benefits of reduced self-reported muscle soreness when wearing garments during and following exercise each day , no improvements in performance or recovery were apparent Objective : To compare the effects of three types of full-body compression garments ( Skins , Adidas and Under Armour ) on repeat-sprint and throwing performance in cricket players . Methods : Following familiarisation , 10 male cricket players performed four r and omised exercise sessions ( 3 garments and a control ) . Each session involved a 30 min repeat-sprint exercise protocol comprising 20 m sprints every minute , separated by submaximal exercise . Throwing tests included a pre-exercise and a postexercise maximal distance test and accuracy throwing tests . During each session , measures of heart rate , skin temperature , change in body mass , rate of perceived exertion and perceived muscle soreness were recorded . Capillary blood sample s were analysed before and after exercise for lactate , pH , O2 saturation and O2 partial pressure , and 24 h after exercise for creatine kinase ( CK ) . Ratings of perceived muscle soreness were also obtained 24 h after exercise . Results : No significant differences ( p>0.05 ) were evident in repeat-sprint performance ( 10 m , 20 m time or total submaximal distance covered ) or throwing performance ( maximum distance or accuracy ) . No significant differences ( p>0.05 ) were observed in heart rate , body mass change or blood measures during exercise . Significant differences ( p<0.05 ) were observed by way of higher mean skin temperature , lower 24 h postexercise CK values and lower 24 h postexercise ratings of muscle soreness when wearing compression garments . Analysis between respective br and s of compression garments revealed no statistical differences ( p>0.05 ) . Conclusions : No benefit was noted when wearing compression garments for repeat-sprint or throwing performance ; however , the use of the garments as a recovery tool , when worn after exercise , may be beneficial to reduce postexercise trauma and perceived muscle soreness PURPOSE This study was conducted to determine if 6 wk of supplementation with vitamins E and C could alleviate exercise-induced muscle damage . We studied 22 runners during a 50-km ultramarathon . METHODS Subjects were r and omly assigned to one of two groups : ( a ) placebos ( PL ) or ( b ) antioxidants ( AO ) ( 1000 mg vitamin C and 300 mg RRR-alpha-tocopheryl acetate ) . Blood sample s were obtained before supplementation ( baseline ) , 24 h pre- , 12 h pre- , and 1 h prerace ; midrace , postrace , 2 h postrace , and for 6 d postrace . Plasma alpha-tocopherol ( alpha-TOH ) , ascorbic acid ( AA ) , and muscle damage markers ( creatine kinase ( CK ) and lactate dehydrogenase ( LDH ) ) , as well as maximal voluntary contraction ( MVC ) of the hamstring and quadriceps were assessed . RESULTS With supplementation , plasma alpha-TOH and AA increased in the AO but not the PL group . LDH and CK increased in response to the race ; LDH peaked at postrace and CK reached maximal values 2 h and 1 d postrace ; neither was affected by treatment . Adjusting for between-subject differences in baseline CK values revealed that men had higher levels of CK than did women throughout the study . Correcting CK values for lean body mass ( kg ) eliminated sex differences , but not changes over time . CK was significantly correlated ( R = 0.52 , P < 0.0001 ) with C-reactive protein , an acute phase response marker . MVC decreased 14 - 26 % in all groups in response to the run . Eccentric hamstring ( EH ) torque and concentric quadriceps ( CQ ) power exhibited the largest deficits , 26 and 24 % , respectively , with no effect of treatment . CQ recovered at a faster rate in women than in men . CONCLUSION Antioxidants appeared to have no effect on exercise-induced increases in muscle damage or recovery , but important sex differences were observed BACKGROUND The true frequency of deep-vein thrombosis ( DVT ) during long-haul air travel is unknown . We sought to determine the frequency of DVT in the lower limb during long-haul economy-class air travel and the efficacy of graduated elastic compression stockings in its prevention . METHODS We recruited 89 male and 142 female passengers over 50 years of age with no history of thromboembolic problems . Passengers were r and omly allocated to one of two groups : one group wore class-I below-knee graduated elastic compression stockings , the other group did not . All the passengers made journeys lasting more than 8 h per flight ( median total duration 24 h ) , returning to the UK within 6 weeks . Duplex ultrasonography was used to assess the deep veins before and after travel . Blood sample s were analysed for two specific common gene mutations , factor V Leiden ( FVL ) and prothrombin G20210A ( PGM ) , which predispose to venous thromboembolism . Asensitive D-dimer assay was used to screen for the development of recent thrombosis . FINDINGS 12/116 passengers ( 10 % ; 95 % CI 4.8 - 16.0 % ) developed symptomless DVT in the calf ( five men , seven women ) . None of these passengers wore elastic compression stockings , and two were heterozygous for FVL . Four further patients who wore elastic compression stockings , had varicose veins and developed superficial thrombophlebitis . One of these passengers was heterozygous for both FVL and PGM . None of the passengers who wore class-I compression stockings developed DVT ( 95 % CI 0 - 3.2 % ) . INTERPRETATION We conclude that symptomless DVT might occur in up to 10 % of long-haul airline travellers . Wearing of elastic compression stockings during long-haul air travel is associated with a reduction in symptomless DVT Jakeman , JR , Byrne , C , and Eston , RG . Efficacy of lower limb compression and combined treatment of manual massage and lower limb compression on symptoms of exercise-induced muscle damage in women . J Strength Cond Res 24(11 ) : 3157 - 3165 , 2010-Strategies to manage the symptoms of exercise-induced muscle damage ( EIMD ) are widespread , though are often based on anecdotal evidence . The aim of this study was to determine the efficacy of a combination of manual massage and compressive clothing and compressive clothing individually as recovery strategies after muscle damage . Thirty-two female volunteers completed 100 plyometric drop jumps and were r and omly assigned to a passive recovery ( n = 17 ) , combined treatment ( n = 7 ) , or compression treatment group ( n = 8) . Indices of muscle damage ( perceived soreness , creatine kinase activity , isokinetic muscle strength , squat jump , and countermovement jump performance ) were assessed immediately before and after 1 , 24 , 48 , 72 , and 96 hours of plyometric exercise . The compression treatment group wore compressive tights for 12 hours after damage and the combined treatment group received a 30-minute massage immediately after damaging exercise and wore compression stockings for the following 11.5 hours . Plyometric exercise had a significant effect on all indices of muscle damage ( p < 0.05 ) . The treatments significantly reduced decrements in isokinetic muscle strength , squat jump performance , and countermovement jump performance and reduced the level of perceived soreness in comparison with the passive recovery group ( p < 0.05 ) . The addition of sports massage to compression after muscle damage did not improve performance recovery , with recovery trends being similar in both treatment groups . The treatment combination of massage and compression significantly moderated perceived soreness at 48 and 72 hours after plyometric exercise ( p < 0.05 ) in comparison with the passive recovery or compression alone treatment . The results indicate that the use of lower limb compression and a combined treatment of manual massage with lower limb compression are effective recovery strategies following EIMD . Minimal performance differences between treatments were observed , although the combination treatment may be beneficial in controlling perceived soreness Davies , V , Thompson , KG , and Cooper , SM . The effect of compression garments on recovery . J Strength Cond Res 23(6 ) : 1786 - 1794 , 2009-The purpose of this study was to investigate whether wearing lower-body compression garments attenuate indices of muscle damage and decrements in performance following drop-jump training . Seven trained female and four trained male subjects undertook blood collection for creatine kinase ( CK ) and lactate dehydrogenase ( LDH ) , a mid-thigh girth measurement , and reported their perceived muscle soreness ( PMS ) . A series of performance tests were then completed including sprints ( 5 m , 10 m , and 20 m ) , a 5 - 0 - 5 agility test , and a countermovement jump test . In a r and omized crossover experimental design , separated by 1 week , subjects completed 5 × 20 maximal drop-jumps , followed immediately after exercise by either wearing graduated compression tights ( CG ) or undertook passive recovery as a control ( CON ) for 48 hours . CK , LDH , mid-thigh girth , and PMS were retested after 24 hours and 48 hours of recovery . The performance tests were repeated after 48 hours of recovery . Analysis of variance for repeated measures indicated that for female subjects , CK values were elevated after 24-hour recovery ( p = 0.020 ) and a greater PMS was observed after 48-hour recovery in the CON condition ( p = 0.002 ) but not for the CG condition . For all the subjects ( n = 11 ) , a greater PMS was observed after 48-hour recovery in the CON condition ( p = 0.001 ) but not the CG condition . Significant increases in time were reported for 10-m ( p = 0.016 , 0.004 ) and 20-m sprints ( p = 0.004 , 0.001 ) in both the CON and CG conditions and for the 5-m sprint ( p = 0.014 ) in the CG condition . All other parameters were unchanged in either condition . Data indicates that CK responses and PMS might be attenuated by wearing compression tights in some participants after drop-jump training ; however , no benefit in performance was observed STUDY DESIGN A between groups design was used to compare recovery following eccentric muscle damage under 2 experimental conditions . OBJECTIVE To determine if a compression sleeve donned immediately after maximal eccentric exercise would enhance recovery of physical function and decrease symptoms of soreness . BACKGROUND Prior investigations using ice , intermittent compression , or exercise have not shown efficacy in relieving symptoms of delayed onset muscle soreness ( DOMS ) . To date , no study has shown the effect of continuous compression on DOMS , yet this would offer a low cost intervention for patients suffering with the symptoms of DOMS . METHODS AND MEASURES Twenty nonimpaired non-strength-trained women participated in the study . Subjects were matched for age , anthropometric data , and one repetition maximum concentric arm curl strength and then r and omly placed into a control group ( n = 10 ) or an experimental compression sleeve group ( n = 10 ) . Subjects were instructed to avoid pain-relieving modalities ( eg , analgesic medications , ice ) throughout the study . The experimental group wore a compressive sleeve garment for 5 days following eccentric exercise . Subjects performed 2 sets of 50 passive arm curls with the dominant arm on an isokinetic dynamometer with a maximal eccentric muscle action superimposed every fourth passive repetition . One repetition maximum elbow flexion , upper arm circumference , relaxed elbow angle , blood serum cortisol , creatine kinase , lactate dehydrogenase , and perception of soreness question naires were collected prior to the exercise bout and daily thereafter for 5 days . RESULTS Creatine kinase was significantly elevated from the baseline value in both groups , although the experimental compression test group showed decreased magnitude of creatine kinase elevation following the eccentric exercise . Compression sleeve use prevented loss of elbow motion , decreased perceived soreness , reduced swelling , and promoted recovery of force production . CONCLUSIONS Results from this study underline the importance of compression in soft tissue injury management Kraemer , WJ , Flanagan , SD , Comstock , BA , Fragala , MS , Earp , JE , Dunn-Lewis , C , Ho , J-Y , Thomas , GA , Solomon-Hill , G , Penwell , ZR , Powell , MD , Wolf , MR , Volek , JS , Denegar , CR , and Maresh , CM . Effects of a whole body compression garment on markers of recovery after a heavy resistance workout in men and women . J Strength Cond Res 24(3 ) : 804 - 814 , 2010-The primary purpose of this investigation was to evaluate the influence of a whole body compression garment on recovery from a typical heavy resistance training workout in resistance-trained men and women . Eleven men ( mean ± SD : age , 23.0 ± 2.9 years ) and 9 women ( mean ± SD : age 23.1 ± 2.2 years ) who were highly resistance trained gave informed consent to participate in the study . A within-group ( each subject acted as their own control ) , balanced , and r and omized treatment design was used . Nutritional intakes , activity , and behavioral patterns ( e.g. , no pain medications , ice , or long showers over the 24 hours ) were replicated 2 days before each test separated by 72 hours . An 8-exercise whole body heavy resistance exercise protocol using barbells ( 3 sets of 8 - 10 repetition maximum , 2.0-to 2.5-minute rest ) was performed after which the subject showered and put on a specific whole body compression garment one design ed for women and one for men ( CG ) or just wore his/her normal noncompression clothing ( CON ) . Subjects were then tested after 24 hours . Dependent measures included sleep quality , vitality rating , resting fatigue rating , muscle soreness , muscle swelling via ultrasound , reaction movement times , bench throw power , countermovement vertical jump power , and serum concentrations of creatine kinase ( CK ) measured from a blood sample obtained via venipuncture of an arm vein . We observed significant ( p ≤ 0.05 ) differences between CG and CON conditions in both men and women for vitality ( CG > CON ) , resting fatigue ratings ( CG < CON ) , muscle soreness ( CG < CON ) , ultrasound measure swelling ( CG < CON ) , bench press throw ( CG > CON ) , and CK ( CG < CON ) . A whole body compression garment worn during the 24-hour recovery period after an intense heavy resistance training workout enhances various psychological , physiological , and a few performance markers of recovery compared with noncompressive control garment conditions . The use of compression appears to help in the recovery process after an intense heavy resistance training workout in men and women |
11,379 | 24,643,851 | Feeding tube rates were the most commonly reported functional outcome .
Crude end points of functional recovery after TORS ± adjuvant therapy suggest promising swallowing outcomes , depending on the functional measure reported | Abstract Summarize functional outcomes after transoral robotic surgery ( TORS ) ± adjuvant therapy for oropharyngeal cancer ( OPC ) . | PURPOSE Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus ( HPV ) infection , but empirical evidence is lacking . PATIENTS AND METHODS HPV status was determined for all 271 oropharyngeal cancers ( 1984 - 2004 ) collected by the three population -based cancer registries in the Surveillance , Epidemiology , and End Results ( SEER ) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping ( Inno-LiPA ) , HPV16 viral load , and HPV16 mRNA expression . Trends in HPV prevalence across four calendar periods were estimated by using logistic regression . Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonr and om selection and to calculate incidence trends . Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses . RESULTS HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay ( P trend < .05 ) . For example , HPV prevalence by Inno-LiPA increased from 16.3 % during 1984 to 1989 to 71.7 % during 2000 to 2004 . Median survival was significantly longer for HPV-positive than for HPV-negative patients ( 131 v 20 months ; log-rank P < .001 ; adjusted hazard ratio , 0.31 ; 95 % CI , 0.21 to 0.46 ) . Survival significantly increased across calendar periods for HPV-positive ( P = .003 ) but not for HPV-negative patients ( P = .18 ) . Population -level incidence of HPV-positive oropharyngeal cancers increased by 225 % ( 95 % CI , 208 % to 242 % ) from 1988 to 2004 ( from 0.8 per 100,000 to 2.6 per 100,000 ) , and incidence for HPV-negative cancers declined by 50 % ( 95 % CI , 47 % to 53 % ; from 2.0 per 100,000 to 1.0 per 100,000 ) . If recent incidence trends continue , the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020 . CONCLUSION Increases in the population -level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection OBJECTIVE To design a reliable and vali date d self-administered question naire whose purpose is to assess dysphagia 's effects on the quality of life ( QOL ) of patients with head and neck cancer . DESIGN Cross-sectional survey study . METHODS Focus groups were convened for question naire development and design . The M. D. And erson Dysphagia Inventory ( MDADI ) included global , emotional , functional , and physical subscales . One hundred consecutive adult patients with a neoplasm of the upper aerodigestive tract who underwent evaluation by our Speech Pathology team completed the MDADI and the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) . Speech pathologists completed the Performance Status Scale for each patient . Validity and reliability properties were calculated . Analysis of variance was used to assess how well the MDADI discriminated between groups of patients . RESULTS The internal consistency reliability of the MDADI was calculated using the Cronbach alpha coefficient . The Cronbach alpha coefficients of the MDADI subscales ranged from 0.85 to 0.93 . Test-retest reliability coefficients of the subscales ranged from 0.69 to 0.88 . Spearman correlation coefficients between the MDADI subscales and the SF-36 subscales demonstrated construct validity . Patients with primary tumors of the oral cavity and oropharynx had significantly greater swallowing disability with an adverse impact on their QOL compared with patients with primary tumors of the larynx and hypopharynx ( P<.001 ) . Patients with a malignant lesion also had significantly greater disability than patients with a benign lesion ( P<.001 ) . CONCLUSIONS The MDADI is the first vali date d and reliable self-administered question naire design ed specifically for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer . St and ardized question naires that measure patients ' QOL offer a means for demonstrating treatment impact and improving medical care . The development and validation of the MDADI and its use in prospect i ve clinical trials allow for better underst and ing of the impact of treatment of head and neck cancer on swallowing and of swallowing difficulty on patients ' QOL OBJECTIVE To evaluate changes in patient-perceived swallowing function over time following transoral robotic surgery ( TORS ) for primary T1 and T2 oropharyngeal squamous cell carcinomas . DESIGN Prospect i ve case series . SETTING Academic tertiary referral center . PATIENTS Forty-two patients with T1 or T2 oropharyngeal squamous cell carcinomas . INTERVENTION TORS-assisted resection of indicated tumors . MAIN OUTCOME MEASURES Changes in patient-perceived swallowing function over time ( using the M. D. And erson Dysphagia Inventory ) and gastrostomy tube dependence . RESULTS Between March 19 , 2007 , and April 21 , 2010 , forty-two patients with primary T1 or T2 oropharyngeal squamous cell carcinomas underwent TORS-assisted resection . Most ( 76 % [ 32 of 42 ] ) patients had stage III disease ; 93 % ( 39 of 42 ) of patients underwent staged neck dissection . The median postoperative follow-up time was 17 months ( range , 4 - 40 months ) . There were no complications or tumor recurrences . Postoperative chemotherapy use predicted gastrostomy tube retention for longer than 3 months ( P = .01 ) . Immediate mean postoperative M. D. And erson Dysphagia Inventory scores in each assessed domain ( global , emotional , physical , and functional ) decreased compared with preoperative baseline scores ; however , ongoing improvement in all domains was observed over time . Nodal status ( P = .049 ) , follow-up time of less than 12 months ( P = .03 ) , and preoperative physical scores of less than 100 ( P = .01 ) predicted poorer physical M. D. And erson Dysphagia Inventory outcomes . Positive pathological margins predicted poorer functional scores ( P = .03 ) . CONCLUSIONS After TORS-assisted resection of T1 and T2 oropharyngeal squamous cell carcinomas , approximately one-third of patients will experience a sustained decrease in perceived swallowing function . However , ongoing improvement of swallowing function over time is likely even after 12 months . Patients receiving adjuvant chemotherapy after TORS should be counseled about the possibility of prolonged gastrostomy tube dependence OBJECTIVE To describe and show the feasibility of a new surgical technique for transoral robotic surgery ( TORS ) radical tonsillectomy . DESIGN A prospect i ve , phase 1 clinical trial . SETTING Academic , tertiary referral center . PATIENTS A total of 27 participants were prospect ively selected using a volunteer sample . All eligible patients agreed to participate in the study . INTERVENTIONS Patients underwent TORS radical tonsillectomy for previously untreated invasive squamous cell carcinoma of the tonsillar region without free-flap reconstruction , staged neck dissection , and adjuvant therapy . MAIN OUTCOME MEASURES Outcome measures included final pathologic margin status , need for short- and long-term tracheotomy tube placement , and need for gastrostomy tube feedings among patients with a minimum 6-month follow-up . The incidence of significant postoperative complications was recorded . RESULTS No mortality occurred . Final margins found to be negative for cancer were achieved in 25 of 27 patients ( 93 % ) . Surgical complications included 1 case each of postoperative mucosal bleeding , delirium tremens , unplanned tracheotomy for temporary exacerbation of sleep apnea , and hypernasality and 2 cases of moderate trismus . Twenty-six of 27 patients ( 96 % ) were swallowing without the use of a gastrostomy . CONCLUSIONS Radical tonsillectomy using TORS is a new technique that offers excellent access for resection of carcinomas of the tonsil with acceptable acute morbidity . Future reports will focus on long-term oncologic and functional outcomes OBJECTIVES /HYPOTHESIS To investigate the feasibility of transoral robotic surgery as a method of surgical treatment of oropharyngeal squamous cell carcinoma . STUDY DESIGN Prospect i ve case study . METHODS Forty-five patients with previously untreated oropharyngeal squamous cell carcinoma underwent transoral robotic surgical removal of the tumor with or without neck dissection and with or without adjuvant therapy . Patients were observed and data were recorded on surgical time , blood loss , surgical complications , tracheostomy tube course , enteral feeding , and resumption of oral diet , speech outcomes , swallowing outcomes , and tumor recurrence . RESULTS All 45 patients underwent complete transoral robotic surgical excision with simultaneous unilateral or bilateral neck dissection . Margins were negative for tumor . Mean operating time for tumor removal was 71.3 minutes for the last 35 cases . There were 15 stage T1 tumors , 18 T2 tumors , 3 T3 tumors , and 9 T4a tumors . Twenty-six patients had base of tongue primary tumors and 19 had tonsillar fossa tumors . Fourteen patients had a tracheostomy tube placed at surgery , and all patients had their tracheostomy tube removed ( mean duration of use , 7.0 days ) . Twenty-two patients ( 48.9 % ) had a nasogastric feeding tube placed , and all patients had their feeding tube removed ( mean duration of use , 12.5 days ) . Eight patients had percutaneous gastrostomy ( PEG ) tubes placed , and all eight eventually had their PEG tubes removed ( mean duration of use , 140.3 days ) . Average hospital stay was 3.8 days . There were no major complications and no procedure was aborted because of an inability to remove the tumor . CONCLUSIONS Transoral robotic surgery is a safe and efficacious method of surgical treatment of oropharyngeal neoplasms . Advantages of the technique include adequate ability to visualize and manipulate with two h and s lesions in the base of tongue . Patients were able to retain or rapidly regain oropharyngeal function in the majority of cases OBJECTIVES To determine the oncologic and functional outcomes in patients undergoing primary transoral robotic surgery followed by adjuvant therapy as indicated with a minimum of 18-month follow-up for advanced oropharyngeal carcinoma . DESIGN Prospect i ve single-center cohort study . SETTING Academic university health system and tertiary referral center . PATIENTS Forty-seven adults with newly diagnosed and previously untreated advanced oropharyngeal carcinoma . INTERVENTION Transoral robotic surgery with staged neck dissection and adjuvant therapy as indicated . MAIN OUTCOME MEASURES Margin status , recurrence , disease-specific and disease-free survival , gastrostomy tube dependence , and safety and efficacy end points . RESULTS In the 47 patients enrolled with stages III and IV advanced oropharyngeal carcinoma , mean follow-up was 26.6 months . There was no intraoperative or postoperative mortality . Resection margins were positive in 1 patient ( 2 % ) . At last follow-up , local recurrence was identified in 1 patient ( 2 % ) , regional recurrence in 2 ( 4 % ) , and distant recurrence in 4 ( 9 % ) . Disease-specific survival was 98 % ( 45 of 46 patients ) at 1 year and 90 % ( 27 of 30 patients ) at 2 years . Based on pathologic risk stratification , 18 of 47 patients ( 38 % ) avoided chemotherapy , and 5 patients ( 11 % ) did not receive adjuvant radiotherapy and concurrent chemotherapy in their treatment regimen . At minimum follow-up of 1 year , only 1 patient required a gastrostomy tube . CONCLUSIONS This novel transoral robotic surgery treatment regimen offers disease control , survival , and safety commensurate with st and ard treatments and an unexpected beneficial outcome of gastrostomy dependency rates that are markedly lower than those reported with st and ard nonsurgical therapies BACKGROUND The aim of this study was to assess the quality of life of patients with oropharyngeal squamous cell carcinoma after transoral robotic surgery ( TORS ) . METHODS Short Form (SF)-8 and Performance Status Scale ( PSS ) question naires were completed prior to surgery , 6 and 12 months of follow-up . RESULTS In all , 38 patients treated with TORS followed by adjuvant therapy as indicated were prospect ively enrolled . For PSS Eating and Diet domains , significant decreases occurred at 6 months ( p ≤ .001 and p ≤ .001 , respectively ) but not at 12 months . Significant declines in PSS Speech were seen at 6 and 12 months ( p ≤ .001 and p ≤ .001 ) . There were no significant declines in the SF-8 domains , except for Bodily Pain and Global Health ( 6 months ) . Significantly higher PSS Eating and Diet scores were seen at 6 months for TORS alone compared with TORS and chemoradiation . CONCLUSIONS Combination TORS and adjuvant therapy caused a temporary decrease in several domains at 6 months , returning to baseline including swallowing function in all patients OBJECTIVE To evaluate the impact of primary reconstruction of postablative defects following transoral robotic surgery on function and the risk of orocutaneous fistula . DESIGN Prospect i ve nonr and omized clinical trial . SETTING Tertiary academic medical center . PATIENTS Thirty-one patients treated with transoral robotic pharyngectomy for malignant disease . Each case was analyzed for patient age , sex , primary site of the tumor , pathologic characteristics , stage of disease , complications , fistula rate , and functional outcomes . Functional outcomes were assessed using the Performance Status Scale for Head and Neck Cancer Patients and the Functional Oral Intake Scale . INTERVENTIONS In 25 patients , the primary treatment was with transoral robotic pharyngectomy , and 6 cases were salvage procedures performed for recurrent disease following radiation ( 3 patients ) or chemoradiation ( 3 patients ) . Twenty-six patients underwent a concomitant unilateral selective neck dissection , and 3 patients underwent concomitant bilateral selective neck dissections ; 2 patients did not require a neck dissection for treatment of the primary malignant tumor . MAIN OUTCOME MEASURES Complication rate , fistula rate , and oral function . RESULTS Primary intraoral reconstruction was performed in all 31 patients . Musculomucosal advancement flap pharyngoplasty was performed in 25 patients with a concomitant velopharyngopasty ( 6 patients ) , and radial forearm free flap reconstruction was performed in 6 patients . There were no intraoperative complications ; however , postoperatively , 1 patient developed a neck hematoma that was treated with bedside drainage and 4 patients sustained minor musculomucosal flap necrosis of the superior aspect of the flap . None of the patients developed a neck infection of salivary fistula . Endoscopic evaluation of swallowing demonstrated that none of the patients experienced aspiration or velopharyngeal reflux , and the performance Status Scale for Head and Neck Cancer Patients and the Functional Oral Intake Scale at 2 weeks , 2 months , 6 months , 9 months , and 1 year demonstrated a progressive improvement in diet , swallowing , and oral function . CONCLUSIONS Primary transoral robotic reconstruction may provide a benefit by decreasing the fistula rate in patients undergoing concomitant neck dissection . Patients regain excellent function following surgery and adjuvant therapy PURPOSE To present pilot toxicity and survival outcomes for a prospect i ve trial investigating adaptive radiotherapy ( ART ) for oropharyngeal squamous cell carcinoma . METHODS AND MATERIAL S A total of 24 patients were enrolled in an institutional review board-approved clinical trial ; data for 22 of these patients were analyzed . Daily CT-guided setup and deformable image registration permitted serial mapping of clinical target volumes and avoidance structures for ART planning . Primary site was base of tongue in 15 patients , tonsil in 6 patient , and glossopharyngeal sulcus in 1 patient . Twenty patients ( 91 % ) had American Joint Committee on Cancer ( AJCC ) Stage IV disease . T stage distribution was 2 T1 , 12 T2 , 3 T3 , 5 T4 . N stage distribution was 1 N0 , 2 N1 , 5 N2a , 12 N2b , and 2 N2c . Of the patients , 21 ( 95 % ) received systemic therapy . RESULTS With a 31-month median follow-up ( range , 13 - 45 months ) , there has been no primary site failure and 1 nodal relapse , yielding 100 % local and 95 % regional disease control at 2 years . Baseline tumor size correlated with absolute volumetric treatment response ( p = 0.018 ) . Parotid volumetric change correlated with duration of feeding tube placement ( p = 0.025 ) . Acute toxicity was comparable to that observed with conventional intensity-modulated radiotherapy ( IMRT ) . Chronic toxicity and functional outcomes beyond 1 year were tabulated . CONCLUSION This is the first prospect i ve evaluation of morbidity and survival outcomes in patients with locally advanced head- and -neck cancer treated with automated adaptive replanning . ART can provide dosimetric benefit with only one or two mid-treatment replanning events . Our preliminary clinical outcomes document functional recovery and preservation of disease control at 1-year follow-up and beyond OBJECTIVE : To evaluate functional outcomes following transoral robotic surgery for head and neck cancer . STUDY DESIGN : Case series with planned data collection . SETTING : Academic hospital . SUBJECTS AND METHODS : Between March 2007 and December 2008 , 54 of 62 c and i date patients underwent transoral robotic tumor resection . Outcomes include airway management , swallowing ( MD And erson Dysphagia Inventory ) , and enterogastric feeding . RESULTS : Tumors were most commonly oropharynx ( 61 % ) or larynx ( 22 % ) and T1 ( 35 % ) or T2 ( 44 % ) . Many received radiotherapy ( 22 % preoperatively , 41 % postoperatively ) and chemotherapy ( 31 % ) . Endotracheal intubation was retained ( 22 % ) for up to 48 hours , tracheostomy less frequently ( 9 % ) , and all were decannulated by 14 days . Most commenced oral intake prior to discharge ( 69 % ) or within two weeks ( 83 % ) . A worse postoperative Dysphagia Inventory score was associated with retained feeding tube ( P = 0.020 ) , age > 60 ( P = 0.017 ) , higher T stage ( P = 0.009 ) , laryngeal site ( P = 0.017 ) , and complications ( P = 0.035 ) . At a mean 12 months ' follow-up , 17 percent retained a feeding tube ( 9.5 % among primary cases ) . Retained feeding tube was associated with preoperative tube requirement ( P = 0.017 ) , higher T stage ( P = 0.043 ) , oropharyngeal/laryngeal site ( P = 0.034 ) , and recurrent/second primary tumor ( P = 0.008 ) . Complications including airway edema ( 9 % ) , aspiration ( 6 % ) , bleeding ( 6 % ) , and salivary fistula ( 2 % ) were managed without major sequelae . CONCLUSION : Transoral robotic surgery provides an emerging alternative for selected primary and salvage head and neck tumors with low morbidity and acceptable functional outcomes . Patients with advanced T stage , laryngeal or oropharyngeal site , and preoperative enterogastric feeding may be at increased risk of enterogastric feeding and poor swallowing outcomes PURPOSE To investigate the feasibility of combining concomitant boost accelerated radiation regimen ( AFX-C ) with cisplatin and to assess its toxicity and the relapse pattern and survival in patients with advanced head and neck carcinoma ( HNC ) . PATIENTS AND METHODS Between April and November of 2000 , 84 patients with stage III to IV HNC who met the eligibility criteria were enrolled ; 76 of these patients were analyzable . Radiation consisted of 72 Gy in 42 fractions over 6 weeks ( daily for 3.5 weeks , then twice a day for 2.5 weeks ) . Cisplatin dose was 100 mg/m(2 ) on days 1 and 22 . Tumor and clinical status were assessed , and acute late toxicities were grade d. RESULTS Sixty-five patients ( 86 % ) received both radiation and chemotherapy per protocol or with minor variations . The estimated 2-year locoregional relapse and distant metastasis rates were 34.7 % and 16.1 % , respectively . The estimated 2-year overall survival and disease-free survival rates were 71.6 % and 53.5 % , respectively . Three patients ( 4 % ) died of complications , 19 patients ( 25 % ) had acute grade 4 toxicity , and 49 patients ( 64 % ) had acute grade 3 toxicity . The 2-year cumulative incidence of late grade 3 to 5 toxicities was 51.3 % . CONCLUSION These data showed that it was feasible to combine AFX-C with cisplatin . The compliance to therapy was high , and the locoregional control and survival rates achieved compared favorably with AFX-C alone or other concurrent chemoradiation regimens tested by the Radiation Therapy Oncology Group . A phase III trial comparing AFX-C plus cisplatin against st and ard radiation plus cisplatin is ongoing to determine whether the use of AFX-C in the concurrent chemoradiation setting further improves outcome PURPOSE To test the hypothesis that intensity modulated radiation therapy ( IMRT ) aim ing to spare the salivary gl and s and swallowing structures would reduce or eliminate the effects of xerostomia and dysphagia on quality of life ( QOL ) . METHODS AND MATERIAL S In this prospect i ve , longitudinal study , 72 patients with stage III-IV oropharyngeal cancer were treated uniformly with definitive chemo-IMRT sparing the salivary gl and s and swallowing structures . Overall QOL was assessed by summary scores of the Head Neck QOL ( HNQOL ) and University of Washington QOL ( UWQOL ) question naires , as well as the HNQOL " Overall Bother " question . Quality of life , observer-rated toxicities ( Common Toxicity Criteria Adverse Effects scale , version 2 ) , and objective evaluations ( videofluoroscopy assessing dysphagia and saliva flow rates assessing xerostomia ) were recorded from before therapy through 2 years after therapy . Correlations between toxicities/ objective evaluations and overall QOL were assessed using longitudinal repeated measures of analysis and Pearson correlations . RESULTS All observer-rated toxicities and QOL scores worsened 1 - 3 months after therapy and improved through 12 months , with minor further improvements through 24 months . At 12 months , dysphagia grade s 0 - 1 , 2 , and 3 , were observed in 95 % , 4 % , and 1 % of patients , respectively . Using all posttherapy observations , observer-rated dysphagia was highly correlated with all overall QOL measures ( P<.0001 ) , whereas xerostomia and mucosal and voice toxicities were significantly correlated with some , but not all , overall QOL measures , with lower correlation coefficients than dysphagia . Late overall QOL ( ≥6 or ≥12 months after therapy ) was primarily associated with observer-rated dysphagia , and to a lesser extent with xerostomia . Videofluoroscopy scores , but not salivary flows , were significantly correlated with some of the overall QOL measures . CONCLUSION After chemo-IMRT , although late dysphagia was on average mild , it was still the major correlate of QOL . Further efforts to reduce swallowing dysfunction are likely to yield additional gains in QOL The treatment of patients with squamous cell carcinoma ( SCC ) of the oropharynx remains controversial . No r and omized trial has addressed adequately the question of whether surgery ( S ) , radiation therapy ( RT ) , or combined treatment is most effective OBJECTIVES /HYPOTHESIS To investigate the impact of treatment modality and radiation technique on oncologic outcomes and toxicity of patients with locally advanced oropharyngeal cancer ( OPC ) . STUDY DESIGN Retrospective analysis of outcomes and toxicity . METHODS Between 2000 and 2011 , 204 consecutive patients with locally advanced OPC were treated with definitive (chemo)radiotherapy using 3-dimensional conformal ( 3DCRT ) or intensity-modulated radiotherapy ( IMRT ) . Endpoints were local control ( LC ) , regional control ( RC ) , disease-free survival ( DFS ) , cause-specific survival ( CSS ) , and overall survival ( OS ) , and toxicity . RESULTS After a median follow-up of 44 months ( range 4 - 134 ) , the 5-year Kaplan-Meier estimates of LC , RC , DFS , CSS , and OS were 78 % , 92 % , 60 % , 64 % , and 48 % , respectively . Grade 3 mucositis and dysphagia ( feeding-tube dependency ) were reported in 75 % and 65 % , respectively . The overall incidence of grade ≥ 2 and grade 3 late toxicities were 44 % and 16 % , respectively . Dysphagia and xerostomia were the most frequently reported late toxicity . Chemotherapy was significantly predictive for improved outcomes and increased toxicity . IMRT was significantly correlated with reduced toxicity . CONCLUSIONS Compared to radiation alone , chemoradiotherapy significantly improved oncologic outcomes , but with significantly increased toxicity . Compared to 3DCRT , the introduction of IMRT result ed in a significant reduction of acute and late toxicity with slightly better , or at least comparable , outcomes . Despite the improvements achieved by the implementation of chemo-IMRT , different new strategies to further improve outcome and reduce toxicity need to be thoroughly investigated in prospect i ve , preferably , r and omized trials BACKGROUND We aim ed to examine deficiencies in established methods of summarising adverse events , and to create a new reporting system ( TAME ) for summarising the toxicity burden of cancer treatment . TAME consoli date s traditional adverse-event data into three risk domains : short-term ( acute ) Toxicity ( T ) , Adverse long-term ( late ) effects ( A ) , and Mortality risk ( M ) generated by a treatment programme ( E = End results ) ; and assigns treatments to risk classes for each risk domain . METHODS We examined formally an established method for summarising adverse events ( the max- grade method ) in five trials of patients with head and neck cancer done between September , 1991 , and August , 2000 , by the Radiation Therapy Oncology Group ( RTOG ) that involved 13 treatment groups ( 2304 patients ) . We calculated TAME summary metrics that included time and multiplicity factors in the same patient groups . We compared relative T values with relative values for toxic effects from the max- grade approach . We also calculated the range of individual patient T scores in two groups from one of the trials ( the laryngeal-preservation trial ) . RESULTS The max- grade method systematic ally excluded 29 - 70 % of total reported high- grade ( grade 3 - 4 ) acute adverse events , contained progressive bias , and favoured higher toxicity programmes . Relative T values in the 13 treatment programmes tested showed an increase of almost 500 % in acute toxicity burden ( 100 - 590 ) between treatment groups compared with a 170 % increase ( 100 - 270 ) between treatment groups by use of the max- grade method . The difference between these two summary systems was statistically significant ( mean difference -102 [ 95 % CI -167 to -37 ] , p=0.005 , t test for paired differences ) . Four risk classes were design ated for acute and relative late effects : low ( 100 - 140 ) , moderate ( 150 - 390 ) , high ( 400 - 490 ) , and extreme ( > or=500 ) . The distribution of individual patient T scores showed that 82 ( 60 % ) patients who received concurrent platinum-radiotherapy for larynx preservation reported two or more high- grade events , and 34 ( 20 % ) reported four or more high- grade events ; these findings differed significantly from the distribution of individual patient T scores for patients who received radiotherapy alone , in which 32 ( 19 % ) reported two or more high- grade events and 3 ( 3 % ) reported four or more high- grade events ( p<0.0001 ) . The max- grade method also systematic ally excluded 26 - 48 % of high- grade ( grade 3 - 4 ) late adverse events . However , less variation was noted in the relative risk of late events ( 100 - 270 ) by the TAME method for late effects . INTERPRETATION Traditional methods for summarising adverse events systematic ally exclude important data , giving an inaccurate impression of the toxicity burden in complex multimodality trials . By contrast , T values use data on all high- grade adverse events . T values are proportional to the intensity of treatment , showing a 500 % increase between treatment groups in acute toxicity burden in RTOG trials of head and neck cancer done during this study interval . TAME reporting provides a concise and uniform method to compare relative risk among treatment options . Future studies should include testing the performance of the TAME system in additional data sets ( from different research organisations and disease sites ) , prospect i ve correlation of TAME endpoints with predefined outcome measures , and assessment of its usefulness in clinical decision making OBJECTIVES To evaluate functional swallowing outcomes in patients undergoing transoral robotic surgery vs primary chemoradiotherapy for the management of advanced-stage oropharynx and supraglottis cancers . DESIGN Prospect i ve nonr and omized clinical trial . SETTING Academic research . PATIENTS We studied 40 patients with stage III or stage IVA oropharynx and supraglottis squamous cell carcinoma . Group 1 comprised 20 patients who received transoral robotic surgery with adjuvant therapy , while group 2 comprised 20 patients whose disease was managed by primary chemoradiotherapy . MAIN OUTCOME MEASURES Patients completed the M. D. And erson Dysphagia Inventory ( MDADI ) before treatment and then at follow-up visits at 3 , 6 , and 12 months . The MDADI scores were analyzed and compared . RESULTS The median follow-up period for both groups was 14 months ( range , 12 - 16 months ) . When comparing the median MDADI scores between group 1 and group 2 , we found no statistically significant differences before treatment or at the 3-month follow-up visit . However , this difference was significant at the posttreatment visits at 6 months ( P = .004 ) and 12 months ( P = .006 ) , where group 1 had better swallowing MDADI scores . We also found significant differences in swallowing MDADI scores between the groups at the 6-month posttreatment visit for patients with T1 , T2 , and T3 disease and at the 12-month follow-up visit for patients with T2 and T3 disease , where group 1 had significantly better MDADI scores . Comparing tumor subsites , group 1 fared significantly better at the follow-up visits at 6 months ( P = .02 ) and 12 months ( P = .04 ) for patients with primary tumor at the tonsil . Compared with group 2 , group 1 patients having base of tongue cancers exhibited significantly better swallowing MDADI scores at the 6-month follow-up visit ( P = .02 ) , and group 1 patients having lateral oropharynx disease had significantly better swallowing MDADI scores at the 12-month follow-up visit ( P = .04 ) . CONCLUSION Advanced-stage oropharynx and supraglottis cancers managed by transoral robotic surgery with adjuvant therapy result ed in significantly better swallowing MDADI outcomes at the follow-up visits at 6 and 12 months compared with tumors treated by primary chemoradiotherapy Objective . To report a single institution ’s experience with transoral robotic surgery ( TORS ) and its clinical outcomes . Study Design . Preliminary clinical data from a prospect i ve TORS study . Setting . University tertiary care facility . Subjects and Methods . Patients who underwent TORS at The Ohio State University Medical Center . Demographic , intraoperative , clinicopathological , and follow-up functional data were collected . Results . Sixty-four patients underwent TORS with a median age of 56.9 years . A total of 113 TORS procedures were performed . Fifty-four patients with squamous cell cancer ( SCCA ) were included in the final analysis . Mean follow-up time was 11.8 months ( range , 2 - 29 ) . There was a trend toward longer TORS setup time , operative time , estimated blood loss , and hospital length of stay with advanced ( T3 ) compared with early-stage tumors ( T1 - 2 ) . There were no major intraoperative complications , and none of the procedures were aborted because of inability to remove the tumor . Negative resection margins were achieved in 93 % of cases of SCCA . No patients experienced immediate postoperative complications , and all of the patients tolerated an oral diet without any airway compromise on the day of surgery . Forty-nine patients ( 91 % ) underwent adjuvant radiation therapy ( RT ) , with 11 patients requiring gastrostomy tube placement during RT . Addition of TORS to overall management of head and neck SCCA spared adjuvant RT or combined chemotherapy and RT ( CRT ) in 50 % of stage I/II tumors and spared chemotherapy in 34 % of stage III/IV tumors . Conclusion . TORS is a safe procedure with minimal complications and favorable clinical and functional outcomes . It is a promising future alternative surgical treatment for laryngopharyngeal tumors OBJECTIVE To examine the long-term functional and oncologic results in patients who underwent transoral robotic surgery ( TORS ) as primary therapy or as part of combined therapy for oropharyngeal squamous cell carcinoma arising in the tonsil or base of tongue . PATIENTS AND METHODS We review ed a prospect i ve TORS data base of patients with squamous cell carcinoma arising in the tonsil or base of tongue treated between March 2007 and February 2009 to determine oncologic outcomes at 24 months or more of follow-up . The presenting tumor stage , histopathologic factors , surgical margins , and adjuvant treatment extent were evaluated . Functional outcomes included gastrostomy tube dependence and tracheostomy dependence . Oncologic outcomes included local , regional , and distant control and disease-specific and recurrence-free survival . RESULTS A total of 66 TORS patients were followed up for a minimum of 2 years . Most ( 97.0 % ; 64 of 66 ) were able to eat orally within 3 weeks after surgery before starting adjuvant therapy . Long-term gastrostomy tube use was required in 3 of the 66 ( 4.5 % ) and long-term tracheotomy in 1 ( 1.5 % ) . Three-year estimated local control and regional control were 97.0 % and 94.0 % , respectively . Two-year disease-specific survival and recurrence-free survival were 95.1 % and 92.4 % , respectively . CONCLUSION With appropriate adjuvant therapy , TORS achieves excellent functional results for patients with oropharyngeal squamous cell carcinoma . Oncologic outcomes are equivalent or superior to results of other surgical and nonsurgical treatments |
11,380 | 29,324,654 | The data presented in our work , although very heterogeneous in the manner of collecting and investigating sample s , have proved to be extremely consistent in witnessing a deficiency of zinc in serum and plasma of patients compared to controls | Zinc is an essential trace element for living organisms and their biological processes .
Zinc plays a key role in more than 300 enzymes and it is involved in cell communication , proliferation , differentiation and survival .
Zinc plays also a role in regulating the immune system with implication s in pathologies where zinc deficiency and inflammation are observed . | The increments in plasma zinc concentrations after an oral dose of elemental zinc ( 50 mg ) as the sulphate were used to assess the intestinal absorption of the metal in 11 patients with dermatitis herpetiformis ( DH ) before starting a gluten-free diet , 12 patients with newly diagnosed celiac disease ( CD ) , 10 patients known to have CD , and 15 healthy volunteers . The areas under the plasma zinc increment curve plotted against time were determined for 3 ( AUC3 ) and 6 ( AUC6 ) h. The AUC3 in healthy volunteers was 401 + /- 48 mumol 1(-1 ) 3 h ( mean + /- SD ) ; it was reduced in newly diagnosed CD 187 + /- 76 mumol 1(-1 ) 3 h ( p less than 0.001 ) , and in dermatitis herpetiformis 206 + /- 87 mumol 1(-1 ) 3 h ( p less than 0.01 ) ; but it was normal in the known CD 396 + /- 204 mumol 1(-1 ) 3 h , the wide variation reflecting the variable compliance with a previously instituted gluten-free diet . The AUC6 was similarly affected , healthy volunteers 700 + /- 111 mumol 1(-1 ) 6 h , new CD 380 + /- 169 mumol 1(-1 ) 6 h ( p less than 0.01 ) ; dermatitis herpetiformis 471 + /- 107 mumol 1(-1 ) 6 h ( p less than 0.01 ) ; known CD 725 + /- 380 mumol 1(-1 ) 6 h. The AUC3 was more consistently abnormal than conventional tests of small intestinal function . In a prospect i ve study the AUC3 and AUC6 improved and reflected compliance with a gluten-free diet Studies of zinc status in insulin-dependent diabetes mellitus ( IDDM ) have shown contradictory results . Zinc is essential for many enzymes involved in the human metabolism and may play a role in the bio synthesis and storage of insulin in the B-cell . We therefore prospect ively followed 26 patients ( 14 males and 12 females ) with newly diagnosed IDDM in order to determine the plasma zinc variation at the time of diagnosis and after 1 , 3 , 6 , 12 and 24 months . Seventy-two healthy persons ( 36 males and 36 females ) served as controls . Only minor differences in plasma zinc were demonstrated during the first 2 years of IDDM . A sex difference was found in healthy controls but only after 24 months in the diabetics . Quantitative changes of the B-cell function , development of insulin antibodies , age , body weight and serum albumin did not correlate with the course of plasma zinc Two main diabetic groups were investigated , viz , one consisting of 19 diabetic children with newly diagnosed insulin-dependent diabetes mellitus ( IDDM ) ( median age 10 years ) where a prospect i ve study was made , and one where a retrospective examination was performed of 73 patients ( median age 14 years ) with a mean duration of IDDM of 7 years ; 83 healthy school children ( median age 13 years ) served as controls . In both groups of diabetic children more zinc was excreted in the urine than in the controls . At onset of IDDM , serum and blood clot zinc concentrations were reduced with a gradual increase towards normal within 1 month of insulin therapy . The zinc concentrations in hair did not differ from those of the controls . No correlation were found between zinc levels in serum , blood clots , urine and hair on one h and and the concentrations of albumin and glucose in serum and urine on the other Disturbances of zinc homeostasis have been observed in several diseases , including diabetes mellitus . To further characterize the association between zinc and diabetes , we recruited 75 patients with type 1 or type 2 diabetes and 75 nondiabetic sex-/age-matched control subjects in order to analyze differences concerning human zinc transporter 8 ( hZnT-8 ) expression , single nucleotide polymorphisms ( SNPs ) in the genes of hZnT-8 as well as metallothionein 1A and serum/intracellular zinc . Furthermore , we investigated the relation between insulin and zinc homeostasis in type 2 diabetic subjects and consoli date d our results by in vitro analysis of the effect of insulin on cellular zinc status and by analysis of the modulation of insulin signal transduction by intracellular zinc homeostasis . Concerning the expression of hZnT-8 and the SNPs analyzed , we did not observe any differences between diabetic and control subjects . Serum zinc was significantly lower in diabetic patients compared to controls , and intracellular zinc showed the same tendency . Interestingly , type 2 diabetes patients treated with insulin displayed lower serum zinc compared to those not injecting insulin . In vitro analyses showed that insulin leads to an increase in intracellular zinc and that insulin signaling was enhanced by elevated intracellular zinc concentrations . In conclusion , we show that type 1 and type 2 diabetic patients suffer from zinc deficiency , and our results indicate that zinc supplementation may qualify as a potential treatment adjunct in type 2 diabetes by promoting insulin signaling , especially in zinc-deficient subjects Rheumatoid arthritis ( RA ) is a chronic autoimmune inflammatory disease , which mainly involves the joints . RA is prevalent worldwide with increasing prevalence in elderly people . The mechanism of RA pathogenesis is still undefined , and it is interplaying between genetic susceptibility and environmental factors . Although risk factors for RA are not fully established , various studies have focused on the role of trace elements in association with RA . Trace elements act as co-factors for most of the enzymes , and their deficiency is associated with many untoward effects on human health . The homeostatic alterations in the metabolism of trace elements may partly be due to inflammatory response in RA . The objective of the present study was to determine the serum concentrations and correlation of zinc , copper , and iron in RA patients and healthy controls . The study comprised of 61 RA patients and 61 age- and sex-related healthy individuals of Pakistani population . Serum levels of Zn , Cu , and Fe were measured in all the participants by atomic absorption spectrophotometer . Serum Zn and Fe were significantly reduced in the RA patients than those in the healthy controls . Serum Cu concentrations were found elevated in the RA patients . Correlation studies of trace elements determine that there was negative correlation between Zn and Cu in the RA patients and no correlation in the control group . It is very important to explore the deficiency of essential trace metals in biological sample s of the RA patients in different population s which may be helpful for diagnosis and supplementary management of rheumatoid arthritis patients The urinary excretion of zinc in individuals with insulin-dependent diabetes mellitus ( IDDM ) is approximately doubled . In the absence of a compensatory mechanism , this hyperzincuria should induce a deficient or marginal Zn status . We examined parameters of Zn status in plasma and in blood cells with respect to urinary Zn losses and Zn supplementation . We measured Zn levels in the urine , plasma , and erythrocytes of 14 IDDM subjects and 15 nondiabetics who kept dietary records for 3 consecutive days . Subsequently , six IDDM subjects and seven nondiabetics were supplemented with 50 mg Zn daily for 28 days . We measured the above parameters , as well as mononuclear leukocyte Zn ( MNL-Zn ) and the plasma subfraction of albumin-bound Zn ( alb-Zn ) . The total plasma Zn-binding capacity was also assessed . Plasma copper and erythrocyte Cu were monitored as indicators of potential Zn toxicity . Individuals with IDDM displayed the expected hyperzincuria , but had normal blood Zn parameters . Zincuria increased by a similar amount in both groups during supplementation , as did the MNL-Zn content . However , erythrocyte Zn ( e-Zn ) was refractory , so a trend toward lower e-Zn among IDDM subjects persisted during Zn supplementation . Hemoglobin A1c ( HbA1c ) increased markedly in the Zn-supplemented IDDM group . Despite their chronic hyperzincuria , individuals with IDDM appear not to be Zn-deficient . Large-dose Zn supplementation increases MNL-Zn and induces an undesirable elevation of HbA1c in all individuals . This is especially disconcerting for those with IDDM , and may reflect an exacerbation of a chronic " Zn diabetes . " These data suggest a potential for toxicity from large-dose Zn supplementation |
11,381 | 30,957,510 | Poor psychosocial function was predicted by longer treatment duration , severe symptoms , poor cognition and poor insight .
Functioning was assessed by either a single or a combination of measures , but was not the primary outcome in most studies .
Conclusion : Long-acting injectable atypical antipsychotics are beneficial for recovery of psychosocial function in comparison with placebo , but the magnitude of superiority over oral antipsychotic treatment was small .
Severe psychopathology at baseline predicted poor psychosocial function . | Objective : Impairment in psychosocial function is common in schizophrenia .
Long-acting injectable atypical antipsychotics are thought to enhance psychosocial function by boosting adherence .
However , no systematic review has examined the effects of long-acting injectable atypical antipsychotics on psychosocial function in clinical trials . | OBJECTIVE To evaluate aripiprazole once-monthly ( AOM ) , a long-acting injectable suspension of aripiprazole , as acute treatment in patients with schizophrenia ( DSM-IV-TR ) . METHOD Adults experiencing an acute psychotic episode were r and omized to 12 weeks of double-blind treatment with AOM 400 mg or placebo ( October 2012-August 2013 ) . The primary efficacy outcome was change from baseline to endpoint ( week 10 ) in Positive and Negative Syndrome Scale ( PANSS ) total score . The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score . Secondary efficacy outcomes included change from baseline in PANSS positive and negative subscale and Personal and Social Performance Scale ( PSP ) scores . The study took place from October 2012 through August 2013 . RESULTS Patients ( N = 340 ; 79 % male , 66 % black ) were r and omized to AOM ( n = 168 ) or placebo ( n = 172 ) . Least squares ( LS ) mean change from baseline to endpoint ( week 10 ) favored AOM versus placebo in PANSS total ( treatment difference , -15.1 [ 95 % CI , -19.4 to -10.8 ] ; P < .0001 ) and CGI-S ( treatment difference , -0.8 [ 95 % CI , -1.1 to -0.6 ] ; P < .0001 ) scores , as it did at all other timepoints through 12 weeks ( all P ≤ .0005 ) . LS mean change from baseline in PANSS positive and negative subscale and PSP scores favored AOM versus placebo ( P < .0001 ) . Common ( > 10 % ) treatment-emergent adverse events ( AOM vs. placebo ) were increased weight ( 16.8 % vs 7.0 % ) , headache ( 14.4 % vs. 16.3 % ) , and akathisia ( 11.4 % vs 3.5 % ) . CONCLUSIONS Symptoms and functioning improved with AOM 400 mg versus placebo in patients with acute schizophrenia , with acceptable safety and tolerability . These data suggest that AOM 400 mg is a viable treatment option for patients experiencing an acute schizophrenia episode . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01663532 BACKGROUND Persons with schizophrenia often come in contact with the criminal justice system ( CJS ) . This analysis of subjects with schizophrenia and a history of contact with the CJS estimated and compared mean cumulative function ( MCF ) of treatment failure events when treated with paliperidone palmitate ( PP ) or oral antipsychotics ( OAs ) . All events identified during the full study period of the Paliperidone Palmitate Research in Demonstrating Effectiveness ( PRIDE ) trial were evaluated . METHODS Subjects were r and omly assigned to flexibly dosed , monthly , injectable PP ( 78 - 234 mg ) or daily OA in a 15-month prospect i ve , open-label , multicenter US study ( May 5 , 2010-December 9 , 2013 ) . Subjects could continue participation after a treatment failure event . Multiple treatment failures in individual subjects were analyzed as recurrent events . Analyses estimated MCF of treatment failure events and MCF of institutionalizations ( arrests , incarcerations , or psychiatric hospitalizations ) during the 15-month study period . RESULTS The ITT population included 226 ( PP ) and 218 ( OA ) subjects , of whom 41.2 % and 40.4 % , respectively , completed 15 months of follow-up . The MCF of treatment failures and institutionalizations differed significantly in favor of PP compared with OA ( P=0.007 and P=0.005 , respectively ) . Overall , TEAEs were reported by 86.3 % of subjects in the PP group and 81.7 % in the OA group . CONCLUSIONS This pragmatic analysis suggests that , compared with OA , PP is not only more effective in delaying median time to treatment failure , but it also reduces the number of treatment failures and institutionalizations per person-year follow-up . CLINICAL TRIALS REGISTRATION Clinical trials.gov identifier : NCT01157351 Abstract Background QUALIFY was a 28-week , r and omized , open-label , head-to-head trial that assessed improvements across multiple measures in stable patients with schizophrenia with aripiprazole once-monthly 400 mg vs paliperidone palmitate . Methods Secondary effectiveness assessment s included physician-rated readiness for work using the Work Readiness Question naire , the Clinical Global Impression – Severity and Clinical Global Impression – Improvement scales , and quality of life with the rater-blinded Heinrichs-Carpenter Quality of Life Scale . Patients assessed their treatment satisfaction and quality of life with Subjective Well-Being under Neuroleptic Treatment−short version and Tolerability and Quality of Life question naires . Results Odds of being ready for work at week 28 were significantly higher with aripiprazole once-monthly 400 mg vs paliperidone palmitate ( adjusted odds ratio , 2.67 ; 95 % CI , 1.39−5.14 ; P=.003 ) . Aripiprazole once-monthly 400 mg produced numerically or significantly greater improvements from baseline vs paliperidone palmitate in all Quality of Life Scale items . With aripiprazole once-monthly 400 mg vs paliperidone palmitate at week 28 , there were significantly more Clinical Global Impression – Severity and Clinical Global Impression – Improvement responders ( adjusted odds ratio , 2.26 ; P=.010 , and 2.51 ; P=.0032 ) and significantly better Clinical Global Impression – Improvement scores ( least squares mean treatment difference , −0.326 ; 95 % CI , −0.60 to −0.05 ; P=.020 ) . Numerically larger improvements with aripiprazole once-monthly 400 mg vs paliperidone palmitate were observed for patient-rated scales Subjective Well-Being under Neuroleptic Treatment−short version and Tolerability and Quality of Life . Partial correlations were strongest among clinician-rated and among patient-rated scales but poorest between clinician and patient-rated scales . Conclusions Consistently greater improvements were observed with aripiprazole once-monthly 400 mg vs paliperidone palmitate across all measures . Partial correlations between scales demonstrate the multidimensionality of various measures of improvement . More patients on aripiprazole once-monthly 400 mg were deemed ready to work by the study end . Trial registry National Institutes of Health registry , NCT01795547 , https:// clinical trials.gov/ct2/ results ? id = NCT01795547 OBJECTIVE To directly compare aripiprazole once-monthly 400 mg ( AOM 400 ) and paliperidone palmitate once-monthly ( PP ) on the Heinrichs-Carpenter Quality -of-Life Scale ( QLS ) , a vali date d health-related quality of life and functioning measure in schizophrenia . METHOD This 28-week , r and omized , non-inferiority , open-label , rater-blinded , head-to-head study ( QUALIFY ) of AOM 400 and PP in adult patients ( 18 - 60 years ) comprised oral conversion , initiation of AOM 400 or PP treatment , and continuation with intramuscular injections every 4weeks . The primary endpoint assessed non-inferiority and superiority on QLS total score analyzed using a mixed model for repeated measurements . RESULTS Of 295 r and omized patients , 100/148 ( 67.6 % ) of AOM 400 and 83/147 ( 56.5 % ) of PP patients completed 28weeks of treatment . A statistically significant least squares mean difference in change from baseline to week 28 on QLS total score ( 4.67 [ 95%CI : 0.32;9.02 ] , p=0.036 ) confirmed non-inferiority and established superiority of AOM 400 vs PP . There were also significant improvements in Clinical Global Impression - Severity scale and the Investigator 's Assessment Question naire for AOM 400 vs PP , and pre-defined sub-group analyses revealed a consistent pattern of significance favoring AOM 400 in patients ≤35years . Common treatment-emergent adverse events in the treatment continuation phase were more frequent with PP vs AOM 400 , and adverse events were the most frequent reason for discontinuation ( 27/137 [ 19.7 % ] for PP and 16/144 [ 11.1 % ] for AOM 400 ) . All-cause discontinuation was numerically lower with AOM 400 . CONCLUSION Superior improvements on clinician-rated health-related quality of life and a favorable tolerability profile suggest greater overall effectiveness for aripiprazole once-monthly vs paliperidone palmitate . Clinical Trials.gov identifier : NCT01795547 This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate ( approved in the USA , August 2009 ) for adult patients with acutely exacerbated schizophrenia . The patients ( N = 652 ) were r and omly assigned ( 1:1:1:1 ) to paliperidone palmitate at 25 , 100 , or 150 mg eq. or placebo in this 13-week double-blind study . The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or muscle on day 8 and then once monthly ( days 36 and 64 ) . No oral supplementation was used . Target plasma levels were achieved by day 8 in all paliperidone palmitate groups . The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly ( P ≤ 0.034 ) in all the paliperidone palmitate dose-groups versus placebo . Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle . Common treatment-emergent adverse events ( ≥2 % of patients in any of the treatment groups ) that occurred more frequently in the total paliperidone palmitate group versus the placebo group ( with ≥1 % difference ) were injection-site pain ( 7.6 % vs 3.7 % ) , dizziness ( 2.5 % vs 1.2 % ) , sedation ( 2.3 % vs 0.6 % ) , pain in the extremity ( 1.6 % vs 0.0 % ) , and myalgia ( 1.0 % vs 0.0 % ) . The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range ( 25 , 100 , or 150 mg eq. ) in adult patients with acutely exacerbated schizophrenia . Abbreviations : BMI - body mass index , CGI-S - Clinical Global Impression-Severity , EPS - extrapyramidal symptoms , ER - extended release , ITT - intent-to-treat , LAI - long-acting injectable , PANSS - Positive and Negative Syndrome Scale , PK - pharmacokinetic , PSP - Personal and Social Performance Scale , TEAE - treatment-emergent adverse events , VAS - Visual Analogue OBJECTIVE The superiority of risperidone long-acting injection ( RLAI ) over oral typical and atypical antipsychotics demonstrated in previous studies may be related to the improved drug compliance . The aim of the 12-week r and omized , single-blind study was to test whether the superiority of RLAI remained among hospitalized patients that drug compliance could be optimally controlled . METHODS Fifty hospitalized stable schizophrenic patients , who had maintained on oral risperidone for more than 3 months , were r and omized to the RLAI and oral risperidone group . Finally 49 patients ( 98 % ) completed the study , and no dose change of oral risperidone , or RLAI was noted among all patients . RESULTS The RLAI group showed significantly increased positive score of Positive and Negative Syndrome Scale ( PANSS ) than the risperidone group ( 0.72 + /- 3.52 vs. -1.24 + /- 3.81 , p = 0.022 ) , but without significance difference for the PANSS total , negative and general psychopathology scores . The RLAI group also showed a significantly improved Udvalg for Kliniske Undersogelser ( UKU ) Scale ( p = 0.037 ) , social life domains of Short-Form Health Survey ( SF-36 ) ( p = 0.011 ) , and reduced prolactin level ( p = 0.001 ) . CONCLUSION The results indicated that with optimal controlling of drug compliance among hospitalized patients , RLAI showed no benefit of efficacy over oral risperidone , but with advantages of improved side-effect profiles , social life ratings , and reduced prolactin levels Until relatively recently , long-acting injectable ( LAI ) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics ( SGA ) increased . Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice , this is not seen in recent r and omized clinical trials . PROACTIVE ( Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy ) relapse prevention study incorporated efficacy and effectiveness features . At 8 US academic centers , 305 patients with schizophrenia or schizoaffective disorder were r and omly assigned to LAI risperidone ( LAI-R ) or physician 's choice oral SGAs . Patients were evaluated during the 30-month study by masked , central ized assessors using 2-way video , and monitored biweekly by on-site clinicians and assessors who knew treatment assignment . Relapse was evaluated by a masked Relapse Monitoring Board . Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant . Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group . In contrast , the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores . There were no other between-group differences in symptoms or functional improvement . Despite the advantage for psychotic symptoms , LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization . Biweekly monitoring , not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm , may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials OBJECTIVE This study examined the effects of 2 doses of long-acting risperidone injection in patients with schizophrenia or schizoaffective disorder . METHOD This 52-week , prospect i ve , r and omized , double-blind , multicenter , international study included clinical ly stable out patients with schizophrenia or schizoaffective disorder ( DSM-IV criteria ) . Setting s included physicians ' offices and clinics . Patients received a fixed dose of long-acting risperidone ( 25 or 50 mg ) every 2 weeks . Primary outcome was time to relapse , defined as either re-hospitalization or other exacerbation criteria . Other assessment s included the Positive and Negative Syndrome Scale , Clinical Global Impressions-Severity of Illness scale , and functional and quality -of-life measures . Safety was assessed via treatment-emergent adverse events , laboratory tests , and movement disorder rating scales . Data were collected from December 2002 to September 2004 . RESULTS A total of 324 patients were r and omized to 25 mg ( N = 163 ) or 50 mg ( N = 161 ) of long-acting risperidone . Time to relapse was comparable ( p = .131 ) for both groups . Projected median time to relapse was 161.8 weeks ( 95 % CI = 103.0 to 254.2 ) with 25 mg and 259.0 weeks ( 95 % CI = 153.6 to 436.8 ) with 50 mg . One-year incidences of relapse were 21.6 % ( N = 35 ) and 14.9 % ( N = 24 ) , respectively ( p = .059 ) . Psychiatric hospitalization was the reason for relapse for 16 ( 10 % ) in the 25-mg group and 10 ( 6 % ) in the 50-mg group . Patients experienced statistically significant but modest improvements at endpoint in most measures ( i.e. , psychotic symptoms , functioning , movement disorder severity ) with both doses , with no significant between-group differences . CONCLUSION In this 1-year study , long-acting risperidone was associated with low relapse and rehospitalization rates , indicating that doses of 25 to 50 mg are appropriate for long-term treatment in schizophrenia OBJECTIVE The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic ( long-acting injectable risperidone ) in patients with schizophrenia . METHOD In a 12-week , multicenter , double-blind , r and omized study , patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone ( 25 mg , 50 mg , or 75 mg ) . The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale . RESULTS Of the 554 patients who were enrolled , 400 entered the double-blind study , and 370 received at least one postbaseline assessment . Mean changes in score of -6.2 , -8.5 , and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25- , 50- , and 75-mg risperidone groups , respectively ; all three change scores were significantly different from that seen with placebo ( + 2.6 ) . Improvements in positive and negative symptoms were also significantly greater in patients receiving risperidone . Long-acting risperidone was well tolerated . Adverse events related to extrapyramidal symptoms were spontaneously reported by 13 % of patients receiving placebo and 10 % of patients in the 25-mg risperidone group , with higher rates in the 50-mg and 75-mg groups . Severity of extrapyramidal symptoms was mild at baseline and throughout the trial in each treatment group . Mean weight changes were small in the 25- , 50- , and 75-mg risperidone groups ( 0.5 kg , 1.2 kg , and 1.9 kg , respectively ) . Injection site pain was rated as low by the patients , consistent with the investigators ' pain ratings . CONCLUSIONS Long-acting injectable risperidone was efficacious and well tolerated and provides both clinicians and patients with a new mode of treatment that can improve the outcome of long-term therapy Background Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection ( LAI ) , and whether observed changes differ from those seen with oral olanzapine . Methods This study describes changes in the levels of functioning among out patients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years . This was a secondary analysis of data from a multicenter , r and omized , open-label , 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI ( 405 mg/4 weeks ; n=264 ) with daily oral olanzapine ( 10 mg/day ; n=260 ) . Levels of functioning were assessed with the Heinrichs – Carpenter Quality of Life Scale . Functional status was also classified as “ good ” , “ moderate ” , or “ poor ” , using a previous data -driven approach . Changes in functional levels were assessed with McNemar ’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student ’s t-test . Results Over the 2-year study , the patients treated with olanzapine-LAI improved their level of functioning ( per Quality of Life total score ) from 64.0–70.8 ( P<0.001 ) . Patients on oral olanzapine also increased their level of functioning from 62.1–70.1 ( P<0.001 ) . At baseline , 19.2 % of the olanzapine-LAI-treated patients had a “ good ” level of functioning , which increased to 27.5 % ( P<0.05 ) . The figures for oral olanzapine were 14.2 % and 24.5 % , respectively ( P<0.001 ) . Results did not significantly differ between olanzapine-LAI and oral olanzapine . Conclusion In this 2-year , open-label , r and omized study of olanzapine-LAI , out patients with schizophrenia maintained or improved their favorable baseline level of functioning over time . Results did not significantly differ between olanzapine-LAI and oral olanzapine INTRODUCTION Cognitive impairment in schizophrenia and schizoaffective disorder is a major determinant of disability . This study explored the relationships among cognitive functioning , clinical symptoms , overall functionality , and demographic characteristics . METHODS This was a post hoc analysis of a 52-week , prospect i ve , r and omized , double-blind study ( N=323 ) comparing 2 doses of risperidone long-acting injectable ( RLAI ) in stable subjects with schizophrenia or schizoaffective disorder . Cognitive evaluations were performed and st and ardized using a healthy age- and sex-matched comparison group . Simple and multiple regression models were used to identify relationships among neurocognitive composite scores ( NCS ) , clinical symptom end points ( Positive and Negative Syndrome Scale [ PANSS ] total and factor scores ) , overall functionality ( Personal and Social Performance [ PSP ] score ) , and demographics . RESULTS A simple regression model identified significant relationships between the NCS at end point and PANSS total score , PANSS disorganized thoughts factor score , functioning ( PSP ) and age . A 1-point decrease on PANSS total score and PANSS disorganized thoughts factor score corresponded to an increase in NCS of 0.126-point , and 0.81-point increases , respectively . A 1-point increase on the PSP corresponded to a 0.186-point increase in the NCS T-score . Among the demographic variables , only age correlated significantly with cognition ( 10-year increase in age corresponded to 1.1-point decrease in NCS T-score ) in a multiple regression model . CONCLUSION Improved cognition was associated with beneficial changes in functional status and clinical symptoms ( particularly disorganization symptoms ) in subjects with schizophrenia/schizoaffective disorder . Older subjects showed less overall cognitive improvement . Improved cognitive and functional outcome is correlated with symptom improvements in RLAI-treated patients with schizophrenia BACKGROUND The efficacy and safety of long-acting injectable risperidone have not been compared with those of an oral atypical antipsychotic . AIMS To compare long-acting risperidone and oral olanzapine in 377 patients with DSM-IV schizophrenia or schizoaffective disorder . METHOD Patients were r and omised to receive long-acting risperidone ( 25 mg or 50 mg every 14 days ) or olanzapine ( 5 - 20 mg/day ) . RESULTS In the 13-week phase , long-acting risperidone was at least as effective as ( not inferior to ) oral olanzapine . In the 12-month phase , significant improvements in the Positive and Negative Syndrome Scale ( PANSS ) total and factor scores from baseline to month 12 and end-point were seen in both groups of patients . Few patients discontinued treatment because of an adverse event . CONCLUSIONS Both treatments were efficacious and well tolerated OBJECTIVE Relapse and acute exacerbation are common in schizophrenia and may impact treatment response and outcome . Evidence is conflicting in respect to superiority of long-acting injectable antipsychotic therapies versus oral antipsychotics in relapse prevention . This r and omized controlled study assessed the efficacy of paliperidone palmitate versus oral antipsychotics for relapse prevention . METHOD Eligible patients with a recent diagnosis of schizophrenia ( within 1 - 5 years ) were r and omized 1:1 to paliperidone palmitate ( n=376 ) or oral antipsychotic monotherapy ( n=388 ) and entered a 2-week initial acute oral treatment phase . Patients who met predefined response criteria were eligible to enter the 24-month rater-blinded core treatment phase . Patients were evaluated for relapse , symptoms , functioning , quality of life , treatment satisfaction , and tolerability . RESULTS In the core treatment phase , time to relapse was significantly longer in the paliperidone palmitate ( n=352 ) compared with the oral antipsychotics arm ( n=363 ) : 85 % of patients were relapse-free at 469 versus 249 days ( P=0.019 ) . Significantly fewer patients receiving paliperidone palmitate met the relapse criteria ( 52 [ 14.8 % ] versus 76 [ 20.9 % , oral antipsychotics ] ; P=0.032 ) , representing a 29.4 % relative risk reduction . For paliperidone palmitate , a significantly greater improvement in Positive and Negative Syndrome Scale total score on Day 8 ( P=0.021 ) and a trend at endpoint ( P=0.075 ) were observed . Functioning improvements were comparable between treatment arms . No new safety signals were identified . CONCLUSION The observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia , including during the early stages of illness Long-acting injectable antipsychotics ( LAIs ) should offer better efficacy and tolerability , compared to oral antipsychotics due to improved adherence and more stable pharmacokinetics . However , data on LAIs has been mixed , with some studies finding that they are more effective and tolerable than oral antipsychotics , and others finding the contrary . One possibility for the disparate results may be that some studies administered different antipsychotics in the oral and injectable form . The present systematic review examined the efficacy and tolerability of LAIs versus their oral equivalents in r and omized and naturalistic studies . In addition , it examined the impact of LAIs on special population s such as patients with first-episode psychosis , substance use disorders , and a history of violence or on involuntary outpatient commitment . R and omized studies suggest that not all LAIs are the same ; for example , long-acting risperidone may be associated with equal or less side effects than oral risperidone , whereas fluphenazine decanoate and enanthate may be associated with equal or more side effects than oral fluphenazine . They also suggest that LAIs reduce risk of relapse versus oral antipsychotics in schizophrenia out patients when combined with quality psychosocial interventions . For their part , naturalistic studies point to a larger magnitude of benefit for LAIs , relative to their oral equivalents particularly among first-episode patients Background Long acting injections ( LAI ) have been associated with perceptions of coercion in cross sectional studies but there have been no longitudinal studies of the effects on clinical relationships with newer depot medications . Method R and omized controlled trial with ( 50 ) participants with a diagnosis of schizophrenia r and omized to risperidone LAI or oral atypical antipsychotic medication . The main outcome was the Working Alliance Inventory ( WAI ) with background variables ( symptoms , side effect , social functioning , quality of life ) measured before r and omization and at two years . Results At follow-up ( 14 risperidone LAI and 16 oral medication ) analyses including predictors of missing data and baseline score showed a trend for those on risperidone LAI to reduce WAI score and those on oral medication showing no change . Sensitivity analyses showed ( i ) a significant detrimental effect of LAI on WAI and ( ii ) the pattern of results was not affected by change in symptoms over the study . Conclusion This is the first study to show that the prescription of depot atypical depot medication is associated with detrimental effects on clinical relationships after 2 years of continual treatment OBJECTIVE To assess the effects of maintenance therapy with aripiprazole once-monthly 400 mg on personal and social functioning . METHODS Data were analyzed from 2 r and omized , double-blind trials of patients with schizophrenia requiring chronic antipsychotic treatment . One study was a 52-week trial of aripiprazole once-monthly 400 mg versus placebo ; the other was a 38-week trial of aripiprazole once-monthly 400 mg , oral aripiprazole ( 10 - 30 mg daily ) , and aripiprazole once-monthly 50 mg ( subtherapeutic dose to test assay sensitivity ) . Functioning was assessed using the Personal and Social Performance ( PSP ) scale , comprising 4 domain subscales . RESULTS In the 52-week study , 403 patients stabilized on aripiprazole once-monthly 400 mg were r and omized to receive aripiprazole once-monthly 400 mg ( n=269 ) or placebo ( n=134 ) . In the 38-week study , 662 patients stabilized on oral aripiprazole were r and omized to receive aripiprazole once-monthly 400 mg ( n=265 ) , oral aripiprazole ( n=266 ) , or aripiprazole once-monthly 50 mg ( subtherapeutic dose ; n=131 ) . In the 52-week study , mean changes from baseline were significantly worsened with placebo compared with aripiprazole once-monthly 400 mg for PSP total score ( P<0.001 ) and domain scores for Personal and Social Relationships ( P<0.001 ) , Self-Care ( P<0.01 ) , and Disturbing and Aggressive Behavior ( P<0.0001 ) . In the 38-week study , mean changes from baseline were significantly worsened with aripiprazole once-monthly 50 mg compared with aripiprazole once-monthly 400 mg for PSP total score ( P<0.05 ) and the Personal and Social Relationships domain score ( P<0.05 ) . CONCLUSION Patient functioning , assessed using the PSP scale , was maintained in stabilized patients treated with aripiprazole once-monthly in 2 pivotal relapse studies Purpose : The aim of this study was to compare the effects of risperidone long-acting injection ( RLAI ) and paliperidone palmitate ( PP ) on non-acute-phase social functioning in patients with schizophrenia . Patients and Methods : In this 6-month pilot , open-label , r and omized controlled study , 30 patients with schizophrenia who had been treated with RLAI were r and omly allocated to the RLAI continuation group or switched to the PP group . Patients were evaluated at baseline and 6 months with the Social Functioning Scale ( SFS ) as the primary outcome variable and University of California San Diego Performance-Based Skills Assessment Brief ( UPSA-B ) , Social Emotional Cognition Task ( SECT ) , Positive and Negative Syndrome Scale ( PANSS ) , and Drug-Induced Extrapyramidal Symptoms Scale ( DIEPSS ) scores as secondary outcomes . Results : At baseline , the two groups did not significantly differ in demographic or clinical features . The two groups did not differ in total score changes for the UPSA-B , the SECT , the PANSS , and the DIEPSS . However , the total scores and the two subscales of the SFS , i.e. independence-competence and independence-performance , were more improved in the PP group compared to the RLAI group ( total scores , p = 0.038 ; competence , p = 0.001 , and performance , p = 0.007 , respectively ) . Conclusion : These results suggest that PP may improve the total social functioning , independent life competence , and performance as compared to the RLAI group . However , these results are preliminary and need independent replication in larger sample s before any definitive statement can be made OBJECTIVE ConstaTRE is an open-label , r and omised , controlled , relapse prevention trial in patients with stable schizophrenia or schizoaffective disorder switched to risperidone long-acting injectable ( RLAI ) or oral quetiapine , and was design ed to test the hypothesis that injectable antipsychotic treatment with risperidone would be more effective than oral therapy with quetiapine . Here we report the functional recovery results from the ConstaTRE trial . METHODS Clinical ly stable adults previously treated with oral risperidone , olanzapine , or oral first-generation antipsychotics were r and omised to RLAI or quetiapine for 24 months . Functional recovery was assessed using the Social and Occupational Functioning Assessment Scale ( SOFAS ) and two quality -of-life ( QoL ) measures [ Medical Outcomes Survey Short Form-12 ( SF-12 ) and Schizophrenia Quality -of-Life Scale Revision 4 ( SQLS-R4 ) ] . RESULTS A total of 666 patients were r and omised and treated with RLAI ( n = 329 ) or quetiapine ( n = 337 ) . Relapse occurred in 16.5 % RLAI and 31.3 % quetiapine patients . Significant improvements in SOFAS , SF-12 , and SQLS-R4 scores were observed from baseline to month 24 with both RLAI and quetiapine . At months 6 , and 12 , and endpoint , improvement in SOFAS score was significantly greater for RLAI than quetiapine ( p < 0.05 ) . CONCLUSIONS Among patients with stable schizophrenia or schizoaffective disorder , the likelihood of functional recovery appears to be higher in those switching to RLAI than to quetiapine , although improvements in functional status and QoL were observed with both treatments BACKGROUND We investigated the impact of treatment with long-acting , injectable risperidone versus placebo on health-related quality of life ( HRQoL ) in patients with schizophrenia . Results are discussed in the context of HRQoL in the general U.S. population . METHOD Patients with DSM-IV schizophrenia entered a r and omized , double-blind , placebo-controlled trial . After screening , previous antipsychotics were discontinued , and oral risperidone was titrated up to a dose of 4 mg/day over 1 week . Patients were then r and omly assigned to receive placebo [ N = 92 ] or long-acting risperidone ( 25 [ N = 93 ] , 50 [ N = 97 ] , or 75 mg [ N = 87 ] every 2 weeks ) for 12 weeks . HRQoL was measured using the Medical Outcomes Study Short-Form 36-item question naire ( SF-36 ) . RESULTS At week 12 , patients receiving long-acting risperidone had improved significantly ( p < .05 ) in 5 domains of the SF-36 ( bodily pain , general health , social functioning , role-emotional , and mental health ) compared with patients receiving placebo . The effect was greatest for the 25-mg group , with significant improvement versus placebo in 6 domains ( p < .05 ) . At baseline , all SF-36 domain scores except bodily pain were significantly lower ( p < .05 ) than normal values in all groups . With placebo , scores in all 8 domains remained below normal values after 12 weeks , while patients receiving long-acting risperidone showed improvement in HRQoL toward normal levels , with clinical ly meaningful improvements in all mental-health domains . In the 25-mg group , scores in 7 domains were not statistically different from normal values after 12 weeks . CONCLUSIONS Long-acting , injectable risperidone improved HRQoL toward normal levels . After 12 weeks , HRQoL of patients receiving 25 mg was not significantly different from normal BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism To assess baseline predictors and consequences of antipsychotic adherence during the long-term treatment of schizophrenia out patients , data were taken from the 3-year , prospect i ve , observational , European Schizophrenia Out patients Health Outcomes ( SOHO ) study , in which out patients starting or changing antipsychotics were assessed every 6 months . Physician-rated adherence was dichotomized as adherence/non-adherence . Regression models tested for predictors of adherence during follow-up , and associations between adherence and outcome measures . Of the 6731 patients analysed , 71.2 % were adherent and 28.8 % were non-adherent over 3 years . The strongest predictor of adherence was adherence in the month before baseline assessment . Other baseline predictors of adherence included initial treatment for schizophrenia and greater social activities . Baseline predictors of non-adherence were alcohol dependence and substance abuse in the previous month , hospitalization in the previous 6 months , independent housing and the presence of hostility . Non-adherence was significantly associated with an increased risk of relapse , hospitalization and suicide attempts . In conclusion , non-adherence is common but can partly be predicted . This may allow strategies to improve adherence to be targeted to high-risk patients . Also , reversal of some risk factors may improve adherence . Non-adherence is associated with a range of poorer long-term outcomes , with clinical and economic implication BACKGROUND There is increased interest in the impact of new long-acting treatments on health-related quality of life ( HRQoL ) in patients with schizophrenia . The aim of this study was to evaluate the impact of treatment with subcutaneous injections of RBP-7000 , a new sustained-release formulation of risperidone , compared with placebo on health status , subjective well-being , treatment satisfaction , and preference of medicine in subjects with acute schizophrenia . METHODS HRQoL data were derived from an 8-week double-blind , r and omized , placebo-controlled , phase 3 study that assessed efficacy , safety , and tolerability of once monthly RBP-7000 ( 90 mg and 120 mg ) compared with placebo in subjects with acute schizophrenia ( n=337 ) . HRQoL was measured with the EuroQol EQ-5D-5L , well-being using the Neuroleptic Treatment-Short Version ( SWN-S ) , satisfaction using the Medication Satisfaction Question naire ( MSQ ) , and preference using the Preference of Medicine Question naire ( POM ) . RESULTS The EQ-5D-5L VAS increased significantly in the RBP-7000 120 mg group compared to Placebo ( p=0.0212 ) . In RBP-7000 120 mg , subjects reported significant improvements in SWN-S physical functioning ( p=0.0093 ) , social integration ( p=0.0368 ) , and total score ( p=0.0395 ) . Subjects were significantly more satisfied with RBP-7000 versus placebo ( 90 mg p=0.0009 , 120 mg p=0.0006 ) and preferred RBP-7000 over their previous medication ( 90 mg p<0.0001 , 120 mg p=0.0619 ) . CONCLUSIONS Significantly greater improvements in HRQoL and overall well-being were demonstrated in patients r and omized to RBP-7000 compared to placebo . The effect was more pronounced in the RBP-7000 120 mg group . Patient satisfaction improved significantly and patient preference for their medicine favored RBP-7000 90 mg and 120 mg versus Placebo OBJECTIVE We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia . METHODS Eligible patients ( Positive and Negative Syndrome Scale [ PANSS ] total score < 120 ) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week , open-label phase . Patients received the first 2 intramuscular injections of paliperidone palmitate ( 50 mg eq ) one-week apart , then subsequent injections ( 25 , 50 , or 100 mg eq , flexibly-dosed ) , once-monthly . Stable patients ( PANSS total score < or = 75 ) continued into the 24-week maintenance phase . At maintenance phase endpoint , stabilized patients were r and omized ( 1:1 ratio ) to either continue paliperidone palmitate ( at stabilized dose ) or begin placebo in the variable- duration , double-blind phase . RESULTS The preplanned interim analysis ( conducted after 68 relapse events ) included 312 patients : mean age = 40 years , 55 % men , 66 % white , and mean transition baseline PANSS total score ( SD ) : placebo , 69.5 ( 16.89 ) ; paliperidone palmitate , 69.3 ( 17.39 ) . Time-to-relapse ( primary endpoint ) favored paliperidone palmitate ( p<0.0001 , log-rank test ) at interim and final analysis ( n=408 ) . The hazard ratio ( placebo/paliperidone palmitate ) at the final analysis was 3.60 ( 95 % CI : 2.45 , 5.28 ) . Treatment-emergent adverse event rates ( final analysis set ) were : 67 % for transition and maintenance phases , and 45 % ( placebo ) and 44 % ( paliperidone palmitate ) for the double-blind phase . Across phases , the incidence of glucose-related adverse events was low ( < or = 4 % ) , while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients . Injection site tolerability was comparable between groups . CONCLUSION Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals 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 It has been suggested that atypical antipsychotic drugs ( A-APDs ) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia ( TRS ) , if both the dose is higher , and the duration of the trial longer , than those which have been ineffective in non-TRS ( NTRS ) patients . This hypothesis was tested with long acting injectable risperidone ( Risperdal Consta ® , RLAI ) . One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations , or both , were r and omized to RLAI , 50 or 100 mg biweekly , in a six month , outpatient , double-blind , multicenter trial . We hypothesized that RLAI , 100 mg , would be more effective than RLAI , 50 mg . However , both doses produced clinical ly significant and equivalent improvement in PANSS Total , Positive , and Negative subscale scores , as well as key cognitive , global and functional measures , with increasing response during the course of the study , confirming the value of longer clinical trial duration for patients with TRS , but not superiority of the higher dose . The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine , another A-APD , in TRS . Both doses of RLAI were equally well tolerated , producing minimal extrapyramidal side effects and few drop outs . Plasma levels of the active moiety , risperidone+9-hydroxyrisperidone , during treatment with RLAI 100 mg , were comparable to those for 6 - 8 mg/day oral risperidone , which have not been effective in TRS . Further study of RLAI , ≥ 50 - 100 mg biweekly , should compare it with clozapine and oral risperidone in TRS , with duration of treatment ≥ six months OBJECTIVES To further characterize the clinical profile of long-term treatment with aripiprazole once-monthly 400 mg ( AOM 400 ) by examining patient-centered outcomes in adults with schizophrenia . METHODS Data are from 2 separate studies : a 52-week , multicenter , r and omized , double-blind , placebo-controlled study and a 38-week , multicenter , r and omized , double-blind , active-controlled study that evaluated the clinical profile of AOM 400 as maintenance treatment in patients with schizophrenia . The studies were conducted from July 2008 through February 2011 and from September 2008 through August 2012 , respectively . Both studies included the Drug Attitude Inventory ( DAI ) , the Medication Adherence Question naire ( MAQ ) , the Patient Satisfaction with Medication Question naire , and a re source utilization and hospitalization form as prespecified patient-centered endpoints . RESULTS A total of 710 patients entered the oral stabilization phase in the 52-week study , and 403 patients were r and omized to double-blind treatment . The corresponding sample sizes in the 38-week study were 842 and 662 , respectively . In both studies , mean DAI and MAQ scores remained stable across all treatment phases ; mean changes from baseline during the double-blind phase were not significantly different between treatment arms . Treatment satisfaction remained high throughout both studies , and most patients reported no or fewer side effects with AOM 400 relative to their prior medication . Most patients did not have unscheduled outpatient visits or hospitalizations throughout the studies . CONCLUSIONS Data from 2 r and omized , double-blind studies indicated that patient perceptions about treatment satisfaction , side effects , and medication adherence were maintained in patients with schizophrenia receiving maintenance treatment with AOM 400 . TRIAL REGISTRATION Clinical Trials.gov : NCT00705783 , NCT00706654 OBJECTIVE This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia . METHOD Consenting patients were enrolled in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) project . In phase 1 , patients were r and omly assigned to receive olanzapine , perphenazine , quetiapine , risperidone , or ziprasidone for up to 18 months . Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy ; all other patients received another second-generation antipsychotic . Psychosocial functioning was assessed using the Quality of Life Scale . RESULTS Psychosocial functioning modestly improved for the one-third of phase 1 patients who reached the primary Quality of Life Scale analysis endpoint of 12 months ( average effect size 0.19 SD units ) . Although for several of the drugs individually there were significant changes from baseline , overall there were no significant differences between the different agents . Results were similar at 6 and 18 months . There were no significant differences among the treatment groups in the amount of change in the Quality of Life Scale total score or subscale scores at 6 , 12 , or 18 months . Patients treated with clozapine in the efficacy pathway made comparable gains . Early treatment discontinuations , especially among patients most impaired at baseline , limited the ability to achieve more substantial functional gains . CONCLUSIONS All antipsychotic treatment groups in all phases made modest improvements in psychosocial functioning . There were no differences among them after 6 , 12 , or 18 months . More substantial improvements would likely require more intensive adjunctive psychosocial rehabilitation interventions OBJECTIVE Schizoaffective disorder is a complex illness for which optimal treatment is not well established . Results of the first controlled , relapse-prevention study of paliperidone palmitate once-monthly injectable ( paliperidone monthly ) in schizoaffective disorder are presented . METHOD The study was conducted between September 20 , 2010 , and October 22 , 2013 . Patients with schizoaffective disorder ( confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders ) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and r and omly assigned ( 1:1 ) to paliperidone monthly or placebo in a 15-month , double-blind , relapse-prevention phase . R and omization was stratified by administration as monotherapy or adjunctive therapy and by study center . The primary endpoint was time to relapse . RESULTS 334 patients were evaluated . Paliperidone monthly significantly delayed time to relapse for psychotic , depressive , and manic symptoms compared with placebo ( P < .001 , log-rank test ) . Relapse risk was 2.49 times greater for placebo ( hazard ratio = 2.49 ; 95 % CI , 1.55 to 3.99 ; P < .001 , Cox proportional hazards model ) . Overall relapse rates were 33.5 % for placebo and 15.2 % for paliperidone monthly . For monotherapy , relapse risk was 3.38 times greater with placebo ( P = .002 ) , and for adjunctive treatment it was 2.03 times greater with placebo ( P = .021 ) . Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale ( P = .014 , mixed-model repeated- measures analysis ) . The most common adverse events ( placebo , paliperidone monthly ) were increased weight ( 4.7 % , 8.5 % ) , insomnia ( 7.1 % , 4.9 % ) , schizoaffective disorder ( 5.9 % , 3.0 % ) , headache ( 3.5 % , 5.5 % ) , and nasopharyngitis ( 3.5 % , 5.5 % ) . Incidence of any extrapyramidal-related adverse event was 7.1 % for placebo and 8.5 % for paliperidone monthly . CONCLUSIONS Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic , depressive , and /or manic relapses ; reduced their risk ; and better maintained functioning in patients with schizoaffective disorder . Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01193153 Abstract Objective : To assess the effects of olanzapine long-acting injection ( olanzapine-LAI ) on levels of functioning in acutely ill patients with schizophrenia . Research design and methods : During this 8-week r and omized , double-blind , placebo-controlled trial , 404 in patients were r and omized to four treatment arms ( olanzapine-LAI 210 mg/2 weeks = 106 ; olanzapine-LAI 300 mg/2 weeks = 100 ; olanzapine-LAI 405 mg/4 weeks = 100 ; placebo = 98 ) . Also , data from the three active dosing arms were combined and compared to placebo data . Clinical trial registration : NCT00088478 Main outcome measures : The treatment group comparison of mean change from baseline to endpoint in the total score and four subdomains of the Heinrichs – Carpenter Quality of Life Scale ( QLS ) and in the 2 summary scores and 8 subscale scores of the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) were assessed using an ANOVA model . Results : All three olanzapine-LAI treatment groups and the combined olanzapine-LAI group were superior to placebo on the QLS total score ( all p-values < 0.01 ) and the Intrapsychic Foundations subdomain ( all p-values < 0.02 ) . Olanzapine-LAI 210 mg/2 weeks ( p < 0.001 ) , 300 mg/2 weeks ( p = 0.006 ) , and the combined olanzapine-LAI group ( p = 0.003 ) were superior to placebo on the Interpersonal Relations subdomain . The 300 mg/2 weeks group ( p = 0.027 ) and the combined olanzapine-LAI group ( p = 0.014 ) were also superior to placebo on the Instrumental Role subdomain . For the SF-36 , the 300 mg/2 weeks and 405 mg/4 weeks olanzapine-LAI groups and the combined olanzapine-LAI group were superior to placebo on the Mental component score ( all p-values < 0.05 ) . Each olanzapine-LAI group and the combined group were superior on the Mental Health scale ( all p-values < 0.05 ) . Significant negative correlations between PANSS scores and measures of functioning indicate that as symptoms decreased , functioning increased . Conclusion : These results suggest that olanzapine-LAI may improve level of functioning in acutely ill patients with schizophrenia within 8 weeks of initiating treatment BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials IMPORTANCE Treatment nonadherence and relapse are common problems in patients with schizophrenia . The long-acting 3-month formulation of paliperidone palmitate , owing to its extended elimination half-life , may offer a valuable therapeutic option for these patients . OBJECTIVE To evaluate the efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo in delaying time to relapse of schizophrenia symptoms . DESIGN , SETTING , AND PARTICIPANTS This r and omized , multicenter trial conducted from April 26 , 2012 , through April 9 , 2014 , in 8 countries consisted of 4 phases : 3-week screening phase , flexible-dose 17-week open-label transition phase , 12-week open-label maintenance phase , and open-ended double-blind ( DB ) phase . Of the 506 patients enrolled ( aged 18 - 70 years ; DSM-IV-TR diagnosis of schizophrenia ) , 305 were r and omized to 3-month paliperidone palmitate ( n = 160 ) or placebo ( n = 145 ) in the DB phase . INTERVENTIONS Patients received once-monthly doses of the 1-month formulation of paliperidone palmitate ( 50 , 75 , 100 , or 150 mg eq ) during the transition phase , followed by a single dose of the 3-month formulation ( 3.5 times the stabilized dose of once-monthly paliperidone palmitate ) during the maintenance phase . Stabilized patients were r and omized to receive either a fixed dose of 3-month paliperidone palmitate ( 175 , 263 , 350 , or 525 mg eq ) or placebo once every 3 months during the DB phase . MAIN OUTCOMES AND MEASURES Time from r and omization to the first relapse event ( time to relapse ) in the DB phase . RESULTS In the interim analysis , time to first relapse was significantly different in favor of the paliperidone palmitate group vs the placebo group ( hazard ratio = 3.45 ; 95 % CI , 1.73 - 6.88 ; P < .001 ) ; median time to relapse was 274 days for placebo but not estimable for 3-month paliperidone palmitate . An independent data monitoring committee recommended early study termination due to efficacy . In the DB phase , 183 of 305 patients ( 62 % with 3-month paliperidone palmitate ; 58 % with placebo ) had at least 1 treatment-emergent adverse event ; those noted more frequently in the group receiving paliperidone palmitate than in the placebo group were headache ( 9 % vs 4 % ) , weight increased ( 9 % vs 3 % ) , nasopharyngitis ( 6 % vs 1 % ) , and akathisia ( 4 % vs 1 % ) . CONCLUSIONS AND RELEVANCE Compared with placebo , the 3-month formulation of paliperidone palmitate administered 4 times yearly significantly delayed time to relapse in patients with schizophrenia . The 3-month formulation was generally tolerable and has a safety profile consistent with other marketed paliperidone formulations . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01529515 Importance It has remained unclear whether there are clinical ly meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia , owing to the impossibility of including large unselected patient population s in r and omized clinical trials , as well as residual confounding from selection biases in observational studies . Objective To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia . Design , Setting , and Participants Prospect ively gathered nationwide data bases were linked to study the risk of rehospitalization and treatment failure from July 1 , 2006 , to December 31 , 2013 , among all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 ( 29 823 patients in the total prevalent cohort ; 4603 in the incident cohort of newly diagnosed patients ) . Within-individual analyses were used for primary analyses , in which each individual was used as his or her own control to eliminate selection bias . Traditional Cox proportional hazards multivariate regression was used for secondary analyses . Main Outcomes and Measures Risk of rehospitalization and treatment failure ( defined as psychiatric rehospitalization , suicide attempt , discontinuation or switch to other medication , or death ) . Results There were 29 823 patients ( 12 822 women and 17 001 men ; mean [ SD ] age , 44.9 [ 12.0 ] years ) . During follow-up , 13 042 of 29 823 patients ( 43.7 % ) were rehospitalized , and 20 225 of 28 189 patients ( 71.7 % ) experienced treatment failure . The risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone ( hazard ratio [ HR ] , 0.51 ; 95 % CI , 0.41 - 0.64 ) , long-acting injectable zuclopenthixol ( HR , 0.53 ; 95 % CI , 0.48 - 0.57 ) , clozapine ( HR , 0.53 ; 95 % CI , 0.48 - 0.58 ) , long-acting injectable perphenazine ( HR , 0.58 ; 95 % CI , 0.52 - 0.65 ) , and long-acting injectable olanzapine ( HR , 0.58 ; 95 % CI , 0.44 - 0.77 ) compared with no use of antipsychotic medication . Oral flupentixol ( HR , 0.92 ; 95 % CI , 0.74 - 1.14 ) , quetiapine ( HR , 0.91 ; 95 % CI , 0.83 - 1.00 ) , and oral perphenazine ( HR , 0.86 ; 95 % CI , 0.77 - 0.97 ) were associated with the highest risk of rehospitalization . Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations ( HR , 0.78 ; 95 % CI , 0.72 - 0.84 in the total cohort ; HR , 0.68 ; 95 % CI , 0.53 - 0.86 in the incident cohort ) . Clozapine ( HR , 0.58 ; 95 % CI , 0.53 - 0.63 ) and all long-acting injectable antipsychotic medications ( HRs 0.65 - 0.80 ) were associated with the lowest rates of treatment failure compared with the most widely used medication , oral olanzapine . The results of several sensitivity analyses were consistent with those of the primary analyses . Conclusions and Relevance Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia . The risk of rehospitalization is about 20 % to 30 % lower during long-acting injectable treatments compared with equivalent oral formulations This 13-week double-blind study was design ed to assess noninferiority of the recently approved ( in the U.S. ) injectable atypical antipsychotic paliperidone palmitate ( PP ) versus risperidone long-acting injectable ( RIS-LAI ) in adult patients with schizophrenia . Patients ( N=1220 ) were r and omized ( 1:1 ) to either a ) PP : deltoid injections on day 1 ( 150 mg eq. ) , day 8 ( 100 mg eq. ) , and once-monthly flexible dosing as deltoid or gluteal injections on day 36 ( 50 mg eq. or 100 mg eq. ) and day 64 ( 50 mg eq. or 100 mg eq. or 150 mg eq. ) or b ) RIS-LAI : gluteal injections days 8 and 22 ( 25 mg ) , days 36 , 50 ( 25 or 37.5 mg ) and days 64 , 78 ( 25 , 37.5 or 50 mg ) . RIS-LAI-treated patients received oral supplementation with RIS 1 - 6 mg/day ( days 1 to 28 ) , and PP-treated patients received oral placebo . The safety analysis set ( n=1214 ) included 58 % men , 78 % white , with mean ( SD ) baseline PANSS total score : PP , 84.1 ( 12.09 ) ; and RIS-LAI , 83.6 ( 11.28 ) . Mean ( SD ) change from baseline to endpoint in PANSS total score decreased similarly in both groups ; PP ( -18.6 [ 15.45 ] ) and RIS-LAI ( -17.9 [ 14.24 ] ) . PP treatment was noninferior to RIS-LAI ( point estimate [ 95 % CI ] : 0.4 [ -1.62;2.38 ] , per- protocol analysis set [ primary analysis ] ) . The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings |
11,382 | 31,515,473 | We found robust evidence for short- to moderate-term beneficial effects of plant-based diets versus conventional diets ( duration ≤ 24 months ) on weight status , energy metabolism and systemic inflammation in healthy participants , obese and type-2 diabetes patients .
Initial experimental studies proposed novel microbiome-related pathways , by which plant-based diets modulate the gut microbiome towards a favorable diversity of bacteria species , yet a functional “ bottom up ” signaling of plant-based diet-induced microbial changes remains highly speculative . | Western societies notice an increasing interest in plant-based eating patterns such as vegetarian and vegan , yet potential effects on the body and brain are a matter of debate .
Therefore , we systematic ally review ed existing human interventional studies on putative effects of a plant-based diet on the metabolism and cognition , and what is known about the underlying mechanisms . | BACKGROUND Few prospect i ve studies have examined the mortality of vegetarians . OBJECTIVE We present results on mortality among vegetarians and nonvegetarians in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Oxford ) . DESIGN We used a prospect i ve study of men and women recruited throughout the United Kingdom in the 1990s . RESULTS Among 64,234 participants aged 20 - 89 y for whom diet group was known , 2965 had died before age 90 by 30 June 2007 . The death rates of participants are much lower than average for the United Kingdom . The st and ardized mortality ratio for all causes of death was 52 % ( 95 % CI : 50 % , 54 % ) and was identical in vegetarians and in nonvegetarians . Comparing vegetarians with meat eaters among the 47,254 participants who had no prevalent cardiovascular disease or malignant cancer at recruitment , the death rate ratios adjusted for age , sex , smoking , and alcohol consumption were 0.81 ( 95 % CI : 0.57 , 1.16 ) for ischemic heart disease and 1.03 ( 95 % CI : 0.90 , 1.16 ) for all causes of death . CONCLUSIONS The mortality of both the vegetarians and the nonvegetarians in this study is low compared with national rates . Within the study , mortality from circulatory diseases and all causes is not significantly different between vegetarians and meat eaters , but the study is not large enough to exclude small or moderate differences for specific causes of death , and more research on this topic is required OBJECTIVE The aim of this study was to determine the effect of plant-based diets on weight loss . METHODS Participants were enrolled in a 6-mo , five-arm , r and omized controlled trial in 2013 in South Carolina . Participants attended weekly group meetings , with the exception of the omnivorous group , which served as the control and attended monthly meetings augmented with weekly e-mail lessons . All groups attended monthly meetings for the last 4 mo of the study . Diets did not emphasize caloric restriction . RESULTS Overweight adults ( body mass index 25 - 49.9 kg/m(2 ) ; age 18 - 65 y , 19 % non-white , and 27 % men ) were r and omized to a low-fat , low-glycemic index diet : vegan ( n = 12 ) , vegetarian ( n = 13 ) , pesco-vegetarian ( n = 13 ) , semi-vegetarian ( n = 13 ) , or omnivorous ( n = 12 ) . Fifty ( 79 % ) participants completed the study . In intention-to-treat analysis , the linear trend for weight loss across the five groups was significant at both 2 ( P < 0.01 ) and 6 mo ( P < 0.01 ) . At 6 mo , the weight loss in the vegan group ( -7.5 % ± 4.5 % ) was significantly different from the omnivorous ( -3.1 % ± 3.6 % ; P = 0.03 ) , semi-vegetarian ( -3.2 % ± 3.8 % ; P = 0.03 ) , and pesco-vegetarian ( -3.2 % ± 3.4 % ; P = 0.03 ) groups . Vegan participants decreased their fat and saturated fat more than the pesco-vegetarian , semi-vegetarian , and omnivorous groups at both 2 and 6 mo ( P < 0.05 ) . CONCLUSIONS Vegan diets may result in greater weight loss than more modest recommendations Importance Defining what represents a macronutritionally balanced diet remains an open question and a high priority in nutrition research . Although the amount of protein may have specific effects , from a broader dietary perspective , the choice of protein sources will inevitably influence other components of diet and may be a critical determinant for the health outcome . Objective To examine the associations of animal and plant protein intake with the risk for mortality . Design , Setting , and Participants This prospect i ve cohort study of US health care professionals included 131 342 participants from the Nurses ' Health Study ( 1980 to end of follow-up on June 1 , 2012 ) and Health Professionals Follow-up Study ( 1986 to end of follow-up on January 31 , 2012 ) . Animal and plant protein intake was assessed by regularly up date d vali date d food frequency question naires . Data were analyzed from June 20 , 2014 , to January 18 , 2016 . Main Outcomes and Measures Hazard ratios ( HRs ) for all-cause and cause-specific mortality . Results Of the 131 342 participants , 85 013 were women ( 64.7 % ) and 46 329 were men ( 35.3 % ) ( mean [ SD ] age , 49 [ 9 ] years ) . The median protein intake , as assessed by percentage of energy , was 14 % for animal protein ( 5th-95th percentile , 9%-22 % ) and 4 % for plant protein ( 5th-95th percentile , 2%-6 % ) . After adjusting for major lifestyle and dietary risk factors , animal protein intake was not associated with all-cause mortality ( HR , 1.02 per 10 % energy increment ; 95 % CI , 0.98 - 1.05 ; P for trend = .33 ) but was associated with higher cardiovascular mortality ( HR , 1.08 per 10 % energy increment ; 95 % CI , 1.01 - 1.16 ; P for trend = .04 ) . Plant protein was associated with lower all-cause mortality ( HR , 0.90 per 3 % energy increment ; 95 % CI , 0.86 - 0.95 ; P for trend < .001 ) and cardiovascular mortality ( HR , 0.88 per 3 % energy increment ; 95 % CI , 0.80 - 0.97 ; P for trend = .007 ) . These associations were confined to participants with at least 1 unhealthy lifestyle factor based on smoking , heavy alcohol intake , overweight or obesity , and physical inactivity , but not evident among those without any of these risk factors . Replacing animal protein of various origins with plant protein was associated with lower mortality . In particular , the HRs for all-cause mortality were 0.66 ( 95 % CI , 0.59 - 0.75 ) when 3 % of energy from plant protein was substituted for an equivalent amount of protein from processed red meat , 0.88 ( 95 % CI , 0.84 - 0.92 ) from unprocessed red meat , and 0.81 ( 95 % CI , 0.75 - 0.88 ) from egg . Conclusions and Relevance High animal protein intake was positively associated with cardiovascular mortality and high plant protein intake was inversely associated with all-cause and cardiovascular mortality , especially among individuals with at least 1 lifestyle risk factor . Substitution of plant protein for animal protein , especially that from processed red meat , was associated with lower mortality , suggesting the importance of protein source OBJECTIVE To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . DESIGN Cohort of men and women recruited through general practice s or by post to include a high proportion of non meat-eaters . Dietary , anthropometric and lifestyle data were collected at baseline and four diet groups were defined . SETTING United Kingdom . PARTICIPANTS In total , 65 429 men and women aged 20 to 97 years , comprising 33 883 meat-eaters , 10 110 fish-eaters , 18 840 lacto-ovo vegetarians and 2596 vegans . RESULTS Nutrient intakes and lifestyle factors differed across the diet groups , with striking differences between meat-eaters and vegans , and fish-eaters and vegetarians usually having intermediate values . Mean fat intake in each diet group was below the UK dietary reference value of 33 % of total energy intake . The mean intake of saturated fatty acids in vegans was approximately 5 % of energy , less than half the mean intake among meat-eaters ( 10 - 11 % ) . Vegans had the highest intakes of fibre , vitamin B1 , folate , vitamin C , vitamin E , magnesium and iron , and the lowest intakes of retinol , vitamin B12 , vitamin D , calcium and zinc . CONCLUSIONS The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world . The average nutrient intakes in the whole cohort are close to those currently recommended for good health . Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre . Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death OBJECTIVE To explore the potential role of the endogenous peptide YY ( PYY ) in the long-term regulation of body weight and energy homeostasis . RESEARCH METHODS AND PROCEDURES Fasting and postpr and ial plasma PYY concentrations were measured after an overnight fast and 30 to 180 minutes after a st and ardized meal in 29 ( 21 men/8 women ) non-diabetic subjects , 16 of whom had a follow-up visit 10.8 + /- 1.4 months later . Ratings of hunger and satiety were collected using visual analog scales . Resting metabolic rate ( RMR ) ( 15-hour RMR ) and respiratory quotient ( RQ ) were assessed using a respiratory chamber . RESULTS Fasting PYY concentrations were negatively correlated with various markers of adiposity and negatively associated with 15-hour RMR ( r = -0.46 , p = 0.01 ) . Postpr and ial changes in PYY ( area under the curve ) were positively associated with postpr and ial changes in ratings of satiety ( r = 0.47 , p = 0.01 ) . The maximal PYY concentrations achieved after the meal ( peak PYY ) were negatively associated with 24-hour RQ ( r = -0.41 , p = 0.03 ) . Prospect ively , the peak PYY concentrations were negatively associated with changes in body weight ( r = -0.58 , p = 0.01 ) . DISCUSSION Our data indicate that the endogenous PYY may be involved in the long-term regulation of body weight . It seems that this long-term effect was not exclusively driven by the modulation of food intake but also by the control of energy expenditure and lipid metabolism Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change . Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression . The animal-based diet increased the abundance of bile-tolerant microorganisms ( Alistipes , Bilophila and Bacteroides ) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia , Eubacterium rectale and Ruminococcus bromii ) . Microbial activity mirrored differences between herbivorous and carnivorous mammals , reflecting trade-offs between carbohydrate and protein fermentation . Foodborne microbes from both diets transiently colonized the gut , including bacteria , fungi and even viruses . Finally , increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat , bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease . In concert , these results demonstrate that the gut microbiome can rapidly respond to altered diet , potentially facilitating the diversity of human dietary lifestyles Regular walnut consumption is associated with better health . We have previously shown that eight weeks of walnut consumption ( 43 g/day ) significantly improves lipids in healthy subjects . In the same study , gut microbiome was evaluated . We included 194 healthy subjects ( 134 females , 63 ± 7 years , BMI 25.1 ± 4.0 kg/m2 ) in a r and omized , controlled , prospect i ve , cross-over study . Following a nut-free run-in period , subjects were r and omized to two diet phases ( eight weeks each ) ; 96 subjects first followed a walnut-enriched diet ( 43 g/day ) and then switched to a nut-free diet , while 98 subjects followed the diets in reverse order . While consuming the walnut-enriched diet , subjects were advised to either reduce fat or carbohydrates or both to account for the additional calories . Fecal sample s were collected from 135 subjects at the end of the walnut-diet and the control-diet period for microbiome analyses . The 16S rRNA gene sequencing data was clustered with a 97 % similarity into Operational Taxonomic Units ( OTUs ) . UniFrac distances were used to determine diversity between groups . Differential abundance was evaluated using the Kruskal – Wallis rank sum test . All analyses were performed using Rhea . Generalized UniFrac distance shows that walnut consumption significantly affects microbiome composition and diversity . Multidimensional scaling ( metric and non-metric ) indicates dissimilarities of approximately 5 % between walnut and control ( p = 0.02 ) . The abundance of Ruminococcaceae and Bifidobacteria increased significantly ( p < 0.02 ) while Clostridium sp. cluster XIVa species ( Blautia ; Anaerostipes ) decreased significantly ( p < 0.05 ) during walnut consumption . The effect of walnut consumption on the microbiome only marginally depended on whether subjects replaced fat , carbohydrates or both while on walnuts . Daily intake of 43 g walnuts over eight weeks significantly affects the gut microbiome by enhancing probiotic- and butyric acid-producing species in healthy individuals . Further evaluation is required to establish whether these changes are preserved during longer walnut consumption and how these are linked to the observed changes in lipid metabolism Introduction : The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie‐restriction mimicking effects . However , the evidence based on human interventional studies is scarce . We therefore aim ed to determine the effects of resveratrol on memory performance , and to identify potential underlying mechanisms using a broad array of blood‐based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra‐high field magnetic resonance imaging ( UHF‐MRI ) . Methods : In this double‐blind , r and omized controlled trial , 60 elderly participants ( 60–79 years ) with a wide body‐mass index ( BMI ) range of 21–37 kg/m2 were r and omized to receive either resveratrol ( 200mg/day ) or placebo for 26 weeks ( registered at Clinical Trials.gov : NCT02621554 ) . Baseline and follow‐up assessment s included the California Verbal Learning Task ( CVLT , main outcome ) , the ModBent task , anthropometry , markers of glucose and lipid metabolism , inflammation and neurotrophins derived from fasting blood , multimodal neuroimaging at 3 and 7 T , and question naires to assess confounding factors . Results : Multivariate repeated‐ measures ANOVA did not detect significant time by group effects for CVLT performance . There was a trend for preserved pattern recognition memory after resveratrol , while performance decreased in the placebo group ( n.s . , p=0.07 ) . Further exploratory analyses showed increases in both groups over time in body fat , cholesterol , fasting glucose , interleukin 6 , high sensitive C‐reactive protein , tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum , as well as decreases in physical activity , brain‐derived neurotrophic factor and insulin‐like growth factor 1at follow‐up , which were partly more pronounced after resveratrol . Discussion : This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range . A non‐significant trend emerged for positive effects on pattern recognition memory , while possible confounding effects of unfavorable changes in lifestyle behavior , neurotrophins and inflammatory markers occurred . Our findings also indicate the feasibility to detect (un)healthy aging‐related changes in measures of hippocampus microstructure after 6 months using 7 T diffusion MRI . More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol enhances memory performance in healthy older adults . HIGHLIGHTSIn this r and omized clinical trial , 6 months resveratrol supplementation showed no significant effects on verbal memory compared to placebo . Unfavorable changes in lifestyle factors at follow‐up might have introduced confounding . Secondary analyses showed a trend towards preserved pattern recognition . We used multimodal ultra high field MRI to detect subtle changes in microstructure of hippocampus subfields Introduction The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis ( RA ) on blood lipids oxidized low-density lipoprotein ( oxLDL ) and natural atheroprotective antibodies against phosphorylcholine ( anti-PCs ) . Methods Sixty-six patients with active RA were r and omly assigned to either a vegan diet free of gluten ( 38 patients ) or a well-balanced non-vegan diet ( 28 patients ) for 1 year . Thirty patients in the vegan group completed more than 3 months on the diet regimen . Blood lipids were analyzed by routine methods , and oxLDL and anti-PCs were analyzed by enzyme-linked immunosorbent assay . Data and serum sample s were obtained at baseline and after 3 and 12 months . Results Mean ages were 50.0 years for the vegan group and 50.8 years for controls . Gluten-free vegan diet induced lower body mass index ( BMI ) and low-density lipoprotein ( LDL ) and higher anti-PC IgM than control diet ( p < 0.005 ) . In the vegan group , BMI , LDL , and cholesterol decreased after both 3 and 12 months ( p < 0.01 ) and oxLDL after 3 months ( p = 0.021 ) and trendwise after 12 months ( p = 0.090 ) . Triglycerides and high-density lipoprotein did not change . IgA anti-PC levels increased after 3 months ( p = 0.027 ) and IgM anti-PC levels increased trendwise after 12 months ( p = 0.057 ) . There was no difference in IgG anti-PC levels . In the control diet group , IgM anti-PC levels decreased both after 3 and 12 months ( p < 0.01 ) . When separating vegan patients into clinical responders and non-responders at 12 months , the effects on oxLDL and anti-PC IgA were seen only in responders ( p < 0.05 ) . Conclusion A gluten-free vegan diet in RA induces changes that are potentially atheroprotective and anti-inflammatory , including decreased LDL and oxLDL levels and raised anti-PC IgM and IgA levels Objective To perform a r and omized trial to determine if there is cardiovascular disease ( CVD ) risk reduction from a plant-based no added fat diet ( PB ) and the American Heart Association Diet ( AHA ) in children . Study design Four-week ( 4/20/2013 - 5/18/2013 ) prospect i ve r and omized trial in a large Midwestern hospital system ’s predominantly middle class outpatient pediatric practice s. Thirty children ( 9–18 years old ) parent pairs with a last recorded child BMI > 95th percentile and child cholesterol > 169 mg/dL were r and omized to PB or AHA with weekly 2-hour classes of nutrition education . Results Children on PB had nine and children on AHA had four statistically significant ( P<0.05 ) beneficial changes from baseline ( mean decreases ) : BMI Z-scorePB ( −0.14 ) , systolic blood pressurePB ( −6.43 mm Hg ) , total cholesterolPB ( −22.5 mg/dL ) , low density lipoproteinPB ( −13.14 mg/dL ) , hsCRPPB ( −2.09 mg/L ) , insulinPB ( −5.42uU/ml ) , myeloperoxidasePB/AHA ( −75.34/69.23 pmol/L ) , mid-arm circumferencePB/AHA ( −2.02/−1.55 cm ) , weightPB/AHA ( −3.05/ −1.14 kg ) and waist circumferenceAHA ( −2.96 cm ) . Adults on PB and AHA had seven and two respectively statistically significant ( P<0.05 ) beneficial changes . The significant change favoring AHA was a 1 % difference in children ’s waist circumference . Difficulty shopping for food for the PB was the only statistically significant acceptability barrier . Conclusions PB and the AHA in both children and adults demonstrated potentially beneficial changes from baseline in risk factors for CVD . Future larger , long-term r and omized trials with easily accessible PB foods will further define the role of the PB in preventing CVD On the basis of the abundance of specific bacterial genera , the human gut microbiota can be divided into two relatively stable groups that might have a role in personalized nutrition . We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets . A total of 62 participants with increased waist circumference were r and omly assigned to receive an ad libitum New Nordic Diet ( NND ) high in fiber/whole grain or an Average Danish Diet for 26 weeks . Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp . divided by Bacteroides spp . ( P/B ratio ) obtained by quantitative PCR analysis . Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models . Among individuals with high P/B the NND result ed in a 3.15 kg ( 95 % confidence interval ( CI ) : 1.55 ; 4.76 , P<0.001 ) larger body fat loss compared with ADD , whereas no differences was observed among individuals with low P/B ( 0.88 kg ( 95 % CI : −0.61 ; 2.37 , P=0.25 ) ) . Consequently , a 2.27 kg ( 95 % CI : 0.09 ; 4.45 , P=0.041 ) difference in responsiveness to the diets were found between the two groups . In summary , subjects with high P/B ratio appeared more susceptible to lose body fat on diets high in fiber and whole grain than subjects with a low P/B ratio BACKGROUND Evidence suggests that brain iron deficiency at any time in life may disrupt metabolic processes and subsequently change cognitive and behavioral functioning . Women of reproductive age are among those most vulnerable to iron deficiency and may be at high risk for cognitive alterations due to iron deficiency . OBJECTIVE We aim ed to examine the relation between iron status and cognitive abilities in young women . DESIGN A blinded , placebo-controlled , stratified intervention study was conducted in women aged 18 - 35 y of varied iron status who were r and omly assigned to receive iron supplements or a placebo . Cognition was assessed by using 8 cognitive performance tasks ( from Detterman 's Cognitive Abilities Test ) at baseline ( n = 149 ) and after 16 wk of treatment ( n = 113 ) . RESULTS At baseline , the iron-sufficient women ( n = 42 ) performed better on cognitive tasks ( P = 0.011 ) and completed them faster ( P = 0.038 ) than did the women with iron deficiency anemia ( n = 34 ) . Factors representing performance accuracy and the time needed to complete the tasks by the iron-deficient but nonanemic women ( n = 73 ) were intermediate between the 2 extremes of iron status . After treatment , a significant improvement in serum ferritin was associated with a 5 - 7-fold improvement in cognitive performance , whereas a significant improvement in hemoglobin was related to improved speed in completing the cognitive tasks . CONCLUSIONS Iron status is a significant factor in cognitive performance in women of reproductive age . Severity of anemia primarily affects processing speed , and severity of iron deficiency affects accuracy of cognitive function over a broad range of tasks . Thus , the effects of iron deficiency on cognition are not limited to the developing brain Introduction Dietary phytochemicals are found in plant-based foods such as fruits , vegetables and grains and may be categorised in a nested hierarchical manner with many hundred individual phytochemicals identified to date . To associate phytochemical intakes with positive health outcomes , a fundamental step is to accurately estimate the dietary phytochemical intake from foods reported . The purpose of this systematic review protocol is to describe the process to be undertaken to summarise the evidence for food-based dietary phytochemical intakes and health outcomes for adults . Methods and analysis The review will be undertaken following the PRISMA guidelines and the Cochrane H and book for Systematic Review s of Interventions using the Review Manager software . Phytochemical subclasses ( phenolic acids , flavanols , etc ) will be used to search for relevant studies using the Web of Science and Scopus scientific data bases . The retrieved studies will be screened based on inclusion of natural whole food items and health outcomes . Phytochemical studies related to cardiovascular disease , cancer , overweight , glucose tolerance , digestive , reproductive , macular and bone health and mental disorders , fatigue and immunity will be examined based on prior scoping . The evidence will be aggregated by the food types and health outcomes . Comparison of differences in the outcomes for r and omised controlled trials and observational studies will be undertaken . The strength of the review lies in its focus on whole food items and health conditions rather than one type of phytochemical related to one single health condition . Subgroup and sensitivity analyses will be conducted where an adequate number of publications are found per phytochemical subclass . Dissemination By comparing the outcomes from experimental and observational studies , the review will determine whether the overall conclusions related to the phytochemical subclasses are the same between study types for the identified health conditions . This is useful to public health policymakers and health professionals alike . Trial registration number # CRD42014015610 BACKGROUND & AIMS Changes in gut microbiota have been reported to alter signaling mechanisms , emotional behavior , and visceral nociceptive reflexes in rodents . However , alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans . We investigated whether consumption of a fermented milk product with probiotic ( FMPP ) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks . METHODS Healthy women with no gastrointestinal or psychiatric symptoms were r and omly assigned to groups given FMPP ( n = 12 ) , a nonfermented milk product ( n = 11 , controls ) , or no intervention ( n = 13 ) twice daily for 4 weeks . The FMPP contained Bifidobacterium animalis subsp Lactis , Streptococcus thermophiles , Lactobacillus bulgaricus , and Lactococcus lactis subsp Lactis . Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity . Multivariate and region of interest analyses were performed . RESULTS FMPP intake was associated with reduced task-related response of a distributed functional network ( 49 % cross-block covariance ; P = .004 ) containing affective , viscerosensory , and somatosensory cortices . Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity , which could explain the observed differences in activity during the task . CONCLUSIONS Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance , visceral fat and oxidative stress markers in subjects with Type 2 diabetes . Methods A 24-week , r and omized , open , parallel design was used . Seventy-four patients with Type 2 diabetes were r and omly assigned to either the experimental group ( n = 37 ) , which received a vegetarian diet , or the control group ( n = 37 ) , which received a conventional diabetic diet . Both diets were isocaloric , calorie restricted ( -500 kcal/day ) . All meals during the study were provided . The second 12 weeks of the diet were combined with aerobic exercise . Participants were examined at baseline , 12 weeks and 24 weeks . Primary outcomes were : insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp ; volume of visceral and subcutaneous fat measured by magnetic resonance imaging ; and oxidative stress measured by thiobarbituric acid reactive substances . Analyses were by intention to treat . Results Forty-three per cent of participants in the experimental group and 5 % of participants in the control group reduced diabetes medication ( P < 0.001 ) . Body weight decreased more in the experimental group than in the control group [ –6.2 kg ( 95 % CI –6.6 to –5.3 ) vs. –3.2 kg ( 95 % CI –3.7 to –2.5 ) ; interaction group × time P = 0.001 ] . An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [ 30 % ( 95 % CI 24.5–39 ) vs. 20 % ( 95 % CI 14–25 ) , P = 0.04 ] . A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group ( P = 0.007 and P = 0.02 , respectively ) . Plasma adiponectin increased ( P = 0.02 ) and leptin decreased ( P = 0.02 ) in the experimental group , with no change in the control group . Vitamin C , superoxide dismutase and reduced glutathione increased in the experimental group ( P = 0.002 , P < 0.001 and P = 0.02 , respectively ) . Differences between groups were greater after the addition of exercise training . Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat . Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks . The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance . The addition of exercise training further augmented the improved outcomes with the vegetarian diet Food synergy is the concept that the non-r and om mixture of food constituents operates in concert for the life of the organism eaten and presumably for the life of the eater . Isolated nutrients have been extensively studied in well- design ed , long-term , large r and omised clinical trials , typically with null and sometimes with harmful effects . Therefore , although nutrient deficiency is a known phenomenon , serious for the sufferer , and curable by taking the isolated nutrient , the effect of isolated nutrients or other chemicals derived from food on chronic disease , when that chemical is not deficient , may not have the same beneficial effect . It appears that the focus on nutrients rather than foods is in many ways counterproductive . This observation is the basis for the argument that nutrition research should focus more strongly on foods and on dietary patterns . Unlike many dietary phenomena in nutritional epidemiology , diet pattern appears to be highly correlated over time within person . A consistent and robust conclusion is that certain types of beneficial diet patterns , notably described with words such as ' Mediterranean ' and ' prudent ' , or adverse patterns , often described by the word ' Western ' , predict chronic disease . Food is much more complex than drugs , but essentially uninvestigated as food or pattern . The concept of food synergy leads to new thinking in nutrition science and can help to forge rational nutrition policy-making and to determine future nutrition research strategies Background / objectives : To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting .Subjects/ methods : Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and /or previous diagnosis of type 2 diabetes were r and omized to either follow a low-fat vegan diet , with weekly group support and work cafeteria options available , or make no diet changes for 18 weeks . Dietary intake , body weight , plasma lipid concentrations , blood pressure and glycated hemoglobin ( HbA1C ) were determined at baseline and 18 weeks . Results : Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups , respectively ( P<0.001 ) . Total and low-density lipoprotein ( LDL ) cholesterol fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group ( P<0.01 ) . HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group , respectively (P<0.01).Among study completers , mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups , respectively ( P<0.001 ) . Total and LDL cholesterol fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group ( P<0.001 ) . HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group , respectively ( P<0.01 ) . Conclusions : An 18-week dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight , plasma lipids , and , in individuals with diabetes , glycemic control Objective : To determine whether the cholesterol-lowering effect of a plant-based low-fat diet can be improved by a flexible control design that controls the extent of fat reduction based on the individual response of blood cholesterol . Design : R and omized , double-blind intervention study . Setting : A hotel in Prerow , Germany . Subjects : A total of 32 participants ( 21 female and 11 male participants ) with total cholesterol level>5.7 mmol/l . Intervention : The control group consumed a plant-based low-fat diet with constantly 20 % of energy as fat ; the intervention group received a diet with either 20 or 15 % of energy as fat , depending on the serum cholesterol response of the preceding week . A flexible control design based on the individual cholesterol response during a run-in period of 1 week was used within a low-fat intervention . Results : During the run-in period , the consumption of a plant-based low-fat diet led to a reduction in total cholesterol by 18±6 mmol/l ( P<0.001 ) , in LDL cholesterol by 19±9 mmol/l ( P<0.001 ) and triglycerides by 13±3 mmol/l ( P<0.001 ) . During the feedback control period , an additional reduction in total cholesterol by 13±8 ( P<0.001 ) and in LDL cholesterol by 17±11 ( P<0.001 ) was observed compared to 15±15 and 7±18 in the control group . The effect of an additional feedback control was only marginal and not statistically significant compared to the effect of the low-fat diet alone . Conclusions : On a level of fat intake already reduced to 20 % of energy , the use of a feedback control to adapt the fat content of the diet depending on the individual serum cholesterol response was not more effective in reducing blood cholesterol levels than a plant-based low-fat diet alone . Sponsorship : Institute of Micro-Ecology , Herborn ; the Stoll VITA Foundation , Waldshut ; ALBAT+WIRSAM Software , Linden ; Reformhaus Technical College , Oberstedten ; Kölln Flocken Werke , Elmshorn , all in Germany BACKGROUND There is limited evidence with regard to the effect of different sources of protein on appetite during weight loss . Vegetarian and meat-based high-protein diets may have contrasting effects on appetite and biomarkers of protein-induced satiety . OBJECTIVE The aim was to assess appetite response to meat or vegetarian high-protein weight-loss ( HPWL ) diets in obese men to monitor plasma amino acid profile and gut peptide response as potential satiety biomarkers . DESIGN Twenty obese [ body mass index ( in kg/m² ) : 34.8 ] men participated in a dietary intervention study . After 3 d of a maintenance diet , they were provided in a crossover design with either a vegetarian HPWL ( Soy-HPWL ) or a meat-based HPWL ( Meat-HPWL ) diet for 2 wk . Both diets comprised 30 % protein , 30 % fat , and 40 % carbohydrate , provided to measured resting metabolic rate . Body weight and the motivation to eat were measured daily . Plasma satiety biomarkers were collected during a test-meal challenge ( 5 h ) at the end of each diet period . RESULTS Over the 2 wk , subjects lost , on average , 2.41 and 2.27 kg with consumption of the Soy- and Meat-HPWL diets , respectively [ P = 0.352 ; SE of the difference ( SED ) : 0.1 ] . ANOVA confirmed that subjectively rated hunger ( P = 0.569 ; SED : 3.8 ) , fullness ( P = 0.404 ; SED : 4.1 ) , desire to eat ( P = 0.356 ; SED : 3.7 ) , preservation of lean body mass ( P = 0.334 ; SED : 0.2 ) , and loss of percentage fat mass ( P = 0.179 ; SED : 0.2 ) did not differ between the 2 HPWL diets . There were differences in absolute concentrations of ghrelin and peptide YY between the 2 HPWL diets , although the response as net area under the curve was not different . CONCLUSIONS Appetite control and weight loss were similar for both HPWL diets . Gut hormone profile was similar between the diets , which suggests that vegetarian diets can be as effective as meat-based diets for appetite control during weight loss The dentate gyrus ( DG ) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline . Causal evidence is needed , however , to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function . We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging ( fMRI ) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site . Then , in a controlled r and omized trial , we applied these tools to study healthy 50–69-year-old subjects who consumed either a high or low cocoa flavanol – containing diet for 3 months . A high-flavanol intervention was found to enhance DG function , as measured by fMRI and by cognitive testing . Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration Background : With obesity rampant , methods to achieve sustained weight loss remain elusive . Objective : To compare the long-term weight-loss efficacy of 2 cal and fat-restricted diets , st and ard ( omnivorous ) versus lacto – ovo – vegetarian , and to determine the effect of a chosen diet versus an assigned diet . Design , subjects : A r and omized clinical trial was conducted with 176 adults who were sedentary and overweight ( mean body mass index , 34.0 kg/m2 ) . Participants were first r and omly assigned to either receive their preferred diet or be assigned to a diet group and second , were given their diet of preference or r and omly assigned to a st and ard weight-loss diet or a lacto – ovo – vegetarian diet . Participants underwent a university-based weight-control program consisting of daily dietary and exercise goals plus 12 months of behavioral counseling followed by a 6-month maintenance phase . Measurements : Percentage change in body weight , body mass index , waist circumference , low- and high-density lipoprotein , glucose , insulin and macronutrient intake . Results : The program was completed by 132 ( 75 % ) of the participants . At 18 months , mean percentage weight loss was greater ( P=0.01 ) in the two groups that were assigned a diet ( st and ard , 8.0 % ( s.d . , 7.8 % ) ; vegetarian , 7.9 % ( s.d . , 8.1 % ) ) than in those provided the diet of their choice ( st and ard , 3.9 % ( s.d . , 6.1 % ) ; vegetarian , 5.3 % ( s.d . , 6.2 % ) ) . No difference was observed in weight loss between the two types of diet . Over the 18-month program , all groups showed significant weight loss . Conclusions : Participants assigned to their dietary preference did not have enhanced treatment outcomes . However , all groups lost weight with losses ranging from 4 to 8 % at 18 months IMPORTANCE Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality , but the relationship is not well established . OBJECTIVE To evaluate the association between vegetarian dietary patterns and mortality . DESIGN Prospect i ve cohort study ; mortality analysis by Cox proportional hazards regression , controlling for important demographic and lifestyle confounders . SETTING Adventist Health Study 2 ( AHS-2 ) , a large North American cohort . PARTICIPANTS A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007 , from which an analytic sample of 73,308 participants remained after exclusions . EXPOSURES Diet was assessed at baseline by a quantitative food frequency question naire and categorized into 5 dietary patterns : nonvegetarian , semi-vegetarian , pesco-vegetarian , lacto-ovo-vegetarian , and vegan . MAIN OUTCOME AND MEASURE The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality ; deaths through 2009 were identified from the National Death Index . RESULTS There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years . The mortality rate was 6.05 ( 95 % CI , 5.82 - 6.29 ) deaths per 1000 person-years . The adjusted hazard ratio ( HR ) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 ( 95 % CI , 0.80 - 0.97 ) . The adjusted HR for all-cause mortality in vegans was 0.85 ( 95 % CI , 0.73 - 1.01 ) ; in lacto-ovo-vegetarians , 0.91 ( 95 % CI , 0.82 - 1.00 ) ; in pesco-vegetarians , 0.81 ( 95 % CI , 0.69 - 0.94 ) ; and in semi-vegetarians , 0.92 ( 95 % CI , 0.75 - 1.13 ) compared with nonvegetarians . Significant associations with vegetarian diets were detected for cardiovascular mortality , noncardiovascular noncancer mortality , renal mortality , and endocrine mortality . Associations in men were larger and more often significant than were those in women . CONCLUSIONS AND RELEVANCE Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality . Results appeared to be more robust in males . These favorable associations should be considered carefully by those offering dietary guidance Background / Objectives : Vegans , and to a lesser extent vegetarians , have low average circulating concentrations of vitamin B12 ; however , the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear . The objectives of this study were to investigate differences in serum vitamin B12 and folate concentrations between omnivores , vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet . Subjects/ Methods : A cross-sectional analysis involving 689 men ( 226 omnivores , 231 vegetarians and 232 vegans ) from the European Prospect i ve Investigation into Cancer and Nutrition Oxford cohort . Results : Mean serum vitamin B12 was highest among omnivores ( 281 , 95 % CI : 270–292 pmol/l ) , intermediate among vegetarians ( 182 , 95 % CI : 175–189 pmol/l ) and lowest among vegans ( 122 , 95 % CI : 117–127 pmol/l ) . In all , 52 % of vegans , 7 % of vegetarians and one omnivore were classified as vitamin B12 deficient ( defined as serum vitamin B12 < 118 pmol/l ) . There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12 . In contrast , folate concentrations were highest among vegans , intermediate among vegetarians and lowest among omnivores , but only two men ( both omnivores ) were categorized as folate deficient ( defined as serum folate < 6.3 nmol/l ) . Conclusion : Vegans have lower vitamin B12 concentrations , but higher folate concentrations , than vegetarians and omnivores . Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids ( LC-n3-FA ) may be beneficial for the aging brain . We tested in a prospect i ve interventional design whether high levels of supplementary LC-n3-FA would improve cognition , and addressed potential mechanisms underlying the effects . Sixty-five healthy subjects ( 50 - 75 years , 30 females ) successfully completed 26 weeks of either fish oil ( 2.2 g/day LC-n3-FA ) or placebo intake . Before and after the intervention period , cognitive performance , structural neuroimaging , vascular markers , and blood parameters were assayed . We found a significant increase in executive functions after LC-n3-FA compared with placebo ( P = 0.023 ) . In parallel , LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal , temporal , parietal , and limbic areas primarily of the left hemisphere , and on carotid intima media thickness and diastolic blood pressure . Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor , and negatively with changes in peripheral fasting insulin . This double-blind r and omized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults , and eluci date s underlying mechanisms . Our findings suggest novel strategies to maintain cognitive functions into old age The emerging concept of psychobiotics — live microorganisms with a potential mental health benefit — represents a novel approach for the management of stress-related conditions . The majority of studies have focused on animal models . Recent pre clinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors , physiology and cognitive performance . Whether such pre clinical effects could be translated to healthy human volunteers remains unknown . We tested whether psychobiotic consumption could affect the stress response , cognition and brain activity patterns . In a within- participants design , healthy volunteers ( N=22 ) completed cognitive assessment s , resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline , post-placebo and post-psychobiotic . Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated . Furthermore , daily reported stress was reduced by psychobiotic consumption . We also observed subtle improvements in hippocampus-dependent visuospatial memory performance , as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption . These subtle but clear benefits are in line with the predicted impact from pre clinical screening platforms . Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory . Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects Objective Several intervention studies have suggested that vegetarian or vegan diets have clinical benefits , particularly in terms of glycemic control , in patients with type 2 diabetes ( T2D ) ; however , no r and omized controlled trial has been conducted in Asians who more commonly depend on plant-based foods , as compared to Western population s. Here , we aim ed to compare the effect of a vegan diet and conventional diabetic diet on glycemic control among Korean individuals . Material s and Methods Participants diagnosed with T2D were r and omly assigned to follow either a vegan diet ( excluding animal-based food including fish ; n = 46 ) or a conventional diet recommended by the Korean Diabetes Association 2011 ( n = 47 ) for 12 weeks . HbA1c levels were measured at weeks 0 , 4 , and 12 , and the primary study endpoint was the change in HbA1c levels over 12 weeks . Results The mean HbA1c levels at weeks 0 , 4 , and 12 were 7.7 % , 7.2 % , and 7.1 % in the vegan group , and 7.4 % , 7.2 % , and 7.2 % in the conventional group , respectively . Although both groups showed significant reductions in HbA1C levels , the reductions were larger in the vegan group than in the conventional group ( -0.5 % vs. -0.2 % ; p-for-interaction = 0.017 ) . When only considering participants with high compliance , the difference in HbA1c level reduction between the groups was found to be larger ( -0.9 % vs. -0.3 % ) . The beneficial effect of vegan diets was noted even after adjusting for changes in total energy intake or waist circumference over the 12 weeks . Conclusion Both diets led to reductions in HbA1c levels ; however , glycemic control was better with the vegan diet than with the conventional diet . Thus , the dietary guidelines for patients with T2D should include a vegan diet for the better management and treatment . However , further studies are needed to evaluate the long-term effects of a vegan diet , and to identify potential explanations of the underlying mechanisms . Trial Registration CRiS Background Limited evidence suggests that dietary interventions may offer a promising approach for migraine . The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency . Methods Forty-two adult migraine sufferers were recruited from the general community in Washington , DC , and divided r and omly into two groups . This 36-week crossover study included two treatments : dietary instruction and placebo supplement . Each treatment period was 16 weeks , with a 4-week washout between . During the diet period , a low-fat vegan diet was prescribed for 4 weeks , after which an elimination diet was used . Participants were assessed at the beginning , midpoint , and end of each period . Significance was determined using student ’s t-tests . Results Worst headache pain in last 2 weeks , as measured by visual analog scale , was initially 6.4/10 cm ( SD 2.1 cm ) , and declined 2.1 cm during the diet period and 0.7 cm during the supplement period ( p=0.03 ) . Average headache intensity ( 0–10 scale ) was initially 4.2 ( SD 1.4 ) per week , and this declined by 1.0 during the diet period and by 0.5 during the supplement period ( p=0.20 ) . Average headache frequency was initially 2.3 ( SD 1.8 ) per week , and this declined by 0.3 during the diet period and by 0.4 during the supplement period ( p=0.61 ) . The Patient ’s Global Impression of Change showed greater improvement in pain during the diet period ( p<0.001 ) . Conclusions These results suggest that a nutritional approach may be a useful part of migraine treatment , but that method ologic issues necessitate further research .Trial registration Clinical trials.gov , NCT01699009 and NCT01547494 BACKGROUND Low-fat vegetarian and vegan diets are associated with weight loss , increased insulin sensitivity , and improved cardiovascular health . OBJECTIVE We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia , weight , and plasma lipids . DESIGN Free-living individuals with type 2 diabetes were r and omly assigned to a low-fat vegan diet ( n = 49 ) or a diet following 2003 American Diabetes Association guidelines ( conventional , n = 50 ) for 74 wk . Glycated hemoglobin ( Hb A(1c ) ) and plasma lipids were assessed at weeks 0 , 11 , 22 , 35 , 48 , 61 , and 74 . Weight was measured at weeks 0 , 22 , and 74 . RESULTS Weight loss was significant within each diet group but not significantly different between groups ( -4.4 kg in the vegan group and -3.0 kg in the conventional diet group , P = 0.25 ) and related significantly to Hb A(1c ) changes ( r = 0.50 , P = 0.001 ) . Hb A(1c ) changes from baseline to 74 wk or last available values were -0.34 and -0.14 for vegan and conventional diets , respectively ( P = 0.43 ) . Hb A(1c ) changes from baseline to last available value or last value before any medication adjustment were -0.40 and 0.01 for vegan and conventional diets , respectively ( P = 0.03 ) . In analyses before alterations in lipid-lowering medications , total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups , respectively ( P = 0.01 ) ; LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups , respectively ( P = 0.03 ) . CONCLUSIONS Both diets were associated with sustained reductions in weight and plasma lipid concentrations . In an analysis controlling for medication changes , a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations . Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established . This trial was registered at clinical trials.gov as NCT00276939 Abstract Background Epidemiologic data suggest that diets rich in nuts have beneficial health effects , including reducing total and cause-specific mortality from cancer and heart disease . Although there is accumulating pre clinical evidence that walnuts beneficially affect the gastrointestinal microbiota and gut and metabolic health , these relations have not been investigated in humans . Objective We aim ed to assess the impact of walnut consumption on the human gastrointestinal microbiota and metabolic markers of health . Methods A controlled-feeding , r and omized crossover study was undertaken in healthy men and women [ n = 18 ; mean age = 53.1 y ; body mass index ( kg/m2 ) : 28.8 ] . Study participants received isocaloric diets containing 0 or 42 g walnuts/d for two 3-wk periods , with a 1-wk washout between diet periods . Fecal and blood sample s were collected at baseline and at the end of each period to assess secondary outcomes of the study , including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health . Results Compared with after the control period , walnut consumption result ed in a 49–160 % higher relative abundance of Faecalibacterium , Clostridium , Dialister , and Roseburia and 16–38 % lower relative abundances of Ruminococcus , Dorea , Oscillospira , and Bifidobacterium ( P < 0.05 ) . Fecal secondary bile acids , deoxycholic acid and lithocholic acid , were 25 % and 45 % lower , respectively , after the walnut treatment compared with the control treatment ( P < 0.05 ) . Serum LDL cholesterol and the noncholesterol sterol campesterol concentrations were 7 % and 6 % lower , respectively , after walnut consumption compared with after the control treatment ( P < 0.01 ) . Conclusion Walnut consumption affected the composition and function of the human gastrointestinal microbiota , increasing the relative abundances of Firmicutes species in butyrate-producing Clostridium clusters XIVa and IV , including Faecalibacterium and Roseburia , and reducing microbially derived , proinflammatory secondary bile acids and LDL cholesterol . These results suggest that the gastrointestinal microbiota may contribute to the underlying mechanisms of the beneficial health effects of walnut consumption . This trial was registered at www . clinical trials.gov as NCT01832909 In a controlled , single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA . In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters . The patients who participated in the clinical trial differed significantly from other RA patients . Firstly , they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale ( MHLCS ) . Secondly , their belief in the effect of ordinary medical treatment , evaluated by a 10-cm visual analogue scale , was lower , and their belief in the effect of ' alternative ' , unconventional forms of treatment was higher . Of the patients who were r and omized to a vegetarian diet , there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores . But , diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders . The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Question naire . Throughout the clinical trial , this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders . We conclude , firstly , that patients with certain psychological characteristics were selected to the clinical trial ; secondly , that the MHLCS scores could not explain the clinical improvement , but it may have been influenced by the patients ' beliefs in ordinary and ' alternative ' forms of treatment ; and thirdly , that dietary treatment decreased psychological distress Objective : To assess the mechanisms of the blood pressure-lowering effect of a vegetarian diet in the early and later stages of dietary intervention Design : After 2 weeks without intervention ( baseline ) , 20 normotensive men were matched for age and body mass index and r and omly allocated to an omnivorous ( control ) or a lacto-ovovegetarian diet for 6 weeks in a parallel trial Methods : Ambulatory blood pressures were recorded between 0800 and 1700 h on alternate days during the first week of intervention , twice in the second week and weekly thereafter . Blood sample s collected after a st and ard breakfast were analysed for plasma noradrenaline , adrenaline , atrial natriuretic peptide ( ANP ) , renin , aldosterone , glucose and insulin . Factor and multiple regression analyses were used to assess the association among neurohormonal factors , blood pressures and diet . Results were analysed for the first week of the diet and for the entire 6 weeks Results : Ambulatory blood pressures at work were lower on the vegetarian diet than in the controls . This blood pressure decrease was associated with a factor representing lower plasma catecholamine and renin activity levels throughout the study , and a factor representing reduced plasma glucose and insulin levels in week 1 of intervention only . Plasma ANP levels were significantly higher during week 1 of the vegetarian diet Conclusions : A blood pressure lowering effect of a vegetarian diet during normal working activity was shown . Using factors derived from the biochemical variables , results were in keeping with the hypothesis that these effects may be mediated by reduced sympatho-adrenal activity consequent to altered glucose and insulin h and ling . An early increase in plasma ANP may contribute to the blood pressure The aim of this r and omized pilot was to assess the feasibility of a dietary intervention among women with polycystic ovary syndrome ( PCOS ) comparing a vegan to a low-calorie ( low-cal ) diet . Overweight ( body mass index , 39.9 ± 6.1 kg/m(2 ) ) women with PCOS ( n = 18 ; age , 27.8 ± 4.5 years ; 39 % black ) who were experiencing infertility were recruited to participate in a 6-month r and omized weight loss study delivered through nutrition counseling , e-mail , and Facebook . Body weight and dietary intake were assessed at 0 , 3 , and 6 months . We hypothesized that weight loss would be greater in the vegan group . Attrition was high at 3 ( 39 % ) and 6 months ( 67 % ) . All analyses were conducted as intention-to-treat and presented as median ( interquartile range ) . Vegan participants lost significantly more weight at 3 months ( -1.8 % [ -5.0 % , -0.9 % ] vegan , 0.0 [ -1.2 % , 0.3 % ] low-cal ; P = .04 ) , but there was no difference between groups at 6 months ( P = .39 ) . Use of Facebook groups was significantly related to percent weight loss at 3 ( P < .001 ) and 6 months ( P = .05 ) . Vegan participants had a greater decrease in energy ( -265 [ -439 , 0 ] kcal/d ) and fat intake ( -7.4 % [ -9.2 % , 0 ] energy ) at 6 months compared with low-cal participants ( 0 [ 0 , 112 ] kcal/d , P = .02 ; 0 [ 0 , 3.0 % ] energy , P = .02 ) . These preliminary results suggest that engagement with social media and adoption of a vegan diet may be effective for promoting short-term weight loss among women with PCOS ; however , a larger trial that addresses potential high attrition rates is needed to confirm these results Purpose . To determine whether a multicomponent nutrition intervention program at a corporate site reduces body weight and improves other cardiovascular risk factors in overweight individuals . Design . Prospect i ve clinical intervention study . Subjects/ Setting . Employees of the Government Employees Insurance Company ( GEICO ) ( N = 113 ) , aged 21 to 65 years , with a body mass index ≥ 25 kg/m2 and /or previous diagnosis of type 2 diabetes . Intervention . A 22-week intervention including a low-fat , vegan diet . Measures . Changes in body weight , anthropometric measures , blood pressure , lipid profile , and dietary intake . Analysis . Multivariate analyses of variance were calculated for clinical and nutrient measures , followed by univariate analyses of variance , to determine the significance of differences between groups in changes over time . Results . Intervention-group participants experienced greater weight changes compared with control-group participants ( mean , – 5.1 [ SE , .6 ] kg vs. + .1 [ SE , .6 ] kg , p < .0001 ) , as well as greater changes in waist circumference ( mean , – 4.7 [ SE , .6 ] cm vs. + .8 [ SE , .6 ] cm , p < .0001 ) and waist : hip ratio ( mean , – .006 [ SE , .003 ] vs. + .014 [ SE , .005 ] , p = .0007 ) . Weight loss of 5 % of body weight was more frequently observed in the intervention group ( 48.5 % ) compared with the control group ( 11.1 % ) ( χ2[1 , N= 113 ] = 16.99 , p < .0001 ) . Conclusions . Among individuals volunteering for a 22-week worksite research study , an intervention using a low-fat , vegan diet effectively reduced body weight and waist circumference BACKGROUND It is widely believed that cancer can be prevented by high intake of fruits and vegetables . However , inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk . METHODS We conducted a prospect i ve analysis of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort to assess relationships between intake of total fruits , total vegetables , and total fruits and vegetables combined and cancer risk during 1992 - 2000 . Detailed information on the dietary habit and lifestyle variables of the cohort was obtained . Cancer incidence and mortality data were ascertained , and hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were estimated using multivariable Cox regression models . Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking . RESULTS Of the initial 142 605 men and 335 873 women included in the study , 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years . The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women . Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar ( 200 g/d increased intake of fruits and vegetables combined , HR = 0.97 , 95 % CI = 0.96 to 0.99 ; 100 g/d increased intake of total vegetables , HR = 0.98 , 95 % CI = 0.97 to 0.99 ) ; intake of fruits showed a weaker inverse association ( 100 g/d increased intake of total fruits , HR = 0.99 , 95 % CI = 0.98 to 1.00 ) . The reduced risk of cancer associated with high vegetable intake was restricted to women ( HR = 0.98 , 95 % CI = 0.97 to 0.99 ) . Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol . CONCLUSIONS A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study . Given the small magnitude of the observed associations , caution should be applied in their interpretation BACKGROUND The role that dietary interventions can play in multiple sclerosis ( MS ) management is of huge interest amongst patients and research ers but data evaluating this is limited . Possible effects of a very-low-fat , plant-based dietary intervention on MS related progression and disease activity as measured by brain imaging and MS related symptoms have not been evaluated in a r and omized-controlled trial . Despite use of disease modifying therapies ( DMT ) , poor quality of life ( QOL ) in MS patients can be a significant problem with fatigue being one of the common disabling symptoms . Effective treatment options for fatigue remain limited . Emerging evidence suggests diet and vascular risk factors including obesity and hyperlipidemia may influence MS disease progression and improve QOL . OBJECTIVES To evaluate adherence , safety and effects of a very-low-fat , plant-based diet ( Diet ) on brain MRI , clinical [ MS relapses and disability , body mass index ( BMI ) ] and metabolic ( blood lipids and insulin ) outcomes , QOL [ Short Form-36 ( SF-36 ) ] , and fatigue [ Fatigue Severity Scale ( FSS ) and Modified Fatigue Impact Scale ( MFIS ) ] , in relapsing-remitting MS ( RRMS ) . METHODS This was a r and omized-controlled , assessor-blinded , one-year long study with 61 participants assigned to either Diet ( N=32 ) or wait-listed ( Control , N=29 ) group . RESULTS The mean age ( years ) [ Control-40.9±8.48 ; Diet-40.8±8.86 ] and the mean disease duration ( years ) [ Control -5.3±3.86 ; Diet-5.33±3.63 ] were comparable between the two groups . There was a slight difference between the two study groups in the baseline mean exp and ed disability status scale ( EDSS ) score [ Control-2.22±0.90 ; Diet-2.72±1.05 ] . Eight subjects withdrew ( Diet , N=6 ; Control , N=2 ) . Adherence to the study diet based on monthly Food Frequency Question naire ( FFQ ) was excellent with the diet group showing significant difference in the total fat caloric intake compared to the control group [ total fat intake/total calories averaged ~15 % ( Diet ) versus ~40 % ( Control ) ] . The two groups showed no differences in brain MRI outcomes , number of MS relapses or disability at 12 months . The diet group showed improvements at six months in low-density lipoprotein cholesterol ( Δ=-11.99mg/dL ; p=0.031 ) , total cholesterol ( Δ=-13.18mg/dL ; p=0.027 ) and insulin ( Δ=-2.82mg/dL ; p=0.0067 ) , mean monthly reductions in BMI ( Rate=-1.125kg/m2 per month ; p<0.001 ) and fatigue [ FSS ( Rate=-0.0639 points/month ; p=0.0010 ) ; MFIS ( Rate=-0.233 points/month ; p=0.0011 ) ] during the 12-month period . CONCLUSIONS While a very-low fat , plant-based diet was well adhered to and tolerated , it result ed in no significant improvement on brain MRI , relapse rate or disability as assessed by EDSS scores in subjects with RRMS over one year . The diet group however showed significant improvements in measures of fatigue , BMI and metabolic biomarkers . The study was powered to detect only very large effects on MRI activity so smaller but clinical ly meaningful effects can not be excluded . The diet intervention result ed in a beneficial effect on the self-reported outcome of fatigue but these results should be interpreted cautiously as a wait-list control group may not completely control for a placebo effect and there was a baseline imbalance on fatigue scores between the groups . If maintained , the improved lipid profile and BMI could yield long-term vascular health benefits . Longer studies with larger sample sizes are needed to better underst and the long-term health benefits of this diet Background / Objective : There is little r and omised evidence using a whole food plant-based ( WFPB ) diet as intervention for elevated body mass index ( BMI ) or dyslipidaemia . We investigated the effectiveness of a community-based dietary programme . Primary end points : BMI and cholesterol at 6 months ( subsequently extended).Subjects : Ages 35–70 , from one general practice in Gisborne , New Zeal and . Diagnosed with obesity or overweight and at least one of type 2 diabetes , ischaemic heart disease , hypertension or hypercholesterolaemia . Of 65 subjects r and omised ( control n=32 , intervention n=33 ) , 49 ( 75.4 % ) completed the study to 6 months . Twenty-three ( 70 % ) intervention participants were followed up at 12 months . Methods : All participants received normal care . Intervention participants attended facilitated meetings twice-weekly for 12 weeks , and followed a non-energy-restricted WFPB diet with vitamin B12 supplementation . Results : At 6 months , mean BMI reduction was greater with the WFPB diet compared with normal care ( 4.4 vs 0.4 , difference : 3.9 kg m−2 ( 95 % confidence interval (CI)±1 ) , P<0.0001 ) . Mean cholesterol reduction was greater with the WFPB diet , but the difference was not significant compared with normal care ( 0.71 vs 0.26 , difference : 0.45 mmol l−1 ( 95 % CI±0.54 ) , P=0.1 ) , unless dropouts were excluded ( difference : 0.56 mmol l−1 ( 95 % CI±0.54 ) , P=0.05 ) . Twelve-month mean reductions for the WFPB diet group were 4.2 ( ±0.8 ) kg m−2 BMI points and 0.55 ( ±0.54 , P=0.05 ) mmol l−1 total cholesterol . No serious harms were reported . Conclusions : This programme led to significant improvements in BMI , cholesterol and other risk factors . To the best of our knowledge , this research has achieved greater weight loss at 6 and 12 months than any other trial that does not limit energy intake or m and ate regular exercise Sixty moderately obese women ( mean BMI = 33 , mean age = 43 ) , r and omized to a lactovegetarian or regular 1300-kcal weight-reducing diet were followed at 3 , 8 and 24 months . Weight follow-up was 92 % , while 47 % complied with the program throughout with no differences between the two diets with respect to compliance rate , weight loss or behavioral test results . Over 24 months compliers lost a mean 3.9 kg compared to a gain of 1.8 kg in the non-compliers . Short-term improvements in mental well-being measured by the Mood Adjective Check List deteriorated after 2 years to lower levels than at entry . Self-assessed motivation to diet was inversely related to mental well-being at two years . Positive long-term changes of functional status ( Sickness Impact Profile ) were found . Though subjective prediction of success measured after 3 weeks on diet predicted short-term and maximum weight loss , it did not predict ultimate outcome . More difficulties in resisting emotional and social eating cues ( high disinhibition score on the Three-Factor Eating Question naire ) before and during the diet predicted weight gain . The more initial health-related dysfunction ( SIP ) the greater the weight regain . Psychological characteristics at baseline did not predict compliance or overall weight loss . The magnitude of weight loss after 24 months was related to amount and duration of maximum weight loss Context People can achieve recommended fat intake while consuming high or low amounts of vegetables , fruits , legumes , and whole grains . Contribution This 4-week r and omized trial compared 2 diets with different vegetable , fruit , legume , and whole-grain content but identical total fat , saturated fat , protein , carbohydrate , and cholesterol content . The 59 adults who consumed high amounts of vegetables , fruits , legumes , and whole grains had greater improvements in total and low-density lipoprotein cholesterol levels than the 61 adults who ate low amounts of these foods . Implication s At least over the short term , greater improvements in low-density lipoprotein and total cholesterol are an additional benefit of diets high in vegetables , fruits , legumes , and whole grains . The Editors It is well established that elevated low-density lipoprotein ( LDL ) cholesterol concentrations are a risk factor for cardiovascular diseases and that dietary modification is considered a first approach to their treatment and control ( 1 , 2 ) . For several decades , dietary modification for lipid management traditionally focused on avoiding saturated fat and cholesterol ( 3 - 5 ) . Previous examples of dietary interventions targeting LDL cholesterol level often reported only modest lipid improvements , leading some to consider diet a relatively ineffective therapy ( 6 ) . However , recent developments have suggested that the traditional focus of lipid management may have been overly simplistic and that diets might be more effective if more attention was focused on including certain foods or factors rather than just avoiding saturated fat and cholesterol . Effective refinements of dietary strategies for lipid management could decrease the gap in effectiveness between dietary approaches and drug therapy . Several dietary factors or foods , including soy protein , soy isoflavones , plant sterols , soluble fiber , oats , nuts , and garlic , have established or potential lipid benefits ( 7 - 13 ) . Each is derived from plant food sources , and it is inclusion of these factors , rather than avoidance , that is reported to confer benefits . However , given that most plant foods contain low or negligible amounts of saturated fat and that all plant foods are devoid of cholesterol , it follows that a plant-based diet is inherently low in saturated fat and cholesterol . Therefore , it is difficult to distinguish between plasma lipid benefits derived from the actual plant-based dietary components and those derived from avoidance of saturated fat and cholesterol . Several studies have been design ed to test the effects on plasma lipids of diets with identical saturated fat and cholesterol intake but varied amounts of 1 or 2 additional dietary components ( 14 - 16 ) . Data are more limited on dietary approaches that hold saturated fat and cholesterol intake constant while modifying multiple other dietary components simultaneously ( 17 ) . Modifying multiple dietary components simultaneously ( for example , increasing intake of vegetables , fruits , and low-fat dairy ) while holding sodium intake constant has been shown to effectively lower elevated blood pressure in the Dietary Approaches to Stop Hypertension trials ( DASH I and II ) ( 18 , 19 ) . Testing a parallel approach to refining dietary intervention for lipid management is warranted . In 2000 , the American Heart Association ( AHA ) reported revised dietary guidelines that substantially modified its 1993 and 1996 guidelines ( 2 , 4 , 5 ) . All 3 versions of the guidelines recommended keeping saturated fat intake at less than 10 % of energy and cholesterol intake below 300 mg/d . A notable modification of the 2000 guidelines was to emphasize foods and overall eating patterns , including increased intakes of vegetables and whole grains ( in general , a plant-based diet ) . It was our hypothesis that a plant-based diet consistent with the revised AHA 2000 guidelines would increase the LDL cholesterol-lowering benefits of the previous AHA Step I guidelines . We theorized that this improvement would be independent of the plant-based diet 's saturated fat and cholesterol content . Therefore , we design ed 2 diets that had identical levels of total fat ( 30 % of energy ) , saturated fat ( 10 % of energy ) , and cholesterol ( < 300 mg/d ) but differed substantially in content of nutrient- and phytochemical-dense plant-based foods . The purpose of the study was to determine whether LDL cholesterol-lowering benefits among adults with moderately elevated cholesterol levels would be greater under weight-stable conditions with a plant-based low-fat diet than with a more typical , convenience-oriented low-fat diet that was identical in intake of total fat , saturated fat , and cholesterol . Methods Participants Participants were recruited from the local community , primarily through newspaper advertisements , letters to previous study participants , and flyers sent to university employees . Men and women were invited to enroll if they were 30 to 65 years of age with fasting plasma LDL cholesterol levels of 3.3 to 4.8 mmol/L ( 130 to 190 mg/dL ) , fasting plasma triglyceride levels less than 2.83 mmol/L ( < 250 mg/dL ) , body mass index between 19 and 31 kg/m2 , and a current diet estimated to derive at least 10 % of energy from saturated fat . Pregnant women , persons who smoked , persons with prevalent heart disease or diabetes , or persons who had been using lipid-lowering or blood pressure-lowering medications within the past month ( all determined through self-report ) were excluded . During the recruitment phase , 1096 individuals were screened by telephone interview and 345 who met the initial inclusion criteria were considered eligible for cholesterol testing . Of these 345 persons , 188 who were found to have eligible concentrations of LDL cholesterol and triglycerides attended an orientation meeting . Fifty-one persons decided not to participate ( primarily because of the time commitment ) , and an additional 12 potential participants were excluded after a 3-day food record showed that their estimated average intake of saturated fat was already less than 10 % of energy . One hundred twenty-five participants were r and omly assigned to 1 of the 2 diet groups . The Stanford University Human Subjects Committee review ed and approved the investigation , all participants signed an informed consent form before enrollment , and the study was performed according to Declaration of Helsinki guidelines ( 20 ) . Design The trial used a parallel design . We r and omly assigned participants in blocks of 20 by selecting , without replacement , from a set of indistinguishable envelopes containing 10 assignments to each of the 2 diet groups . R and omization of the envelopes was done by h and , without a computer algorithm . No stratification criteria were used . Each participant was provided with meals , snacks , and beverages on an outpatient basis for 28 days , as described later . Diets Both study diets were design ed to provide 30 % of energy from total fat , 10 % of energy from saturated fat , and approximately 100 mg of cholesterol per 1000 kcal per day . During the menu- design ing stage of the study , the nutrient composition of the diets was determined by using the data base of Food Processor software , version 7.0 ( ESHA Research , Salem , Oregon ) . Menus were design ed by using commonly available foods from local markets . The Low-Fat diet was design ed to include many reduced-fat prepared-food items ( for example , reduced-fat cheeses , low-fat frozen lasagna , and low-fat and sugar-rich snack foods ) . In contrast , the Low-Fat Plus diet was design ed to include considerably more vegetables , legumes , whole grains , and fruits . Butter , cheese , and eggs were added to the daily menus for the Low-Fat Plus diet , increasing the saturated fat and cholesterol content to match the Low-Fat diet . A 7-day menu cycle was design ed for each of the 2 study diets ; therefore , each menu was repeated 4 times during the 28 days . The diets included breakfast , lunch , dinner , beverages , and snacks for each day . Each weekday , the participants ate either lunch or dinner at the dining facility of the Stanford General Clinical Research Center . After their on-site meal , they were given coolers that contained meals and snacks to be consumed off-site . On Fridays , participants received weekend meals to be consumed off-site . Appendix Table 1 and Appendix Table 2 list the daily menus . One free-choice evening meal was allowed each weekend . For this meal , participants were given guidelines for choosing low-fat meals consistent with their diet assignments and were required to keep a record of foods consumed . These records were analyzed for nutritional content and were used to determine the impact of the free-choice meals on the overall study diets . Adherence was measured by using daily log sheets kept by participants that tracked incomplete consumption of study foods or consumption of any non study foods . The 28 daily food logs for each participant were examined for deviations from the diets . The energy contribution of each deviation was determined and then totaled for the entire 28-day protocol period . Each of the 14 daily menus ( 7-day cycle 2 diets ) was analyzed chemically for nutrient content before the study and then again during the study ( Covance Laboratories , Madison , Wisconsin ) . The chemical analyses performed before the study confirmed that the average composition of the daily menus provided 30 % of energy from total fat , 10 % of energy from saturated fat , and approximately 100 mg of cholesterol per 1000 kcal per day . When the 2 diets were first design ed , we attempted to match their mono- and polyunsaturated fat content . However , the data base used in the design phase was missing values for these nutrients for approximately 20 % of the foods . In addition , many of the specific products purchased locally for the study provided incomplete information for the content of these unsaturated fats . The first round of chemical analyses of the diets , performed before enrollment began , indicated a modest discrepancy The effect of a strict , low-salt , uncooked vegan diet rich in lactobacteria on symptoms in 18 fibromyalgia patients during and after a 3-month intervention period in an open , non-r and omized controlled study was evaluated . As control 15 patients continued their omnivorous diet . The groups did not differ significantly from each other in the beginning of the study in any other parameters except in pain and urine sodium . The results revealed significant improvements in Visual analogue scale of pain ( VAS ) ( p=0.005 ) , joint stiffness ( p=0.001 ) , quality of sleep ( p=0.0001 ) , Health assessment question naire ( HAQ ) ( p=0.031 ) , General health question naire ( GHQ ) ( p=0.021 ) , and a rheumatologist 's own question naire ( p=0.038 ) . The majority of patients were overweight to some extent at the beginning of the study and shifting to a vegan food caused a significant reduction in body mass index ( BMI ) ( p=0.0001 ) . Total serum cholesterol showed a statistically significant lowering ( p=0.003 ) . Urine sodium dropped to 1/3 of the beginning values ( p=0.0001 ) indicating good diet compliance . It can be concluded that vegan diet had beneficial effects on fibromyalgia symptoms at least in the short run Dietary intake data of 43 Finnish rheumatoid arthritis patients were collected using 7-day food records . The subjects were r and omized into a control and a vegan diet groups , consisting of 22 and 21 subjects , respectively . The subjects in the vegan diet group received an uncooked vegan diet ( ' living food ' ) for 3 months , and they were tutored daily by a living-food expert . The subjects in the control group continued their usual diets and received no tutoring . Adherence to the strict vegan diet was assessed on the basis of urinary sodium excretion and by the information on consumption of specific food items ( wheatgrass juice and the rejuvelac drink ) . The use of these drinks was variable , and some boiled vegetables were consumed occasionally . However , only one of the subjects in the vegan diet group lacked a clear decrease in urinary sodium excretion . Rheumatoid patients had lower than recommended intakes of iron , zinc and niacin , and their energy intake was low compared to mean daily energy intake of the healthy Finnish females of the same age . Shifting to the uncooked vegan diet significantly increased the intakes of energy and many nutrients . In spite of the increased energy intake , the group on the vegan diet lost 9 % of their body weight during the intervention period , indicating a low availability of energy from the vegan diet Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease . We evaluated the long‐term prospect i ve association between dementia and high‐sensitivity C‐reactive protein , a nonspecific marker of inflammation . Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program ( 1968–1970 ) and subsequently were reexamined 25 years later for dementia in the Honolulu‐Asia Aging Study ( 1991–1996 ) . In a r and om sub sample of 1,050 Honolulu‐Asia Aging Study cases and noncases , high‐sensitivity C‐reactive protein concentrations were measured from serum taken at the second examination ; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria . Compared with men in the lowest quartile ( < 0.34mg/L ) of high‐sensitivity C‐reactive protein , men in the upper three quartiles had a 3‐fold significantly increased risk for all dementias combined , Alzheimer 's disease , and vascular dementia . For vascular dementia , the risk increased with increasing quartile . These relations were independent of cardiovascular risk factors and disease . These data support the view that inflammatory markers may reflect not only peripheral disease , but also cerebral disease mechanisms related to dementia , and that these processes are measurable long before clinical symptoms appear Studies have examined nutrient differences among people following different plant-based diets . However , all of these studies have been observational . The aim of the present study was to examine differences in nutrient intake and Dietary Inflammatory Index ( DII ) scores among overweight and obese ( body mass index 25.0 - 49.9 kg/m(2 ) ) adults r and omized to receive dietary instruction on a vegan ( n = 12 ) , vegetarian ( n = 13 ) , pescovegetarian ( n = 13 ) , semivegetarian ( n = 13 ) , or omnivorous ( n = 12 ) diet during a 6-month r and omized controlled trial . Nutrient intake , nutrient adequacy , and DII score were assessed via two 24-hour dietary recalls ( Automated Self-Administered 24-Hour Dietary Recall ) at baseline and at 2 and 6 months . Differences in nutrient intake and the DII were examined using general linear models with follow-up tests at each time point . We hypothesized that individuals r and omized to the vegan diet would have lower DII scores and greater improvements in fiber , carbohydrate , fat , saturated fat , and cholesterol at both 2 and 6 months as compared with the other 4 diets . Participants r and omized to the vegan diet had significantly greater changes in most macronutrients at both time points , including fat and saturated fat , as well as cholesterol and , at 2 months , fiber , as compared with most of the other diet groups ( Ps < .05 ) . Vegan , vegetarian , and pescovegetarian participants all saw significant improvements in the DII score as compared with semivegetarian participants at 2 months ( Ps < .05 ) with no differences at 6 months . Given the greater impact on macronutrients and the DII during the short term , finding ways to provide support for adoption and maintenance of plant-based dietary approaches , such as vegan and vegetarian diets , should be given consideration Objective : The study objective was to compare the effect of a st and ard calorie- and fat-restricted diet ( STD-D ) and a calorie- and fat-restricted lacto-ovo-vegetarian diet ( LOV-D ) on total and high-molecular-weight ( HMW ) adiponectin levels after 6 months of behavioral intervention . Design : This study is an ancillary study to a r and omized clinical trial . Subjects : Subjects included 143 overweight/obese adults ( STD-D = 79 ; LOV-D = 64 ) . Intervention : Both groups received the same st and ard behavioral intervention ; the only difference was that LOV-D participants were instructed to eliminate meat , poultry , and fish from their diet . Measures : Weight , dietary intake with the 3-day food diary , and total and HMW adiponectin levels were measured . Results : Both groups significantly increased total ( STD-D + 7.2 ± 17.8 % ; LOV-D + 9.4 ± 21.8 % ) and HMW adiponectin levels ( STD-D + 18.5 ± 32.9 % ; LOV-D + 15.8 ± 34.5 % ; ps < 0.05 ) with no significant differences between the groups . We found significant associations between weight loss and increases in total ( β ( SE ) = −.071(.27 ) ; p = 0.003 ) and HMW adiponectin ( β ( SE ) = −1.37(.47 ) ; p = 0.001 ) levels independent of the diet type . Weight loss at the higher quartile was associated with improvements of adiponectin levels ( p < 0.05 ) . Conclusion : Weight loss was associated with increased total and HMW adiponectin levels regardless of the diet type . Enhancing weight loss may be a means to improve adiponectin levels Objectives : We examined whether accordance to the DASH ( Dietary Approach to Stop Hypertension ) and Mediterranean diets is associated with slower cognitive decline in a prospect i ve Chicago cohort study of older persons , the Memory and Aging Project . Methods : The sample comprised 826 Memory and Aging Project participants ( aged 81.5 ± 7.1 years ) who completed a 144-item food frequency question naire at baseline and 2 or more cognitive assessment s over 4.1 years . Dietary scores were computed for accordance to the DASH diet ( 0–10 ) and the Mediterranean diet ( MedDietScore ) ( 0–55 ) . For both , higher scores reflect greater accordance . Both patterns share at least 3 common food components . Cognitive function was assessed annually with 19 cognitive tests from which global cognitive scores and summary measures are computed . Results : The mean global cognitive score at baseline was 0.12 ( range , −3.23 to 1.60 ) with an overall mean annual change in score of −0.08 st and ardized units . Only 13 participants had possible dementia . The mean DASH score was 4.1 ( range , 1.0–8.5 ) and the MedDietScore was 31.3 ( range , 18–46 ) . In mixed models adjusted for covariates , a 1-unit difference in DASH score was associated with a slower rate of global cognitive decline by 0.007 st and ardized units ( st and ard error of estimate = 0.003 , p = 0.03 ) . Similarly , a 1-unit-higher MedDietScore was associated with a slower rate of global cognitive decline by 0.002 st and ardized units ( st and ard error of estimate = 0.001 , p = 0.01 ) . Conclusions : These findings support the hypothesis that both the DASH and Mediterranean diet patterns are associated with slower rates of cognitive decline in the same cohort of older persons OBJECTIVE The objective was to assess the effect of a low-fat , vegan diet compared with the National Cholesterol Education Program ( NCEP ) diet on weight loss maintenance at 1 and 2 years . RESEARCH METHODS AND PROCEDURES Sixty-four overweight , postmenopausal women were r and omly assigned to a vegan or NCEP diet for 14 weeks , and 62 women began the study . The study was done in two replications . Participants in the first replication ( N = 28 ) received no follow-up support after the 14 weeks , and those in the second replication ( N = 34 ) were offered group support meetings for 1 year . Weight and diet adherence were measured at 1 and 2 years for all participants . Weight loss is reported as median ( interquartile range ) and is the difference from baseline weight at years 1 and 2 . RESULTS Individuals in the vegan group lost more weight than those in the NCEP group at 1 year [ -4.9 ( -0.5 , -8.0 ) kg vs. -1.8 ( 0.8 , -4.3 ) ; p < 0.05 ] and at 2 years [ -3.1 ( 0.0 , -6.0 ) kg vs. -0.8 ( 3.1 , -4.2 ) kg ; p < 0.05 ] . Those participants offered group support lost more weight at 1 year ( p < 0.01 ) and 2 years ( p < 0.05 ) than those without support . Attendance at meetings was associated with improved weight loss at 1 year ( p < 0.001 ) and 2 years ( p < 0.01 ) . DISCUSSION A vegan diet was associated with significantly greater weight loss than the NCEP diet at 1 and 2 years . Both group support and meeting attendance were associated with significant weight loss at follow-up Purpose Experimental investigations in rodents have contributed significantly to our current underst and ing of the potential importance of the gut microbiome and brain interactions for neurotransmitter expression , neurodevelopment , and behaviour . However , clinical evidence to support such interactions is still scarce . The present study used a double-blind , r and omized , pre- and post-intervention assessment design to investigate the effects of a 4-week multi-strain probiotic administration on whole-brain functional and structural connectivity in healthy volunteers . Methods Forty-five healthy volunteers were recruited for this study and were divided equally into three groups ( PRP : probiotic , PLP : placebo , and CON : control ) . All the participants underwent resting-state functional MRI and diffusion MRI brain scans twice during the course of study , at the beginning ( time point 1 ) and after 4 weeks ( time point 2 ) . MRI data were acquired using a 3 T whole-body MR system ( Magnetom Skyra , Siemens , Germany ) . Results Functional connectivity ( FC ) changes were observed in the default mode network ( DMN ) , salience network ( SN ) , and middle and superior frontal gyrus network ( MFGN ) in the PRP group as compared to the PLP and CON groups . PRP group showed a significant decrease in FC in MFGN ( in frontal pole and frontal medial cortex ) and in DMN ( in frontal lobe ) as compared to CON and PLP groups , respectively . Further , significant increase in FC in SN ( in cingulate gyrus and precuneus cortex ) was also observed in PRP group as compared to CON group . The significance threshold was set to p < 0.05 FWE corrected . No significant structural differences were observed between the three groups . Conclusions This work provides new insights into the role of a multi-strain probiotic administration in modulating the behaviour , which is reflected as changes in the FC in healthy volunteers . This study motivates future investigations into the role of probiotics in context of major depression and stress disorders The effects of carbohydrates on body weight and insulin sensitivity are controversial . In this 16-week r and omized clinical trial , we tested the role of a low-fat , plant-based diet on body weight , body composition and insulin resistance . As a part of this trial , we investigated the role of changes in carbohydrate intake on body composition and insulin resistance . Participants ( n = 75 ) were r and omized to follow a plant-based high-carbohydrate , low-fat ( vegan ) diet ( n = 38 ) or to maintain their current diet ( n = 37 ) . Dual-energy X-ray absorptiometry was used to measure body composition . Insulin resistance was assessed with the Homeostasis Model Assessment ( HOMA-IR ) index . A repeated measure ANOVA model was used to test the between-group differences from baseline to 16 weeks . A linear regression model was used to test the relationship between carbohydrate intake , and body composition and insulin resistance . Weight decreased significantly in the vegan group ( treatment effect −6.5 [ 95 % CI −8.9 to −4.1 ] kg ; Gxt , p < 0.001 ) . Fat mass was reduced in the vegan group ( treatment effect −4.3 [ 95 % CI −5.4 to −3.2 ] kg ; Gxt , p < 0.001 ) . HOMA-IR was reduced significantly in the vegan group ( treatment effect −1.0 [ 95 % CI −1.2 to −0.8 ] ; Gxt , p = 0.004 ) . Changes in consumption of carbohydrate , as a percentage of energy , correlated negatively with changes in BMI ( r = −0.53 , p < 0.001 ) , fat mass ( r = −0.55 , p < 0.001 ) , volume of visceral fat ( r = −0.35 , p = 0.006 ) , and HOMA ( r = −0.27 , p = 0.04 ) . These associations remained significant after adjustment for energy intake . Changes in consumption of total and insoluble fiber correlated negatively with changes in BMI ( r = −0.43 , p < 0.001 ; and r = −0.46 , p < 0.001 , respectively ) , fat mass ( r = −0.42 , p < 0.001 ; and r = −0.46 , p < 0.001 , respectively ) , and volume of visceral fat ( r = −0.29 , p = 0.03 ; and r = −0.32 , p = 0.01 , respectively ) . The associations between total and insoluble fiber and changes in BMI and fat mass remained significant even after adjustment for energy intake . Increased carbohydrate and fiber intake , as part of a plant-based high-carbohydrate , low-fat diet , are associated with beneficial effects on weight , body composition , and insulin resistance BACKGROUND Although vegan diets improve diabetes management , little is known about the nutrient profiles or diet quality of individuals with type 2 diabetes who adopt a vegan diet . OBJECTIVE To assess the changes in nutrient intake and dietary quality among participants following a low-fat vegan diet or the 2003 American Diabetes Association dietary recommendations . DESIGN A 22-week r and omized , controlled clinical trial examining changes in nutrient intake and diet quality . SUBJECTS/ SETTING Participants with type 2 diabetes ( n=99 ) in a free-living setting . RESEARCH DESIGN AND METHODS Participants were r and omly assigned to a low-fat vegan diet or a 2003 American Diabetes Association recommended diet . MAIN OUTCOME MEASURES Nutrient intake and Alternate Healthy Eating Index ( AHEI ) scores were collected at baseline and 22 weeks . STATISTICAL ANALYSES PERFORMED Between-group t tests were calculated for changes between groups and paired comparison t tests were calculated for changes within-group . Pearson 's correlation assessed relationship of AHEI score to hemoglobin A1c and body weight changes . RESULTS Both groups reported significant decreases in energy , protein , fat , cholesterol , vitamin D , selenium , and sodium intakes . The vegan group also significantly reduced reported intakes of vitamin B-12 and calcium , and significantly increased carbohydrate , fiber , total vitamin A activity , beta carotene , vitamins K and C , folate , magnesium , and potassium . The American Diabetes Association recommended diet group also reported significant decreases in carbohydrate and iron , but reported no significant increases . The vegan group significantly improved its AHEI score ( P<0.0001 ) , while the American Diabetes Association recommended diet group did not ( P=0.7218 ) . The difference in AHEI score at 22 weeks between groups was significant ( P<0.0001 ) . With both groups combined , AHEI score was negatively correlated with both changes in hemoglobin A1c value ( r=-0.24 , P=0.016 ) and weight ( r=-0.27 , P=0.007 ) . CONCLUSIONS Vegan diets increase intakes of carbohydrate , fiber , and several micronutrients , in contrast with the American Diabetes Association recommended diet . The vegan group improved its AHEI score whereas the American Diabetes Association recommended diet group 's AHEI score remained unchanged BACKGROUND Data on the long-term association between low-carbohydrate diets and mortality are sparse . OBJECTIVE To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men . DESIGN Prospect i ve cohort study of women and men who were followed from 1980 ( women ) or 1986 ( men ) until 2006 . Low-carbohydrate diets , either animal-based ( emphasizing animal sources of fat and protein ) or vegetable-based ( emphasizing vegetable sources of fat and protein ) , were computed from several vali date d food-frequency question naires assessed during follow-up . SETTING Nurses ' Health Study and Health Professionals ' Follow-up Study . PARTICIPANTS 85 168 women ( aged 34 to 59 years at baseline ) and 44 548 men ( aged 40 to 75 years at baseline ) without heart disease , cancer , or diabetes . MEASUREMENTS Investigators documented 12 555 deaths ( 2458 cardiovascular-related and 5780 cancer-related ) in women and 8678 deaths ( 2746 cardiovascular-related and 2960 cancer-related ) in men . RESULTS The overall low-carbohydrate score was associated with a modest increase in overall mortality in a pooled analysis ( hazard ratio [ HR ] comparing extreme deciles , 1.12 [ 95 % CI , 1.01 to 1.24 ] ; P for trend = 0.136 ) . The animal low-carbohydrate score was associated with higher all-cause mortality ( pooled HR comparing extreme deciles , 1.23 [ CI , 1.11 to 1.37 ] ; P for trend = 0.051 ) , cardiovascular mortality ( corresponding HR , 1.14 [ CI , 1.01 to 1.29 ] ; P for trend = 0.029 ) , and cancer mortality ( corresponding HR , 1.28 [ CI , 1.02 to 1.60 ] ; P for trend = 0.089 ) . In contrast , a higher vegetable low-carbohydrate score was associated with lower all-cause mortality ( HR , 0.80 [ CI , 0.75 to 0.85 ] ; P for trend < /= 0.001 ) and cardiovascular mortality ( HR , 0.77 [ CI , 0.68 to 0.87 ] ; P for trend < 0.001 ) . LIMITATIONS Diet and lifestyle characteristics were assessed with some degree of error . Sensitivity analyses indicated that results were probably not substantively affected by residual confounding or an unmeasured confounder . Participants were not a representative sample of the U.S. population . CONCLUSION A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women , whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates . PRIMARY FUNDING SOURCE National Institutes of Health |
11,383 | 32,184,575 | Only seven of the identified tools showed somewhat favorable characteristics for a potential use of the respective method in the context of polypharmacy . | Purpose The aim of this systematic review was to identify methods used to assess medication preferences in older adults and evaluate their advantages and disadvantages with respect to their applicability to the context of multimorbidity and polypharmacy . | Objective To improve medication appropriateness and adherence in elderly patients with multimorbidity , we developed a complex intervention involving general practitioners ( GPs ) and their healthcare assistants ( HCA ) . In accordance with the Medical Research Council guidance on developing and evaluating complex interventions , we prepared for the main study by testing the feasibility of the intervention and study design in a cluster r and omised pilot study . Setting 20 general practice s in Hesse , Germany . Participants 100 cognitively intact patients ≥65 years with ≥3 chronic conditions , ≥5 chronic prescriptions and capable of participating in telephone interviews ; 94 patients completed the study . Intervention The HCA conducted a checklist-based interview with patients on medication-related problems and reconciled their medications . Assisted by a computerised decision-support system ( CDSS ) , the GPs discussed medication intake with patients and adjusted their medication regimens . The control group continued with usual care . Outcome measures Feasibility of the intervention and required time were assessed for GPs , HCAs and patients using mixed methods ( question naires , interviews and case vignettes after completion of the study ) . The feasibility of the study was assessed concerning success of achieving recruitment targets , balancing cluster sizes and minimising drop-out rates . Exploratory outcomes included the medication appropriateness index ( MAI ) , quality of life , functional status and adherence-related measures . MAI was evaluated blinded to group assignment , and intra-rater/inter-rater reliability was assessed for a sub sample of prescriptions . Results 10 practice s were r and omised and analysed per group . GPs/HCAs were satisfied with the interventions despite the time required ( 35/45 min/patient ) . In case vignettes , GPs/HCAs needed help using the CDSS . The study made no patients feel uneasy . Intra-rater/inter-rater reliability for MAI was excellent . Inclusion criteria were challenging and potentially inadequate , and should therefore be adjusted . Outcome measures on pain , functionality and self-reported adherence were unfeasible due to frequent missing values , an incorrect manual or potentially invalid results . Conclusions Intervention and trial design were feasible . The pilot study revealed important limitations that influenced the design and conduct of the main study , thus highlighting the value of piloting complex interventions . Trial registration number IS RCT N99691973 ; Results BACKGROUND Beliefs concerning the causes of mental illness may help to explain why there are significant disparities in the rates of formal mental health service use among racial/ethnic minority elderly as compared with their white counterparts . This study applies the cultural influences on mental health framework to identify the relationship between race/ethnicity and differences in 1 ) beliefs on the cause of mental illness , 2 ) preferences for type of treatment , and 3 ) provider characteristics . METHOD Analyses were conducted using baseline data collected from participants who completed the cultural attitudes toward healthcare and mental illness question naire , developed for the Primary Care Research in Substance Abuse and Mental Health for the Elderly study , a multisite r and omized trial for older adults ( 65 + ) with depression , anxiety , or at-risk alcohol consumption . The final sample consisted of 1,257 non-Latino whites , 536 African Americans , 112 Asian Americans , and 303 Latinos . RESULTS African Americans , Asian Americans , and Latinos had differing beliefs regarding the causes of mental illness when compared with non-Latino whites . Race/ethnicity was also associated with determining who makes healthcare decisions , treatment preferences , and preferred characteristics of healthcare providers . CONCLUSIONS This study highlights the association between race/ethnicity and health beliefs , treatment preferences , healthcare decisions , and consumers ' preferred characteristics of healthcare providers . Accommodating the values and preferences of individuals can be helpful in engaging racial/ethnic minority patients in mental health services BACKGROUND General Practitioners ( GPs ) often have to simultaneously tackle multiple health problems of older patients . A patient-centred process that engages the patient in setting health priorities for treatment is needed . We investigated whether a structured priority- setting consultation reconciles the often-differing doctor-patient views on the importance of problems . DESIGN Cluster r and omised controlled trial with 40 GPs and their 317 consecutively recruited older patients . PROCEDURE Following a geriatric assessment , patients and doctors independently rated the importance of each uncovered problem . GPs then selected priorities with their patients in a consultation . Trained intervention GPs held a structured consultation and utilised the list of uncovered patient problems with their importance ratings to agree priorities . Untrained control GPs only used the patient 's problem list without importance ratings . MAIN OUTCOME Doctor-patient agreement on independent importance ratings two weeks after the priority- setting consultation . ANALYSIS Weighted kappa ( κw ) and multilevel logistic regression model . RESULTS Intervention GPs and their patients determined mutual priorities for 20 % of individual problems . In this process , GPs often succeeded in convincing their patients of the importance of vaccinations , lifestyle and cognitive issues . Likewise , patients convinced their GPs to prioritise their social and functional problems . Further treatment plans ensued in 84 % of these priority areas . The regression model adjusting for clusters and baseline characteristics did not demonstrate significant differences in doctor-patient agreement on problems between groups a two weeks later . CONCLUSION Differing views on the importance of health problems between GPs and older patients were not sustainably reconciled . The special consultation facilitated identification of priority problems for treatment despite differences in perceived importance of problems between patients and GPs . German clinical trials register drks 00000792 BACKGROUND It is unknown what minimal benefit in disease-free survival older patients with breast cancer require from adjuvant systemic therapy , and if this differs from that required by younger patients . We prospect ively examined patients ' preferences for adjuvant chemotherapy ( aCT ) and adjuvant hormonal therapy ( aHT ) , factors related to minimally-required benefit , and patients ' self-reported motivations . PATIENTS AND METHODS Fifty-two younger ( 40 - 64 years ) and 29 older ( ≥ 65 years ) women with a first primary , invasive tumor were interviewed post-surgery , prior to receiving aCT/aHT recommendation . RESULTS The proportions of younger versus older participants who would accept , refuse , or were undecided about therapy were 92 % versus 62 % , 4 % versus 24 % , and 4 % versus 14 % for aCT , and 92 % versus 59 % , 8 % versus 17 % , and 0 % versus 24 % for aHT . The proportion of older participants who would refuse rather than accept aCT was larger than that of younger participants ( P = .005 ) . No significant difference was found for aHT ( P = .12 ) . Younger and older participants ' minimally-required benefit , in terms of additional 10-year disease-free survival , to accept aCT ( median , 5 % vs. 4 % ; P = .13 ) or aHT ( median , 10 % vs. 8 % ; P = .15 ) did not differ . Being single/divorced/widowed ( odds ratio [ OR ] , 0.16 ; P = .005 ) , presence of geriatric condition ( inability to perform daily activities , incontinence , severe sensory impairment , depression , polypharmacy , difficulties with walking ; OR , 0.27 ; P = .047 ) , and having a preference to make the treatment decision either alone or after considering the clinician 's opinion ( active role ; OR , 0.15 ; P = .012 ) were independently related to requiring larger benefits from aCT . The most frequent motivations for/against therapy included the wish to survive/avoid recurrence , clinician 's recommendation , side effects , and treatment duration ( only aHT ) . CONCLUSION Whereas older participants were less willing to accept aCT than younger participants , no significant difference was found for aHT . However , a majority of older participants would still accept both therapies . Adjuvant systemic therapy should be discussed with eligible patients regardless of age Background : Decision aids have been shown to be useful in selected situations to assist patients in making treatment decisions . Important features such as the format of decision aids and their graphic presentation of data on benefits and harms of treatment options have not been well studied . Methods : In a r and omized trial with a 3 × 2 factorial design , we investigated the effects of decision aid format ( decision board , decision booklet with audiotape , or interactive computer program ) and graphic presentation of data ( pie graph or pictogram ) on patients ' comprehension and choices of 3 treatments for anticoagulation , identified initially as “ treatment A ” ( warfarin ) , “ treatment B ” ( acetylsalicylic acid ) and “ treatment C ” ( no treatment ) . Patients aged 65 years or older without known atrial fibrillation and not currently taking warfarin were included . The effect of blinding to the treatment name was tested in a before – after comparison . The primary outcome was change in comprehension score , as assessed by the Atrial Fibrillation Information Question naire . Secondary outcomes were treatment choice , level of satisfaction with the decision aid , and decisional conflict . Results : Of 102 eligible patients , 98 completed the study . Comprehension scores ( maximum score 10 ) increased by an absolute mean of 3.1 ( p < 0.01 ) after exposure to the decision aid regardless of the format or graphic presentation . Overall , 96 % of the participants felt that the decision aid helped them make their treatment choice . Unblinding of the treatment name result ed in 36 % of the participants changing their initial choice ( p < 0.001 ) . Interpretation : The decision aid led to significant improvement in patients ' knowledge regardless of the format or graphic representation of data . Revealing the name of the treatment options led to significant shifts in declared treatment preferences 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 Lung cancer chemotherapy decisions in patients ≥70 years old are complex because of toxicity , comorbidity and the limited data on patient preferences . We examined the relationships between preferences and chemotherapy use in this group of patients . Methods and patients We used a question naire describing four hypothetical lung cancer treatment options . Eighty-three elderly ( ≥70 years old ) lung cancer patients were informed about their diagnosis and therapeutic choices and then asked to choose one of the four options . Patients had previously been included in a prospect i ve study to explore geriatric evaluation in an oncology unit and all had given written informed consent . Results Older patients ( n=83 ) diagnosed with lung cancer ( non-small- and small-cell lung cancer ) from January 2006 to February 2008 were recruited from a single centre . The mean patient age was 77 years ( range : 70–91 ) . Eighty-one patients ( 97.6 % ) were men . Non-small-cell lung cancer ( NSCLC ) was the diagnosis in 63 patients ( 76 % ) . Most patients selected active treatment ( 38.6 % most survival benefit , 18 % less survival benefit ) and 31.3 % selected no active treatment . Elderly lung cancer patients were significantly more likely to accept aggressive treatments despite high reported toxicities . Although most of the patients were symptomatic at diagnosis , the “ symptom relief ” option was chosen less frequently than the options that could prolong survival . Factors significantly related to patients ’ attitude toward chemotherapy were age ( p<0.001 ) , frailty ( p=0.0039 ) , depression and poor performance status ( PS ) . Conclusion Elderly lung cancer patients want to be involved in the decision-making process . Survival was the main treatment objective for more than half of the patients in this study . We have not found other published studies about elderly lung cancer patients ’ decisions about chemotherapy BACKGROUND Anticoagulants are effective in preventing stroke in those with atrial fibrillation , but most patients remain untreated . AIM To investigate the prevalence of disability , cognitive impairment , and problems with compliance in a representative sample of the elderly with atrial fibrillation , and to determine whether they would want treatment and how they would like services to be arranged . METHOD In a survey of a r and om sample of 4843 elderly subjects , those with atrial fibrillation were identified using electrocardiograms . Views on treatment were obtained using a structured interview . Disability was assessed using the Office of Population Censuses and Surveys Disability Scale and cognitive status using the Mini Mental State Examination . General practitioners were asked , via question naire , for their views on each subject 's compliance . RESULTS Two hundred and seven elderly people with atrial fibrillation were identified . Almost all subjects expressed a willingness to undertake treatment to prevent stroke and preferred blood testing performed outside of hospital . Disability ( 82.7 % ) , cognitive impairment ( 25.7 % ) , and problems with compliance ( 25.0 % ) were common , but the prevalence of these difficulties was not substantially different from the general elderly population , and in many cases they could be overcome ( e.g. only 10 % of subjects had problems with compliance and no-one who could help them to comply ) . CONCLUSIONS Most elderly people with atrial fibrillation would accept treatment to prevent stroke . Disability , cognitive impairment , and problems with compliance may make it difficult to treat this patient group . An increase in the use of anticoagulants should be accompanied by the development of services appropriate to this frail population Since the introduction of new oral anticoagulants ( NOACs ) , besides vitamin-K antagonists , an additional option for stroke prevention of patients with atrial fibrillation ( AF ) is available . The objective of this study was to assess AF patients ’ preferences with regard to the attributes of these different treatment options . We conducted a multicenter study among r and omly selected physicians . Preferences were assessed by computer-assisted telephone interviews . We used a discrete-choice-experiment ( DCE ) with four convenience-related treatment dependent attributes ( need of bridging : yes/no , interactions with food/nutrition : yes/no , need of INR controls/dose adjustment : yes/no ; frequency of intake : once/twice daily ) and one comparator attribute ( distance to practitioner : < 1 km/>15 km ) . Preferences measured in the interviews were analyzed descriptively and based on a conditional logit regression model . A total of 486 AF patients ( age : 73.9 ± 8.2 years ; 43.2 % female ; mean CHA2DS2-VASc : 3.7 ± 1.6 ; current medication : 48.1 % rivaroxaban , 51.9 % VKA ) could be interviewed . Regardless of type of medication , patients significantly preferred the attribute levels ( in order of patients ’ importance ) “ once daily intake ” ( Level : once = 1 vs. twice = 0 ; Coefficient = 0.615 ; p < 0.001 ) , “ bridging necessary ” ( yes = 1 vs. no = 0 ; −0.558 ; p < 0.001 ) , “ distance to practitioner of ≤1 km ( > 15 km = 0 vs. ≤1 km = 1 ; 0.494 ; p < 0.001 ) , “ interactions with food/nutrition ” ( yes = 1 vs. no = 0 ; −0.332 ; p < 0.001 ) and “ need of INR controls/dose adjustment ” ( yes = 1 vs. no = 0 ; −0.127 ; p < 0.001 ) . In our analyses , “ once daily frequency of intake ” was the most important OAC-attribute for patients ’ choice followed by “ no bridging necessary ” and “ no interactions with food/nutrition ” . Thus , patients with AF seem to prefer treatment options which are easier to administer 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 BACKGROUND Dissatisfaction with treatment is common among those with psoriasis . While incorporating patients ' preferences into the process of treatment decision-making may improve satisfaction , this relationship has not been clearly established . OBJECTIVE To assess the extent to which matching physicians ' treatment recommendations to patients ' treatment preferences is associated with improvement in treatment satisfaction in patients with moderate-to-severe psoriasis . METHODS This prospect i ve cohort study design examined change from baseline to 3-month follow-up in four subscales of an established measure of treatment satisfaction . Separate multivariate regression models investigated the association of change in these subscale scores with an index measuring the match between physicians ' treatment recommendations and patients ' treatment preferences at the initial study visit . RESULTS A closer match between physicians ' recommendations and patients ' preferences was associated with greater improvement in treatment satisfaction over time in each of the four subscales : effectiveness ( β = 0.53 , P < 0.001 ) , side-effects ( β = 0.25 , P = 0.009 ) , convenience ( β = 0.78 , P < 0.001 ) and global satisfaction ( β = 0.49 , P < 0.001 ) . Adjusted models explained as much as 76 % of the variation in change in treatment satisfaction subscales over 3 months . CONCLUSIONS Further efforts to incorporate patients ' preferences in treatment decision-making appear justified given the strength of independent associations between preference matching and improved treatment satisfaction and the extent to which our models explained variation in this relationship . An approach based on preference matching shows promise for increasing satisfaction in the management of other chronic diseases Background . Decision analysis ( DA ) and the probability-tradeoff technique ( PTOT ) are patient preference-based methods of determining optimal therapy for individuals . Using aspirin therapy for the primary prevention of stroke and myocardial infa rct ion ( MI ) in elderly persons as an example , the objective of this study was to determine whether group-level treatment thresholds and individual-level treatment recommendations derived using PTOT are identical to those of DA incorporating the patients ' own values . Methods . Persons in a pilot study of the efficacy of aspirin in the prevention of stroke and MI were asked to participate . Participant values and utilities for pertinent health states ( e.g. , minor and major stroke , MI , major bleeding episode ) were determined . Then , in three hypothetical clinical situations in which the chance of stroke or MI was varied , PTOT was used to directly determine treatment thresholds for aspirin therapy ( i.e. , the smallest reduction in MI or stroke risk for which participants would be willing to take aspirin ) . Using DA modeling , with the same probabilities of events as in the PTOT exercise and incorporating participants ' own values , treatment thresholds for the three clinical situations were determined . The thresholds determined by the two approaches were compared . Finally , based on these treatment thresholds , using the best estimates of the efficacy of aspirin to prevent first-time stroke and MI , PTOT and DA treatment recommendations for individual participants were compared . Results . The 42 participants reported that a major stroke was the least desirable health state , followed by MI , minor stroke , and major bleeding . The minimum risk reduction required to take aspirin was greater for MI prevention compared with stroke prevention . For the two clinical situations in which the hypothetical efficacy of aspirin to prevent stroke was varied , treatment thresholds for the PTOT versus DA approaches differed ( p < 0.04 ) , but this difference was not significant ( p = 0.19 ) for the MI-based clinical situation . Using the best estimate of the efficacy of aspirin to prevent first-time stroke and MI , PTOT and DA treatment recommendations whether or not to take aspirin were discordant for 38 % of participants ( 16 of 42 ) ( p < 0.001 ) . Conclusions . Patient preference-based group-level treatment thresholds and individual-level treatment recommendations can differ significantly depending on whether PTOT or DA is used , apparently because the two emphasize different aspects of the decision-making process . DA theory assumes that effective therapeutic decision making should maximize both quality and quantity of life ; with PTOT , the emphasis for effective clinical decision making allows patients to be fully engaged in the process , thus hopefully leading to fully informed decisions that may result in satisfaction and compliance . Key words : decision making ; decision analysis ; patient preferences ; treatment thresholds . ( Med Decis Making 2000;20:394 - 403 Background and objectives Several studies have been conducted to determine the frequency and characteristics of adverse drug reactions ( ADRs ) in elderly population s , focusing on those leading to hospital admission . However , most of these studies have been limited in their ability to assess risk factors , particularly the renal status of patients . Thus , the aim of this prospect i ve study was to assess the incidence of ADRs and associated factors leading to hospital admissions in the elderly population . Methods All patients aged ≥65 years admitted to the Toulouse University Hospital through the Emergency Department during four non-consecutive weeks in 2002–3 were included in this study except for patients in ambulatory care or admitted for intentional overdoses . The characteristics of patients admitted for a suspected ADR were compared with those of patients admitted for other reasons . Results The incidence of hospital admissions for ADRs was 8.37 per 100 admissions ( 95 % CI 6.52 , 10.52 ) , corresponding to 66 patients with ADRs among 789 admissions . The most important factors associated with ADRs were the number of drugs being taken ( odds ratio [ OR ] 1.18 ; 95 % CI 1.08 , 1.29 ) , self-medication ( OR 2.34 ; 95 % CI 1.18 , 4.66 ) , use of antithrombotics ( Anatomic Therapeutic and Chemical [ ATC ] classification B01 ; OR 2.26 ; 95 % CI 1.33 , 3.88 ) and use of antibacterial drugs ( ATC J01 ; OR 4.04 ; 95 % CI 1.50 , 10.83 ) . Surprisingly , exposure to drugs for acid-related disorders was associated with a low risk of ADRs ( OR 0.26 ; 95 % CI 0.09 , 0.76 ) . Conclusion A significant incidence of ADRs leading to hospital admissions was found among elderly people . Our study showed that there is a need to increase the availability of information for the general public concerning potential ADRs due to self-medication and for prescribers concerning ADRs due to drug-drug interactions and polypharmacy OBJECTIVE The authors hypothesized that the depression treatment preferences of elderly home care patients would vary by their experience of depression and that preferences for active treatment would be associated with current depression and with antidepressant treatment . METHODS The authors conducted cross-sectional secondary analyses of data from the TRIAD study ( Training in the Assessment of Depression ) of 256 r and omly selected elderly patients newly admitted to home care . The study assessed preference for active treatments ( medication or psychotherapy ) and nonactive or complementary approaches ( such as religious activities or doing nothing ) . Nondepressed patients were asked to choose as if they had serious depression . Two separate indicators of depression experience were used : a current diagnosis of major or minor depression and current or previous antidepressant treatment . RESULTS Of the 256 patients , 16 % ( N=41 ) met criteria for major or minor depression . Forty-seven percent of the sample ( N=121 ) preferred an active treatment as their first choice , and others preferred nonactive or complementary approaches . Logistic regression indicated that current antidepressant use , previous psychotherapy experience , white or Hispanic race-ethnicity ( versus black ) , greater impairment in instrumental activities of daily living , and less personal stigma about depression were independently associated with preference for an active treatment . CONCLUSIONS Elderly home care patients had a variety of treatment preferences , ranging from active treatments , to religious or spiritual activities , to no treatment . Several factors were associated with a preference for active treatment , including treatment experience , physical impairment , race-ethnicity , and attitudes and beliefs . An underst and ing of patient preferences may help engage older depressed home care patients in treatment Abstract Objective : To investigate the impact of patients ' preferences for the treatment of atrial fibrillation , by using individualised decision analysis combining probability and utility assessment s into a decision tree . Design : Observational study based on interviews with patients . Setting : Eight general practice s in Avon . Participants : 260 r and omly selected patients aged 70–85 years with atrial fibrillation . Main outcome measures : Patients ' treatment preferences regarding anticoagulation treatment ( warfarin ) after individualised decision analysis ; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription . Results : Of 195 eligible patients , 97 participated in decision making using decision analysis . Among these 97 , the decision analysis indicated that 59 ( 61 % ; 95 % confidence interval 50 % to 71 % ) would prefer anticoagulation treatment — considerably fewer than those who would be recommended treatment according to guidelines . There was marked disagreement between the decision analysis and guideline recommendations ( kappa = 0.25 or less ) . Of 38 patients whose decision analysis indicated a preference for anticoagulation , 17 ( 45 % ) were being prescribed warfarin ; on the other h and , 28 ( 47 % ) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be . Conclusions : In the context of shared decision making , individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation . Taking account of patients ' preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations . Decision analysis as a shared decision making tool should be evaluated in a r and omised controlled trial The factors contributing to the use of antiresorptive therapies ( ARTs ) and differentiating the ARTs used were examined . A list of names of community-dwelling persons 65 years or older living in Wisconsin was obtained , and 2100 individuals were selected ( 1050 men and 1050 women ) to receive the 10-page survey instrument . The survey requested information on health status , prescription drug use , preferences for using prescription drugs versus self-treatment strategies , demographic characteristics , and status and type of prescription drug and medical insurance . Only the responses from female respondents were evaluated . Descriptive statistics were calculated for each variable . The simultaneous relationships among all variables were modeled sequentially using a binary logistic regression model and a multinomial logistic regression model . Usable responses were received from 629 women , yielding an adjusted response rate of 59.9 % ; 169 ( 26.9 % ) reported current use of at least one ART , 110 ( 17.5 % ) reported using hormone replacement therapy ( HRT ) , and 59 ( 9.4 % ) were using newer ARTs . The typical respondent did not use any prescription medicines for the treatment or prevention of osteoporosis , was married , and did not have a four-year college degree . Married , younger women with high medical care preferences scores were more likely to use antiresorptive agents . Married women were more likely to use HRT versus no treatment . A higher number of family practice physicians per 100,000 population reduced the likelihood of the use of any ART . Lower age was also related to the use of ARTs . Marital status , age , medical care preferences , prescription drug insurance , a regular source of care , and the diagnosis of osteoporosis were all significantly associated with the use of any antiresorptive agent Background The importance of respecting patients ’ preferences when making treatment decisions is increasingly recognized . Efficiently retrieving papers from the scientific literature reporting on the presence and nature of such preferences can help to achieve this goal . The objective of this study was to create a search filter for PubMed to help retrieve evidence on patient preferences for treatment outcomes . Methods A total of 27 journals were h and - search ed for articles on patient preferences for treatment outcomes published in 2011 . Selected articles served as a reference set . To develop optimal search strategies to retrieve this set , all articles in the reference set were r and omly split into a development and a validation set . MeSH-terms and keywords retrieved using PubReMiner were tested individually and as combinations in PubMed and evaluated for retrieval performance ( e.g. sensitivity ( Se ) and specificity ( Sp ) ) . Results Of 8238 articles , 22 were considered to report empirical evidence on patient preferences for specific treatment outcomes . The best search filters reached Se of 100 % [ 95 % CI 100 - 100 ] with Sp of 95 % [ 94–95 % ] and Sp of 97 % [ 97–98 % ] with 75 % Se [ 74–76 % ] . In the validation set these queries reached values of Se of 90 % [ 89–91 % ] with Sp 94 % [ 93–95 % ] and Se of 80 % [ 79–81 % ] with Sp of 97 % [ 96–96 % ] , respectively . Conclusions Narrow and broad search queries were developed which can help in retrieving literature on patient preferences for treatment outcomes . Identifying such evidence may in turn enhance the incorporation of patient preferences in clinical decision making and health technology assessment |
11,384 | 32,256,559 | Our results indicate that various forms of physical exercise may lead to changes in various markers of neuroplasticity . | Parkinson 's disease ( PD ) is a neurodegenerative disorder for which there is currently only symptomatic treatment .
During the last decade , there has been an increased interest in investigating physical exercise as a neuroprotective mechanism in PD .
Animal studies have suggested that exercise may in fact induce neuroplastic changes , but evidence in humans is still scarce .
A h and ful of review s have previously reported on exercise-induced neuroplasticity in humans with PD , but few have been systematic , or have mixed studies on both animals and humans , or focused on one neuroplastic outcome only . | Objective : To compare the effects of 2 forms of exercise , i.e. , a 6-week trial of treadmill training with virtual reality ( TT + VR ) that targets motor and cognitive aspects of safe ambulation and a 6-week trial of treadmill training alone ( TT ) , on brain activation in patients with Parkinson disease ( PD ) . Methods : As part of a r and omized controlled trial , patients were r and omly assigned to 6 weeks of TT ( n = 17 , mean age 71.5 ± 1.5 years , disease duration 11.6 ± 1.6 years ; 70 % men ) or TT + VR ( n = 17 , mean age 71.2 ± 1.7 years , disease duration 7.9 ± 1.4 years ; 65 % men ) . A previously vali date d fMRI imagery paradigm assessed changes in neural activation pretraining and post-training . Participants imagined themselves walking in 2 virtual scenes projected in the fMRI : ( 1 ) a clear path and ( 2 ) a path with virtual obstacles . Whole brain and region of interest analyses were performed . Results : Brain activation patterns were similar between training arms before the interventions . After training , participants in the TT + VR arm had lower activation than the TT arm in Brodmann area 10 and the inferior frontal gyrus ( cluster level familywise error – corrected [ FWEcorr ] p < 0.012 ) , while the TT arm had lower activation than TT + VR in the cerebellum and middle temporal gyrus ( cluster level FWEcorr p < 0.001 ) . Changes in fall frequency and brain activation were correlated in the TT + VR arm . Conclusions : Exercise modifies brain activation patterns in patients with PD in a mode-specific manner . Motor-cognitive training decreased the reliance on frontal regions , which apparently result ed in improved function , perhaps reflecting increased brain efficiency Introduction Physical rehabilitation is commonly used in patients with Parkinson ’s disease ( PD ) to improve their health and alleviate the symptoms . Objective We compared the effects of three programs , strength training ( ST ) , aerobic training ( AT ) , and physiotherapy , on motor symptoms , functional capacity , and electroencephalographic ( EEG ) activity in PD patients . Methods Twenty-two patients were recruited and r and omized into three groups : AT ( 70 % of maximum heart rate ) , ST ( 80 % of one repetition maximum ) , and physiotherapy ( in groups ) . Subjects participated in their respective interventions twice a week for 12 weeks . The assessment s included measures of disease symptoms ( Unified Parkinson ’s Disease Rating Scale [ UPDRS ] ) , functional capacity ( Senior Fitness Test ) , and EEG before and after 12 weeks of intervention . Results The PD motor symptoms ( UPDRS-III ) in the group of patients who performed ST and AT improved by 27.5 % ( effect size [ES]=1.25 , confidence interval [CI]=−0.11 , 2.25 ) and 35 % ( ES=1.34 , CI=−0.16 , 2.58 ) , respectively , in contrast to the physiotherapy group , which showed a 2.9 % improvement ( ES=0.07 , CI=−0.85 , 0.99 ) . Furthermore , the functional capacity of all three groups improved after the intervention . The mean frequency of the EEG analysis mainly showed the effect of the interventions on the groups ( F=11.50 , P=0.0001 ) . Conclusion ST and AT in patients with PD are associated with improved outcomes in disease symptoms and functional capacity Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the principles might also apply . The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct . We followed recommended good practice to develop the extension , including carrying out a Delphi survey , holding a consensus meeting and research team meetings , and piloting the checklist . The aims and objectives of pilot and feasibility r and omised studies differ from those of other r and omised trials . Consequently , although much of the information to be reported in these trials is similar to those in r and omised controlled trials ( RCTs ) assessing effectiveness and efficacy , there are some key differences in the type of information and in the appropriate interpretation of st and ard CONSORT reporting items . We have retained some of the original CONSORT statement items , but most have been adapted , some removed , and new items added . The new items cover how participants were identified and consent obtained ; if applicable , the prespecified criteria used to judge whether or how to proceed with a future definitive RCT ; if relevant , other important unintended consequences ; implication s for progression from pilot to future definitive RCT , including any proposed amendments ; and ethical approval or approval by a research review committee confirmed with a reference number . This article includes the 26 item checklist , a separate checklist for the abstract , a template for a CONSORT flowchart for these studies , and an explanation of the changes made and supporting examples . We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials . Editor ’s note : In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites Forced-rate lower-extremity exercise has recently emerged as a potential safe and low-cost therapy for Parkinson 's disease ( PD ) . The efficacy is believed to be dependent on pedaling rate , with rates above the subjects ' voluntary exercise rates being most beneficial . In this study , we use functional connectivity magnetic resonance imaging ( MRI ) to further eluci date the mechanism underlying this effect . Twenty-seven PD patients were r and omized to complete 8 weeks of forced-rate exercise ( FE ) or voluntary-rate exercise ( VE ) . Exercise was delivered using a specialized stationary bicycle , which can augment patients ' voluntary exercise rates . The FE group received assistance from the cycle . Imaging was conducted at baseline , end of therapy , and after 4 weeks of follow-up . Functional connectivity ( FC ) was determined via seed-based correlation analysis , using activation-based seeds in the primary motor cortex ( M1 ) . The change in FC after exercise was compared using linear correlation with pedaling rate . Results of the correlation analysis showed a strong positive correlation between pedaling rate and change in FC from the most affected M1 to the ipsilateral thalamus . This effect persisted after 4 weeks of follow-up . These results indicate that a plausible mechanism for the therapeutic efficacy of high-rate exercise in PD is that it improves thalamo-cortical connectivity The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the principles might also apply . The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct . We followed recommended good practice to develop the extension , including carrying out a Delphi survey , holding a consensus meeting and research team meetings , and piloting the checklist . The aims and objectives of pilot and feasibility r and omised studies differ from those of other r and omised trials . Consequently , although much of the information to be reported in these trials is similar to those in r and omised controlled trials ( RCTs ) assessing effectiveness and efficacy , there are some key differences in the type of information and in the appropriate interpretation of st and ard CONSORT reporting items . We have retained some of the original CONSORT statement items , but most have been adapted , some removed , and new items added . The new items cover how participants were identified and consent obtained ; if applicable , the prespecified criteria used to judge whether or how to proceed with a future definitive RCT ; if relevant , other important unintended consequences ; implication s for progression from pilot to future definitive RCT , including any proposed amendments ; and ethical approval or approval by a research review committee confirmed with a reference number . This article includes the 26 item checklist , a separate checklist for the abstract , a template for a CONSORT flowchart for these studies , and an explanation of the changes made and supporting examples . We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials . Editor ’s note : In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Background . Exercise may decrease the risk of Parkinson ’s disease ( PD ) in humans and reduce PD symptoms in animal models . The beneficial effects have been linked to increased levels of neurotrophic factors . Objective . We examined whether intensive rehabilitation treatment reduces motor disability in patients in the early stages of PD and increases brain-derived neurotrophic factor ( BDNF ) serum levels . Methods . Thirty participants in the early stages of PD treated with rasagiline were r and omly assigned to 3 hours of rehabilitation treatment that included aerobic exercise for 28 days ( Group 1 ) or to not therapy ( control ; Group 2 ) . BDNF serum levels were assessed at time T0 ( baseline , before treatment ) , T1 ( 10 days ) , T2 ( 20 days ) , and T3 ( 28 days ) . At T0 and T3 , we assessed the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) III in both groups , as well as the UPDRS II and total , Berg Balance Scale , and 6-minute walking test only in Group 1 . Results . BDNF levels significantly increased at T1 in Group 1 , an increase that was maintained throughout the treatment period . At T3 compared to T0 , UPDRS III scores significantly improved in Group 1 along with scores for UPDRS II , total , Berg Balance Scale , and 6-minute walking test . Conclusions . Intensive rehabilitation treatment increases the BDNF levels and improves PD signs in patients in the early stages of the disease . These results are in line with studies on animal models of PD and healthy subjects INTRODUCTION A programme of rehabilitation using auditory cues has previously been shown to decrease movement variability in the gait of Parkinsonian patients . OBJECTIVE AND METHODS We studied the temporal variability of finger-tapping and gait in 9 patients with Parkinson 's disease ( PD ) before and after they undertook a physical rehabilitation programme . Positron Emission Tomography ( PET ) using 2-deoxy-2[(18)F]fluoro-D-glucose ( FDG ) was performed in these subjects to look for changes in metabolic brain activity after completion of the rehabilitation program . RESULTS The reduction of variability was seen not only in gait but also other repetitive movements such as finger tapping . Furthermore , here we show differences in resting regional cerebral glucose utilisation in these patients compared to healthy controls ( significant hypometabolism-p < 0.001-for the PD group in the right parietal and temporal lobes , left temporal and frontal lobes and a hypermetabolism in the left cerebellum ) and specific changes following the improvements in repetitive movement abilities ( significant metabolic increment-p < 0.001-in the PD group in the right cerebellum and in the right parietal and temporal lobes ) . CONCLUSIONS Although our study does not allow us to draw firm conclusions , it provides new information on the neural basis of auditory stimulation in PD . Our results extend those from previous studies to show improvement in the temporal variability of two types of rhythmic movements after participation by PD patients in a physical rehabilitation programme , along with changes in glucose uptake in several brain areas involved in sensorimotor processing We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson ’s disease ( PD ) , including an increase in the dopamine D2 receptor ( DA-D2R ) , using noninvasive PET imaging with the radiolig and [18F]fallypride . The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D2R expression using PET imaging with [18F]fallypride in individuals with early-stage PD . In this pilot study , four patients with early-stage PD were r and omized to receive intensive exercise ( treadmill training sessions three times/week for 8 weeks ) or no exercise . Two healthy age-matched individuals participated in treadmill training . Alterations in the DA-D2R binding potential ( BP ) as a marker for receptor expression were determined using PET imaging with [18F]fallypride . Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson ’s Disease Rating Scale scores pre-exercise and postexercise were determined . Our data showed an exercise-induced increase in [18F]fallypride BP as well as improved postural control in patients with PD who exercised . Changes in DA-D2R BP were not observed in patients with PD who did not exercise . These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific ( postural control ) in early-stage PD OBJECTIVES To obtain preliminary data on the effects of high-intensity exercise on functional performance in people with Parkinson 's disease ( PD ) relative to exercise at low and no intensity and to determine whether improved performance is accompanied by alterations in corticomotor excitability as measured through transcranial magnetic stimulation ( TMS ) . DESIGN Cohort ( prospect i ve ) , r and omized controlled trial . SETTING University-based clinical and research facilities . PARTICIPANTS Thirty people with PD , within 3 years of diagnosis with Hoehn and Yahr stage 1 or 2 . INTERVENTIONS Subjects were r and omized to high-intensity exercise using body weight-supported treadmill training , low-intensity exercise , or a zero-intensity education group . Subjects in the 2 exercise groups completed 24 exercise sessions over 8 weeks . Subjects in the zero-intensity group completed 6 education classes over 8 weeks . MAIN OUTCOME MEASURES Unified Parkinson 's Disease Rating Scales ( UPDRS ) , biomechanic analysis of self-selected and fast walking and sit-to-st and tasks ; corticomotor excitability was assessed with cortical silent period ( CSP ) duration s in response to single-pulse TMS . RESULTS A small improvement in total and motor UPDRS was observed in all groups . High-intensity group subjects showed postexercise increases in gait speed , step and stride length , and hip and ankle joint excursion during self-selected and fast gait and improved weight distribution during sit-to-st and tasks . Improvements in gait and sit-to-st and measures were not consistently observed in low- and zero-intensity groups . The high-intensity group showed lengthening in CSP . CONCLUSIONS The findings suggest the dose-dependent benefits of exercise and that high-intensity exercise can normalize corticomotor excitability in early PD Background Depression is common in people with Parkinson ’s disease ( PD ) , and exercise is known to improve depression and PD . However , lack of motivation and low self-efficacy can make exercise difficult for people with PD and comorbid depression ( PD-Dep ) . A combined group exercise and chronic disease self-management ( CDSM ) program may improve the likeli-hood that individuals will engage in exercise and will show a reduction in depression symptoms . The purpose of this study was to compare changes in depression in PD-Dep between individual versus group exercise plus CDSM and to examine participant adherence and perception of the interventions . Methods Participants ( N=30 ) were r and omized to either Enhanced EXerCisE thErapy for PD ( EXCEED ; group CDSM and exercise ) or self-guided CDSM plus exercise . Outcomes were change in depression assessed with the Montgomery – Asberg Depression Rating Scale ( MADRS ) , cognition , apathy , anxiety , sleep , quality of life , motor function , self-efficacy , and patient satisfaction . Results Both groups showed significant improvement in MADRS ( P<0.001 ) with no significant group difference . Individuals in EXCEED group enjoyed the group dynamics but noted difficulty with the fixed-time sessions . Conclusion Both group CDSM plus exercise and self-guided CDSM plus exercise can improve depression in PD-Dep . These findings suggest that development of a remotely delivered group-based CDSM format plus manualized exercise program could be useful for this population It has been demonstrated that physical training increases serum brain-derived neurotrophic factor ( BDNF ) in healthy people . The aim of this study was to establish the effect of physical training on the basal serum level of the BDNF in the Parkinson 's disease patients ( PD patients ) in relation to their health status . Twelve PD patients ( mean ± S.E.M : age 70 ± 3 years ; body mass 70 ± 2 kg ; height 163 ± 3 cm ) performed a moderate-intensity interval training ( three 1-hour training sessions weekly ) , lasting 8 weeks . Basal serum BDNF in the PD patients before training amounted to 10,977 ± 756 pg x mL(-1 ) and after 8 weeks of training it has increased to 14,206 ± 1256 pg x mL(-1 ) ( i.e. by 34 % , P=0.03 ) . This was accompanied by an attenuation of total Unified Parkinson 's Disease Rating Scale ( UPDRS ) ( P=0.01 ) . The training result ed also in a decrease of basal serum soluble vascular cell adhesion molecule 1 ( sVCAM-1 ) ( P=0.001 ) and serum tumor necrosis factor-α ( TNF-α ) ( P=0.03 ) levels . We have concluded that the improvement of health status of the Parkinson 's disease patients after training could be related to the increase of serum BDNF level caused by the attenuated inflammation in those patients |
11,385 | 27,642,608 | Based on current evidence , we found that BCAA is a useful biomarker for early detection of IR and later diabetic risk .
These factors might not only contribute to the elevated BCAA level but also show obvious associations with insulin resistance .
Genes related to BCAA catabolism might serve as potential targets for the treatment of IR associated metabolic disorders . | Recent studies have shown the positive association between increased circulating BCAAs ( valine , leucine , and isoleucine ) and insulin resistance ( IR ) in obese or diabetic patients .
However , results seem to be controversial in different races , diets , and distinct tissues .
Our aims were to evaluate the relationship between BCAA and IR as well as later diabetes risk and explore the phenotypic and genetic factors influencing BCAA level based on available studies . | Plasma concentrations of amino acids are frequently elevated in insulin-resistant states , and a protein-enriched diet can impair glucose metabolism . This study examined effects of short-term plasma amino acid ( AA ) elevation on whole-body glucose disposal and cellular insulin action in skeletal muscle . Seven healthy men were studied for 5.5 h during euglycemic ( 5.5 mmol/l ) , hyperinsulinemic ( 430 pmol/l ) , fasting glucagon ( 65 ng/l ) , and growth hormone ( 0.4 microg/l ) somatostatin clamp tests in the presence of low ( approximately 1.6 mmol/l ) and increased ( approximately 4.6 mmol/l ) plasma AA concentrations . Glucose turnover was measured with D-[6,6-(2)H(2)]glucose . Intramuscular concentrations of glycogen and glucose-6-phosphate ( G6P ) were monitored using (13)C and (31)P nuclear magnetic resonance spectroscopy , respectively . A approximately 2.1-fold elevation of plasma AAs reduced whole-body glucose disposal by 25 % ( P < 0.01 ) . Rates of muscle glycogen synthesis decreased by 64 % ( 180 - -315 min , 24 plus minus 3 ; control , 67 plus minus 10 micromol center dot l(-1 ) center dot min(-1 ) ; P < 0.01 ) , which was accompanied by a reduction in G6P starting at 130 min ( DeltaG6P(260 - -300 min ) , 18 plus minus 19 ; control , 103 plus minus 33 micromol/l ; P < 0.05 ) . In conclusion , plasma amino acid elevation induces skeletal muscle insulin resistance in humans by inhibition of glucose transport/phosphorylation , result ing in marked reduction of glycogen synthesis |
11,386 | 25,061,854 | Studies on the topical treatment of atopic dermatitis largely supported the recommended use of topical corticosteroids and topical calcineurin inhibitors .
Lipoxin A4 , an eicosanoid with anti-inflammatory properties , and a 5 % cis-urocanic acid emulsion cream were effective in the treatment of atopic dermatitis , although studies were small .
Adjunct therapy with bleach baths , natural oils , and textiles all showed some benefit ; however , studies are limited .
SUMMARY There is strong evidence for the use of topical anti-inflammatory therapies in the treatment of atopic dermatitis .
There is little evidence to suggest that one emollient is better than others | PURPOSE OF REVIEW To review recent literature on the topical treatment of allergic skin diseases to help clinicians make informed evidence -based decisions .
Barrier therapy continues to play an important role without evidence supporting use of one emollient over another . | BACKGROUND Hydration with topical emollients forms the backbone of treatment for mild atopic dermatitis ( AD ) , but few r and omized controlled trials have assessed their efficacy in young children . OBJECTIVES Assess the efficacy and tolerability of long-term emollient therapy in the treatment of moderate to severe xerosis in young children with AD . METHODS This was a phase III , multicentre , double-blind , r and omized , vehicle-controlled trial . Children ( n = 251 ) aged 2 - 6 years with AD-associated xerosis were r and omized 1 : 1 to a 28-day treatment with an emollient combining glycerol and paraffin or its vehicle . Non-responders at the end of the double-blind period were treated open label with emollient until day 84 . Responders stopped treatment until re assessment on day 56 . Those who relapsed after stopping treatment were treated open label with emollient until day 84 . RESULTS During the double-blind period , xerosis score ( XS ) of the scoring atopic dermatitis ( SCORAD ) index , objective SCORAD and visual analogue score decreased and skin hydration increased more in the emollient group than in the vehicle group ( P < 0.001 for all measures ) . More patients were responders with emollient than with vehicle ( 66.1 % vs. 45.6 % , P < 0.001 ) . During the open-label period , stopping emollient treatment led to relapse but improvement returned if treatment was restarted with emollient . Regular use of the emollient also yielded improvement in children who did not initially respond . Adverse events were similar in the two groups , and no treatment-related severe adverse events were reported . CONCLUSIONS Long-term therapy with emollient is effective and well tolerated for the treatment of xerosis in children with atopic dermatitis Background : Atopic dermatitis ( AD ) is characterized by barrier abnormalities , including insufficient ceramides in the stratum corneum ( SC ) . Objective : To measure the effects of a new moisturizer ( CRM ) containing a ceramide precursor in improving skin barrier function in patients with controlled atopic dermatitis . Methods : In this r and omized , intra-individual comparison , investigator-blinded study , CRM was applied to the test area of one lower leg for 27 days ( the other leg remained as untreated control ) . Evaluations at baseline and day 28 included transepidermal water loss ( TEWL ) , skin hydration by corneometry , dryness severity , Raman spectroscopy , and collection of adverse events . Results : After 4 weeks of treatment , results showed a significantly greater reduction of TEWL and clinical dryness scores , and increased skin hydration ( all p < 01 ) in the CRM-treated than untreated area . A significantly higher level of ceramide ( p < 05 ) and a trend toward increased water content was observed with Raman in the SC for CRM than for the control . There were no related AEs . Conclusion : Skin barrier function and hydration were significantly improved after CRM treatment New treatment modalities are needed in atopic dermatitis . We evaluated the pharmacokinetics , safety , tolerability , and efficacy of topical cis-urocanic acid ( cis-UCA ) cream in r and omised vehicle-controlled double-blinded clinical trials . The subjects received 5 % cis-UCA emulsion cream and control vehicle on volar forearms after right-left r and omisation . Study 1 : 16 healthy subjects received one dose on the skin and , a week later , on DMSO-irritated skin . Study 2 : 16 healthy subjects received 2 daily doses for 10 days . Study 3 : 13 patients with mild to moderate disease were treated on selected skin lesions twice daily for 28 days . Study treatments were well tolerated . cis-UCA remained close to endogenous levels in plasma and urine . cis-UCA reduced transepidermal water loss ( TEWL ) both in healthy subjects and in the patients . Eczema area severity index and physician 's global assessment improved from baseline with both treatments . cis-UCA cream improved skin barrier function and suppressed inflammation in the human skin Patients with atopic dermatitis ( AD ) have an epidermal barrier dysfunction , which allows invasion of allergens to occur . Stratum corneum skin barrier is formed by corneocytes and extracellular lipids extruded from the epidermal lamellar bodies . In a controlled , r and omized , double-blinded , right-left comparison study we investigated the effect of pimecrolimus ( PIM ) cream compared with triamcinolone acetonide cream ( TA ) on the skin barrier in 15 patients with symmetrical elbow lesions of AD . In punch biopsies , before and after treatment , skin lipid bilayer and lamellar body structure were examined by transmission electron microscopy ( TEM ) . Partial Eczema Area and Severity Index ( pEASi ) , stratum corneum hydration , and transepidermal water loss ( TEWL ) were monitored on days 1 , 8 and 22 . The pEASi was significantly more improved with TA compared with PIM , whereas stratum corneum hydration was slightly more improved after treatment with PIM . The TEM revealed a strong reduction in lamellar bodies in lesional skin of AD ; only 32 % of the lamellar bodies were normal . A significantly higher number of normal lamellar bodies was found after 3 weeks of treatment with PIM ( 58 % ; p < 0.005 ) . An increase in lamellar bodies also occurred with TA treatment ( 46 % ; p < 0.05 ) ; however , significantly less than with PIM ( p < 0.05 ) . Clinical score and TEWL were more improved after treatment with TA , whereas the lamellar bodies were more normal after treatment with PIM Background : Pruritus ani ( PA ) is defined as intense chronic itching affecting perianal skin . Objective : We aim ed to determine the efficacy of topical tacrolimus treatment in atopic dermatitis ( AD ) patients who have PA . Methods : The study included 32 patients with AD who were suffering PA . Patients were r and omized into two groups . In total , 16 patients used 0.03 % tacrolimus ointment and 16 patients used vaseline as placebo . All groups applied topical treatments to their perianal area twice daily for 4 weeks . The treatments were then reversed for 4 weeks after a 2 weeks wash out period . Results : In total , 32 patients with AD who had refractory anal itching were enrolled in this study . None of the patients had obtained successful results with previous treatments . There was a statistically significant decrease in the recorded EASI , DLQI and itching scores for the tacrolimus group compared to the placebo group at weeks 4 and 6 of treatment ( p < 0.05 ) . Conclusion : Topical tacrolimus treatment was well tolerated and effective in controlling persistent PA in AD patients Background : No study has clearly demonstrated the steroid-sparing effect of emollients in the treatment of atopic dermatitis ( AD ) . Aim : Evaluating the effect of an emollient containing oat extracts on the amount of topical corticosteroids used in infants with moderate to severe AD . Study Design : During 6 weeks , 173 infants under 12 months old treated for inflammatory lesions by moderate- and /or high-potency topical corticosteroids r and omly received the emollient or not ( control group ) . Methods : Evaluation of corticosteroid consumption by weighing the tubes , disease severity by the Scoring Atopic Dermatitis Index ( SCORAD ) , and infants ’ and parents ’ quality of life by Infant ’s Dermatitis Quality of Life Index and Dermatitis Family Impact scores at D0 , D21 and D42 . Results : Compared to the control group , the amount of moderate- and high-potency corticosteroids used in 6 weeks decreased by 7.5 % ( not significant ) and 42 % ( p < 0.05 ) , respectively , in the emollient group . The SCORAD index , and infants ’ and parents ’ quality of life significantly improved ( p < 0.0001 ) in both groups . Conclusion : The emollient treatment significantly reduced the high-potency topical corticosteroid consumption in infants with AD Parental education is important in managing childhood atopic dermatitis ( AD ) . We evaluated the long-term effects of a 2-day parental education program ( PEP ) on childhood AD . In an investigator-blinded , r and omized controlled trial , 59 children age 6 months to 6 years with moderate to severe AD and their mothers were recruited in Japan . Participants were given a booklet about AD and received conventional treatment alone or in combination with a 2-day PEP comprising three lectures , three practical sessions , and a group discussion . The primary outcome was evaluation of eczema severity using SCORing Atopic Dermatitis ( SCORAD ) at 6 months . Secondary outcomes included changes in symptom scores , amount of corticosteroid used , parental quality of life as determined according to the Dermatitis Family Impact question naire , and change in parental anxiety regarding the use of corticosteroids in their children . Participants in the PEP group had a significantly lower SCORAD score than those in the control group at 6 months ( mean difference 10.0 , 95 % confidence interval [ CI ] = 2.3 - 17.7 , p = 0.01 ) and objective SCORAD score ( mean difference 7.1 , 95 % CI = 0.8 - 13.5 , p = 0.03 ) . The sleeplessness symptom score ( mean difference 1.6 , 95 % CI = 0.0 - 3.1 , p = 0.048 ) and corticosteroid anxiety score ( p = 0.02 ) in the PEP group were significantly better than in the control group at 6 months . There was no significant difference between groups in the amount of corticosteroid used or quality of life . The PEP had positive long-term effects on eczema severity and parental anxiety about corticosteroid usage Abstract Background : Atopic dermatitis ( AD ) is a disease with multifactorial etiology . Staphylococcus aureus is one of the predominant environmental factors acting on the course and intensity of the disease . Objectives : The aims of the study were to evaluate the efficacy and safety of clothing made of cellulose fibers with seaweed enriched with silver ions in the treatment of children with AD . Methods : A prospect i ve , r and omized and double-blinded controlled selection was done to recruit 19 children with diagnosis of AD . This sample was divided in two groups with similar demographic and clinical characteristics ( the “ control ” group of seven children who wore placebo clothing and the “ trial textile ” group of 12 children who wore clothing with the new textile ) . The severity of AD and clinical response were assessed by the SCORAD index , the intensity of pruritus and the changes in sleep characteristics , at the start of the study and after 7 and 90 d. Results : The SCORAD index improvement in the group with the fiber under study was statistically significant after the first 7 d of treatment ( p < 0.001 ) and was reduced by about 45 % after 90 d. There was also a statistically relevant reduction of the intensity of pruritus and an improvement in the sleep quality after the initial 7 d and at day 90 . Conclusion : The results showed that the textile clothing with seaweed enriched with silver ions brings a quicker improvement of the patients in the first days in opposition to the use of st and ard all-cotton clothes . The results also reinforce the importance of non-pharmacological measures , like clothing , in the management of patients with a diagnosis of AD Introduction : The natural cyclic tetrahydropyrimidine , ectoine , is a low-molecular , water-binding , organic osmolyte . Previously , topical application of ectoine to healthy human skin was shown to improve skin hydration as well as skin barrier function . Objectives : We therefore speculated that topical application of ectoine would be beneficial for patients with atopic dermatitis ( AD ) , in which a genetically defined defect in skin barrier function is of major pathogenetic relevance . We assessed the efficacy of an ectoine-containing cream ( EHK02 - 01 ) in the management of 65 patients with mild to moderate AD in a r and omized , intra-individual , double-blind , multi-center trial , in which the efficacy of ectoine was compared to a nonsteroidal anti-inflammatory cream previously found to primarily act on skin barrier function and therefore with a comparable mode of action . Methods : Sixty-five patients with mild to moderate AD aged 18 - 65 years were enrolled . The patients applied EHK02 - 01 and the control cream on two symmetrical lesions twice daily for 28 days . At the beginning , after 7 and after 28 days , treated skin areas were assessed by modified , objective local SCORAD ( Scoring Atopic Dermatitis ) and IGA ( Investigator 's Global Assessment ) as well as the patients ' judgment of efficacy and their assessment of pruritus . Results : EHK02 - 01 was found to be very well tolerated . Even more important , efficacy of EHK02 - 01 treatment was equivalent to that achieved with the reference product . Conclusion : These results indicate that topical treatment with EHK02 - 01 may represent a novel option for the treatment of patients with AD Natural oils are advocated and used throughout the world as part of neonatal skin care , but there is an absence of evidence to support this practice . The goal of the current study was to ascertain the effect of olive oil and sunflower seed oil on the biophysical properties of the skin . Nineteen adult volunteers with and without a history of atopic dermatitis were recruited into two r and omized forearm-controlled mechanistic studies . The first cohort applied six drops of olive oil to one forearm twice daily for 5 weeks . The second cohort applied six drops of olive oil to one forearm and six drops of sunflower seed oil to the other twice daily for 4 weeks . The effect of the treatments was evaluated by determining stratum corneum integrity and cohesion , intercorneocyte cohesion , moisturization , skin-surface pH , and erythema . Topical application of olive oil for 4 weeks caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of atopic dermatitis . Sunflower seed oil preserved stratum corneum integrity , did not cause erythema , and improved hydration in the same volunteers . In contrast to sunflower seed oil , topical treatment with olive oil significantly damages the skin barrier , and therefore has the potential to promote the development of , and exacerbate existing , atopic dermatitis . The use of olive oil for the treatment of dry skin and infant massage should therefore be discouraged . These findings challenge the unfounded belief that all natural oils are beneficial for the skin and highlight the need for further research Staphylococcus aureus is frequently found in patients with atopic dermatitis ( AD ) and contributes to disease exacerbation . The objective of this study was to evaluate the efficacy and safety of bleach baths as an adjunctive treatment in AD patients . Patients between 2 and 30 years old with moderate to severe AD were enrolled in a prospect i ve , r and omized , placebo-controlled study . Patients soaked in diluted bleach or distilled water baths for 10 min , twice a week for 2 months . Efficacy assessment s included the Eczema Area and Severity Index ( EASI ) scores and S. aureus density was determined using quantitative bacterial cultures . Patients in the treatment group showed significant reductions in EASI scores . A 41.9 % reduction in S. aureus density from baseline was seen at 1 month further reducing to 53.3 % at 2 months . Equal numbers of patients in both groups experienced mild side-effects . This study demonstrates that diluted bleach baths clinical ly improved AD in as little as 1 month . No patient withdrew from the treatment arm because of intolerance to the baths Atopic dermatitis ( AD ) is a chronic skin disease characterized by defects in the epidermal barrier function and cutaneous inflammation , in which transepidermal water loss ( TEWL ) is increased and the ability of the stratum corneum to hold water is impaired , causing decreased skin capacitance and hydration . This study investigated the effects of topical virgin coconut oil ( VCO ) and mineral oil , respectively , on SCORAD ( SCORing of Atopic Dermatitis ) index values , TEWL , and skin capacitance in pediatric patients with mild to moderate AD , using a r and omized controlled trial design in which participants and investigators were blinded to the treatments allocated . Patients were evaluated at baseline , and at 2 , 4 , and 8 weeks . A total of 117 patients were included in the analysis . Mean SCORAD indices decreased from baseline by 68.23 % in the VCO group and by 38.13 % in the mineral oil group ( P < 0.001 ) . In the VCO group , 47 % ( 28/59 ) of patients achieved moderate improvement and 46 % ( 27/59 ) showed an excellent response . In the mineral oil group , 34 % ( 20/58 ) of patients showed moderate improvement and 19 % ( 11/58 ) achieved excellent improvement . The VCO group achieved a post-treatment mean TEWL of 7.09 from a baseline mean of 26.68 , whereas the mineral oil group demonstrated baseline and post-treatment TEWL values of 24.12 and 13.55 , respectively . In the VCO group , post-treatment skin capacitance rose to 42.3 from a baseline mean of 32.0 , whereas that in the mineral oil group increased to 37.49 from a baseline mean of 31.31 . Thus , among pediatric patients with mild to moderate AD , topical application of VCO for eight weeks was superior to that of mineral oil based on clinical ( SCORAD ) and instrumental ( TEWL , skin capacitance ) assessment |
11,387 | 9,773,168 | However , most suggest that post-exercise massage may alleviate symptoms of DOMS .
CONCLUSIONS Massage therapy may be a promising treatment for DOMS . | BACKGROUND Delayed onset muscle soreness ( DOMS ) is a frequent problem after unaccustomed exercise .
No universally accepted treatment exists .
Massage therapy is often recommended for this condition but uncertainty exists about its effectiveness .
AIM To determine whether post-exercise massage alleviates the symptoms of DOMS after a bout of strenuous exercise . | This study monitored plasma and skeletal muscle markers of free-radical-mediated damage following maximum eccentric and concentric exercise , to examine the potential role of free radicals in exercise-induced muscle damage . Fourteen male volunteers performed either ( 1 ) a bout of 70 maximum eccentric and a bout of 70 maximum concentric muscle actions of the forearm flexors ( the bouts being separated by 4 weeks ; n = 8) or ( 2 ) a bout of 80 maximum eccentric and a bout of 80 maximum concentric muscle actions of the knee extensors ( the bouts being separated by 1 week ; n=6 ) . Plasma markers of lipid peroxidation , thiobarbituric acid-reactive substances ( TBARS ) and diene-conjugated compounds ( DCC ) were monitored in the arm protocol and skeletal muscle markers of oxidative lipid and protein damage , malondialdehyde ( MDA ) and protein carbonyl derivatives ( PCD ) respectively , were monitored in the leg protocol . In both protocol s , the contralateral limb was used for the second bout and the order of the bouts was r and omised between limbs . Repeated measures ANOVA indicated significant changes from baseline following eccentric arm work on the measures of serum creatine kinase activity ( P < 0.05 ) , maximum voluntary torque production ( P < 0.01 ) and relaxed arm angle ( P < 0.01 ) . Subjective muscle soreness peaked 2 days after eccentric arm work ( P < 0.05 , Wilcoxon test ) . However , there were no changes in the plasma levels of TBARS or DCC following the eccentric or concentric arm exercise . Immediately after concentric leg exercise , skeletal muscle PCD concentrations was significantly higher than that observed immediately after eccentric work ( P < 0.05 ) . However , no significant difference between the eccentric and concentric knee extensor bouts was observed on the measure of skeletal muscle MDA concentration . The results of this study offer no support for the involvement of oxygen free radicals in exercise-induced muscle damage OBJECTIVES : The ability to maximally generate active muscle tension during resistance training has been established to be a primary determinant for strength development . The influence of intrasession rest intervals may have a profound effect on strength gains subsequent to short-term high intensity training . The purpose of this study was to examine the effects of rest interval on strength and functional performance after four weeks of isokinetic training . METHODS : Fifteen healthy college aged individuals were r and omly assigned to either a short rest interval group ( group 1 , n = 8) or a long rest interval group ( group 2 , n = 7 ) . Subjects were evaluated for quadriceps and hamstring isokinetic strength at 60 ( five repetitions ) and 180 ( 30 repetitions ) degrees/second and functional performance with the single leg hop for distance test . One leg of each subject was r and omly assigned to a four week , three days/week isokinetic strength training programme for concentric knee extension and flexion performed at 90 degrees/second . Subjects in group 1 received a 40 second rest interval in between exercise sets , whereas subjects in group 2 received a 160 second rest period . RESULTS : A two factor analysis of variance for the pre-test -- post-test gain scores ( % ) showed significantly greater improvements for isokinetic hamstring total work and average power at 180 degrees/second for the trained limb of subjects in group 2 than their contralateral non-trained limb and the subjects in group 1 . Significantly greater improvements for the single leg hop for distance were also found for the trained limbs of subjects in both groups as compared with the non-trained limbs . CONCLUSIONS : The findings indicate that a relatively longer intrasession rest period result ed in a greater improvement in hamstring muscle strength during short term high intensity training The effects of warm underwater water-jet massage on neuromuscular functioning , selected biochemical parameters ( serum creatine kinase , lactic dehydrogenase , serum carbonic anhydrase , myoglobin , urine urea and creatinine ) and muscle soreness were studied among 14 junior track and field athletes . Each subject spent , in a r and omized order , two identical training weeks engaged in five strength/power training sessions lasting 3 days . The training weeks differed from each other only in respect of underwater water jet massage treatments . These were used three times ( 20 min each ) during the treatment week and not used during the control week . During the treatment week continuous jumping power decreased and ground contact time increased significantly less ( P < 0.05 ) and serum myoglobin increased more than during the control week . It is suggested that underwater water-jet massage in connection with intense strength/power training increases the release of proteins from muscle tissue into the blood and enhances the maintenance of neuro-muscular performance capacity The effect of a combination of a warm-up , stretching exercises and massage on subjective scores for delayed onset muscle soreness ( DOMS ) and objective functional and biochemical measures was studied . Fifty people , r and omly divided in a treatment and a control group , performed eccentric exercise with the forearm flexors for 30 min . The treatment group additionally performed a warm-up and underwent a stretching protocol before the eccentric exercise and massage afterwards . Functional and biochemical measures were obtained before , and 1 , 24 , 48 , 72 and 96h after exercise . The median values at the five post-exercise time points differed significantly for DOMS measured when the arm was extended ( p = 0.043 ) . Significant main effects for treatment were found on the maximal force ( p = 0.026 ) , the flexion angle of the elbow ( p = 0.014 ) and the creatine kinase activity in blood ( p = 0.006 ) . No time-by-treatment interactions were found . DOMS on pressure , extension angle and myoglobin concentration in blood did not differ between the groups . This combination of a warm-up , stretching and massage reduces some negative effects of eccentric exercise , but the results are inconsistent , since some parameters were significantly affected by the treatment whereas others were not , despite the expected efficacy of a combination of treatments . The objective measures did not yield more unequivocal results than the subjective DOMS scores It was hypothesized that athletic massage administered 2 hours after eccentric exercise would disrupt an initial crucial event in acute inflammation , the accumulation of neutrophils . This would result in a diminished inflammatory response and a concomitant reduction in delayed onset muscle soreness ( DOMS ) and serum creatine kinase ( CK ) . Untrained males were r and omly assigned to a massage ( N = 7 ) or control ( N = 7 ) group . All performed five sets of isokinetic eccentric exercise of the elbow flexors and extensors . Two hours after exercise , massage subjects received a 30-minute athletic massage ; control subjects rested . Delayed onset muscle soreness and CK were assessed before exercise and at 8 , 24 , 48 , 72 , 96 , and 120 hours after exercise . Circulating neutrophils were assessed before and immediately after exercise , and at 30-minute intervals for 8 hours ; cortisol was assessed before and immediately after exercise , and at 30-minute intervals for 8 hours ; cortisol was assessed at similar times . A trend analysis revealed a significant ( p < 0.05 ) treatment by time interaction effect for 1 ) DOMS , with the massage group reporting reduced levels ; 2 ) CK , with the massage group displaying reduced levels ; 3 ) neutrophils , with the massage group displaying a prolonged elevation ; and 4 ) cortisol , with the massage group showing a diminished diurnal reduction . The results of this study suggest that sports massage will reduce DOMS and CK when administered 2 hours after the termination of eccentric exercise . This may be due to a reduced emigration of neutrophils and /or higher levels of serum cortisol Manual massage is commonly assumed to enhance long term muscle recovery from intense exercise , partly due to its ability to speed healing via enhanced muscle blood flow . We tested these assumptions by daily ( for four days ) massaging the quadriceps muscles of one leg on subjects who had previously completed an intense bout of eccentric quadriceps work with both legs . Immediate post-exercise isometric and dynamic quadriceps peak torque measures had declined to approximately 60 - 70 % of pre-exercise values in both legs . Peak torques for both the massage and control leg tended to slowly return toward pre-exercise values through the subsequent four days ( 96 hrs ) . There was no significant difference between the isometric and dynamic peak torques between massage and control legs up to 96 hours post-exercise . Leg blood flow was estimated by determining femoral artery and vein mean blood velocities via pulsed Doppler ultrasound velocimetry . Massage of the quadriceps muscles did not significantly elevate arterial or venous mean blood velocity above resting levels , while light quadriceps muscle contractions did . The perceived level of delayed onset muscle soreness tended to be reduced in the massaged leg 48 - 96 hours post-exercise . It was concluded that massage was not an effective treatment modality for enhancing long term restoration of post-exercise muscle strength and its use for this purpose in athletic setting s should be question ed The purpose of this study was to compare the analgesic effect of pulsating ultrasound treatment and placebo on delayed onset of muscle soreness produced by an eccentric exercise bout . In addition , the effect of pulsed ultrasound on muscular performance following an eccentric exercise bout was studied . Eighteen untrained subjects were r and omly assigned to : 1 ) ultrasound ( A ) [ N = 6 ] over the areas of concentrated muscle soreness , i.e. proximal vastus lateralis and distal vastus medialis ; 2 ) placebo ultrasound ( B ) [ N = 6 ] ; and 3 ) no therapeutic intervention ( C ) [ N = 6 ] . Baseline data were recorded for maximum isometric knee extension contraction ( MVC ) , maximum knee extension torque ( MT ) , knee extension work ( W ) , and soreness perception ( SP ) . All values were subsequently reassessed 24 and 48 hours after intense muscular activity . Immediately following the 24 hour re assessment the A group received ultrasound treatment , the B group received placebo ultrasound , while the C group received no treatment . Percent deviation from baseline of SP , MVC , MT and W were significantly less for A than B and C ( p less than 0.05 ) at 48 hours post muscle soreness bout . These data indicate that pulsed ultrasound accelerates restoration of normal muscle performance , and thus is effective in decreasing delayed onset of muscle soreness . The mechanism for decreasing soreness perception in the muscle is unknown , but may be related to decreasing intramuscular pressure and /or decreasing the inflammatory response |
11,388 | 21,233,290 | Elevated BMI is associated with risk of prostate cancer-specific mortality in prospect i ve cohort studies and biochemical recurrence in prostate cancer patients . | Increasing evidence suggested obesity , measured by body mass index ( BMI ) , was associated with prostate cancer-specific mortality , and its impact on biochemical recurrence was also inconclusive . | Epidemiologic studies have failed to support the hypothesis that circulating and rogens are positively associated with prostate cancer risk and some recent studies have even suggested that high testosterone levels might be protective particularly against aggressive cancer . We tested this hypothesis by measuring total testosterone , and rostanediol glucuronide , and rostenedione , DHEA sulfate , estradiol , and sex hormone – binding globulin in plasma collected at baseline in a prospect i ve cohort study of 17,049 men . We used a case-cohort design , including 524 cases diagnosed during a mean 8.7 years follow-up and a r and omly sample d subcohort of 1,859 men . The association between each hormone level and prostate cancer risk was tested using Cox models adjusted for country of birth . The risk of prostate cancer was ∼30 % lower for a doubling of the concentration of estradiol but the evidence was weak ( Ptrend = 0.07 ) . None of the other hormones was associated with overall prostate cancer ( Ptrend ≥ 0.3 ) . None of the hormones was associated with nonaggressive prostate cancer ( all Ptrend ≥ 0.2 ) . The hazard ratio [ HR ; 95 % confidence interval ( 95 % CI ) ] for aggressive cancer almost halved for a doubling of the concentration of testosterone ( HR , 0.55 ; 95 % CI , 0.32 - 0.95 ) and and rostenedione ( HR , 0.51 ; 95 % CI , 0.31 - 0.83 ) , and was 37 % lower for a doubling of the concentration of DHEA sulfate ( HR , 0.63 ; 95 % CI , 0.46 - 0.87 ) . Similar negative but nonsignificant linear trends in risk for aggressive cancer were obtained for free testosterone , estradiol , and sex hormone – binding globulin ( Ptrend = 0.06 , 0.2 , and 0.1 , respectively ) . High levels of testosterone and adrenal and rogens are thus associated with reduced risk of aggressive prostate cancer but not with nonaggressive disease . ( Cancer Epidemiol Biomarkers Prev 2006;15(1):86–91 PURPOSE Several lines of evidence suggest that diet and weight gain may be important environmental factors implicated in prostate carcinogenesis , especially in tumor progression . The purpose of this study was to evaluate obesity at different ages in a well-characterized cohort of prostate cancer patients treated with prostatectomy and to develop a prognostic model that incorporates body mass index ( BMI ) as a measure of obesity . EXPERIMENTAL DESIGN We carried out a prospect i ve study of 526 patients registered at the M.D. And erson Cancer Center from 1992 to 2001 . Kaplan-Meier and Cox proportional hazard analyses were done . RESULTS During an average follow-up of 54 months , 97 ( 18 % ) post-prostatectomy patients experienced biochemical failure . Patients who were obese ( BMI > or = 30 kg/m2 ) at diagnosis had a higher rate of biochemical failure than nonobese men ( P = 0.07 ) . Those obese at 40 years had an even greater rate of biochemical failure ( P = 0.001 ) . Higher BMI at diagnosis [ hazard ratio ( HR ) , 1.07 ; P = 0.01 ] and Gleason score = 7(4 + 3 ) and > or = 8 ( HR , 3.9 ; P = 0.03 and HR , 10.0 ; P < or = 0.001 , respectively ) remained significant independent predictors of biochemical failure in multivariate analysis . Men who gained weight at the greatest rate ( > 1.5 kg/y ) between 25 years and diagnosis progressed significantly sooner ( mean time , 17 months ) than those who exhibited a slower weight gain ( mean time , 39 months ; P(trend ) = 0.005 ) . The inclusion of obesity to the clinical nomogram improved performance . CONCLUSIONS Our findings vali date the importance for a role of obesity in prostate cancer progression and suggest a link to the biological basis of prostate cancer progression that can be therapeutically exploited Background : Prior prospect i ve cohort studies found that obesity was associated with increased risk of prostate cancer death . However , in the last 20 years dramatic changes in both the extent of obesity and prostate cancer screening and treatment have occurred . Whether the association between obesity and aggressive disease has changed as a result of these temporal changes is unclear . Methods : The study population consisted of 2,832 men treated by anatomic radical retropubic prostatectomy between 1985 and 2004 by a single surgeon . We evaluated the associations of obesity ( body mass index ≥30 kg/m2)with tumor stage and grade using logistic regression and with biochemical progression using Cox proportional hazards regression . We examined whether these associations have changed over the last 20 years . Results : On multivariable analysis , the strength of the positive association between obesity and high- grade disease increased over time whereas the strength of the positive association between obesity and positive surgical margins decreased over time . The strength of the positive association between obesity and extraprostatic extension fluctuated over time , although the strongest and only statistically significant association was among men treated since 2000 . The association between obesity and biochemical progression was strongest among men treated since 1995 ( relative risk , 1.90 ; 95 % confidence interval , 1.09 - 3.30 ; P = 0.02 ) . Conclusions : In the current study , with the exception of positive surgical margins , the positive association between obesity and high- grade disease , advanced stage , and biochemical progression after radical retropubic prostatectomy was in general strongest among men treated in the last 10 years . The reasons for these findings are not clear , although factors possibly related to prostate-specific antigen – based screening and /or other temporal changes in prostate cancer diagnosis and treatment may play a role PURPOSE Obesity has been proposed as an independent risk factor for patients undergoing surgery or radiotherapy ( RT ) for prostate cancer . Using body mass index ( BMI ) as a measure of obesity , we tested its role as a risk factor for patients receiving salvage RT after prostatectomy . METHODS AND MATERIAL S Rates of subsequent biochemical relapse were examined in 90 patients who underwent salvage RT between 1984 and 2004 for biochemical failure after radical prostatectomy . Median follow-up was 3.7 years . The BMI was tested as a continuous and categorical variable ( stratified as < 25 , 25-<30 , and > or=30 kg/m(2 ) ) . Univariate and multivariate proportional hazards regression analyses were performed for clinical , pathologic , and treatment factors associated with time to relapse after salvage RT . RESULTS There were 40 biochemical failures after salvage RT with a median time to failure of 1.2 years . The BMI was not associated with adverse clinical , pathologic , or treatment factors . On multivariate analysis , obesity was independently significant ( hazard ratio [ HR ] , 1.2 ; p = 0.01 ) , along with RT dose ( HR , 0.7 ; p = 0.003 ) and pre-RT prostate-specific antigen level ( HR , 1.2 ; p = 0.0003 ) . CONCLUSIONS This study is weakly suggestive that obesity may be a risk factor for salvage RT patients . Whether this results from greater biologic aggressiveness or technical inadequacies can not be answered by this study . Given the very high failure rate observed for severely obese patients , we propose that technical difficulties with RT are at play . This hypothesis is supported by the RT literature and could be prospect ively investigated . Techniques that optimize targeting , especially in obese patients , perhaps seem warranted at this time PURPOSE We examined the impact of obesity on disease specific and overall survival in patients with prostate cancer . MATERIAL S AND METHODS We identified 7,274 men from the Cancer of the Prostate Strategic Urological Research Endeavor data base with clinical ly localized prostate cancer , known body mass index and clinicopathological disease characteristics . Patients were classified by body mass index as normal ( less than 25 kg/m(2 ) ) , overweight ( 25 to 29.9 kg/m(2 ) ) , obese ( 30 to 34.9 kg/m(2 ) ) and severely obese ( 35 kg/m(2 ) or greater ) . Associations between body mass index and need for secondary treatment , disease specific survival and overall survival were analyzed using univariate and multivariate models . RESULTS Patients were classified by body mass index category as normal ( 28.8 % ) , overweight ( 50 % ) , obese ( 16.4 % ) and very obese ( 4.8 % ) . Mean followup was 51.3 + /- 38.5 months . During followup there were 1,044 deaths with 220 ( 21.1 % ) from prostate cancer . Stratified by body mass index category the groups differed with regard to the need for secondary treatment ( p = 0.05 ) and overall mortality ( p < 0.01 ) but there were no significant differences with regard to disease specific survival ( p = 0.09 ) . On multivariate analysis age 65 to 74 years ( HR 2.4 , p = 0.002 ) , age older than 75 years ( HR 3.2 , p = 0.0001 ) , high risk disease ( HR 1.6 , p < 0.0001 ) , conservative treatment ( HR 1.2 , p < 0.0001 ) and presence of diabetes ( HR 1.6 , p < 0.0001 ) were associated with decreased overall survival . Only conservative treatment ( HR 1.4 , p < 0.0001 ) , high risk disease ( HR 8.4 , p < 0.0001 ) and intermediate risk disease ( HR 2.5 , p = 0.004 ) were associated with decreased disease specific survival . CONCLUSIONS In a prospect i ve , community based cohort we were unable to establish a relationship between body mass index and prostate cancer disease specific survival or overall survival BACKGROUND The influence of excess body weight on the risk of death from cancer has not been fully characterized . METHODS In a prospect ively studied population of more than 900,000 U.S. adults ( 404,576 men and 495,477 women ) who were free of cancer at enrollment in 1982 , there were 57,145 deaths from cancer during 16 years of follow-up . We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites , while controlling for other risk factors in multivariate proportional-hazards models . We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population . RESULTS The heaviest members of this cohort ( those with a body-mass index [ the weight in kilograms divided by the square of the height in meters ] of at least 40 ) had death rates from all cancers combined that were 52 percent higher ( for men ) and 62 percent higher ( for women ) than the rates in men and women of normal weight . For men , the relative risk of death was 1.52 ( 95 percent confidence interval , 1.13 to 2.05 ) ; for women , the relative risk was 1.62 ( 95 percent confidence interval , 1.40 to 1.87 ) . In both men and women , body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus , colon and rectum , liver , gallbladder , pancreas , and kidney ; the same was true for death due to non-Hodgkin 's lymphoma and multiple myeloma . Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast , uterus , cervix , and ovary in women . On the basis of associations observed in this study , we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women . CONCLUSIONS Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites Increasing body mass index ( BMI ) is associated with shorter time to prostate‐specific antigen ( PSA ) failure after radical prostatectomy . Whether BMI is associated with time to PSA failure was investigated in men treated with and rogen suppression therapy ( AST ) and radiation therapy ( RT ) for clinical ly localized prostate cancer Greater body mass index ( BMI ) is associated with shorter time to prostate‐specific antigen ( PSA ) failure following radical prostatectomy and radiation therapy ( RT ) . Whether BMI is associated with prostate cancer‐specific mortality ( PCSM ) was investigated in a large r and omized trial of men treated with RT and and rogen deprivation therapy ( ADT ) for locally advanced prostate cancer BACKGROUND In the European R and omized Study of Screening for Prostate Cancer ( ERSPC , Rotterdam region ) , men aged 55 - 74 years are screened for prostate cancer by prostate-specific antigen ( PSA ) sampling , digital rectal examination ( DRE ) , and transrectal ultrasound investigation ( TRUS ) . All men with a PSA > or = 4 ng/ml and /or a suspicious DRE and /or a suspicious TRUS are biopsied . METHODS Logistic regression analysis was applied to derive a predictive index that equals the chance to find prostate cancer in a biopsy given the outcomes of the screening tests . This model was used to assess the number of cancers that could have been detected if all men had been biopsied ( extrapolation ) . Furthermore , the model was used to study the possibilities for improvement of the current screening protocol . RESULTS PSA was the dominant predictor for prostate cancer in a biopsy , followed by prostate volume , DRE , and TRUS result . It is assessed that 69 % ( 95 % CI , 52 - 86 % ) of cancers that could be identified if all men were biopsied are currently detected . Application of the same methods to screening data obtained in Göteborg ( the Swedish ERSPC partner ) yielded almost identical results . It was found that , in the Rotterdam protocol , a considerable number of men were biopsied according to the screening protocol with an assessed lower chance to have prostate cancer than men who were not biopsied according to the protocol . CONCLUSIONS The chance to detect prostate cancer in a biopsy can be modeled quite accurately as a function of serum PSA , prostate volume , DRE , and TRUS results . Important improvements in the screening protocol can be achieved by the application of the predictive index BACKGROUND Excess body-mass index ( BMI ) has been associated with adverse outcomes in prostate cancer , and hyperinsulinaemia is a c and i date mediator , but prospect i ve data are sparse . We assessed the effect of prediagnostic BMI and plasma C-peptide concentration ( reflecting insulin secretion ) on prostate cancer-specific mortality after diagnosis . METHODS This study involved men diagnosed with prostate cancer during the 24 years of follow-up in the Physicians ' Health Study . BMI measurements were available at baseline in 1982 and eight years later in 1990 for 2546 men who developed prostate cancer . Baseline C-peptide concentration was available in 827 men . We used Cox proportional hazards regression models controlling for age , smoking , time between BMI measurement and prostate cancer diagnosis , and competing causes of death to assess the risk of prostate cancer-specific mortality according to BMI and C-peptide concentration . FINDINGS Of the 2546 men diagnosed with prostate cancer during the follow-up period , 989 ( 38.8 % ) were overweight ( BMI 25.0 - 29.9 kg/m(2 ) ) and 87 ( 3.4 % ) were obese ( BMI > /=30 kg/m(2 ) ) . 281 men ( 11 % ) died from prostate cancer during this follow-up period . Compared with men of a healthy weight ( BMI < 25 kg/m(2 ) ) at baseline , overweight men and obese men had a significantly higher risk of prostate cancer mortality ( proportional hazard ratio [ HR ] 1.47 [ 95 % CI 1.16 - 1.88 ] for overweight men and 2.66 [ 1.62 - 4.39 ] for obese men ; p(trend)<0.0001 ) . The trend remained significant after controlling for clinical stage and Gleason grade and was stronger for prostate cancer diagnosed during the PSA screening era ( 1991 - 2007 ) compared with during the pre-PSA screening era ( 1982 - 1990 ) or when using BMI measurements obtained in 1990 compared with those obtained in 1982 . Of the 827 men with data available for baseline C-peptide concentration , 117 ( 14 % ) died from prostate cancer . Men with C-peptide concentrations in the highest quartile ( high ) versus the lowest quartile ( low ) had a higher risk of prostate cancer mortality ( HR 2.38 [ 95 % CI 1.31 - 4.30 ] ; p(trend)=0.008 ) . Compared with men with a BMI less than 25 kg/m(2 ) and low C-peptide concentrations , those with a BMI of 25 kg/m(2 ) or more and high C-peptide concentrations had a four-times higher risk of mortality ( 4.12 [ 1.97 - 8.61 ] ; p(interaction)=0.001 ) independent of clinical predictors . INTERPRETATION Excess bodyweight and a high plasma concentration of C-peptide both predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of their disease . Patients with both factors have the worst outcome . Further studies are now needed to confirm these findings OBJECTIVE To investigate the nature of the relation between body weight and all-cause mortality . DESIGN Prospect i ve cohort study , following up men from 1962 or 1966 ( 1962/1966 ) through 1988 . SETTING / PARTICIPANTS Harvard University alumni with a mean age of 46.6 years in 1962/1966 and without self-reported , physician-diagnosed coronary heart disease , stroke , or cancer , who completed question naires on weight , height , cigarette smoking habit , and physical activity ( n = 19,297 ) . We calculated body mass index ( weight in kilograms divided by the square of height in meters ) using self-reported measures . MAIN OUTCOME MEASURE All-cause mortality ( 4370 deaths ) . RESULTS In multivariate analysis adjusting for age , cigarette smoking habit , and physical activity , we found a J-shaped relation between body mass index and mortality . Relative risks of dying for men with a body mass index of less than 22.5 , 22.5 to less than 23.5 , 23.5 to less than 24.5 , 24.5 to less than 26.0 , and 26.0 or greater were 1.00 ( referent ) , 0.99 ( 95 % confidence interval , 0.89 to 1.20 ) , 0.95 ( 0.87 to 1.05 ) , 1.01 ( 0.91 to 1.10 ) , and 1.18 ( 1.08 to 1.28 ) , respectively ( P for linear trend = .0008 ) . Among current smokers , the relation between body mass index and mortality was U-shaped , with lowest risk of death at a body mass index of 23.5 to less than 24.5 . During early follow-up ( 1962/1966 through 1974 ) , we also observed a U-shaped curve , this time with lowest mortality risk at a body mass index of 24.5 to less than 26.0 . To minimize confounding by cigarette smoking and bias from antecedent disease and early mortality , we conducted analysis only among never smokers and omitted the first 5 years of follow-up ( 510 deaths ) . The corresponding relative risks from this analysis , adjusted for age and physical activity , were 1.00 , 1.23 ( 95 % confidence interval , 0.90 to 1.67 ) , 1.06 ( 0.80 to 1.42 ) , 1.27 ( 0.96 to 1.68 ) , and 1.67 ( 1.29 to 2.17 ) , respectively ( P for linear trend = .0001 ) . CONCLUSIONS In these prospect i ve data , body weight and mortality were directly related . After accounting for confounding by cigarette smoking and bias result ing from illness-related weight loss or inappropriate control for the biologic effects of obesity , we found no evidence of excess mortality among lean men . Indeed , lowest mortality was observed among men weighing , on average , 20 % below the US average for men of comparable age and height CONTEXT Recent studies have suggested that obese men have lower serum prostate-specific antigen ( PSA ) concentrations than nonobese men . Because men with higher body mass index ( BMI ) have greater circulating plasma volumes , lower PSA concentrations among obese men may be due to hemodilution . OBJECTIVE To determine the association between hemodilution and PSA concentration in obese men with prostate cancer . DESIGN , SETTING , AND PARTICIPANTS Retrospective study of men who underwent radical prostatectomy for prostate adenocarcinoma from 1988 to 2006 , using data from the data bases of the Shared Equal Access Regional Cancer Hospital ( n = 1373 ) , Duke Prostate Center ( n = 1974 ) , and Johns Hopkins Hospital ( n = 10 287 ) . Multivariate linear regression models adjusting for clinicopathological characteristics were used to analyze the main outcome measures . MAIN OUTCOME MEASURES Associations between BMI and mean adjusted PSA concentrations , mean plasma volume , and mean adjusted PSA mass ( total circulating PSA protein , calculated as PSA concentration multiplied by plasma volume ) , assessed by determining P values for trend . RESULTS After controlling for clinicopathological characteristics , higher BMI was significantly associated with higher plasma volume ( P < .001 for trend ) and lower PSA concentrations ( P < or = .02 for trend ) in all cohorts . In 2 of the 3 cohorts , PSA mass did not change significantly with increasing BMI . In the third cohort , higher BMI was associated with increased PSA mass ( P < .001 for trend ) , but only between BMI category less than 25 and the other categories . CONCLUSIONS In men undergoing radical prostatectomy , higher BMI was associated with higher plasma volume ; hemodilution may therefore be responsible for the lower serum PSA concentrations among obese men with prostate cancer . Prospect i ve studies are needed to evaluate this association in screened population BACKGROUND Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes . METHODS In the Physicians ' Health Study , we prospect ively examined the association of prediagnostic plasma concentrations of adiponectin and leptin with risk of developing incident prostate cancer ( 654 cases diagnosed 1982 - 2000 and 644 age-matched controls ) and , among cases , risk of dying from prostate cancer by 2007 . RESULTS Adiponectin concentrations were not associated with risk of overall prostate cancer . However , men with higher adiponectin concentrations had lower risk of developing high- grade or lethal cancer ( metastatic or fatal disease ) . The relative risk ( 95 % CI ) comparing the highest quintile to the lowest ( Q5 vs Q1 ) was 0.25 ( 95 % CI 0.07 - 0.87 ; P(trend ) = 0.02 ) for lethal cancer . Among all the cases , higher adiponectin concentrations predicted lower prostate cancer-specific mortality [ hazard ratio (HR)(Q5 vs Q1)= 0.39 ; 95 % CI 0.17 - 0.85 ; P(trend ) = 0.02 ] , independent of body mass index ( BMI ) , plasma C-peptide ( a marker of insulin secretion ) , leptin , clinical stage , and tumor grade . This inverse association was apparent mainly among men with a BMI > or=25 kg/m(2 ) ( HR(Q5 vs Q1)= 0.10 ; 95 % CI 0.01 - 0.78 ; P(trend ) = 0.02 ) , but not among men of normal weight ( P(trend ) = 0.51 ) . Although the correlation of leptin concentrations with BMI ( r = 0.58 , P < 0.001 ) was stronger than that of adiponectin ( r = -0.17 , P < 0.001 ) , leptin was unrelated to prostate cancer risk or mortality . CONCLUSIONS Higher prediagnostic adiponectin ( but not leptin ) concentrations predispose men to a lower risk of developing high- grade prostate cancer and a lower risk of subsequently dying from the cancer , suggesting a mechanistic link between obesity and poor prostate cancer outcome PURPOSE Diabetes is associated with lower risk of prostate cancer . Most men with diabetes are obese , and obesity is associated with greater prostate cancer mortality . Whether diabetes influences outcomes after prostate cancer diagnosis is unknown . PATIENTS AND METHODS We assessed the relationship between prevalent diabetes and mortality using data from Radiation Therapy Oncology Group Protocol 92 - 02 , a large r and omized trial of men ( N = 1,554 ) treated with radiation therapy and short-term versus long-term adjuvant goserelin for locally advanced prostate cancer . Regression and proportional hazard models were performed to evaluate relationships between prevalent diabetes and all-cause mortality , prostate cancer mortality , and non-prostate cancer mortality . Covariates included age , race , tumor stage , Gleason score , prostate-specific antigen , weight , and treatment arm . RESULTS There were a total of 765 deaths ; 210 ( 27 % ) were attributed to prostate cancer . In univariate analyses , prevalent diabetes was associated with greater all-cause mortality and non-prostate cancer mortality but not prostate cancer mortality . After controlling for other covariates , prevalent diabetes remained significantly associated with greater all-cause mortality and non-prostate cancer mortality ( hazard ratio [ HR ] = 2.12 ; 95 % CI , 1.69 to 2.66 ; P < .0001 ) but not prostate cancer mortality ( HR = 0.80 ; 95 % CI , 0.51 to 1.25 ; P = .34 ) . In contrast , weight was associated with greater prostate cancer mortality ( HR = 1.77 ; 95 % CI , 1.22 to 2.55 ; P = .002 ) but not all-cause or non-prostate cancer mortality . CONCLUSION Weight but not prevalent diabetes is associated with greater prostate cancer mortality in men receiving combined modality treatment for locally advanced disease . These observations suggest that the association between obesity and greater prostate cancer mortality is mediated by mechanism(s ) other than the characteristic metabolic alterations of diabetes |
11,389 | 27,820,532 | Until further studies prove otherwise , nonsurgical patients requiring glycemic management are best served with less intensive regimens than their surgical counterparts .
Based on the results of this review and data from the four included studies , glycemic management for medical patients in the intensive care unit should differ from that of surgical patients . | BACKGROUND Intensive Insulin Therapy ( IIT ) as a means to achieve tight glycemic control ( TGC ) has become controversial in the medical intensive care unit ( ICU ) or mixed medical-surgical ICU .
The question still remains as to the benefit of tight glycemic control in all patient population s and the optimal target blood glucose range . | People with diabetes are more likely to be hospitalized and to have longer duration s of hospital stay than those without diabetes . A recent survey estimated that 22 % of all hospital inpatient days were incurred by people with diabetes and that hospital inpatient care accounted for half of the 174 billion USD total U.S. medical expenditures for this disease ( 1 ) . These findings are due , in part , to the continued expansion of the worldwide epidemic of type 2 diabetes . In the U.S. alone , there are ∼1.6 million new cases of diabetes each year , with an over all prevalence of 23.6 million people ( 7.8 % of the population , with one-fourth of the cases remaining undiagnosed ) . An additional 57 million American adults are at high risk for type 2 diabetes ( 2 ) . Although the costs of illness-related stress hyperglycemia are not known , they are likely to be considerable in light of the poor prognosis of such patients ( 3–6 ) . There is substantial observational evidence linking hyperglycemia in hospitalized patients ( with or without diabetes ) to poor outcomes . Cohort studies as well as a few early r and omized controlled trials ( RCTs ) have suggested that intensive treatment of hyperglycemia improved hospital outcomes ( 5–8 ) . In 2004 , this evidence led the American College of Endocrinology ( ACE ) and the American Association of Clinical Endocrinologists ( AACE ) , in collaboration with the American Diabetes Association ( ADA ) and other medical organizations , to develop recommendations for treatment of inpatient hyperglycemia ( 9 ) . In 2005 , the ADA added recommendations for treatment of hyperglycemia in the hospitalto itsannual St and ards of Medical Care ( 10 ) . Recommendations from the ACE and the ADA generally endorsed tight glycemic control in critical care units . For patients in general medical and surgical units , where RCT evidence regarding treatment targets was lacking , glycemic goals similar to those advised for out patients were advocated ( 9 , Objectives : To examine the predisposing factors for hypoglycemia in medical-surgical intensive care unit patients treated with intensive insulin therapy and to assess its association with mortality . Design : Nested-cohort study within a r and omized controlled trial . Setting : Tertiary care intensive care unit . Participants : Medical-surgical intensive care unit patients with admission blood glucose of > 6.1 mmol/L or 110 mg/dL who were enrolled in a r and omized controlled trial comparing intensive insulin therapy with conventional insulin therapy . Interventions : None . Exposure : Hypoglycemia was defined as blood glucose ≤2.2 mmol/L or 40 mg/dL and intensive care unit mortality was the primary outcome . Measurements and Main Results : Among the 523 patients included in the study , hypoglycemia occurred in 84 ( 16 % ) . Intensive insulin therapy was independently associated with increased risk of hypoglycemia ( adjusted odds ratio , 50.65 ; 95 % confidence interval , 17.36–147.78 ; p < .0001 ) . Other variables associated with an increased risk of hypoglycemia included female gender , diabetes , Acute Physiology and Chronic Health Evaluation II , mechanical ventilation , continuous veno-venous hemodialysis , and intensive care unit length of stay . When adjusted to potential confounders , hypoglycemia was not significantly associated with increased mortality ( adjusted hazard ratio , 1.31 ; 95 % confidence interval , .70–2.46 ; p = .40 ) . Patients with admission blood glucose of ≤10 mmol/L had an increased mortality with hypoglycemia ( adjusted hazard ratio , 4.43 ; 95 % confidence interval , 1.36–14.44 ; p = .01 ) . Crude analysis showed significant association of mortality with blood glucose levels of ≤1.2 mmol/L ( adjusted hazard ratio , 2.92 ; 95 % confidence interval , 1.05–8.11 ; p = .04 ) . When adjusted analysis was performed , similar trend was seen but was not statistically significant ( adjusted hazard ratio , 2.56 ; 95 % confidence interval , .85–7.70 ; p = .10 ) . Conclusions : Our study showed significant increase of hypoglycemia with intensive insulin therapy . Although hypoglycemia was not independently associated with increased risk of death , increased mortality could not be excluded with severe hypoglycemia and in patients admitted with blood glucose of ≤10 Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients ; however , it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome . The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes . We review ed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center , a community teaching hospital in downtown Atlanta , GA , from July 1 , 1998 , to October 20 , 1998 . New hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl ( 7 mmol/liter ) or more or a r and om blood glucose level of 200 mg/dl ( 11.1 mmol/liter ) or more on 2 or more determinations . Hyperglycemia was present in 38 % of patients admitted to the hospital , of whom 26 % had a known history of diabetes , and 12 % had no history of diabetes before the admission . Newly discovered hyperglycemia was associated with higher in-hospital mortality rate ( 16 % ) compared with those patients with a prior history of diabetes ( 3 % ) and subjects with normoglycemia ( 1.7 % ; both P < 0.01 ) . In addition , new hyperglycemic patients had a longer length of hospital stay , a higher admission rate to an intensive care unit , and were less likely to be discharged to home , frequently requiring transfer to a transitional care unit or nursing home facility . Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes . Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia Introduction Intensive insulin therapy ( IIT ) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world . However , there is only one r and omized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients . We aim ed to determine the association between IIT and mortality in a mixed population of critically ill patients . Methods We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center : period I ( no protocol ) ; period II , target glucose 80 to 130 mg/dL ; and period III , target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units ( ICUs ) between 1 March 2001 and 28 February 2005 . The main study endpoints were ICU and hospital mortality , Sequential Organ Failure Assessment score , and occurrence of hypoglycemia . Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I. Results Insulin administration increased over time ( 9 % period I , 25 % period II , and 42 % period III ) . Nonetheless , patients in period III had a tendency toward higher adjusted hospital mortality ( odds ratio [ OR ] 1.15 , 95 % confidence interval [ CI ] 0.98 , 1.35 ) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less ( OR 1.47 , 95 % CI 1.11 , 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III . Conclusion A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality . These results , combined with the findings from several recent r and omized trials , suggest that further study is needed prior to widespread implementation of IIT in critically ill patients BACKGROUND The role of intensive insulin therapy in patients with severe sepsis is uncertain . Fluid resuscitation improves survival among patients with septic shock , but evidence is lacking to support the choice of either crystalloids or colloids . METHODS In a multicenter , two-by-two factorial trial , we r and omly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10 % pentastarch , a low-molecular-weight hydroxyethyl starch ( HES 200/0.5 ) , or modified Ringer 's lactate for fluid resuscitation . The rate of death at 28 days and the mean score for organ failure were co primary end points . RESULTS The trial was stopped early for safety reasons . Among 537 patients who could be evaluated , the mean morning blood glucose level was lower in the intensive-therapy group ( 112 mg per deciliter [ 6.2 mmol per liter ] ) than in the conventional-therapy group ( 151 mg per deciliter [ 8.4 mmol per liter ] , P<0.001 ) . However , at 28 days , there was no significant difference between the two groups in the rate of death or the mean score for organ failure . The rate of severe hypoglycemia ( glucose level , < or = 40 mg per deciliter [ 2.2 mmol per liter ] ) was higher in the intensive-therapy group than in the conventional-therapy group ( 17.0 % vs. 4.1 % , P<0.001 ) , as was the rate of serious adverse events ( 10.9 % vs. 5.2 % , P=0.01 ) . HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer 's lactate . CONCLUSIONS The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia . As used in this study , HES was harmful , and its toxicity increased with accumulating doses . ( Clinical Trials.gov number , NCT00135473 . OBJECTIVE To determine the safety and efficacy of an intensive insulin regimen compared with a conventional insulin regimen in general intensive care unit patients . METHODS A phase II , r and omised controlled trial was conducted in 70 critically ill patients in a closed multidisciplinary ICU of a university-affiliated tertiary hospital . We assessed patient characteristics at baseline . Trial process measures included number of blood glucose measurements per day and number in target range , type and quantity of caloric intake , patient outcome and insulin dosing . The primary outcome was the median blood glucose concentration . Secondary outcome measures were incidence of hypoglycaemia ( blood glucose level < 2.2 mmol/L ) , clinical sequelae of hypoglycaemia and hospital mortality . RESULTS Thirty-five patients were r and omised to each of the two groups . More blood glucose sample s were taken per day in the intensive insulin group ( 16 versus 9 ) , but the number of sample s in the normoglycaemic range was 48.5 % , compared with 79.8 % within the target glucose range in the conventional insulin group . The median ( interquartile range ) blood glucose concentrations in the intensive and conventional insulin therapy groups were 5.4 ( 5.1 - 5.7 ) mmol/L and 7.9 ( 7.2 - 9.0 ) mmol/L , respectively ( difference , 2.5 mmol/L ; P < 0.0001 ) . Five patients ( 14.3 % ) in the intensive insulin therapy group became hypoglycaemic versus none in the conventional insulin therapy group . There were no detected clinical sequelae of hypoglycaemia . CONCLUSION The intensive insulin regimen was effective in achieving the target blood glucose concentration , with clear separation from the conventional insulin regimen . Although the incidence of hypoglycaemia was increased , there was no detectable harm Objective Elevated blood glucose is associated with poor outcome in patients resuscitated from out-of-hospital cardiac arrest ( OHCA ) . Our aim was to determine whether strict glucose control with intensive insulin treatment improves outcome of OHCA patients . Design A r and omized , controlled trial . Setting Two university hospital intensive care units . Patients Ninety patients resuscitated from OHCA with ventricular fibrillation detected as the initial rhythm were treated with therapeutic hypothermia . Interventions Patients were r and omized into two treatment groups : a strict glucose control group ( SGC group ) , with a blood glucose target of 4–6 mmol/l , or a moderate glucose control group ( MGC group ) , with a blood glucose target of 6–8 mmol/l . Both groups were treated with insulin infusion for 48 h , because a control group with no treatment was considered unethical . Measurements and results Baseline data were similar in both groups . In the SGC group 71 % of the glucose measurements were within the target range compared with 41 % in the MGC group . Median glucose was 5.0 mmol/l in the SGC group and 6.4 mmol/l in the MGC group . The occurrence of moderate hypoglycemic episodes was 18 % in the SGC group and 2 % in the MGC group ( p = 0.008 ) . No episodes of severe hypoglycemia occurred . Mortality by day 30 was 33 % in the SGC group and 35 % in the MGC group ( p = 0.846 ) ; the difference was 2 % ( 95 % CI –18 % to + 22 % ) . Conclusions We found no additional survival benefit from strict glucose control compared with moderate glucose control with a target between 6 and 8 mmol/l in OHCA patients Introduction Critically ill patients can develop hyperglycaemia even if they do not have diabetes . Intensive insulin therapy decreases morbidity and mortality rates in patients in a surgical intensive care unit ( ICU ) and decreases morbidity in patients in a medical ICU . The effect of this therapy on patients in a mixed medical/surgical ICU is unknown . Our goal was to assess whether the effect of intensive insulin therapy , compared with st and ard therapy , decreases morbidity and mortality in patients hospitalised in a mixed ICU . Methods This is a prospect i ve , r and omised , non-blinded , single-centre clinical trial in a medical/surgical ICU . Patients were r and omly assigned to receive either intensive insulin therapy to maintain glucose levels between 80 and 110 mg/dl ( 4.4 to 6.1 mmol/l ) or st and ard insulin therapy to maintain glucose levels between 180 and 200 mg/dl ( 10 and 11.1 mmol/l ) . The primary end point was mortality at 28 days . Results Over a period of 30 months , 504 patients were enrolled . The 28-day mortality rate was 32.4 % ( 81 of 250 ) in the st and ard insulin therapy group and 36.6 % ( 93 of 254 ) in the intensive insulin therapy group ( Relative Risk [ RR ] : 1.1 ; 95 % confidence interval [ CI ] : 0.85 to 1.42 ) . The ICU mortality in the st and ard insulin therapy group was 31.2 % ( 78 of 250 ) and 33.1 % ( 84 of 254 ) in the intensive insulin therapy group ( RR : 1.06 ; 95%CI : 0.82 to 1.36 ) . There was no statistically significant reduction in the rate of ICU-acquired infections : 33.2 % in the st and ard insulin therapy group compared with 27.17 % in the intensive insulin therapy group ( RR : 0.82 ; 95%CI : 0.63 to 1.07 ) . The rate of hypoglycaemia ( ≤ 40 mg/dl ) was 1.7 % in the st and ard insulin therapy group and 8.5 % in the intensive insulin therapy group ( RR : 5.04 ; 95 % CI : 1.20 to 21.12 ) . Conclusions IIT used to maintain glucose levels within normal limits did not reduce morbidity or mortality of patients admitted to a mixed medical/surgical ICU . Furthermore , this therapy increased the risk of hypoglycaemia . Trial Registration clinical trials.gov Identifiers : 4374 - 04 - 13031 ; 094 - 2 in OBJECTIVE To describe the main findings of the Portl and Diabetic Project , which eluci date s the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineates the protective effects of intravenous insulin therapy in reducing those adverse outcomes . RESULTS In this ongoing 17-year prospect i ve , nonr and omized , interventional study of 4,864 patients with diabetes who underwent an open-heart surgical procedure , we investigated the effects of hyperglycemia , and its subsequent reduction by continuous intravenous insulin ( CII ) therapy , on in-hospital outcomes . Increasing blood glucose levels were found to be directly associated with increasing rates of death , deep sternal wound infections ( DSWI ) , length of hospital stay ( LOS ) , and hospital cost . In separate multivariate analyses , increasing hyperglycemia was found to be independently predictive of increasing mortality ( P<0.0001 ) , DSWI ( P = 0.017 ) , and LOS ( P<0.002 ) . Conversely , CII therapy , design ed to achieve predetermined target blood glucose levels , independently reduced the risks of death and DSWI by 57 % and 66 % , respectively ( P<0.0001 for both ) . Target blood glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the effect of the CII therapy on improved outcomes . Coronary artery bypass grafting-related mortality ( 2.5 % ) and DSWI rates ( 0.8 % ) in patients with diabetes were normalized to those of the nondiabetic population by the use of the Portl and CII Protocol . CONCLUSION Perioperative hyperglycemia in patients undergoing a cardiac surgical procedure affects biochemical and physiologic functions , which , in turn , adversely alter mortality , LOS , and infection rates . The Portl and CII Protocol is a cost-efficient method that effectively eliminates hyperglycemia and reduces postoperative morbidity and mortality in patients with diabetes undergoing an open-heart operation . CII protocol s should be the st and ard care for glycometabolic control in all patients undergoing cardiac surgical procedures Objective : The role of intensive insulin therapy in medical surgical intensive care patients remains unclear . The objective of this study was to examine the effect of intensive insulin therapy on mortality in medical surgical intensive care unit patients . Design : R and omized controlled trial . Setting s : Tertiary care intensive care unit . Patients : Medical surgical intensive care unit patients with admission blood glucose of > 6.1 mmol/L or 110 mg/dL. Intervention : A total of 523 patients were r and omly assigned to receive intensive insulin therapy ( target blood glucose 4.4–6.1 mmol/L or 80–110 mg/dL ) or conventional insulin therapy ( target blood glucose 10–11.1 mmol/L or 180–200 mg/dL ) . Measurements and Main Outcomes : The primary end point was intensive care unit mortality . Secondary end points included hospital mortality , intensive care unit and hospital length of stay , mechanical ventilation duration , the need for renal replacement therapy and packed red blood cells transfusion , and the rates of intensive care unit acquired infections as well as the rate of hypoglycemia ( defined as blood glucose ≤2.2 mmol/L or 40 mg/dL ) . There was no significant difference in intensive care unit mortality between the intensive insulin therapy and conventional insulin therapy groups ( 13.5 % vs. 17.1 % , p = 0.30 ) . After adjustment for baseline characteristics , intensive insulin therapy was not associated with mortality difference ( adjusted hazard ratio 1.09 , 95 % confidence interval 0.70–1.72 ) . Hypoglycemia occurred more frequently with intensive insulin therapy ( 28.6 % vs. 3.1 % of patients ; p < 0.0001 or 6.8/100 treatment days vs. 0.4/100 treatment days ; p < 0.0001 ) . There was no difference between the intensive insulin therapy and conventional insulin therapy in any of the other secondary end points . Conclusions : Intensive insulin therapy was not associated with improved survival among medical surgical intensive care unit patients and was associated with increased occurrence of hypoglycemia . Based on these results , we do not advocate universal application of intensive insulin therapy in intensive care unit patients . Trial Registration : Current Controlled Trials registry ( IS RCT N07413772 ) http://www.controlled-trials.com/IS RCT N07413772/07413772 ; 2005 BACKGROUND Our objectives were to determine whether persistent hyperglycemia when compared with normoglycemia was predictive of outcome in the later stages of hospitalization in critically injured trauma patients . METHODS A prospect i ve study was conducted on 896 consecutive trauma patients admitted to the intensive care unit during a 2-year period . Patients were stratified by serum glucose level on day 1 to day 28 ( low = 0 - 139 mg/dL , medium to high = 140 - 219 mg/dL , and high = > 220 mg/dL ) , age , gender , race , insulin dependent diabetes , obesity , and Injury Severity Score ( ISS ) . Patients were further stratified by pattern of glucose control ( all low , all moderate , all high , improving , worsening , highly variable . Outcome was measured by ventilator days , infection , hospital and intensive care unit length of stay , and mortality . Multiple variable logistic and linear regression models were used to determine level of significance . RESULTS Eighty-three percent were victims of blunt trauma . The majority ( 74 % ) were male , with a mean ISS of 26 + /- 12 . Hyperglycemia ( moderate , worsening , and highly variable ) in the first week was associated with significantly greater hospital and intensive care unit length of stay , ventilator time , infection , and mortality when controlling for age , race , gender , ISS , mechanism of injury , obesity , and insulin dependent diabetes ( p < 0.03 ) . However , hyperglycemia in later weeks was not associated with infection and only weakly associated with mortality when analyzed by the same model . When controlling for glucose levels in subsequent weeks , patients who were normoglycemic in the first week had a lower infection rate and were less likely to die even when controlling for age , ISS , and obesity ( p < 0.05 ) . CONCLUSIONS Early euglycemia is associated with improved outcome and appears to be protective regardless of glucose levels in subsequent weeks . Further studies are warranted to determine the etiology of this protective effect BACKGROUND Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units ( ICUs ) , but its role in patients in medical ICUs is unknown . METHODS In a prospect i ve , r and omized , controlled study of adult patients admitted to our medical ICU , we studied patients who were considered to need intensive care for at least three days . On admission , patients were r and omly assigned to strict normalization of blood glucose levels ( 80 to 110 mg per deciliter [ 4.4 to 6.1 mmol per liter ] ) with the use of insulin infusion or to conventional therapy ( insulin administered when the blood glucose level exceeded 215 mg per deciliter [ 12 mmol per liter ] , with the infusion tapered when the level fell below 180 mg per deciliter [ 10 mmol per liter ] ) . There was a history of diabetes in 16.9 percent of the patients . RESULTS In the intention-to-treat analysis of 1200 patients , intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality ( 40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group , P=0.33 ) . However , morbidity was significantly reduced by the prevention of newly acquired kidney injury , accelerated weaning from mechanical ventilation , and accelerated discharge from the ICU and the hospital . Although length of stay in the ICU could not be predicted on admission , among 433 patients who stayed in the ICU for less than three days , mortality was greater among those receiving intensive insulin therapy . In contrast , among 767 patients who stayed in the ICU for three or more days , in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent ( P=0.009 ) and morbidity was also reduced . CONCLUSIONS Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU . Although the risk of subsequent death and disease was reduced in patients treated for three or more days , these patients could not be identified before therapy . Further studies are needed to confirm these preliminary data . ( Clinical Trials.gov number , NCT00115479 . Objective : To investigate whether tight glycemic control , in patients with sepsis , may restore a normal fibrinolysis by lowering plasminogen activator inhibitor (PAI)-1 levels . Design : Prospect i ve r and omized clinical trial . Setting : Three Italian university hospital intensive care units . Patients : Ninety patients with severe sepsis/septic shock . Interventions : Patients were r and omized to receive either tight glycemic control ( treatment group , target glycemia , 80–110 mg/dL ) or conventional glycemic control ( control group , target glycemia , 180–200 mg/dL ) . Measurements : Inflammation , coagulation , and fibrinolysis markers were assessed , along with Sepsis-related Organ Failure Assessment scores , > 28 days . Main Results : In the whole population , at enrolment , inflammation and coagulation were activated in > 80 of 90 patients , whereas fibrinolysis , as assessed by PAI-1 activity and concentration , was impaired in only 34 patients . The extent of the inflammatory reaction or of the coagulation activation was unrelated to outcome . In contrast , 90-day mortality rate of the 34 patients in whom fibrinolysis was definitely inhibited at study entry was twice that of the 56 patients in whom fibrinolysis was intact ( 44 % vs. 21 % , p = 0.02 ) . After r and omization , during the study , daily glycemia averaged 112 ± 23 mg/dL in the treatment group and 159 ± 31 mg/dL in controls ( p < 0.001 ) , with total daily administered insulin 57 ± 59 IU and 36 ± 44 IU , respectively ( p < 0.001 ) . A small , but significant , enhancement of fibrinolysis could be observed in the treatment group , as indicated by the time course of PAI-1 activity ( p < 0.001 ) , PAI-1 concentration ( p = 0.004 ) , and plasmin – antiplasmin complexes ( p < 0.001 ) . Morbidity , rated with the Sepsis-related Organ Failure Assessment score , became significantly lower ( p = 0.03 ) in the treatment group . Conclusions : Fibrinolysis inhibition , in severe sepsis/septic shock , seems to have a relevant pathogenetic role . In this context , tight glycemic control seems to reduce , with time , the fibrinolytic impairment and morbidity BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear . METHODS Within 24 hours after admission to an intensive care unit ( ICU ) , adults who were expected to require treatment in the ICU on 3 or more consecutive days were r and omly assigned to undergo either intensive glucose control , with a target blood glucose range of 81 to 108 mg per deciliter ( 4.5 to 6.0 mmol per liter ) , or conventional glucose control , with a target of 180 mg or less per deciliter ( 10.0 mmol or less per liter ) . We defined the primary end point as death from any cause within 90 days after r and omization . RESULTS Of the 6104 patients who underwent r and omization , 3054 were assigned to undergo intensive control and 3050 to undergo conventional control ; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients , respectively . The two groups had similar characteristics at baseline . A total of 829 patients ( 27.5 % ) in the intensive-control group and 751 ( 24.9 % ) in the conventional-control group died ( odds ratio for intensive control , 1.14 ; 95 % confidence interval , 1.02 to 1.28 ; P=0.02 ) . The treatment effect did not differ significantly between operative ( surgical ) patients and nonoperative ( medical ) patients ( odds ratio for death in the intensive-control group , 1.31 and 1.07 , respectively ; P=0.10 ) . Severe hypoglycemia ( blood glucose level , < or = 40 mg per deciliter [ 2.2 mmol per liter ] ) was reported in 206 of 3016 patients ( 6.8 % ) in the intensive-control group and 15 of 3014 ( 0.5 % ) in the conventional-control group ( P<0.001 ) . There was no significant difference between the two treatment groups in the median number of days in the ICU ( P=0.84 ) or hospital ( P=0.86 ) or the median number of days of mechanical ventilation ( P=0.56 ) or renal-replacement therapy ( P=0.39 ) . CONCLUSIONS In this large , international , r and omized trial , we found that intensive glucose control increased mortality among adults in the ICU : a blood glucose target of 180 mg or less per deciliter result ed in lower mortality than did a target of 81 to 108 mg per deciliter . ( Clinical Trials.gov number , NCT00220987 . OBJECTIVE To assess the effect of an intensive glucose management protocol in a heterogeneous population of critically ill adult patients . PATIENTS AND METHODS This study consisted of 800 consecutive patients admitted after institution of the protocol ( treatment group , between February 1 , 2003 , and January 10 , 2004 ) and 800 patients admitted immediately preceding institution of the protocol ( baseline group , between February 23 , 2002 , and January 31 , 2003 ) . The setting was a 14-bed medical-surgical intensive care unit ( ICU ) in a university-affiliated community teaching hospital . The protocol involved intensive monitoring and treatment to maintain plasma glucose values lower than 140 mg/dL. Continuous intravenous insulin was used if glucose values exceeded 200 mg/dL on 2 successive occasions . RESULTS The 2 groups of patients were well matched , with similar age , sex , race , prevalence of diabetes mellitus , Acute Physiology and Chronic Health Evaluation II scores , and distribution of diagnoses . After institution of the protocol , the mean glucose value decreased from 152.3 to 130.7 mg/dL ( P<.001 ) , marked by a 56.3 % reduction in the percentage of glucose values of 200 mg/dL or higher , without a significant change in hypoglycemia . The development of new renal insufficiency decreased 75 % ( P=-.03 ) , and the number of patients undergoing transfusion of packed red blood cells decreased 18.7 % ( P=.04 ) . Hospital mortality decreased 29.3 % ( P=.002 ) , and length of stay in the ICU decreased 10.8 % ( P=.01 ) . CONCLUSION The protocol result ed in significantly improved glycemic control and was associated with decreased mortality , organ dysfunction , and length of stay in the ICU in a heterogeneous population of critically ill adult patients . These results support the adoption of this low-cost intervention as a st and ard of care for critically ill patients Purpose An optimal target for glucose control in ICU patients remains unclear . This prospect i ve r and omized controlled trial compared the effects on ICU mortality of intensive insulin therapy ( IIT ) with an intermediate glucose control . Methods Adult patients admitted to the 21 participating medico-surgical ICUs were r and omized to group 1 ( target BG 7.8–10.0 mmol/L ) or to group 2 ( target BG 4.4–6.1 mmol/L ) . Results While the required sample size was 1,750 per group , the trial was stopped early due to a high rate of unintended protocol violations . From 1,101 admissions , the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed . The groups were well balanced . BG levels averaged in group 1 8.0 mmol/L ( IQR 7.1–9.0 ) ( median of all values ) and 7.7 mmol/L ( IQR 6.7–8.8 ) ( median of morning BG ) versus 6.5 mmol/L ( IQR 6.0–7.2 ) and 6.1 mmol/L ( IQR 5.5–6.8 ) for group 2 ( p < 0.0001 for both comparisons ) . The percentage of patients treated with insulin averaged 66.2 and 96.3 % , respectively . Proportion of time spent in target BG was similar , averaging 39.5 % and 45.1 % ( median ( IQR ) 34.3 ( 18.5–50.0 ) and 39.3 (26.2–53.6)% ) in the groups 1 and 2 , respectively . The rate of hypoglycaemia was higher in the group 2 ( 8.7 % ) than in group 1 ( 2.7 % , p < 0.0001 ) . ICU mortality was similar in the two groups ( 15.3 vs. 17.2 % ) . Conclusions In this prematurely stopped and therefore underpowered study , there was a lack of clinical benefit of intensive insulin therapy ( target 4.4–6.1 mmol/L ) , associated with an increased incidence of hypoglycaemia , as compared to a 7.8–10.0 mmol/L target . ( Clinical Trials.gov # NCT00107601 , EUDRA-CT Number : 200400391440 ) Growing evidence suggests that glycaemic variability increases diabetic complications . However , the significance of glycaemic variability in critically ill patients remains unclear . We evaluated the predictors of glycaemic fluctuation and its association with critical care outcomes . This is a nested-cohort study within a clinical trial in which 523 patients at a medical surgical intensive care unit were r and omised to either intensive insulin therapy ( target glycaemic control : 4.4 to 6.1 mmol/l ) or conventional insulin therapy ( target control : 10.0 to 11.1 mmol/l ) . Glycaemic fluctuation was defined as the mean difference between the highest and lowest daily blood glucose . Patients were divided into wide and narrow fluctuation groups according to the median glycaemic fluctuation ( 6.0 mmol/l ) . The association between glycaemic fluctuation and different intensive care unit outcomes was studied . Predictors of glycaemic fluctuation were age ( odds ratio for each year increment 1.03 , 95 % confidence interval 1.02 to 1.05 ) , diabetes mellitus ( odds ratio 3.00 , 95 % confidence interval 1.74 to 5.17 ) , and daily insulin dose ( odds ratio for each unit increment 1.04 , 95 % confidence interval 1.03 to 1.05 ) . Similar levels of glucose fluctuation were observed in intensive insulin therapy and conventional insulin therapy patients . Wide glycaemic fluctuation was associated with higher mortality ( 22.2 vs 8.4 % , P < 0.001 ) . Glycaemic fluctuation was identified as an independent predictor of intensive care unit mortality ( odds ratio per mmol 1.08 , 95 % confidence interval 1.00 to 1.18 ) and hospital mortality ( odds ratio per mmol 1.09 , 95 % confidence interval 1.02 to 1.17 ) using multivariate logistic regression analysis . In conclusion , wide glycaemic fluctuation is an independent predictor of mortality in critically ill patients . Whether reducing glycaemic fluctuation would lead to better outcomes needs further evaluation INTRODUCTION The benefits , harms and feasibility of intensive insulin therapy in critically ill patients remain unclear . Several single center studies have attempted to demonstrate the benefit of intensive insulin therapy in critically ill patients with variable results . OBJECTIVES We conducted a pilot r and omized trial to assess the feasibility , safety and clinical outcomes of preprinted glucose management algorithms before the initiation of a large multicenter trial . PATIENTS AND METHODS Within 48 hours of admission to the intensive care unit , we r and omized mechanically ventilated patients to either the " high " group ( target serum glucose concentration 9 - 11 mmol/l ) or the " low " group ( target serum glucose concentration 5 - 7 mmol/l ) . To assess feasibility we measured the time to reach target glucose range , time in target range , morning glucose concentrations , average daily glucose concentrations , and number of crossovers . To assess safety , we measured the number of hypoglycemic events ( serum glucose < 2.2 mmol/l ) , and other serious adverse events such as cardiac arrests and seizures . RESULTS Sixty-eight patients were enrolled ( 35 in the high group and 33 in the low group ) . During the first week , the median proportions of time spent in the target range were 35.7 % and 53.0 % for the high and low groups , respectlively ( p = 0.0001 ) . Morning glucose concentrations were 8.3 + /-1.6 mmol/l and 6.2 -/+1.2 mmol/l . One ( 2.9 % ) and 8 ( 24.2 % ) episodes of hypoglycemia ( < 2.2 mmol/l ) occurred in the high and low groups , reflecting 0.002 and 0.03 hypoglycemic events per patient-day , respectlively . CONCLUSIONS This pilot trial of intensive insulin therapy identified numerous challenges that helped in the preparation of an international multicenter r and omized trial of intensive insulin therapy to evaluate benefits and harms PURPOSE The objective of our study was to evaluate the beneficial effect of IIT in reducing mortality and morbidity in critically ill trauma patients admitted to ICU . METHOD AND MATERIAL Nested cohort study within a R and omized Controlled Trial . All trauma patients with GCS < or = 9 included in the original trial were included in this study . Primary outcome was ICU mortality . RESULT There was no difference in ICU mortality between IIT and CIT groups ( 6.5 % vs. 5.5 % , p = 0.67 ) . After adjustment for baseline characteristics , IIT therapy was also not associated with mortality ( Adjusted Hazard Ratio 1.33 , 95 % CI 0.35 - 5.05 ) . IIT therapy was associated with a significant increase in the incidence of hypoglycemia as compared to CIT , at least one hypoglycemia episode occurred in 18.5 % of patients in IIT and 1.3 % in the CIT group ( P < 0.0001 ) . CONCLUSION IIT was not associated with survival improvement in trauma patients admitted to ICU and was associated with increased incidence of hypoglycemia Introduction To investigate the risks and possible benefits of routine versus intensive insulin therapy , assessed by the frequency of hypoglycemic events defined as a glucose concentration less than 80 mg/dl ( < 4.44 mmol/l ) in patients admitted to the intensive care unit ( ICU ) after severe traumatic brain injury ( TBI ) . Methods and Results Ninety-seven patients admitted after severe TBI , were enrolled and r and omly assigned to two groups of target glycemia . Insulin was infused at conventional rates when blood glucose levels exceeded 220 mg/dl ( 12.22 mmol/l ) or at intensive rates , to maintain glycemia at 80–120 mg/dl ( 4.44–6.66 mmol/l ) . The following primary and outcome variables were measured during follow-up : hypoglycemic episodes , duration of ICU stay , infection rate , and 6-month mortality and neurologic outcome measured using the Glasgow Outcome Scale ( GOS ) . Episodes of hypoglycemia ( defined as blood glucose < 80 mg/dl or 4.44 mmol/l ) were significantly higher in patients receiving intensive insulin therapy : median ( min – max ) conventional insulin therapy 7 ( range 0–11 ) vs. intensive insulin therapy 15 ( range 6–33 ) ; P<0.0001 . Duration of ICU stay was shorter in patients receiving intensive insulin therapy ( 7.3 vs. 10.0 days ; P < 0.05 ) ; while infection rates during ICU stay ( 25.0 % vs. 38.8 % , P = 0.15 ) , and GOS scores and mortality at 6 months were similar in the two groups . Conclusions Intensive insulin therapy significantly increases the risk of hypoglycemic episodes . Even though patients receiving intensive insulin therapy have shorter ICU stays and infection rates similar to those receiving conventional insulin therapy , both groups have similar follow-up mortality and neurologic outcome . Hence if intensive insulin therapy is to be used , great effort must be taken to avoid hypoglycemia |
11,390 | 31,572,234 | Main findings : Although literature on the role of inflammation in alcohol use-related cognitive deficiency remains scarce , current findings indicate that pro-inflammatory processes indeed result in exacerbation of several domains of cognitive deterioration .
Interestingly , microglia , the immune cells of the brain , appear to exert initial compensatory neuroprotective functionalities upon acute ethanol exposure while chronic alcohol intake seems to attenuate these responses and overall microglial activity . | Rationale : Of late , evidence emerges that the pathophysiology of psychiatric diseases and their affiliated symptomatologies are at least partly contributable to inflammatory processes .
Also in alcohol use disorders ( AUD ) , this interaction is strongly apparent , with severely immunogenic liver cirrhosis being one of the most critical sequelae of chronic abusive drinking .
This somatic immune system activation negatively impacts brain functioning , and additionally , alcohol abuse appears to have a direct detrimental effect on the brain by actively stimulating its immune cells and responses .
As cognitive decline majorly contributes to AUD 's debility , it is important to know to what extent impairment of cognitive functioning is due to these (neuro-)inflammatory aberrations . | BACKGROUND The adverse effects of alcohol on brain function result , in part , from inflammatory processes . The sex-specific neuropsychiatric consequences and inflammatory status of active alcohol dependence and early remission from dependence have not been investigated . METHODS Neuropsychiatric symptoms , inflammatory factors , and liver enzymes were compared in a prospect i ve cohort study of adults with ( n=51 ) or without ( n=31 ) a current or recent history of alcohol dependence . RESULTS Neuropsychiatric profiles were similar in adults with current or recent alcohol dependence regardless of sex . In male and female participants measures of depression ( female p<0.05 , male p<0.001 ) , anxiety ( female p<0.001 , male p<0.001 ) , and memory complaints ( female p<0.001 , male p<0.05 ) were elevated , relative to non-dependent controls . Significant sex × alcohol dependence history interactions were observed for plasma levels of tissue inhibitor of metalloproteinase 1 ( TIMP-1 ) and brain derived neurotrophic factor ( BDNF ) , with women in the alcohol dependent group exhibiting increased levels of both analytes ( p<0.05 ) relative to controls . Positive correlations between TIMP-1 levels and measures of depression ( r2=0.35 , p<0.01 ) , anxiety ( r2=0.24 , p<0.05 ) and memory complaints ( r2=0.44 , p<0.01 ) were found in female , but not male , participants . CONCLUSIONS Though neuropsychiatric profiles were similar for men and women with current or recent alcohol dependence , plasma factors associated with increases in depression , anxiety , and memory impairment differed and support the need to tailor treatments based on sex Background : Minimal hepatic encephalopathy ( MHE ) is common in cirrhosis but its pathophysiologic basis remains undefined . We evaluated whether the presence of MHE was associated with severity of liver disease , ammonia levels or the presence of inflammation and assessed factors determining neuropsychological deterioration accompanying induction of hyperammonemia . Methods : Eighty four cirrhotics were studied . A neuropsychological test battery was performed and blood taken for ammonia , WCC , CRP , nitrate/nitrite , IL-6 and amino acids , before and after , induction of hyperammonemia by administration of a solution mimicking the amino acid composition of haemoglobin ( 60 ) or placebo ( 24 ) . Results : The presence and severity of MHE were independent of severity of liver disease and ammonia concentration but markers of inflammation were significantly higher in those with MHE compared with those without . Induction of hyperammonemia produced deterioration in one or more neuropsychological tests by ≥1 SD in 73.3 % . This was independent of the magnitude of change in plasma ammonia and severity of liver disease but was significantly greater in those with more marked inflammation . Conclusion : Our data show that inflammation is an important determinant of the presence and severity of MHE . The change in neuropsychological function following induced hyperammonemia is greater in those with more severe inflammation AIMS The aim of the study was to investigate factors hypothesized to influence the relapse process , with a focus on the role of self-efficacy , alcohol dependence and cognitive functioning . DESIGN The study was conducted in the context of a controlled trial of a relapse prevention programme . Subjects were assessed prior to treatment , at immediate conclusion of treatment and at 6- and 12-month follow-up . SETTING The study was conducted in an Alcohol Treatment Unit ( ATU ) in Scotl and . PARTICIPANTS Subjects were 60 male problem drinkers who were patients at the ATU . They were heavy drinkers , with corresponding high levels of alcohol dependence and alcohol-related harm . MEASUREMENTS The independent variables were post-treatment self-efficacy , alcohol dependence , cognitive functioning , level of depression and alcohol consumption prior to admission to treatment . The dependent variables were post-treatment drinking behaviour and functioning and time to lapse and relapse . FINDINGS Although the methodology does not allow identification of causality , support was found for the hypothesis that post-treatment self-efficacy was an intervening variable between treatment and outcome . Higher post-treatment self-efficacy predicted better outcome at 6-month follow-up and was associated with a reduced risk of lapse and relapse over the 12-month follow-up . Poorer cognitive functioning was significantly associated with being categorized as a problem drinker at 6-month follow-up and with higher risk of a lapse over the 12-month follow-up . Level of alcohol dependence did not predict outcome . CONCLUSIONS It was concluded that post-treatment self-efficacy rating is a predictor of treatment outcome and time to lapse and relapse and that cognitive functioning is a predictor of treatment outcome and time to lapse |
11,391 | 24,096,715 | The evidence gap remains regarding user-held , personalised , accessible clinical information for people with psychotic illnesses for many of the outcomes of interest .
However , based on moderate quality evidence , this review suggests that there is no effect of the intervention on hospital or outpatient appointment use for individuals with psychotic disorders . | BACKGROUND It is important to seek cost-effective methods of improving the care and outcome of those with serious mental illnesses .
User-held records , where the person with the illness holds all or some personal information relating to the course and care of their illness , are now the norm in some clinical setting s. Their value for those with severe mental illnesses is unknown .
OBJECTIVES To evaluate the effects of personalised , accessible , user-held clinical information for people with a severe mental illness ( defined as psychotic illnesses ) . | Background : Psychiatric advance directives are intended to enable self-determined treatment for patients who lose decisional capacity , and thus reduce the need for coercive interventions such as police transport , involuntary commitment , seclusion and restraints , and involuntary medications during mental health crises ; whether PADs can help prevent the use of these interventions in practice is unknown . Aims : This study examined whether completion of a Facilitated Psychiatric Advance Directive ( F-PAD ) was associated with reduced frequency of coercive crisis interventions . Method : The study prospect ively compared a sample of PAD completers ( n = 147 ) to non-completers ( n = 92 ) on the frequency of any coercive interventions , with follow-up assessment s at 6 , 12 , and 24 months . Repeated- measures multiple regression analysis was used to estimate the effect of PADs . Models controlled for relevant covariates including a propensity score for initial selection to PADs , baseline history of coercive interventions , concurrent global functioning and crisis episodes with decisional incapacity . Results : F-PAD completion was associated with lower odds of coercive interventions ( adjusted OR = 0.50 ; 95 % CI = 0.26–0.96 ; p < 0.05 ) . Conclusions : PADs may be an effective tool for reducing coercive interventions around incapacitating mental health crises . Less coercion should lead to greater autonomy and self-determination for people with severe mental illness Background Crises and ( involuntary ) admissions have a strong impact on patients and their caregivers . In some countries , including the Netherl and s , the number of crises and ( involuntary ) admissions have increased in the last years . There is also a lack of effective interventions to prevent their occurrence . Previous research has shown that a form of psychiatric advance statement – joint crisis plan – may prevent involuntary admissions , but another study showed no significant results for another form . The question remains which form of psychiatric advance statement may help to prevent crisis situations . This study examines the effects of two other psychiatric advance statements . The first is created by the patient with help from a patient 's advocate ( Patient Advocate Crisis Plan : PACP ) and the second with the help of a clinician only ( Clinician facilitated Crisis Plan : CCP ) . We investigate whether patients with a PACP or CCP show fewer emergency visits and ( involuntary ) admissions as compared to patients without a psychiatric advance statement . Furthermore , this study seeks to identify possible mechanisms responsible for the effects of a PACP or a CCP . Methods / Design This study is a r and omised controlled trial with two intervention groups and one control condition . Both interventions consist of a crisis plan , facilitated through the patient 's advocate or the clinician respectively . Out patients with psychotic or bipolar disorders , who experienced at least one psychiatric crisis during the previous two years , are r and omly allocated to one of the three groups . Primary outcomes are the number of emergency ( after hour ) visits , ( involuntary ) admissions and the length of stay in hospital . Secondary outcomes include psychosocial functioning and treatment satisfaction . The possible mediator variables of the effects of the crisis plans are investigated by assessing the patient 's involvement in the creation of the crisis plan , working alliance , insight into illness , recovery style , social support , locus of control , service engagement and coping with crises situations . The interviews take place before r and omisation , nine month later and finally eighteen months after r and omisation . Discussion This study examines the effects of two types of crisis plans . In addition , the results offer an underst and ing of the way these advance statements work and whether it is more effective to include a patients ' advocate in the process of creating a psychiatric advance statement . These statements may be an intervention to prevent crises and the use of compulsion in mental health care . The strength and limitations of this study are discussed . Trial registration Current Controlled Trails NTR1166 At an antenatal clinic in St. Thomas 's Hospital , London , 246 expectant mothers were r and omly allocated to hold either their own maternity case notes or the st and ard co-operation card . Information was collected on three occasions during their care on attitudes and health behaviour . Clinical outcomes were recorded and the effects of the two systems on clinic administration were observed . More of the notes group expressed satisfaction with most aspects of their care and delivery and significantly more of the notes group felt well informed and satisfied with their companion during labour . There were no differences in clinical outcomes between the two groups except that , for no identifiable systematic reason , there were more assisted deliveries among the notes group . A number of administrative advantages result ed from mothers holding their own notes and although initial reservations were found amongst professional staff interviewed at the start of the study , the results proved persuasive and the practice of giving mothers their own notes is now to be extended throughout the department BACKGROUND An advance directive is a statement of a person 's preferences for treatment , should he or she lose capacity to make treatment decisions in the future . AIMS To evaluate whether use of advance directives by patients with mental illness leads to lower rates of compulsory readmission to hospital . METHOD In a r and omised controlled trial in two psychiatric services in inner London , 156 in- patients about to be discharged from compulsory treatment under the Mental Health Act were recruited . The trial compared usual psychiatric care with usual care plus the completion of an advance directive . The primary outcome was the rate of compulsory readmission . RESULTS Fifteen patients ( 19 % ) in the intervention group and 16 ( 21 % ) in the control group were readmitted compulsorily within 1 year of discharge . There was no difference in the numbers of compulsory readmissions , numbers of patients readmitted voluntarily , days spent in hospital or satisfaction with psychiatric services . CONCLUSIONS Users ' advance instruction directives had little observable impact on the outcome of care at 12 months BACKGROUND Patients and doctors often have divergent views on care needs . AIMS To examine whether providing patients with an opportunity to identify and discuss their needs would improve communication and induce changes in care . METHOD Patients with schizophrenia ( n=134 ) were r and omly allocated to either st and ard care or use of the Two-Way Communication Checklist ( 2-COM ) . Before seeing their clinician for a routine follow-up , participants in the active intervention group were given 2-COM , a list of 20 common needs , and told to indicate those areas they wanted to discuss with their doctor . Outcomes were assessed immediately and again after 6 weeks . RESULTS Using 2-COM induced a stable improvement of patient-reported quality of patient-doctor communication ( B=0.33 , P=0.031 ) , and induced changes in management immediately after the intervention ( OR=3.7 , P=0.009 ; number needed to treat , 6 ) . Treatment change was more likely in patients with more reported needs , and needs most likely to induce treatment change displayed stronger associations with non-medication than with medication changes . CONCLUSIONS A simple intervention to aid people in discussion of their needs results in improved communication and changes in management The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Abstract Objective To investigate whether a form of advance agreement for people with severe mental illness can reduce the use of inpatient services and compulsory admission or treatment . Design Single blind r and omised controlled trial , with r and omisation of individual patients . The investigator was blind to allocation . Setting Eight community mental health teams in southern Engl and . Participants 160 people with an operational diagnosis of psychotic illness or non-psychotic bipolar disorder who had experienced a hospital admission within the previous two years . Intervention The joint crisis plan was formulated by the patient , care coordinator , psychiatrist , and project worker and contained contact information , details of mental and physical illnesses , treatments , indicators for relapse , and advance statements of preferences for care in the event of future relapse . Main outcome measures Admission to hospital , bed days , and use of the Mental Health Act over 15 month follow up . Results Use of the Mental Health Act was significantly reduced for the intervention group , 13 % ( 10/80 ) of whom experienced compulsory admission or treatment compared with 27 % ( 21/80 ) of the control group ( risk ratio 0.48 , 95 % confidence interval 0.24 to 0.95 , P = 0.028 ) . As a consequence , the mean number of days of detention ( days spent as an inpatient while under a section of the Mental Health Act ) for the whole intervention group was 14 compared with 31 for the control group ( difference 16 , 0 to 36 , P = 0.04 ) . For those admitted under a section of the Mental Health Act , the number of days of detention was similar in the two groups ( means 114 and 117 , difference 3 , −61 to 67 , P = 0.98 ) . The intervention group had fewer admissions ( risk ratio 0.69 , 0.45 to 1.04 , P = 0.07 ) . There was no evidence for differences in bed days ( total number of days spent as an inpatient ) ( means 32 and 36 , difference 4 , −18 to 26 , P = 0.15 for the whole sample ; means 107 and 83 , difference −24 , −72 to 24 , P = 0.39 for those admitted ) . Conclusions Use of joint crisis plans reduced compulsory admissions and treatment in patients with severe mental illness . The reduction in overall admission was less . This is the first structured clinical intervention that seems to reduce compulsory admission and treatment in mental health services Psychiatric advance directives ( PADs ) statutes presume competence to complete these documents , but the range and dimensions of decisional competence among people who actually complete PADs is unknown . This study examines clinical and neuropsychological correlates of performance on a measure to assess competence to complete PADs and investigates the effects of a facilitated PAD intervention on decisional capacity . N=469 adults with psychotic disorders were interviewed at baseline and then r and omly assigned to either a control group in which they received written material s about PADs or to an intervention group in which they were offered an opportunity to meet individually with a trained facilitator to create a PAD . At baseline , domains on the Decisional Competence Assessment Tool for PADs ( DCAT-PAD ) were most strongly associated with IQ , verbal memory , abstract thinking , and psychiatric symptoms . At one-month follow-up , participants in the intervention group showed more improvement on the DCAT-PAD than controls , particularly among participants with pre-morbid IQ estimates below the median of 100 . The results suggest that PAD facilitation is an effective method to boost competence of cognitively-impaired clients to write PADs and make treatment decisions within PADs , thereby maximizing the chances their advance directives will be valid Background The use of compulsory treatment under the Mental Health Act ( MHA ) has continued to rise in the UK and in other countries . The Joint Crisis Plan ( JCP ) is a statement of service users ' wishes for treatment in the event of a future mental health crisis . It is developed with the clinical team and an independent facilitator . A recent pilot RCT showed a reduction in the use of the MHA amongst service users with a JCP . The JCP is the only intervention that has been shown to reduce compulsory treatment in this way . The CRIMSON trial aims to determine if JCPs , compared with treatment as usual , are effective in reducing the use of the MHA in a range of treatment setting s across the UK . Methods / Design This is a 3 centre , individual-level , single-blind , r and omised controlled trial of the JCP compared with treatment as usual for people with a history of relapsing psychotic illness in Birmingham , London and Lancashire/Manchester . 540 service users will be recruited across the three sites . Eligible service users will be adults with a diagnosis of a psychotic disorder ( including bipolar disorder ) , treated in the community under the Care Programme Approach with at least one admission to a psychiatric inpatient ward in the previous two years . Current in patients and those subject to a community treatment order will be excluded to avoid any potential perceived pressure to participate . Research assessment s will be conducted at baseline and 18 months . Following the baseline assessment , eligible service users will be r and omly allocated to either develop a Joint Crisis Plan or continue with treatment as usual . Outcome will be assessed at 18 months with assessors blind to treatment allocation . The primary outcome is the proportion of service users treated or otherwise detained under an order of the Mental Health Act ( MHA ) during the follow-up period , compared across r and omisation groups . Secondary outcomes include overall costs , service user engagement , perceived coercion and therapeutic relationships . Sub-analyses will explore the effectiveness of the JCP in reducing use of the MHA specifically for Black Caribbean and Black African service users ( combined ) . Qualitative investigations with staff and service users will explore the acceptability of the JCPs . Discussion JCPs offer a potential solution to the rise of compulsory treatment for individuals with psychotic disorders and , if shown to be effective in this trial , they are likely to be of interest to mental health service providers worldwide . Trial registration Current Controlled Trials IS RCT To assess a policy of women holding and thus having constant access to their own obstetric records , 290 women attending a peripheral consultant clinic in Newbury , West Berkshire , were r and omly allocated to hold either their full case notes , or the more usual co‐operation card . Women holding their full records were significantly more likely to feel in control of their antenatal care ( rate ratio 1·45 ; 95 % confidence interval 1·08–1·95 ) and to feel it was easier to talk to doctors and midwives ( rate ratio 1·73 ; 95 % confidence interval 1·16‐2·59 ) . No other beneficial effects were detected . Asked about their preferences for any subsequent pregnancies , women holding their own records in the index pregnancy were more likely to say they would prefer to hold the same kind of record again in a subsequent pregnancy than were women holding a co‐operation card ( rate ratio 1·56 ; 95 % confidence interval 1·34–1·81 ) . There was no evidence of negative effects . In particular , women holding their case notes did not feel more anxious than co‐operation card holders . The policy of women holding their notes result ed in savings in elerical time , without evidence of an increase in the rate of lost notes OBJECTIVE Studies show a high potential dem and for psychiatric advance directives but low completion rates . The authors conducted a r and omized study of a structured , manualized intervention to facilitate completion of psychiatric advance directives . METHOD A total of 469 patients with severe mental illness were r and omly assigned to a facilitated psychiatric advance directive session or a control group that received written information about psychiatric advance directives and referral to re sources in the public mental health system . Completion of an advance directive , its structure and content , and its short-term effects on working alliance and treatment satisfaction were recorded . RESULTS Sixty-one percent of participants in the facilitated session completed an advance directive or authorized a proxy decision maker , compared with only 3 % of control group participants . Psychiatrists rated the advance directives as highly consistent with st and ards of community practice . Most participants used the advance directive to refuse some medications and to express preferences for admission to specific hospitals and not others , although none used an advance directive to refuse all treatment . At 1-month follow-up , participants in the facilitated session had a greater working alliance with their clinicians and were more likely than those in the control group to report receiving the mental health services they believed they needed . CONCLUSIONS The facilitation session is an effective method of helping patients complete psychiatric advance directives and ensuring that the documents contain useful information about patients ' treatment preferences . Achieving the promise of psychiatric advance directives may require system-level policies to embed facilitation of these instruments in usual-care care setting BACKGROUND Patient-held records can improve communication across the primary - secondary interface . There has been no previous rigorous assessment of the utility of patient-held records for people with schizophrenia from a primary care perspective and their value for this population is unclear . AIM To evaluate the effectiveness of a patient-held record for patients with schizophrenia receiving shared care . DESIGN OF STUDY Cluster r and omised controlled trial . SETTING Seventy-four general practice s and six community mental health localities in Birmingham , Engl and between June 1998 and June 1999 . METHOD A sample of 201 patients with schizophrenia ( ICD-10 classification F20 ) was recruited ; of these , 100 were intervention and 101 were control . Patient-held records were given to the intervention patients . At 12-month follow-up , all patients were accounted for and 191 ( 95 % ) were revisited . Primary outcomes were the Verona Service Satisfaction Scale-54 ( VSSS-54 ) and the Krawiecka and Goldberg ( K & G ) rating scale of psychopathology at 12-month follow-up . Secondary outcomes were use of primary and secondary care services . RESULTS A total of 63/92 ( 68.5 % ) patients still had the patient-held record , 64/92 ( 69.6 % ) had used it , and 39 ( 60.9 % ) of the 64 who had used it said the patient-held record was regularly used by their keyworker . However the patient-held record had no significant effect on primary outcomes ( VSSS-54 : F1,116 = 0.06 , P = 0.801 , K & G : F1,116 = 0.6 , P = 0.439 ) or on use of services . A higher symptom score was associated with not using the patient-held record . CONCLUSIONS The trial provides no good evidence to suggest that patient-held records should be introduced as part of routine shared care for all patients with schizophrenia . However , the patient-held record was acceptable to patients with schizophrenia and acted as a communication tool , particularly between patients and keyworkers Freedom of information , access to and ownership of medical records are current and controversial issues in Australia . Relating to pregnancy and birth the debate provokes emotional responses and raises important questions about access to information , decision‐making , responsibility , power and control BACKGROUND Few formalized shared care schemes exist within psychiatry and the evidence base for sharing psychiatric care is weak . AIMS To evaluate the utility of patient-held shared care records for individuals with long-term mental illness . METHOD Cluster-r and omised controlled parallel-group 12-month trial involving 90 patients with long-term mental illness drawn from 28 general practice s. RESULTS Carrying a shared care record had no significant effect on mental state or satisfaction with psychiatric services . Compared with controls , patients in the shared care group were no more likely to be admitted ( relative risk 1.2 , 95 % CI 0.86 - 1.67 ) and attend clinic ( relative risk 0.96 , 95 % CI 0.67 - 1.36 ) over the study period . Uptake of the shared care scheme was low by patients and professionals alike . Subjects with psychotic illness were significantly less likely to use their records ( relative risk 0.51 , 95 % CI 0.27 - 0.99 ) . CONCLUSIONS Patient-held records may not be helpful for patients with long-term mental illness This paper describes a pilot study of information giving in an oncology setting . This was achieved by r and omly allocating patients to having their consultation tape-recorded or not . The results suggest that this approach increases the retention of information in patients as well as reducing their levels of anxiety . The method is cheap and easy to use , acceptable to patients and their families , and does not inhibit the consultation process OBJECTIVE To examine the use and impact of a computer generated , patient held health record ( PHR ) on information sharing , responsibility sharing and preventive health care . SETTING An academic group , private solo and private group general practice in Adelaide , South Australia . METHODS Patients with chronic health problem(s ) were r and omly assigned to an experimental control or post test only group . Pre and post intervention data were collected using a st and ardised audit and abstract ion of the patient records into a computer based record system . In addition , patient and doctor question naires , telephone follow ups and face to face interviews were conducted . OUTCOME MEASURES Patient and GP use of , and satisfaction with the PHR ; effectiveness of information and responsibility sharing ; and uptake and performance of selected preventive health care by patient and GP . RESULTS Seventy-two patients were recruited ( 29 received the PHR , and 22 each were in the control and post test only groups ) . The PHR was well received and used in both primary and secondary care setting s. No statistically significant differences in the outcome measures were found between the groups as well as before and after the intervention ( Kruskal-Wallis , p > 0.05 ) . Data trends suggested that the PHR may increase information and responsibility sharing as well as improve patient awareness of the issues involved , with patient participation in information sharing , preventive health care and clinical decision making . Provided training and re sources were made available , participating GPs believed that the computer based methodology developed was a practical option for use in practice . CONCLUSION The computer generated PHR is an important determinant of patient participation in information and responsibility sharing , health promotion , and disease management . Implementation and evaluation studies are recommended BACKGROUND Established legal m and ates and high expectations for psychiatric advance directives are not matched by empirical evidence documenting their actual implementation . AIMS To explore the interests , concerns and planning activities of informed mental health service users contemplating such directives . METHOD St and ard qualitative research techniques were used : field observations , interviews , focus groups , archival research and key informant interviews ; 33 persons participated in the interviews and focus groups . Transcripts were coded and analysed for thematic content , and results were member-checked . RESULTS Training set in motion labour-intensive projects : conceptualising how a psychiatric advance directive would work in one 's life , mobilising re sources , review ing past experiences and assessing risks . Especially meaningful was the prospect of being treated as a responsible agent in future interactions with the mental health system . CONCLUSIONS Advance directives are best thought of as complex planning tools for future psychiatric crisis management , rather than focal interventions to enhance compliance . Research is needed to explore the institutional response to this prospect i ve decision-sharing initiative This study examined the effect of providing patients with an audiotape of a previous consultation on their level of participation during a subsequent consultation . 117 newly referred medical oncology patients r and omised to receive a tape ( n = 63 ) or not ( n = 54 ) had two linked consultations which were both audiotaped . A content analysis revealed no significant differences between tape and control group in the mean number of questions asked during the second consultation . However , significantly more tape group patients ( 77 % ) asked for clarification of at least one piece of information compared to the control group ( 57 % ) ( P = 0.04 ) . A larger number of control group patients ( 61 % ) made at least one request for facts already provided in their first consultation compared to tape group patients ( 39 % ) ( P = 0.05 ) . Audiotapes appear to facilitate patients ' requests for the clarification of previously given information and permit the re-absorption of complex information given when patients may have been too distressed for it to be assimilated BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials |
11,392 | 31,673,228 | Polyphenols did not appear to interfere with iron status , and most studies reported improvements in inflammatory markers and lipid profile . | The prevalence of cardiovascular disease ( CVD ) is rising worldwide , remaining the major cause of death in developed countries .
Polyphenols have been shown to have cardioprotective properties ; however , their impact on iron bioavailability and potential impact on other aspects of health is unclear .
A systematic review was undertaken to evaluate the current status of the relationship between habitual polyphenol consumption , iron status , and circulating biomarkers of CVD . | The consumption of green tea has been associated with cardiovascular and metabolic diseases . There have been some studies on the influence of green tea on the mineral status of obese subjects , but they have not yielded conclusive results . The aim of the present study is to examine the effects of green tea extract on the mineral , body mass , lipid profile , glucose , and antioxidant status of obese patients . A r and omized , double-blind , placebo-controlled study was conducted . Forty-six obese patients were r and omly assigned to receive either 379 mg of green tea extract , or a placebo , daily for 3 months . At baseline , and after 3 months of treatment , the anthropometric parameters , blood pressure , and total antioxidant status were assessed , as were the levels of plasma lipids , glucose , calcium , magnesium , iron , zinc , and copper . We found that 3 months of green tea extract supplementation result ed in decreases in body mass index , waist circumference , and levels of total cholesterol , low-density cholesterol , and triglyceride . Increases in total antioxidant level and in zinc concentration in serum were also observed . Glucose and iron levels were lower in the green tea extract group than in the control , although HDL-cholesterol and magnesium were higher in the green tea extract group than in the placebo group . At baseline , a positive correlation was found between calcium and body mass index , as was a negative correlation between copper and triglycerides . After 3 months , a positive correlation between iron and body mass index and between magnesium and HDL-cholesterol , as well as a negative correlation between magnesium and glucose , were observed . The present findings demonstrate that green tea influences the body 's mineral status . Moreover , the results of this study confirm the beneficial effects of green tea extract supplementation on body mass index , lipid profile , and total antioxidant status in patients with obesity The effect of the phenolic compounds in wine was examined in this study by performing radioiron-absorption measurements from extrinsically labeled test meals in 33 human subjects . In four separate studies we observed that absorption was 2- to 3-fold higher from white wine containing a low concentration of polyphenols than from two red wines containing a 10-fold higher concentration of polyphenols . The interaction between the polyphenols and alcohol in wine was evaluated by reducing the alcohol content of the wines by approximately 90 % . When the alcohol concentration was reduced , there was a significant 28 % decrease in nonheme-iron absorption with red wine but no effect with white wine . The inhibitory effect of red wines with reduced alcohol content was about twofold greater when they were consumed with a small bread roll than when taken without food . Our findings indicate that the inhibitory effect of phenolic compounds in red wine is unlikely to affect iron balance significantly Hydroxytyrosol ( HT ) is a main phenolic component of olive oil . In this study , we investigated the safety and effects produced by HT purified ( 99.5 % ) from olive mill waste . HT was administered at a daily dosage of 45 mg for 8 weeks to volunteers with mild hyperlipidemia ( n=14 ) . We measured markers of cardiovascular disease risk , enzyme markers of several clinical conditions , hematology , antioxidant parameters , vitamins and minerals at baseline ( T0 ) , 4 weeks ( T4 ) and 8 weeks ( T8 ) . The values obtained at T4 and T8 were compared with baseline . We found that the HT dose administered was safe and mostly did not influence markers of cardiovascular disease , blood lipids , inflammatory markers , liver or kidney functions and the electrolyte balance . Serum iron levels remained constant but a significant ( P<0.05 ) decrease in ferritin at T4 and T8 was found . Serum folate and red blood cell folate levels were also reduced at T4 and T8 . Finally , vitamin C increased by two-fold at T4 and T8 compared with levels at baseline . These results indicate a physiologically relevant antioxidant function for HT through increasing endogenous vitamin C levels Tumour necrosis factor-alpha ( TNF alpha ) is a mediator of reactive oxygen species , which are implicated in endothelial dysfunction and atherosclerosis . Type II diabetes is associated with endothelial dysfunction and elevated circulating TNF alpha . We hypothesized that reducing serum levels of TNFalpha , using pentoxifylline , would improve endothelial function . Thirteen subjects [ age 58+/-2 ( S.E.M. ) years ] with Type II diabetes ( disease duration 74+/-13 months ) undertook a r and omized , crossover study of 8 weeks pentoxifylline and 8 weeks placebo . Endothelium-dependent and -independent vasodilation in resistance arteries was assessed via bilateral forearm venous occlusion plethysmography during intra-brachial infusions of acetylcholine ( ACh ) , sodium nitroprusside ( SNP ) and N(G)-monomethyl-L-arginine ( L-NMMA ) . High-resolution ultrasound of the brachial artery in response to ischaemia was used to determine endothelium-dependent conduit vessel flow-mediated dilation ( FMD ) , and endothelium-independent conduit function was assessed by sublingual administration of glyceryl trinitrate ( GTN ) . Serum concentrations of TNF alpha were also determined . Pentoxifylline lowered serum TNF alpha from 4.1+/-0.7 to 2.9+/-0.6 pg x ml(-1 ) ( P=0.001 ) . Forearm blood flow ( FBF ) responses at each dose of ACh did not differ with treatment ( P=0.4 ) . Similarly , FBF responses to SNP ( P=0.8 ) and L-NMMA ( P=0.2 ) did not differ . There was also no significant difference in brachial artery diameter during FMD ( P=0.2 ) or GTN administration ( P=0.06 ) . Despite lowering serum TNF alpha concentration , pentoxifylline at a dose of 400 mg three times a day for 8 weeks did not improve vascular function in either conduit or resistance vessels in this group of Type II diabetic subjects OBJECTIVE Endothelial function is an independent predictor of prognosis in heart failure ( HF ) subjects . Statins , beyond their lipid lowering role , exert beneficial effect in patients with atherosclerosis . In the present study we examined the impact of low and intermediate dose atorvastatin treatment on endothelial function , bone marrow-derived endothelial progenitor cells ( EPC ) mobilization and inflammatory status according to HF patient status . METHODS We studied the effect of 4 weeks administration of atorvastatin in 26 patients with ischemic HF . The study was carried out on two separate arms , one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d ( r and omized , double-blind , cross-over design ) . The number of circulating CD34(+)/CD133(+)/KDR(+ ) EPCs was evaluated by flow cytometry . Endothelial function was evaluated by flow mediated dilation ( FMD ) in the brachial artery . Serum levels of tumor necrosis factor alpha ( TNF-α ) were measured by ELISA . RESULTS Treatment with atorvastatin 40 mg/d significantly increased circulating EPC ( p = 0.002 ) , FMD ( p = 0.001 ) and reduced TNF-α ( p = 0.01 ) compared to baseline . Similarly , treatment with atorvastatin 10 mg/day increased circulating EPC ( p = 0.01 ) , FMD ( p = 0.08 ) and reduced TNF-α ( p = 0.01 ) compared to baseline . Interestingly , with 40 mg/day atorvastatin treatment the increase in EPC was higher in subjects categorized as NYHA class II compared to subjects categorized as NYHA class III ( p = 0.03 ) . CONCLUSIONS Our results confirmed the distinct impact of atorvastatin treatment on the restoration of endothelial function due to EPC mobilization in ischemic HF subjects . Moreover , these findings provide the potential clinical significance of EPC status monitoring to individualize treatment in HF subjects Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults . The aim of this systematic review was to determine the evidence for these cl aims from the scientific literature in r and omised , double-blinded , controlled trials ( duration : ≥1 year ; participants : n≥100 ; age(mean ) : ≥65 years ) . Following Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines , we search ed four electronic data bases ( PubMed , Scopus , CINAHL and Web of Science ) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016 . Interventions included B-vitamins , n-3 fatty acids , antioxidant vitamins and herbs . Of the B-vitamin studies , four found benefits to cognition with supplementation . The first of these B-vitamin studies , in individuals with mild cognitive impairment ( n 266 ; duration = 2 years ) , included benefit to executive function ( P=0·015 ) and improvements in the Mini-Mental State Examination ( MMSE ) among participants with baseline homocysteine above 11·3 µmol/l ( P<0·001 ) . In the same sample , the second study found cognitive benefits of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status . The third B-vitamin study ( n 900 ; duration = 2 years ) reported improved performance in immediate ( P=0·046 ) and delayed recall ( P=0·013 ) , whereas the fourth study ( n 856 ; duration = 2 years ) reported slower rate of cognitive decline in the MMSE ( P=0·05 ) . One study investigating DHA treatment ( n 402 ; duration = 1·5 years ) revealed the slower rate of cognitive change in apoE e4 non-carriers ( P=0·03 ) . As only five included studies revealed notable benefits , presently based on the specific compounds explored here , there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly . Future long-term trials of nutraceuticals should investigate interactions with lifestyle , blood biomarkers and genetic risk factors Background : Tea has been shown to be a potent inhibitor of nonheme iron absorption , but it remains unclear whether the timing of tea consumption relative to a meal influences iron bioavailability . Objective : The aim of the study was to investigate the effect of a 1-h time interval of tea consumption on nonheme iron absorption in an iron-containing meal in a cohort of iron-replete , nonanemic female subjects with the use of a stable isotope ( 57Fe ) . Design : Twelve women ( mean ± SD age : 24.8 ± 6.9 y ) were administered a st and ardized porridge meal extrinsically labeled with 4 mg 57Fe as FeSO4 on 3 separate occasions , with a 14-d time interval between each test meal ( TM ) . The TM was administered with water ( TM-1 ) , with tea administered simultaneously ( TM-2 ) , and with tea administered 1 h postmeal ( TM-3 ) . Fasted venous blood sample s were collected for iron isotopic analysis and measurement of iron status biomarkers . Fractional iron absorption was estimated by the erythrocyte iron incorporation method . Results : Iron absorption was 5.7 % ± 8.5 % ( TM-1 ) , 3.6 % ± 4.2 % ( TM-2 ) , and 5.7 % ± 5.4 % ( TM-3 ) . Mean fractional iron absorption was found to be significantly higher ( 2.2 % ) when tea was administered 1 h postmeal ( TM-3 ) than when tea was administered simultaneously with the meal ( TM-2 ) ( P = 0.046 ) . An ∼50 % reduction in the inhibitory effect of tea ( relative to water ) was observed , from 37.2 % ( TM-2 ) to 18.1 % ( TM-3 ) . Conclusions : This study shows that tea consumed simultaneously with an iron-containing porridge meal leads to decreased nonheme iron absorption and that a 1-h time interval between a meal and tea consumption attenuates the inhibitory effect , result ing in increased nonheme iron absorption . These findings are not only important in relation to the management of iron deficiency but should also inform dietary advice , especially that given to those at risk of deficiency . This trial was registered at clinical trials.gov as NCT02365103 Abstract Background Iron deficiency anemia ( IDA ) remains a global health issue , affecting mainly children and adolescent and pregnant women . Because of problems associated with current iron compounds used in both supplementation and fortification areas , there is an emerging interest in new natural iron sources to combat IDA . Objective The objective of this study was to compare the iron absorption of iron-enriched Aspergillus oryzae [ Aspiron ( ASP ) ] with FeSO4 in humans . Methods Iron absorption was assessed using stable isotope and serum iron response methods after oral intake of iron by healthy women in 2 separate studies . In the first study , ASP was intrinsically labelled with 58Fe into a dry form containing 8 % iron . Subjects ( n = 16 , 18–35 y ) were r and omly assigned to consume liquid semipurified meals labelled with 2 stable iron isotopes , 57FeSO4 ( 10 mg ) and ASP containing 2 mg 58Fe and 8 mg natural abundance iron , in 2 visits . Isotope enrichment was measured 2 wk after the last meal was eaten . In the second study , 17 subjects were r and omly assigned to consume a test meal with 3 iron supplements during 3 separate visits : FeSO4 , 10 mg Fe , and ASP in 2 iron doses , 10 mg and 20 mg . Changes in serum iron were measured at regular intervals for 4 h after supplementation . Results The first study showed that the difference in iron absorption from FeSO4 and ASP was not significant ( 17.18 % ± 14.2 % compared to 15.14 % ± 12.3 % ; P = 0.07 ) . The results of the second study suggested that the iron from ASP was released slowly compared to FeSO4 and the area under the curve did not reflect the absorption of ASP iron , but rather the rate of iron release . Conclusions Iron-enriched A. oryzae has high relative bioavailability and may cause lower iron surges into the blood compared to FeSO4 Chokeberry polyphenols have been suggested to reduce cholesterol and blood pressure and thus protect against cardiovascular diseases ( CVD ) , but the evidence in humans is limited and inconsistent . This r and omized double-blinded three-parallel groups trial investigated the changes in various anthropometric and clinical biomarkers , and in plasma phospholipids fatty acids ( PPFA ) in volunteers at cardiovascular risk after a four-week intervention with 100 mL/day of ( 1 ) chokeberry juice with a high-dose of polyphenols ( 1177.11 mg gallic acid equivalents , GAE ) ; ( 2 ) chokeberry juice with a low-dose of polyphenols ( 294.28 mg GAE ) and ; ( 3 ) a nutritionally matched polyphenol-free placebo drink . Our results indicate that the intake of chokeberry juice containing either the low or the high dose of polyphenols can not be linked with a reduction in total- and low-density lipoprotein (LDL)cholesterol or in systolic ( SBP ) and diastolic ( DBP ) blood pressure in comparison with the consumption of the placebo drink . However , we found evidence of moderate changes in the PPFA , i.e. , increased saturated fatty acids ( SFA ) , mostly palmitic acid , and reduced n-6 polyunsaturated fatty acids ( PUFA ) , principally linoleic acid ( LA ) with the intake of chokeberry against the placebo . These effects may be associated with the polyphenols but we could not differentiate a clear dose-response effect . Further research is still needed to eluci date the contribution of the polyphenolic fraction to the potential cardiovascular effects of the chokeberry and to build up the evidence of its potential benefit via the modulation of PPFA composition |
11,393 | 32,327,689 | Overall , in well-selected patients , conservative surgery with adjunctive PN may provide greater relief from midline pain and a similarly low rate of operative complications relative to conservative surgery alone but may increase the risk of constipation postoperatively . | The objective of this review was to compare the efficacy and safety of conservative surgery with or without adjunctive presacral neurectomy ( PN ) for chronic endometriosis-related pelvic pain . | OBJECTIVE To explore the effectiveness and safety of laparoscopic presacral neurectomy ( LPN ) in treating endometriosis-associated pain . METHODS Totally 64 patients with endometriosis were divided into two groups using prospect i ve non-r and om method . Patients in the control group received only the conventional laparoscopic resection of endometriosis lesions , while patients in the LPN group underwent LPN in addition to the resection of endometriosis lesions . The pre-operative pain scores , intra-operative staging results , surgical duration , intra-surgical blood loss , post-operative pain relief were compared between these two groups . RESULTS These two groups showed no significant differences in terms of age , body weight , pre-operative pain score , surgery staging , surgical duration , and intra-operative blood loss ( all P > 0.05 ) . All patients were followed up for 6 to 18 months ( median : 12.8 months ) . The post-operative pain relief rate was 89.28 % ( 25/ 28 ) in LPN group and 61.29 % ( 19/31 ) in the control group ( P = 0.030 ) . CONCLUSION LPN can effectively and safely in treating endometriosis and its associated pain OBJECTIVE The purpose of this study was to assess the effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis that was treated with conservative surgical intervention . STUDY DESIGN One hundred forty-one sexually active women of fertile age with chronic severe dysmenorrhea caused by endometriosis were treated with conservative laparoscopic surgery . Patients were assigned r and omly to not receive ( group A ) or receive ( group B ) presacral neurectomy . At 6 and 12 months after the surgical procedures , the cure rate was evaluated in each patient . The frequency and severity of dysmenorrhea , dyspareunia , and chronic pelvic pain were also evaluated at the same time intervals . RESULTS The cure rate was significantly higher in group B compared with group A at a follow-up examination at 6 months ( 87.3 % vs 60.3 % ) and 12 months ( 85.7 % vs 57.1 % ) . At follow-up visits , the frequency and severity of dysmenorrhea , dyspareunia , and chronic pelvic pain were significantly lower in both groups compared with baseline values ; in particular , significantly lower values were observed in group B versus group A for the severity . CONCLUSION Presacral neurectomy improves the cure rate in women who are treated with conservative laparoscopic surgery for severe dysmenorrhea caused by endometriosis A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis STUDY OBJECTIVE To assess the long-term effectiveness of presacral neurectomy ( PSN ) in women with severe dysmenorrhea due to endometriosis treated with conservative laparoscopic surgical intervention . DESIGN R and omized , controlled trial ( Canadian Task Force classification I ) . SETTING University-affiliated department of obstetrics and gynecology . PATIENTS One hundred forty-one sexually active women of reproductive age . INTERVENTION Conservative laparoscopic surgery without ( group A ) or with ( group B ) PSN . MEASUREMENTS AND MAIN RESULTS At entry and 24-months after surgical procedures , cure rates ; frequency and severity of dysmenorrhea , dyspareunia , and chronic pelvic pain ; and quality of life were evaluated . At follow-up visit , the cure rate was significantly ( P<0.05 ) higher in group B ( 83.3 % ) than in group A ( 53.3 % ) . The frequency and severity of dysmenorrhea , dyspareunia , and chronic pelvic pain were significantly ( P<0.05 ) lower in both groups compared with baseline values , and only severity was significantly ( P<0.05 ) lower in group B. A significant ( P<0.05 ) improvement in quality of life was observed after surgery in both groups and was significantly ( P<0.05 ) increased in group B compared with group A. CONCLUSION PSN improves long-term cure rates and quality of life in women treated with conservative laparoscopic surgery for severe dysmenorrhea due to endometriosis OBJECTIVE Our objective was to evaluate the efficacy of presacral neurectomy combined with conservative surgery for the treatment of pelvic pain associated with endometriosis . STUDY DESIGN In a r and omized , controlled study performed in a tertiary institution 71 patients with moderate or severe endometriosis and midline dysmenorrhea were r and omly assigned to conservative surgery alone ( n = 36 ) or conservative surgery and presacral neurectomy ( n = 35 ) . Main outcome measures were relief of dysmenorrhea , pelvic pain , and deep dyspareunia after surgery according to a multidimensional and an analog pain scale . RESULTS Presacral neurectomy markedly reduced the midline component of menstrual pain , but no statistically significant differences were observed between the two groups in the frequency and severity of dysmenorrhea , pelvic pain , and dyspareunia in the long-term follow-up . After presacral neurectomy , constipation developed or worsened in 13 patients and urinary urgency occurred in three and a painless first stage of labor in two . CONCLUSION Presacral neurectomy should be combined with conservative surgery for endometriosis only in selected cases This study was carried out to determine the efficacy of laparoscopic presacral neurectomy ( LPSN ) and to define its role in modern gynecology using a prospect i ve consecutive cohort . One hundred three patients underwent LPSN , and 87 were included in this study . After LPSN , 91 % of these 87 patients experienced some decrease in pelvic pain , and a majority of patients had 50 % or greater reduction in pain score . There was a highly significant difference among the preoperative and postoperative pain levels ( p less than 0.0001 ) . Patients with pain of endometriosis ( 72 ) , primary dysmenorrhea ( 5 ) , and chronic pelvic inflammatory disease ( 10 ) responded with a decrease in pain score to this procedure . Complications included 1 patient with intraoperative bleeding , 2 with postoperative vaginal dryness , and 1 with constipation . We conclude that LPSN is as effective as that performed by laparotomy and should be offered to patients undergoing operative laparoscopy for central dysmenorrhea and pelvic pain . This procedure should be performed only by expert endoscopists experienced in the anatomy of this region The present study was undertaken to evaluate prospect ively the efficacy of presacral neurectomy for the treatment of midline dysmenorrhea . All patients had moderate to severe dysmenorrhea and stage III-IV endometriosis . Of the patients undergoing presacral neurectomy ( N=17 ) , only two had a recurrence of pain . The remainder of the patients undergoing presacral neurectomy remain pain-free at 42 months of follow-up . Of the patients undergoing resection of endometriosis but not presacral neurectomy ( N=9 ) , none received relief of midline pain . Relief of lateral pain , back pain , and dyspareunia was variable in both groups . Our findings corroborate previous retrospective studies showing that presacral neurectomy is highly effective in the treatment of dysmenorrhea . We speculate that the most common reasons for failure of presacral neurectomy are inappropriate selection of patients and incomplete resection of the presacral nerve |
11,394 | 32,420,389 | Conclusion : The present meta- analysis suggests that intramedullary nailing without distal locking is reliable and acceptable option for treating intertrochanteric fracture .
The advantages are reduced operative time , decreased fluoroscopy time , smaller size of incision and decreased complication rate . | Objective : To compare the outcome of distal locked and unlocked intramedullary nailing in patients with intertrochanteric fractures through systematic review and meta- analysis of r and omized and non-r and omized clinical trials . | The proximal femoral nail ( PFN ) is a recently introduced intramedullary system , design ed to improve treatment of unstable trochanteric fractures of the hip . In a multicentre prospect i ve clinical study , the intra-operative use , complications and outcome of treatment using the PFN ( n = 211 ) were compared with those using the gamma nail ( GN ) ( n = 213 ) . The intra-operative blood loss was lower with the PFN ( 220 ml v 287 ml , p = 0.001 ) . Post-operatively , more lateral protrusion of the hip screws of the PFN ( 7.6 % ) was documented , compared with the gamma nail ( 1.6 % , p = 0.02 ) . Most local complications were related to suboptimal reduction of the fracture and /or positioning of the implant . Functional outcome and consolidation were equal for both implants . Generally , the results of treatment of unstable trochanteric fractures were comparable for the PFN and GN . The pitfalls and complications were similar , and mainly surgeon- or fracture-related , rather than implant-related We investigated whether a proximal femoral nail can be implanted without a distal locking screw in AO/OTA 31-A1 and 31-A2 pertrochanteric stable femur fractures . A multicentre , r and omised study was conducted in six level-two trauma centres in our area ( Puglia , Italy ) . A total of 333 patients received their allocated intervention ( 162 in the locking group [ LG ] and 171 in the unlocking group [ UG ] ) and 266 patients were included in the final analysis at 1year . Our data showed no statistically significant difference between the two groups at 1-year follow-up for ability to walk , SF-36 question naire results , residual pain ( visual analogue scale [ VAS ] score ) and level of overall satisfaction . There were also no statistically significant differences between groups for mortality and length of hospital stay . Conversely , the UG was associated with shorter operation and fluoroscopy times , shorter surgical incision length , and less blood loss and residual thigh pain . Pertrochanteric stable fractures ( 31-A1 , 31-A2 ) can be treated successfully with intramedullary nails without distal locking , reducing patient and clinical personnel radiation exposure and sanitary costs ( surgery time and screws costs ) Background : Most hip fractures are treated surgically , with use of either internal fixation or prosthetic replacement of the femoral head . The presence of these implants increases the risk of a later femoral fracture in susceptible osteoporotic patients . The purpose of this study was to analyze the incidence of and risk factors for implant-related fractures of the femur after previous hip fracture surgery . Methods : Over a ten-year period from January 1988 to December 1997 , 6230 patients ( median age , eighty-two years ; male : female ratio , 1247:4983 ) who sustained a total of 6696 hip fractures were admitted to the Edinburgh Orthopaedic Trauma Unit . Demographic information on the patients and details of the original treatment of the hip fracture were prospect ively coded and entered into a trauma data base . All subsequent readmissions due to a femoral fracture related to the implant were prospect ively audited and extracted for the purpose s of this study . Results : One hundred and forty-one patients sustained an ipsilateral fracture of the femur at a median of twenty-four weeks following the original hip fracture surgery . Survivorship analysis of the hip fracture population revealed an overall rate of subsequent femoral fracture of 2.9 % at five years , which increased to 5.1 % at ten years . The median age and gender distribution of the patients who sustained a subsequent femoral fracture were similar to those of the hip fracture population as a whole . Two-thirds of the fractures propagated from the tip of the implant . Analysis of the subsequent fractures according to the type of implant used to treat the original fracture revealed considerable differences in incidence . The incidence was relatively high in the patients initially treated with a Gamma nail ( 18.74 fractures per 1000 person-years ) or a cementless hemiarthroplasty ( 11.72 per 1000 person-years ) and was relatively low in those treated with a compression hip screw ( 4.46 per 1000 person-years ) , cannulated screws ( 4.50 per 1000 person-years ) , or a primary arthroplasty with cement ( 6.2 per 1000 person-years ) . The highest incidence of fracture was seen in the patients who had required an arthroplasty with cement as a revision procedure following failure of a primary implant ( 22.39 per 1000 person-years ) . Conclusions : Implant-related fractures following hip fracture surgery are more common than has previously been appreciated . The risk of later ipsilateral femoral fracture is increased by the use of a Gamma nail or a cementless hemiarthroplasty to treat the original hip fracture The aim of this non-r and omised prospect i ve study was to evaluate the short-term outcome of Gamma nail and dynamic hip screw ( DHS ) fixation in the treatment of subtrochanteric hip fractures due to low-energy trauma in the elderly . All of the 1,624 femoral hip fractures in 1,511 patients of the Oulu Hospital , aged over 49 years , were prospect ively registered from 1991−1999 using special forms . Seventy-three ( 4.5 % ) of the fractures were subtrochanteric . After exclusions , 58 patients constituted the final study group . Of these , 43 were treated with Gamma nails and 15 with DHS . Background factors before the fracture , complications , reoperations and functional parameters at 4 months were recorded using st and ardised forms . Intraoperative and hospital data were collected from patient records . The Seinsheimer fracture types IIIA , IIC and V were the most common fracture patterns when the Seinsheimer classification system was used , and Fielding II and AO 31A3.3 , respectively , were the most common types in the Fielding and AO classification system . There were four ( 9 % ) intraoperative complications in the Gamma nail group as compared to none in the DHS group . On the other h and , postoperative complications were more common in the DHS group ( 27 % ) than in the Gamma nail group ( 7 % ) . We recognised a correlation between certain fracture types and the likelihood of typical intra- or postoperative complications or difficulties with both devices : In Gamma nailing , difficulty in closed reduction as well as the rate of open reduction and the use of supplementary fixation were most frequent in the Seinsheimer IIC fractures . It is also noticeable that all of the postoperative device failures and fracture displacements of the DHS group occurred in the Seinsheimer type IIIA category . Detailed fracture classification is essential for the choice of the fixation device , and the present study confirms the presumption that , despite the perioperative problems associated with Gamma nailing , this technique may be preferable to plate fixation for specific fracture types with medial cortical comminution , such as Seinsheimer type IIIA.RésuméLe but de cette étude prospect i ve non r and omisée est d’évaluer l’évolution à court terme du traitement par clou Gamma ou par vis DHS des fractures sous-trochantériennes par traumatisme à basse énergie chez le sujet agé . Parmi les 1,624 fratures de la hanche enregistrées chez 1,511 patients de plus de 49 ans , de janvier 1989 à decembre 1996 , 73 ( 4,5 % ) étaient des fractures sous-trochantériennes . Le groupe d’étude était de 58 patients do nt 43 traités par clou Gamma et 15 avec vis DHS . Les antécédents , les complications et les paramètres fonctionnels à 4 mois étaient notés avec recueil st and ardisé et les informations sur l’hospitalisation étaient relevées dans les dossiers des patients . Les fractures les plus fréquentes étaient de type Seinsheimer IIIA , IIC , et V ou de type Fielding II et AO 31A3 dans ce dernier système . Il y avait 4 complications opératoires dans le groupe Gamma et aucune dans le groupe DHS t and is que les complications post-opératoires étaient plus fréquentes dans le groupe DHS que dans l’autre . Il existait une corrélation entre certains types de fractures et la survenue de complications avec les 2 matériels utilisés : dans le groupe Gamma la difficulté de réduction et la nécessité d’une fixation complémentaire étaient plus fréquent avec les fractures de type Seinsheimer IIC ; dans le groupe DHS tous les échecs de fixation survenaient pour des fractures de type Seinsheimer IIIA . La classification précise des fractures est essentielle pour le choix du matériel . L’étude présente confirme que l’ostéosynthèse par clou Gamma est préférable lorsqu’il existe une comminution corticale interne comme dans les fractures de type Seinsheimer IIIA INTRODUCTION Few clinical studies have analyzed the utility of distal interlocking screws in stable and unstable intertrochanteric fractures treated with intramedullary devices . We performed a prospect i ve analysis comparing short unlocked versus short dynamic and short static distal locked intramedullary nails . MATERIAL S AND METHODS Nine level-II trauma centres were involved in the study . 240 patients over the age of 65 with a stable ( AO/OTA 31-A1 ) or unstable intertrochanteric fracture ( AO/OTA 31-A2 ) were prospect ively investigated . The same type of nail was used in every patient . Patients were r and omly divided into 3 groups according to the type of distal locking used . Intra-operative variables were examined and patients were followed clinical ly and radiographically at 1 , 3 , 6 , 12 months postoperatively . All complications were recorded . RESULTS A total of 212 patients completed 1 year of follow-up visits . In the Unlocking Group ( UG ) the operation time , blood loss , fluoroscopy time , total length of incision were significantly decreased compared to both the Dynamic Group ( DG ) and the Static Group ( SG ) ( p < 0.05 ) . Conversely , no reliable differences in intraoperative variables were noted between the Dynamic Group and the Static Group ( p > 0.05 ) . In terms of time of fracture union we found no differences among the three Groups ( p > 0.05 ) . Moreover , no cases of limb shortening > 1 cm or varus collapse were detected in any group . The 3 Groups were similar in terms of HHS , SF-12 and Barthel index results at 1-year follow-up ( p > 0.05 ) . Finally , no significant differences were demonstrated across the three Groups in terms of major complications . CONCLUSIONS This clinical study further confirms the hypothesis that short intramedullary nails do not need to be locked for stable and unstable intertrochanteric fractures Objectives : This study compared the torsional properties of stable intertrochanteric femur fractures in a cadaveric bone model using 2 different distal fixation strategies : unlocked long cephalomedullary nailing versus dynamically locked nailing . Methods : Fourteen matched pairs of cadaveric femora were r and omly assigned to 1 of 2 distal fixation treatment groups : a single distal interlock screw placed in the dynamic orientation or no distal screw fixation . A stable 2-part intertrochanteric fracture was produced . Specimens were potted and mounted in a double gimbal fixture , facilitating unconstrained motion in the sagittal and coronal planes . Specimens were cyclically loaded dynamically in both internal and external rotation . Range of motion , internal and external rotation stiffness , torsion stiffness , torsion yield , and ultimate torsion magnitude were calculated . Results : The sample s instrumented with a distal locking screw reported statistically significantly greater internal ( 1.54 ± 0.81 N·m per degree vs. 1.08 ± 0.35 N·m per degree ; P = 0.026 ) and external rotational stiffness ( 1.42 ± 0.72 N·m per degree vs. 0.86 ± 0.36 N·m per degree ; P = 0.009 ) . Sample s with locked distal fixation were statistically stiffer and displayed statistically less displacement at the yield and peak torque . The yield torque was statistically significantly higher in the sample s without distal fixation ( 14.2 ± 3.3 N·m per degree vs. 10.6 ± 3.8 N·m per degree ; P = 0.037 ) . The peak torque was comparable between locked and unlocked sample s ( 15.0 ± 4.6 N·m per degree vs. 16.2 ± 4.2 N·m per degree ; P = 0.492 ) . Conclusions : Distal locking of femoral intramedullary nails increases the stiffness of the nail – femur construct . Unlocked sample s displayed statistically significant higher yield torque while maintaining comparable peak torque as the locked sample s. This study indicates that treating stable intertrochanteric fractures with unlocked long intramedullary nails may be an acceptable option , although further clinical study will be needed to test this assertion |
11,395 | 26,428,333 | Behavioural interventions were effective and had a dose – response effect .
Both nicotine replacement and bupropion therapy were safe and effective , with no observed differences .
Conclusions Multicomponent/complex interventions in PC are effective and safe , appearing to achieve greater long-term continuous smoking cessation than usual care and counselling alone .
Our results show that smoking interventions should include more than one component and a strong follow-up of the patient to maximise results | Objective The objective of the present review is to evaluate multicomponent/complex primary care ( PC ) interventions for their effectiveness in continuous smoking abstinence by adult smokers . | Objectives Primary : To compare the effectiveness of intensive group and individual interventions for smoking cessation in a primary health care setting ; secondary : to identify the variables associated with smoking cessation . Methods Three-pronged clinical trial with r and omisation at the individual level . We performed the following : an intensive individual intervention ( III ) , an intensive group intervention ( IGI ) and a minimal intervention ( MI ) . Included in the study were smokers who were prepared to quit smoking . Excluded from the study were individuals aged less than 18 years or with severe mental conditions or terminal illnesses . The outcome measure was continued abstinence at 12 months confirmed through CO-oximetry ( CO ) . The analysis was based on intention to treat . Results In total , 287 smokers were recruited : 81 in the III , 111 in the IGI , and 95 in the MI . Continued abstinence at 12 months confirmed through CO was 7.4 % in the III , 5.4 % in the IGI , and 1 % in the MI . No significant differences were noted between III and MI on the one h and , and between IGI and MI on the other [ RR 7.04 ( 0.9 - 7.2 ) and RR 5.1 ( 0.6 - 41.9 ) , respectively ] . No differences were noted between IGI and III [ RR 0.7 ( 0.2 - 2.2 ) ] . In multivariate analysis , only overall visit length showed a statistically significant association with smoking cessation . Conclusions The effectiveness of intensive smoking interventions in this study was lower than expected . No statistically significant differences were found between the results of individual and group interventions .Trial registration numberIS RCT Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly OBJECTIVE To evaluate the smoking cessation efficacy of nicotine patch therapy as an adjunct to low-intensity , primary care intervention . DESIGN R and omized , placebo-controlled , double-blind , multisite trial . SETTING S Twenty-one primary care sites in Nebraska . PATIENTS A total of 369 smokers of 20 or more cigarettes per day . INTERVENTION Two brief primary care visits for smoking intervention with 10 weeks of active or placebo-patch therapy . MAIN OUTCOME MEASURES Confirmed self-reported abstinence 3 , 6 , and 12 months after the quit day . RESULTS Compared with placebo control subjects , participants assigned nicotine patches had higher 3-month ( 23.4 % vs 11.4 % ; P < .01 ) and 6-month ( 18.5 % vs 10.3 % ; P < .05 ) abstinence rates . The 1-year abstinence rates for the active and placebo patch groups were 14.7 % and 8.7 % , respectively ( P = .07 ) . Of smokers aged 45 years and older , 9 ( 18.8 % ) of 48 using active patches compared with 0 of 31 using placebo patches achieved 12-month abstinence ( chi 2 = 6.56 ; P < .05 ) . Among those with high nicotine dependency scores ( Fagerstrom score > or = 7 ) , 1-year abstinence rates were significantly higher in the nicotine patch group ( 19.1 % ) compared with the placebo group ( 5.0 % ) ( chi 2 = 10.7 ; P = .001 ) . However , there was no significant difference in 1-year quit rates for participants with low Fagerstrom scores ( < 7 ) . CONCLUSIONS Nicotine patch therapy enhanced 6 month quit rates as an adjunct to brief primary care intervention . The highest quit rates were achieved by participants who specifically contacted the site to enroll in the study or to obtain a prescription for nicotine patches . Differences in participant selection factors may account , in part , for the lower smoking cessation rates associated with primary care intervention . Duration of counseling , patient age , and Fagerstrom scores may be important factors related to the long-term smoking cessation success of nicotine patch therapy Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease ( COPD ) . But a fewer smoking cessation measures were conducted in communities for smokers with COPD in China . The aim of our study was to assess the preventive effects of behavioral interventions for smoking cessation and potential impact factors in smokers with COPD in China . Methods In a r and omised controlled smoking cessation trial 3562 patients with COPD who were current smoker were allocated to intervention group received behavioral intervention and control group received the usual care for two years . The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of month 24 to the end of month 30 . Participants were followed up at month 48 . Results Continuous smoking abstinence rates from month 24 to 30 were significantly higher in participants receiving behavioral intervention than in those receiving usual care ( 46.4 % vs 3.4 % , p < 0.001 ) . Continuous abstinence rates from months 24 to 36 ( 45.8 % vs 4.0 % ) and months 24 to 48 ( 44.3 % vs 5.1 % ) were also higher in participants receiving behavioral intervention than in those control group . Family members or family physicians/nurses smoking were first identified to influence smoking cessation . Conclusions Behavioral intervention doubled the smoking cessation rate in patients with COPD and was complied well by the general practitioners . The family members and family physicians/nurses smoking were the main risk factors for smoking cessation . Trial registration Chinese Clinical Trials Registration ( ChiCTR-TRC-12001958 ) Background Although effective smoking cessation interventions exist , information is limited about their cost-effectiveness and cost-utility . Objective To assess the cost-effectiveness and cost-utility of an Internet-based multiple computer-tailored smoking cessation program and tailored counseling by practice nurses working in Dutch general practice s compared with an Internet-based multiple computer-tailored program only and care as usual . Methods The economic evaluation was embedded in a r and omized controlled trial , for which 91 practice nurses recruited 414 eligible smokers . Smokers were r and omized to receive multiple tailoring and counseling ( n=163 ) , multiple tailoring only ( n=132 ) , or usual care ( n=119 ) . Self-reported cost and quality of life were assessed during a 12-month follow-up period . Prolonged abstinence and 24-hour and 7-day point prevalence abstinence were assessed at 12-month follow-up . The trial-based economic evaluation was conducted from a societal perspective . Uncertainty was accounted for by bootstrapping ( 1000 times ) and sensitivity analyses . Results No significant differences were found between the intervention arms with regard to baseline characteristics or effects on abstinence , quality of life , and addiction level . However , participants in the multiple tailoring and counseling group reported significantly more annual health care – related costs than participants in the usual care group . Cost-effectiveness analysis , using prolonged abstinence as the outcome measure , showed that the mere multiple computer-tailored program had the highest probability of being cost-effective . Compared with usual care , in this group € 5100 had to be paid for each additional abstinent participant . With regard to cost-utility analyses , using quality of life as the outcome measure , usual care was probably most efficient . Conclusions To our knowledge , this was the first study to determine the cost-effectiveness and cost-utility of an Internet-based smoking cessation program with and without counseling by a practice nurse . Although the Internet-based multiple computer-tailored program seemed to be the most cost-effective treatment , the cost-utility was probably highest for care as usual . However , to ease the interpretation of cost-effectiveness results , future research should aim at identifying an acceptable cutoff point for the willingness to pay per abstinent participant Background The prevalence of smoking in Spain is high in both men and women . The aim of our study was to evaluate the role of gender in the effectiveness of a specific smoking cessation intervention conducted in Spain . Methods This study was a secondary analysis of a cluster r and omized clinical trial in which the r and omization unit was the Basic Care Unit ( family physician and nurse who care for the same group of patients ) . The intervention consisted of a six-month period of implementing the recommendations of a Clinical Practice Guideline . A total of 2,937 current smokers at 82 Primary Care Centers in 13 different regions of Spain were included ( 2003 - 2005 ) . The success rate was measured by a six-month continued abstinence rate at the one-year follow-up . A logistic mixed-effects regression model , taking Basic Care Units as r and om-effect parameter , was performed in order to analyze gender as a predictor of smoking cessation . Results At the one-year follow-up , the six-month continuous abstinence quit rate was 9.4 % in men and 8.5 % in women ( p = 0.400 ) . The logistic mixed-effects regression model showed that women did not have a higher odds of being an ex-smoker than men after the analysis was adjusted for confounders ( OR adjusted = 0.9 , 95 % CI = 0.7 - 1.2 ) . Conclusions Gender does not appear to be a predictor of smoking cessation at the one-year follow-up in individuals presenting at Primary Care Centers . Clinical Trials.gov IdentifierNCT00125905 OBJECTIVES To determine the long-term effect of a community-based risk reduction intervention at five years after completion of a one-year r and omized clinical trial and to determine the sustainability of the beneficial effects seen one year after the intervention . METHODS 30- to 59- year-old African American siblings of prob and s with premature coronary heart disease ( CHD ) were r and omized for care of multiple CHD risk factors to either one year of community-based care ( CBC ) provided by a nurse practitioner/community health worker team or enhanced usual care ( EUC ) . At five years , 307 ( 84.6 % ) of the siblings returned for reevaluation . MAIN OUTCOME MEASURES Changes in and achievement of goal levels of low-density lipoprotein cholesterol ( LDL-C ) , systolic and diastolic blood pressure ( SBP and DBP , respectively ) , and smoking cessation at five years . RESULTS No significant differences were seen between groups in mean LDL-C , SBP , and DBP or in the overall percentages achieving goal LDL-C , blood pressure , or smoking status . Changes after completion of the intervention suggest that the CBC group lost the beneficial effects for mean LDL-C and for percentage at goal LDL-C , while the EUC group continued to improve . CBC was associated with greater sustainability and less refractoriness of one-year results for LDL-C and blood pressure goals . CONCLUSIONS Although no group differences were found in mean risk factor levels at five years , data indicate that CBC is both feasible and associated with earlier sustainability of positive risk factor changes compared with EUC BACKGROUND Smoking-related morbidity and mortality , and benefits associated with quitting , extend across the life span . Health care provider interventions enhance quitting . The present study examined perceived influence of physician advice to quit and characteristics of subjects receiving this advice . METHODS Subjects were 1,454 smokers ages 50 + with at least one physician visit in the past year . Subjects were surveyed at baseline for receipt of and reactions to physician advice to quit and for smoking , health , and demographic characteristics . RESULTS Over half of subjects welcomed physician advice to quit , about half said the advice influenced their quitting decision " extremely " or " quite a lot , " and about one-third indicated that it increased their confidence in quitting . Physicians were more likely to advise sicker patients , indicated by poorer health status , at least one past year hospitalization , and presence of cardiovascular , cerebrovascular , or respiratory diseases . CONCLUSIONS Midlife and older smokers reacted generally favorably to physician advice to quit . Physicians were more likely to advise patients with commonly recognized smoking-related diseases . Discrepancies were noted in advice given to sicker vs healthier patients . Additional physician training in less commonly recognized smoking-related illnesses , intervening with healthier patients to prevent disease , and enhancing patients ' confidence in quitting may improve outcomes Smokers ( N = 3,030 ) were r and omized to receive 1 of 3 interventions : ( a ) a self-help quit kit , ( b ) a quit kit plus 1 telephone counseling session , or ( c ) a quit kit plus up to 6 telephone counseling sessions , scheduled according to relapse probability . Both counseling groups achieved significantly higher abstinence rates than the self-help group . The rates for having quit for at least 12 months by intention to treat were 5.4 % for self-help , 7.5 % for single counseling , and 9.9 % for multiple counseling . The 12-month continuous abstinence rates for those who made a quit attempt were 14.7 % for self-help , 19.8 % for single counseling , and 26.7 % for multiple counseling . A dose-response relation was observed , as multiple sessions produced significantly higher abstinence rates than a single session . The first week after quitting seems to be the critical period for intervention The aim of this study was to assess the effectiveness of relapse prevention taught as a problem-solving procedure in increasing the efficacy of a behavioral program for smoking cessation at short- and longer-term , 12-mo . follow-up . 75 smokers were assigned r and omly to two treatment groups , using an additional 40 smokers who attended an information session but did not receive any treatment session as a control group . The first group ( n = 40 ) received the st and ard behavioral multicomponent program of Becoña . The program included motivational contract , self-monitoring , information on smoking , nicotine fading , stimulus control , avoidance of withdrawal symptoms , physiological feedback , and progressive self-control . The second group ( n = 36 ) , the relapse prevention group , were given the above program and an additional component of relapse prevention using a problem solving procedure . Both groups had 8 sessions of treatment . Analysis showed that at the end of treatment abstinence in the two groups was 80.0 % and 61.1 % , respectively , at the 12-mo . follow-ups 30.0 % and 36.1 % . These differences were not significant ; however , both groups were significantly different from the control group at the end of treatment ( 0 % abstinence ) and at 12-mo . follow-ups ( 2.5 % abstinence ) . These results show that the addition of this relapse prevention does not increase the number of smokers who quit or decrease the number who relapse . Further research should focus on the process of relapse and develop more effective procedures to help maintain abstinence Objective : To evaluate new strategies to enhance the promotion of smoking cessation in general practice . Design : Cluster r and omised trial , 2 × 2 factorial design . Setting : 82 medical practice s in Germany , including 94 general practitioners . Participants : 577 patients who smoked at least 10 cigarettes per day ( irrespective of their intention to stop smoking ) and were aged 36–75 years . Interventions : Provision of a 2-h physician group training in smoking cessation methods and direct physician payments for every participant not smoking 12 months after recruitment ( TI , training+incentive ) ; provision of the same training and direct participant reimbursements for pharmacy costs associated with nicotine replacement therapy or bupropion treatment ( TM , training+medication ) . Main outcome measure : Self-reported smoking abstinence obtained at 12 months follow-up and vali date d by serum cotinine . Results : In intention-to-treat analysis , smoking abstinence at 12 months follow-up was 3 % ( 2/74 ) , 3 % ( 5/144 ) , 12 % ( 17/140 ) and 15 % ( 32/219 ) in the usual care , and interventions TI , TM and TI+TM , respectively . Applying a mixed logistic regression model , no effect was identified for intervention TI ( odds ratio ( OR ) 1.26 , 95 % confidence interval ( CI ) 0.65 to 2.43 ) , but intervention TM strongly increased the odds of cessation ( OR 4.77 , 95 % CI 2.03 to 11.22 ) . Conclusion : Providing cost-free effective drugs to patients along with improved training opportunities for general practitioners could be an effective measure to achieve successful promotion of smoking cessation in general practice AIM To evaluate the effectiveness in primary care of a stepped smoking cessation intervention based on the transtheoretical model of change . DESIGN Cluster r and omized trial ; unit of r and omization : basic care unit ( family physician and nurse who care for the same group of patients ) ; and intention-to-treat analysis . SETTING All interested basic care units ( n = 176 ) that worked in 82 primary care centres belonging to the Spanish Preventive Services and Health Promotion Research Network in 13 regions of Spain . PARTICIPANTS A total of 2,827 smokers ( aged 14 - 85 years ) who consulted a primary care centre for any reason , provided written informed consent and had valid interviews . MEASUREMENTS The outcome variable was the 1-year continuous abstinence rate at the 2-year follow-up . The main variable was the study group ( intervention/control ) . Intervention involved 6-month implementation of recommendations from a Clinical Practice Guideline which included brief motivational interviews for smokers at the precontemplation-contemplation stage , brief intervention for smokers in preparation-action who do not want help , intensive intervention with pharmacotherapy for smokers in preparation-action who want help and reinforcing intervention in the maintenance stage . Control group involved usual care . Among others , characteristics of tobacco use and motivation to quit variables were also collected . FINDINGS The 1-year continuous abstinence rate at the 2-year follow-up was 8.1 % in the intervention group and 5.8 % in the control group ( P = 0.014 ) . In the multivariate logistic regression , the odds of quitting of the intervention versus control group was 1.50 ( 95 % confidence interval = 1.05 - 2.14 ) . CONCLUSIONS A stepped smoking cessation intervention based on the transtheoretical model significantly increased smoking abstinence at a 2-year follow-up among smokers visiting primary care centres OBJECTIVE To explore a potential " priming effect " of physician advice on patient responses to behavioral change interventions . DESIGN R and omized controlled trial with a 3-month follow-up . SETTING Four community-based group family medicine clinics in southeastern Missouri . PARTICIPANTS Adult patients ( N = 915 ) . INTERVENTIONS Printed educational material s design ed to encourage patients to quit smoking , eat less fat , and increase physical activity . MAIN OUTCOME MEASURES Recall , rating , and use of the educational material s ; changes in smoking behavior , dietary fat consumption , and physical activity . RESULTS Patients who received physician advice to quit smoking , eat less fat , or get more exercise prior to receiving intervention material s on the same topic were more likely to remember the material s , show them to others , and perceive the material s as applying to them specifically . They were also more likely to report trying to quit smoking ( odds ratio [ OR ] = 1.54 , 95 % confidence interval [ CI ] = 0.95 - 2.40 ) , quitting for at least 24 hours ( OR = 1.85 , 95 % CI = 1.02 - 3.34 ) , and making some changes in diet ( OR = 1.35 , 95 % CI = 1.00 - 1.84 ) and physical activity ( OR = 1.51 , 95 % CI = 0.95 - 2.40 ) . CONCLUSIONS Findings support an integrated model of disease prevention in which physician advice is a catalyst for change and is supported by a coordinated system of information and activities that can provide the depth of detail and individualization necessary for sustained behavioral change BACKGROUND Smoking cessation clinical practice guidelines are based on r and omised clinical trials reporting outcomes in persons who participate in these studies . However , many practitioners are sceptical about the effectiveness of these recommendations when applied to the general population in everyday routine consultation . AIM To evaluate the results of a comprehensive smoking cessation programme in routine primary care practice . METHOD All smokers consulting in 10 general practice s during one year participated in a non-r and omised controlled trial . The percentages of subjects in the intervention ( n = 1203 , seven practice s ) and control ( n = 565 , three practice s ) groups who reported sustained abstinence between six and 12 months follow-up and were vali date d biochemically were compared . The effect of the programme was adjusted to baseline differences in both groups by multiple logistic regression analyses . RESULTS The programme result ed in an increase of five percentage points ( 95 % CI = 3.1%-6.8 % ) in the vali date d and sustained one-year abstinence probability , with 7.1 % for all of the intervention practice s ( adjusted OR = 3.7 , 95 % CI = 2.4 - 5.7 ) . CONCLUSION Programmes that combine advice to stop smoking to all smokers attending general practice s with the offering of support , follow-up , and nicotine patches to those willing to stop are feasible and effective in routine practice , as primary care clinicians need only identify 20 smokers to get one additional success attributable to the programme The purpose of this study was to compare the effectiveness of three smoking cessation programs of varying intensity applied in a primary care setting . Participants were 89 individuals r and omly assigned to one of three treatment groups : brief counseling plus information pamphlet , self-help program with telephone follow-up , and intensive behavioral treatment . At the 12-mo . follow-up , intensive behavioral treatment ( 42.8 % abstinence ) was more effective than the self-help program ( 27.5 % ) , which was in turn more effective than counseling ( 12.9 % ) . Continued abstinence was also higher in the intensive treatment group ( 37.9 % ) than in the self-help ( 17.2 % ) and the counseling groups ( 9.7 % ) , although these differences only reached statistical significance in the first and third of these groups . Treatment adherence was higher in the intensive behavioral group ( 82.8 % of participants atended all the sessions ) than in the self-help group ( 61.8 % completed the program ) . The results appear to confirm a dose-response effect in the treatment of smokers and indicate satisfactory acceptability of intensive behavioral programs applied in primary care OBJECTIVE The main objective was to compare the efficacy of one-off tobacco counselling and of the systematic minimum intervention on making people give up smoking . A secondary aim was to evaluate the efficacy of nicotine replacement therapy ( NRT ) in the context of a primary care consultation . DESIGN Controlled and r and omised clinical trial . SETTING Primary care . PARTICIPANTS Smokers who over 12 months attended a primary care clinic at an urban health centre ( 304 patients ) . INTERVENTIONS Two kinds of intervention were conducted at r and om on patients with low nicotine dependence ( one-off medical counselling and counselling integrated into what is known as the minimal intervention , but conducted systematic ally ) . NRT was administered through nicotine patches ( 11 % nicotine ) to patients with moderate-to-high nicotine dependence . MEASUREMENTS AND MAIN RESULTS Short-term cessation a year after the minimal intervention was 39 % ( 29.4 - 49.3 % ) , and maintained cessation 30.9 % ( 29.4 - 49.3 % ) , as against 11 % ( 5.6 - 18.8 % ) short-term cessation in the group that received one-off counselling ( p < 0.0001 ) . Short-term tobacco cessation in the NRT group was 35.3 % ( 24.1 - 47.8 % ) , and maintained cessation 30.8 % . CONCLUSIONS Primary care is a suitable context for an intervention against tobacco dependency , through the use of any of the established interventions : one-off medical counselling , systematic minimal intervention , or specialist drug treatment through NRT . Therefore , these kinds of intervention must form part of PC clinics ' daily activity PRINCIPLES Cigarette smoking causes an estimated 13 % of all deaths in Switzerl and . Though most smokers will eventually become ex-smokers of their own volition , physicians play an important role in accelerating the process of quitting among smoking patients . Even brief advice from physicians is effective in doing so . The purpose of this study was to investigate which smokers were asked about their smoking habits , and how often , whether they received advice to quit , and how this correlates with the patient 's desire to quit . METHODS Telephone interviews were carried out with a r and om sample of smokers and ex-smokers from the German-speaking Swiss population ( n = 993 ) . We collected information on personal characteristics , smoking habits , and recall of physicians ' advice . Data was analysed descriptively and by logistic regression . RESULTS 88 % recalled being asked by a doctor about their smoking habits . In contrast , only 34 % of smoking patients recalled being advised to stop . Women , older people and those in poor subjective health were asked more frequently . Heavier smokers and those in poor subjective health were advised more frequently . Current smokers more frequently express the desire to quit if they are heavier smokers and have been advised to quit by their physician , compared with those who have not received such advice . CONCLUSIONS Similarly to the international findings , smoking patients in Switzerl and receive brief advice with insufficient frequency . Action should therefore be taken to encourage health professionals not only to question all smoking patients but to advise and motivate them to quit smoking BACKGROUND / AIMS Smoking cessation has been shown to be effective in r and omized controlled trials . It is unclear though , whether interventions also work in routine primary care . METHODS In 167 primary care setting s we conducted a r and omized four-armed smoking cessation trial to examine the efficacy of a minimal intervention ( MI ; n = 81 ) , cognitive-behavioral therapy ( CBT ; n = 175 ) , bupropion ( BUP ; n = 108 ) and nicotine replacements ( NRT ; n = 103 ) . Overall , 467 current smokers were enrolled . Abstinence rates at the end of treatment ( 12 weeks ) were 32.8 % for MI patients , 34.8 % for CBT , 35.3 % for NRT , and 46.5 % for BUP patients ( ITT , intention to treat ) ( no differential effects ) . Retention rates were highest in the BUP group ( 59.3 % ) and lowest in the NRT group ( 50.5 % ) . Completer findings were : MI , 56.4 % ; CBT , 64 % ; BUP , 79.3 % ; NRT , 69.2 % ( LOCF , lost to follow-up ) . No serious adverse events occurred during or after the medication phase . At 12-month follow-up continuous abstinence rates were : BUP , 29.0 % ; CBT , 20.9 % ; NRT , 29.6 % ; MI , 29.6 % . CONCLUSION Our findings suggest that established smoking cessation treatments are effective when applied by non-specialist primary care physicians . Our data supports a structured , multimodal treatment structure as core ingredient of successful smoking cessation in primary care |
11,396 | 28,293,928 | Our meta- analysis indicates that SLIT provided significant symptom relief and reduced the need for medications in PAR .
In this study , significant evidence was obtained despite heterogeneity with regard to the use of mite extract . | PURPOSE Allergic rhinitis ( AR ) has become a global issue for a large part of the general population .
Sublingual immunotherapy ( SLIT ) has been used extensively to treat persistent allergic rhinitis ( PAR ) .
Although systematic review s have confirmed the effectiveness of SLIT for the treatment of AR , a considerable number of studies using extracts of house dust mites ( HDMs ) for immunotherapy found no consensus on basic treatment parameters and question ed the efficacy of SLIT . | UNLABELLED SAFETY and efficacy of sublingual ( sublingual-swallow ) immunotherapy ( IT ) with house dust mite extract were evaluated in 30 children ( 6 - 15 2/3 years of age ) over the first 12 months of an ongoing study . The cumulative dose was 570 micrograms Der p I ( five times that administered with subcutaneous therapy ) . SAFETY One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness , question ably induced by the therapy . Five patients on active therapy and one patient on placebo reported minor local side effects . EFFICACY Pulmonary symptoms were reduced after 12 months in actively treated asthmatics , but this was not consistent with the lack of improvement in bronchial reactivity , skin sensitivity and specific IgG and IgG4 against D.pt . in this group . In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score . Specific IgE ( D.pt . and D.f . ) increased significantly more in the active treatment group after 3 and 12 months . We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated , but there was no consistent clinical or immunological benefit compared to placebo BACKGROUND House dust extract is used in conventional immunotherapy for house dust-mite ( HDM ) allergic rhinitis in Japan . However , an alternative administration route is desired . The aims of the present double blind , placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy ( SLIT ) with house dust extract in pediatric patients with HDM allergic rhinitis . METHODS The study population comprised 31 subjects ( 21 males and 10 females ) aged from 7 to 15 years old . Twenty patients ( the active group ) received house dust extract and 11 received placebo via sublingual administration . Extract or placebo ( 1 ml ) was administered at 10-fold dilution once weekly for 40 weeks . During the study period , the subjects recorded their daily nasal symptoms and use ( dose and frequency ) of other medications in a nasal allergy diary . RESULTS The symptom scores in the active group began to decrease about 24 weeks after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks . The average scores for the last four weeks of the study were significantly lower than those for the first four weeks in the active group but not in the placebo group . The only local adverse effect was a bitter taste reported by one patient . There were no other local or systemic adverse effects associated with SLIT . CONCLUSIONS Our results suggest that SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children The aim of this study was to evaluate the clinical and immunologic effects of sublingual-swallow immunotherapy ( SLIT ) . A six-month , multicenter , double-blind , placebo-controlled trial was carried out in 59 patients aged 6 to 18 years with allergic rhinitis who were sensitized to mites only . Patients were r and omly assigned to placebo or SLIT with a st and ardized Dermatophagoides pteronyssinus (D.p.)/D. farinae ( D.f ) 50/50 extract . Nasal symptom scores and use of medications were recorded . Skin sensitivity , mite-specific IgE , IgG4 , and IgG4/IgE were evaluated before and after treatment . The skin sensitivity , total nasal symptom scores and medication consumption did not differ significantly after treatment . Specific IgG4 ( both p < 0.001 ) and IgG4/IgE to D.p . and D.f ( p = 0.010 , p = 0.001 , respectively ) increased significantly in the treatment group . Specific IgE increased significantly in both placebo and SLIT groups after treatment but did not differ between the two groups . The medication was well tolerated . SLIT did not significantly improve clinical manifestations of allergic rhinitis when used for 6 months . We demonstrated SLIT did significantly increase specific IgG4 and IgG4/IgE compared to treatment with placebo BACKGROUND House dust mite ( HDM ) allergy is associated with persistent allergic rhinitis ( AR ) and allergic asthma . OBJECTIVE To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease and report the AR results . METHODS Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were r and omized 1:1:1:1 to double-blinded daily treatment with 1 , 3 , 6 SQ-HDM or placebo . End-of-treatment rhinoconjunctivitis symptoms and medication score were predefined extrapulmonary end points . A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score ( TCRS ) > 0 ( ie , with AR symptoms and /or AR medication use during the 4-week baseline period ) . The subgroup was comprised of 498 subjects ( 82 % ) . RESULTS In the subgroup , the absolute difference in end-of-treatment TCRS between 6 SQ-HDM and placebo was -0.78 ( 95 % confidence interval -1.47 to -0.07 , relative difference 28.8 % , P = .0357 ) . Furthermore , a significant difference was found for the total score of the Rhinitis Quality of Life Question naire with St and ardized Activities RQLQ(S ) and for the individual domains : activities , sleep , non-nose and non-eye symptoms , and nasal symptoms . For the TCRS and Rhinitis Quality of Life Question naire score , a dose response was seen , with numerically lower , nonsignificant differences for 1 and 3 SQ-HDM . The predefined analysis for the entire trial population showed no statistically significant difference between the placebo and actively treated groups . No safety concerns were observed . CONCLUSION Efficacy in mild to severe AR of 6 SQ-HDM compared with placebo was demonstrated by statistically significant improvements in TCRS and Rhinitis Quality of Life Question naire score in subjects with AR present at baseline . The treatment was well tolerated . TRIAL REGISTRATION EudraCT , no 2006 - 001795 - 20 ; Clinical Trials.gov , identifier NCT00389363 BACKGROUND Although sublingual immunotherapy ( SLIT ) has been demonstrated to be a safe and efficient treatment in children with seasonal allergic rhinitis ( AR ) , there is little evidence on the efficacy of SLIT with house-dust-mite ( HDM ) extract in children with isolated perennial AR . OBJECTIVES We sought to assess the clinical efficacy and safety of HDM-SLIT in children with isolated allergic rhinitis-conjunctivitis mono-sensitized to HDM without asthma symptoms . METHODS Twenty-two children ( aged 5 - 10 years ) with perennial AR and conjunctivitis symptoms mono-sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae were enrolled . During a 2 months run-in period , symptom and medication scores , lung functions , bronchial hyperreactivity , nasal provocation and skin prick tests were evaluated . Subjects were r and omized to active or placebo using a double-blind method . A total of eighteen subjects were r and omised to receive either active SLIT or placebo for 12 months . Daily symptom and medication scores , baseline lung functions , bronchial hyperreactivity , nasal provocation and skin prick tests were recorded and re-evaluated at the end of treatment . RESULTS After one year of treatment , no significant differences were detected in the between groups and within group comparisons based on total rhinitis symptom/medication scores ( p > 0.05 ) . Skin reactivity to Dermatophagoides pteronyssinus was significantly reduced in HDM-SLIT compared to placebo group ( p = 0.018 ) . A significant reduction in nasal sensitivity was observed in SLIT group after one year treatment when compared to baseline ( p = 0.04 ) . Total conjunctivitis symptoms were reduced significantly in both active and lacebo group at the end of treatment compared to baseline . The proportion of patients with non-specific bronchial hyperreactivity increased to almost 3-fold in placebo group compared to baseline . CONCLUSION HDM-SLIT was not superior to placebo in reducing isolated rhinoconjunctivitis symptoms within 12 months of treatment . However , HDM-SLIT has a modulating effect on allergen-specific nasal and skin reactivity in isolated perennial AR children . CLINICAL TRIAL REGISTRATION The trial was registered at Anzctr.org.au number , ACTRN12613000315718 Background Sublingual immunotherapy ( SLIT ) is recommended for allergic diseases . However , clinical studies containing evidence -based data of this treatment in young children , which is rarely reported in the literature , are needed . This study was design ed to assess the efficacy and safety of SLIT in children , including very young children . Methods Two hundred sixty-four children aged 3–13 years old ( 133 children , 3–5 years old ) with Dermatophagoides farinae – induced allergic rhinitis with or without asthma treated by st and ard pharmacotherapy had r and omly received either SLIT ( SLIT group ) or no SLIT ( control group ) for 12 months . Symptoms , medications , visual analog scale ( VAS ) and presence of adverse events ( AEs ) were assessed at monthly visits . Skin-prick test and Dermatophagoides farinae – specific IgE and IgG4 were measured before and after treatment . Results Both treatments were effective in the global clinical scores during the first seven visits when compared with baseline ( all , p < 0.01 ) , and SLIT showed lower symptoms scores and VAS scores throughout this period ( all , p < 0.01 ) . These improvements continued until the later visits only in the SLIT group . Also , the asthma medication consumption was decreased by SLIT treatment only at the end of study ( p < 0.01 ) . The specific IgG4 was significantly increased after SLIT treatment when compared with the control group , but no significant change of specific IgE was observed in either groups . In the SLIT group , there was no significant difference between children less than or more than 5 year old in terms clinical efficacy , onset of action , immunologic parameters , and safety . No severe systemic AEs were reported . Conclusion SLIT is effective and well-tolerated in children with allergic rhinitis 3–13 years old Background : It has been reported that both sublingual ( SLIT ) and subcutaneous ( SCIT ) allergen-specific immunotherapy have clinical efficacy , yet there are rather few comparative placebo studies of children . We aim ed to investigate the clinical and immunological efficacy of mite-specific SLIT and SCIT versus a placebo in rhinitis and asthma in children . Methods : The outcomes of this 1-year , r and omized , placebo-controlled , double-blind , double-dummy study were symptom and medication scores , visual analog scores ( VAS ) , titrated skin prick tests , nasal and bronchial allergen provocation doses , serum house dust mite-specific immunglobulin E ( HDM-sIgE ) , sIgG4 , IL-10 and IFN-γ levels . Results : Clinical and laboratory parameters were evaluated in 30 patients . SCIT significantly diminished symptom and medication scores for rhinitis and asthma ( p = 0.03 and p = 0.05 for rhinitis ; p = 0.01 and p = 0.05 for asthma ) and VAS . SLIT also reduced VAS , symptoms associated with rhinitis and asthma as well as medication usage for rhinitis , but this reduction was not significant when compared with the placebo . Skin reactivitiy to HDM and HDM-sIgE levels was reduced significantly in both immunotherapy groups . Serum IL-10 levels and nasal provocative doses increased significantly with both SCIT and SLIT . Nasal eosinophil increments after nasal challenge decreased with two treatment modes , but bronchial provocative doses and sputum eosinophil increments after bronchial challenge were reduced only with SCIT . In both treatment arms , there was no change in IFN-γ levels . Serum sIgG4 levels increased significantly only in the SCIT group . Conclusion : Based on the limited number of patients at the end of the 1-year immunotherapy , the clinical efficacy of SCIT on rhinitis and asthma symptoms was more evident when compared with the placebo Immunotherapy in elderly patients is controversial , and there is still no evidence supporting this treatment 's safety and efficacy in this population . This study was performed to evaluate the safety and efficacy of specific sublingual immunotherapy for house dust mite ( HDM ) allergens in patients over 60 years of age with allergic rhinitis and a confirmed allergy to HDM BACKGROUND Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy . We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy . METHODS We used a double-blind placebo-controlled design . 20 patients with mite-induced rhinoconjunctivitis ( six of whom also had mild asthma ) were r and omly assigned sublingual/oral immunotherapy ( n=10 ) or placebo ( n=10 ) for 2 years . We assessed symptom score by diary cards and inflammatory-cell infiltrate , and expression of intercellular adhesion molecule 1 ( ICAM-1 ) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment . FINDINGS We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months ( p=0.05 ) . Compared with the placebo group , inflammatory-cell infiltration after conjunctival challenge , and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group ( p=0.04 and p=0.02 , respectively ) . These effects were also seen for the minimum persistent inflammation , in symptom-free patients exposed constantly to allergens ( p=0.02 ) . Serum concentrations of eosinophil cationic protein decreased significantly ( p=0.04 ) . Immunotherapy was well tolerated and compliance was good . INTERPRETATION Our results suggest that this immunotherapy is clinical ly effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen RATIONALE Sublingual allergen-specific immunotherapy is gaining popularity for treatment of allergic diseases , but underlying immunological mechanisms are unresolved . OBJECTIVES To perform detailed immunological investigation of sublingual house dust mite ( HDM ) immunotherapy . METHODS A 12-month r and omized double-blind placebo-controlled study of sublingual HDM immunotherapy in 30 HDM-allergic subjects was performed , with 1-year open extension in 9 patients on active treatment . HDM-stimulated blood mononuclear cells were analyzed for proliferation , cytokines , and regulatory T cells ( Tregs ) by flow cytometry and ELISA . Effects of blocking transforming growth factor (TGF)-beta and IL-10 on proliferation were determined . Treg suppressor function and allergen-specific antibody levels were measured . Clinical efficacy was assessed by symptom , medication , and Juniper quality -of-life scores . MEASUREMENTS AND MAIN RESULTS Allergen-induced CD4(+ ) T-cell division and IL-5 production were significantly decreased after 6- and 12-months ' active treatment but not placebo . sTGF-betaRII blocked immunotherapy-induced suppression of allergen-specific T-cell proliferation , maximal at 6 months . Decreased allergen-specific CD4(+ ) T-cell proliferation and increased IL-10 secretion and serum Der p 2-specific IgG(4 ) were maximal at 24 months ' active treatment . Treg ( CD4(+)CD25(+)CD127(lo)/Foxp3(+ ) ) function was demonstrated by suppression of allergen-specific effector T-cell ( CD4(+)CD25(-)CD127(hi ) ) proliferation and cytokine production . Clinical efficacy of immunotherapy was supported by significantly decreased rhinitis symptom score , total asthma score , and Juniper quality -of-life score . CONCLUSIONS This study establishes the novel finding that TGF-beta mediates the immunological suppression seen early in clinical ly effective sublingual HDM immunotherapy in addition to an increase in Tregs with suppressor function . Clinical trial registered with www . clinical trials.gov ( NCT00250263 ) To evaluate the efficacy of specific sublingual immunotherapy ( SLIT ) , we enrolled 15 children with asthma and rhinitis ( 7 girls , 8 boys , mean + /- SD age of 11.7 + /- 3.3 ) allergic to house dust mite ( HDM ) into a double-blind , placebo-controlled study . After a run-in period , patients were r and omized to receive either placebo ( n = 7 ) or SLIT ( n = 8) with a st and ardized Dermatophagoides pteronyssinus ( D. pteronyssinus ) + Dermatophagoides farinea ( D. farinea ) 50/50 extract . They received increasing doses up to 100 index units of reactivity ( IR ) every day for 4 weeks , then 100 IR/day for another 4 weeks , followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months . Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores , serum total IgE levels , results of lung function tests , methacholine provocation tests , and skin prick tests . Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group ( P = 0.05 , P = 0.028 , respectively ) , whereas no such difference was observed in the placebo group . At the end of follow-up , mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group ( P = 0.04 ) . Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups , whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group ( P = 0.026 ) . At the end of 6 months , peak expiratory flow ( PEF ) values in the placebo group was significantly lower than in the SLIT group ( P = 0.049 ) . Throughout the treatment period , the SLIT group was found to have less asthma exacerbations than the placebo group ( P = 0.007 ) . The provocation concentration causing a 20 % drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups . None of the patients reported local or systemic side effects from SLIT . Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM Fifty eight patients under 12 years of age , positive to mites ( Dermatophagoides pteronyssinus and D. farinae ) according to prick , " in vitro " specific IgE and challenge tests , suffering from asthma and rhinitis , were r and omly assigned on a double blind basis to receive per os either a biologically st and ardized extract of mites ( active therapy TA = 30 patients ) or a saline buffered solution ( placebo = 28 patients ) . Patients took sublingually increasing doses of the solution , followed by maintenance therapy consisting of 15 drops 3 times a week . The results of the trial were assessed after 12 an 18 months , according to the following parameters : symptom scores recorded in diary cards , total and specific IgE levels , total IgG level , IgG1 and IgG4 levels , lymphocytes under population s , nasal challenge test , side effects . During the first 18 months , the patients on active therapy had significantly lower scores ( p less than 0.001 ) and clear variations of rhinomanometric parameters ( p less than 0.01 ) ; IgG also significantly increased . After 12 months , bronchial specific and specific challenge tests showed significantly higher threshold values in comparison to initial values ( p less than 0.05 ) . No statistically significative variation was registered in the placebo group Background : Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy ( SLIT ) in children is still poor BACKGROUND Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite ( HDM ) extracts in adults with allergic rhinitis . OBJECTIVES We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year . METHODS Adults with HDM-associated allergic rhinitis were r and omized in a double-blind , placebo-controlled study to receive 500 index of reactivity ( IR ) tablets , 300IR tablets , or placebo administered once daily for 1 year and were followed for the subsequent year . The primary efficacy variable was the Average Adjusted Symptom Score over the year 1 primary period ( ie , October 1 to December 31 ) . Symptoms and rescue medication scores , onset of action , patient-reported outcomes , and safety were secondary variables . The same end points were evaluated during the immunotherapy-free year . The primary efficacy end point was analyzed by using analysis of covariance . RESULTS Five hundred nine participants were r and omized , and 427 continued in the immunotherapy-free year . Both the 500IR and 300IR HDM sublingual tablets significantly reduced mean Average Adjusted Symptom Scores compared with placebo by -20.2 % ( P = .0066 ) and -17.9 % ( P = .0150 ) , respectively . Efficacy of both doses was maintained during the treatment-free follow-up phase . The onset of action was at 4 months . Participants ' global evaluation of treatment success was significantly higher in the 500IR and 300IR groups compared with the placebo group ( P = .0206 and P = .0001 , respectively ) . Adverse events were generally application-site reactions . There were no reports of anaphylaxis . CONCLUSIONS Twelve months of treatment with 500IR and 300IR sublingual tablets of HDM allergen extracts was efficacious and well tolerated . Efficacy was maintained during the treatment-free follow-up year OBJECTIVES /HYPOTHESIS To investigate how quickly an allergic rhinitis ( AR ) patients ' symptoms will improve with sublingual immunotherapy ( SLIT ) . STUDY DESIGN Double-blind placebo study . METHODS This is a multicenter , r and omized , double-blind , placebo-controlled study of SLIT used to treat house dust mite-induced AR . A total of 120 AR patients , aged 4 to 60 years , were treated for 6 months and r and omized into two groups : 1 ) SLIT with Dermatophagoides pteronyssinus ( D.p . ) and Dermatophagoides farina ( D.f . ) extract ( n = 60 ) ; and 2 ) matched placebo controls ( n = 60 ) . Symptom , medications received , and a visual analog scale score were recorded during the whole study . Serum-specific IgE and IgG4 to D. p. and D. f. were assessed before and after the treatment . RESULTS Eighty-five patients ( 70.8 % ) completed the study . Twelve patients ( 20 % ) chose to withdraw from the SLIT group , but none because of serious adverse effects . The total symptom and visual analog scores VAS in the SLIT group decreased significantly when compared to the placebo controls ( P < 0.05 ) after week 14 , as well as for the significant ( P < 0.05 ) improvement of all individual AR symptoms in the SLIT group ( e.g. , sneezing , nasal discharge , itching , and nasal obstruction ) after week 22 . There was a significant ( P < 0.05 ) increase of IgG4 to both D.f . and D.p . in the SLIT , but not in the placebo group after treatment . CONCLUSION SLIT with a mixture of D.f . and D.p . extract is an effective and safe treatment for patients with house dust mite-induced AR . Its onset of action can be observed as early as 14 weeks after treatment The clinical efficacy of sublingual immunotherapy ( SLIT ) has been demonstrated , but its mechanism of action is still controversial . The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines , such as interleukin-4 ( IL-4 ) , IL-5 and IL-13 , by co-stimulatory molecules , such as CD40 on B cells , and by hormones and neuropeptides . To better underst and whether SLIT affects immune responses we used a double-blind placebo-controlled design . Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus ( 33 of whom also had rhinoconjunctivitis ) were r and omly assigned SLIT ( n = 47 ) or placebo ( n = 39 ) . We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP , IL-13 , prolactin ( PRL ) and ACTH at enrolment and after 6 months of therapy . We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group , no variation in CD40 and ACTH , but a significant decrease in ECP , IL-13 and PRL after 6 months of therapy ( p < 0.01 ) . Our results confirm the efficacy and safety of SLIT , and lead us to believe that it could modulate the synthesis of Th2 cytokines , as revealed from the decrease of IL-13 . In addition , the reduction of PRL might be a signal of reduced activation of T lymphocytes BACKGROUND Cytokine responses accompanying sublingual immunotherapy ( SLIT ) responder phenotypes have not previously been reported . OBJECTIVE To investigate clinical and cytokine responses of house dust mite ( HDM ) sensitive patients with allergic rhinitis receiving HDM SLIT or placebo for 2 years . METHODS Sixty adults were r and omized to receive SLIT or placebo . Clinical symptoms were measured using the Total 5 Symptom Score ( TSS5 ) and Juniper Rhinitis Quality of Life Question naire . HDM specific IgE , IgG , skin prick tests , and HDM-stimulated release of interleukin ( IL ) 5 and interferon γ ( IFN-γ ) in peripheral blood mononuclear cells was studied at 0 , 6 , 12 , and 24 months and IL-13 , IL-4 , and IL-10 at 0 and 24 months . RESULTS A total of 32 of 39 SLIT and 16 of 21 placebo patients completed the study . There was significant clinical improvement in both the SLIT and placebo groups . Median T5SS decreased from 14.75 to 5.25 in the SLIT group ( P < .001 ) and 12.7 to 6.0 in the placebo group ( P = .003 ) . The median quality -of-life score also decreased in the SLIT group ( P < .001 ) and the placebo group ( P < .001 ) . A subgroup analysis of patients found a 60 % or greater improvement ( on the T5SS and the Juniper Rhinitis Quality of Life Question naire ) in the good responders group and a 30 % to 59 % improvement or no improvement in the intermediate responders group . This subgroup analysis also found more good responders in the SLIT group ( 47 % ) compared with the placebo group ( 25 % ; P = .07 ) . Significant decreases in the IL-5/IFN-γ ( P < .001 ) , IL-13/IFN-γ ( P < .001 ) , and IL-4/IFN-γ ( P = .03 ) ratios were found in the combined good clinical improvement group at 24 months . CONCLUSION A good clinical response ( ≥60 % improvement in both TSS5 and quality of life ) is associated with significant decreases in IL-5 , IL-13 , and IL-4 relative to IFN-γ during 2 years of SLIT therapy for HDMs OBJECTIVE To evaluate the efficacy and safety of the sublingual immunotherapy with dermatophagoides farinae drops on patients with allergic rhinitis . METHOD One hundred and twelve cases were collected from adult patients with dust-mite allergic rhinitis of our hospital who could adhere to treatment and regular follow-up . These patients were r and omly allocated to receive either sublingual immunotherapy ( SLIT group , n = 56 ) or medical treatment ( Control group , n = 56 ) . To evaluate the clinical efficacy by side effects which were registered , symptom and medication scores which were assessed and rhinoconjunctivitis quality of life question naire ( RQLQ ) which was completed in the baseline and two years after treatment . RESULT Dropouts after the 2 years ' treatment were 5 of SLIT group and 4 of Control group respectively . SLIT group induced the significant reductions on both the symptom scores ( 7.81 ± 3.14 to 3.89 ± 2.01 , P < 0.0 1 ) and the medication scores ( 2.86 ± 0.75 to 0.44 ± 0.06 , P < 0.01 ) . Meanwhile , Control group induced the reductions on both the symptom scores ( 8.01 ± 3.32 to 5.20 ± 2.43 ) and the medication scores ( 2.95 ± 0.80 to 1.75 ± 0.40 ) . There were significant differences ( P < 0 . 01 ) in symptom and medication scores between the two groups after 2-year treatment . The patients in SLIT group had fewer symptoms and lower intake of medication . There were statistically significant differences in RQLQ between SLIT group [ 19 ( 15,22 ) ] and Control group [ 36 ( 26,47 ) ] after two years treatment ( Z = -5 . 21 , P < 0.01 ) . SLIT group also had significant improvement in RQLQ ( Z = -6.10 , P < 0.01 ) between before and after the treatment . There were 4 patients who showed adverse reactions in SLIT group ( 3 occurred in increment period , and 1 occurred in the maintenance period ) . The incidence of adverse reactions was 7.14 % . No severe systemic side effects were registered . CONCLUSION SLIT with st and ardized dermatophagoides farinae drops in China is safe and effective to patients with allergic rhinitis Background : The safety and efficacy of sublingual‐swallow immunotherapy ( SLIT ) in rhinitis caused by house‐dust mite were evaluated in a double‐blind , placebo‐controlled study including 75 patients for 24 months BACKGROUND The efficacy of therapy with sublingual allergen extracts is unproven . OBJECTIVE To evaluate the clinical and immunologic outcome of sublingual immunotherapy and to compare the results with subcutaneous immunotherapy and placebo in 36 patients with rhinitis and asthma due to mite allergy . METHOD Thirty-six patients with rhinitis and asthma due to mite allergy were r and omly divided into three groups in order to receive subcutaneous injections with allergenic extracts , sublingual drops with solutions of purified st and ardized allergen preparations , or sublingual placebo for a period of 1 year . Assessment of clinical and immunologic efficacy included symptom and medication scores , methacholine provocation tests , skin prick tests , and specific IgE and IgG4 antibody concentrations . RESULTS Subcutaneous immunotherapy for both rhinitis and asthma was clinical ly effective . Patients treated with sublingual immunotherapy had decreased rhinitis symptoms ( P < .01 ) but no change in asthma scores . Medication scores significantly decreased in both actively treated groups ( P < .01 ) at the first year compared with baseline . When skin prick tests were evaluated , the subcutaneously treated group had a significant decrease in the wheal diameter of D. pteronyssinus ( P < .01 ) , D. farinae ( P < .05 ) , and histamine ( P < .05 ) while other two groups showed no difference . There was no significant change in methacholine PC20 values in all groups at the end of the first year when compared with baseline . No change in D. pteronyssinus and D. farinae specific IgE levels were observed ; however , specific IgG4 concentrations were significantly higher than baseline both in sublingual and subcutaneous immunotherapy groups ( P < .05 ) after 1 year immunotherapy . No significant difference was obtained in any of these parameters in the placebo group . CONCLUSION Sublingual immunotherapy may be effective in patients with allergic rhinitis . Further , we believe it is a potential therapy for allergic asthmatic patients . The clinical usefulness of this form of immunotherapy ( when administered to larger study groups for a longer time ) and the mechanisms underlying its immunologic effect deserve additional studies BACKGROUND The magnitude of effect of sublingual immunotherapy for house dust mite (HDM)-induced allergic rhinitis with or without conjunctivitis is uncertain , partly because there are few well-controlled trials with well-defined doses . OBJECTIVE We sought to determine the dose-related efficacy and onset of action of the HDM sublingual immunotherapy tablet MK-8237 ( Merck/ALK-Abelló ) using the Vienna Challenge Chamber . METHODS In this r and omized , double-blind , single-site trial , adults with HDM-induced allergic rhinitis with or without conjunctivitis and with or without asthma ( n = 124 ) received 12 developmental units ( DU ) of MK-8237 , 6 DU of MK-8237 , or placebo daily for 24 weeks . Subjects underwent 6-hour exposure challenges at screening and weeks 8 , 16 , and 24 . The total nasal symptom score ( TNSS ) during chamber challenge at week 24 was the primary end point . The TNSS was the sum of 4 nasal symptom scores ( maximum = 12 ) . Total ocular symptom scores ( TOSSs ; 2 symptoms ; maximum = 6 ) and total symptom scores ( TSSs ; TSS = TNSS plus TOSS ; maximum = 18 ) were secondary end points . RESULTS Dose- and time-dependent improvements with MK-8237 versus placebo were observed . At week 24 , TNSS improvement relative to placebo was 48.6 % ( 95 % CI , 35.3 % to 60.2 % ) with 12 DU of MK-8237 and 26.6 % ( 95 % CI , 11.2 % to 39.6 % ) with 6 DU of MK-8237 . Statistically significant improvements for TNSSs were also observed at weeks 8 ( 12 DU of MK-8237 ) and 16 ( 6 and 12 DU of MK-8237 ) and for TOSSs and TSSs by both doses at week 24 . MK-8237 was well tolerated . No investigator-assessed anaphylactic allergic reactions or reactions requiring epinephrine were observed . CONCLUSIONS MK-8237 , 12 DU , reduced nasal and ocular symptoms and exceeded World Allergy Organization-established clinical efficacy criteria ( ≥20 % improvement vs placebo ) . The onset of action for 12 DU of MK-8237 was week 8 . MK-8237 , 12 DU , is appropriate for further evaluation to determine the magnitude of effect in an uncontrolled allergen exposure environment BACKGROUND The SQ HDM SLIT-tablet ( ALK ) has been developed for treatment of house dust mite (HDM)-induced respiratory allergic disease . OBJECTIVE This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis ( AR ) . METHODS The trial was a r and omized , double-blind , placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy . Subjects were r and omized 1:1:1 to 1 year of daily treatment with placebo , 6 SQ-HDM , or 12 SQ-HDM . The primary end point was the total combined rhinitis score ( ie , the sum of rhinitis symptom and medication scores ) during the efficacy assessment period ( approximately the last 8 weeks of the treatment period ) . Key secondary end points were rhinitis symptoms , medication scores , quality of life , and the combined rhinoconjunctivitis score . RESULTS Analysis of the primary end point ( observed data ) demonstrated absolute reductions in total combined rhinitis score of 1.18 ( P = .002 ) and 1.22 ( P = .001 ) compared with placebo for 6 SQ-HDM and 12 SQ-HDM , respectively . The statistically significant treatment effect was evident from 14 weeks of treatment onward . For all key secondary end points , efficacy was confirmed for 12 SQ-HDM , with statistically significant reductions of rhinitis symptoms and medication scores , improved quality of life , and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo . The treatment was well tolerated . CONCLUSION The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR . The treatment effect was present from 14 weeks of treatment onward |
11,397 | 20,651,185 | Scanner and reconstruction parameters can significantly affect SUV measurements . | OBJECTIVE There is growing interest in using PET/CT for evaluating early response to therapy in cancer treatment .
Although widely available and convenient to use , st and ardized uptake value ( SUV ) measurements can be influenced by a variety of biologic and technologic factors .
Many of these factors can be addressed with close attention to detail and appropriate quality control .
This article will review factors potentially affecting SUV measurements and provide recommendations on ways to minimize when using serial PET to assess early response to therapy . | Purpose The presence of contrast material s on computed tomography ( CT ) images can cause problems in the attenuation correction of positron emission tomography ( PET ) images . These are because of errors converting the CT attenuation of contrast to 511-keV attenuation and by the change in tissue enhancement over the duration of the PET emission scan . Newer CT-based attenuation correction ( CTAC ) algorithms have been developed to reduce these errors . Methods To evaluate the effectiveness of the modified CTAC technique , we performed a retrospective analysis on 20 patients , comparing PET images using unenhanced and contrast-enhanced CT scans for attenuation correction . A phantom study was performed to simulate the effects of contrast on radiotracer concentration measurements . Results There was a maximum difference in calculated radiotracer concentrations of 5.9 % within the retrospective data and 7 % within the phantom data . Conclusion Using a CTAC algorithm that de-emphasizes high-density areas , contrast-enhanced CT can be used for attenuation mapping without significant errors in quantitation Objectives The aim of this prospect i ve study was to assess the influence of different normalization procedures on relative changes in st and ardized uptake values ( SUV ) of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography ( FDG-PET ) for the assessment of chemotherapy response in patients with colorectal carcinoma ( CRC ) and nonsmall cell lung carcinoma ( NSCLC ) . Methods In 97 patients with CRC ( n = 48 ) and NSCLC ( n = 49 ) , FDG-PET was performed before and during the course of chemotherapy . Relative changes in SUV ( ΔSUV ) were determined after correction for injected dose and bodyweight , lean body mass , body surface area or a combination of bodyweight and plasma glucose . The predictive value for overall and progression-free survival with respect to the different normalized ΔSUVs was assessed . Results In both CRC and NSCLC , no differences were seen in the degree of change between the four SUV-normalizations during chemotherapy . Cox regression analysis for overall survival showed significant hazard ratios of 1.14–1.16 per 10 % SUV change in CRC and 1.10–1.13 in NSCLC and for progression-free survival hazard ratios of 1.15 per 10 % ΔSUV change in CRC and 1.10–1.12 in NSCLC . Conclusion Relative changes in SUV is a strong predictor for survival in both CRC and NSCLC . None of the four normalization methods showed statistical advantage over the other . Therefore , simplifying the methods for analysis of FDG-PET data can improve the incorporation of FDG-PET in clinical treatment – response monitoring and may facilitate application in multicentre trials UNLABELLED This study evaluated various quantitative criteria for analysis of breast imaging with PET using the radiolabeled glucose analog 18F-fluorodeoxyglucose ( FDG ) . METHODS In a prospect i ve study , 73 patients with abnormal mammography or palpable breast masses scheduled for biopsy were investigated with PET . A total of 97 breast tumors were evaluated by histology , including 46 benign and 51 malignant tumors . Using a whole-body PET scanner , attenuation-corrected images were acquired between 40 and 60 min after tracer injection . For Patlak analysis , dynamic data acquisition was obtained in 24 patients . To differentiate between benign and malignant breast tumors , receiver operating characteristic curves were calculated using incrementally increasing threshold values for tumor/ nontumor ratios based on average and maximum activity values per region of interest , st and ardized uptake values ( corrected for partial volume effect , normalized to blood glucose , partial volume effect and blood glucose , using the lean body mass as well as the body surface area ) and calculating the FDG influx rate ( K ) assessed by Patlak analysis . RESULTS Quantification of FDG uptake in breast tumors provided objective criteria for differentiation between benign and malignant tissue with similar diagnostic accuracy as compared with visual analysis . Applying correction for partial volume effect and normalization by blood glucose yielded the highest diagnostic accuracy . CONCLUSIONS These quantitative methods provided accurate evaluation of PET data for differentiating benign from malignant breast tumors . Quantitative assessment is recommended to complement visual image interpretation with the potential benefit of reduced interobserver variability UNLABELLED St and ardized uptake values ( SUVs ) are widely used to measure 18F-fluorodeoxyglucose ( FDG ) uptake in various tumors . It has been reported that normalization of FDG uptake for patient body weight ( SUVbw ) overestimates FDG uptake in heavy patients , as their fraction of body fat ( with low FDG uptake ) is often increased . The objective of this study was to determine if " normalization of FDG uptake for the body surface area " ( SUVbsa ) is independent of the patient 's body size and is more reliable than SUVbw . METHODS FDG-PET images were acquired on 44 patients ( body weight range : 45 - 115 kg ) with cancer . SUVbw [ ( mCi/g of tissue)/(mCi injected/patient body weight in g ) ] and SUVbsa [ ( mCi/g of tissue)/(mCi injected/patient BSA in m2 ) ] were determined for the liver . Since most observers are accustomed to using the SUVbw , the two values were compared by setting the mean SUVbsa equal to that of SUVbw . RESULTS SUVbw and SUVbsa were 3.42 + /- 0.85 ( mean + /- s.d . ) and 3.42 + /- 0.60 , respectively . The st and ard deviation of the SUVbsa was smaller than that of SUVbw . More importantly , there was a strong positive correlation between SUVbw and , not only body weight ( r = 0.75 ) but also BSA ( r = 0.68 ) , whereas only a weak correlation between SUVbsa and body weight ( r = 0.41 ) or BSA ( r = 0.38 ) was found with a near flat regression line . CONCLUSION SUVbw overestimates FDG uptake in large patients . SUVbsa appears preferable to SUVbw , since it is minimally affected by the body size 18F-FDG PET is increasingly being used to monitor the early response of malignant tumors to chemotherapy . Underst and ing the reproducibility of st and ardized uptake values ( SUVs ) is an important prerequisite in estimating what constitutes a significant change . Methods : Twenty-six patients were studied on 2 separate occasions ( mean interval ± SD , 3 ± 2 d ; range , 1–5 d ) . A static PET/CT scan was performed 94 ± 9 min after the intravenous injection of 383 ± 15 MBq of 18F-FDG . Mean and maximum SUVs ( SUVmean and SUVmax , respectively ) were determined for regions of interest drawn around the tumor on the first study and for the same regions of interest transferred to the second study . Results : SUVmean in tumors ranged from 1.49 to 17.48 and SUVmax ranged from 2.99 to 24.09 . The correlation between SUVmean determined on the 2 separate visits was 0.99 ; the mean difference between the 2 measurements was 0.01 ± 0.27 SUV . The 95 % confidence limits for the measurements were ±0.53 . For SUVmax , the mean difference was −0.05 ± 1.14 SUV . Conclusion : Our study demonstrates that repeated measurements of SUVmean performed a few days apart are highly reproducible . A decrease of 0.5 in the SUV is statistically significant Over the years several analytical methods have been proposed for the measurement of glucose metabolism using fluorine-18 fluorodeoxyglucose ( [18F]FDG ) and positron emission tomography ( PET ) . The purpose of this study was to evaluate which of these ( often simplified ) methods could potentially be used for clinical response monitoring studies in breast cancer . Prior to chemotherapy , dynamic [18F]FDG scans were performed in 20 women with locally advanced ( n=10 ) or metastasised ( n=10 ) breast cancer . Additional PET scans were acquired after 8 days ( n=8 ) , and after one , three and six courses of chemotherapy ( n=18 , 10 and 6 , respectively ) . Non-linear regression ( NLR ) with the st and ard two tissue compartment model was used as the gold st and ard for measurement of [18F]FDG uptake and was compared with the following methods : Patlak graphical analysis , simplified kinetic method ( SKM ) , SUV-based net influx constant ( " Sadato " method ) , st and ard uptake value [ normalised for weight , lean body mass ( LBM ) and body surface area ( BSA ) , with and without corrections for glucose ( g ) ] , tumour to non-tumour ratio ( TNT ) , 6P model and total lesion evaluation ( TLE ) . Correlation coefficients between each analytical method and NLR were calculated using multilevel analysis . In addition , for the most promising methods ( Patlak , SKM , SUVLBMg and SUVBSAg ) it was explored whether correlation with NLR changed with different time points after the start of therapy . Three methods showed excellent correlation ( r>0.95 ) with NLR for the baseline scan : Patlak10–60 and Patlak10–45 ( r=0.98 and 0.97 , respectively ) , SKM40–60 ( r=0.96 ) and SUVLBMg ( r=0.96 ) . Good correlation was found between NLR and SUV-based net influx constant , TLE and SUVBSAg ( 0.90<r<0.95 ) . The 6P model and TNT had the lowest correlation ( r≤0.84 ) . SUV was least accurate in predicting changes in [18F]FDG uptake over time during therapy . For all methods , correlation with NLR was significantly lower for bone metastases than for other ( primary or metastatic ) tumour lesions ( P<0.05 ) . In conclusion , three methods with different degrees of complexity appear to be promising alternatives to NLR for measuring glucose metabolism in breast cancer : Patlak , SKM and SUV ( normalised for LBM and with a correction for plasma glucose ) The aim of chemotherapy for mesothelioma is to palliate symptoms and improve survival . Measuring response using CT is challenging because of the circumferential tumor growth pattern . This study aims to evaluate the role of serial 18F-FDG PET in the assessment of response to chemotherapy in patients with mesothelioma . Methods : Patients were prospect ively recruited and underwent both 18F-FDG PET and conventional radiological response assessment before and after 1 cycle of chemotherapy . Quantitative volume-based 18F-FDG PET analysis was performed to obtain the total glycolytic volume ( TGV ) of the tumor . Survival outcomes were measured . Results : Twenty-three patients were suitable for both radiological and 18F-FDG PET analysis , of whom 20 had CT measurable disease . After 1 cycle of chemotherapy , 7 patients attained a partial response and 13 had stable disease on CT assessment by modified RECIST ( Response Evaluation Criteria in Solid Tumors ) criteria . In the 7 patients with radiological partial response , the median TGV on quantitative PET analysis fell to 30 % of baseline ( range , 11%–71 % ) . After 1 cycle of chemotherapy , Cox regression analysis demonstrated a statistically significant relationship between a fall in TGV and improved patient survival ( P = 0.015 ) . Neither a reduction in the maximum st and ardized uptake value ( P = 0.097 ) nor CT ( P = 0.131 ) demonstrated a statistically significant association with patient survival . Conclusion : Semiquantitative 18F-FDG PET using the volume-based parameter of TGV is feasible in mesothelioma and may predict response to chemotherapy and patient survival after 1 cycle of treatment . Therefore , metabolic imaging has the potential to improve the care of patients receiving chemotherapy for mesothelioma by the early identification of responding patients . This technology may also be useful in the assessment of new systemic treatments for mesothelioma Objectives Peristalsis can lead to confusing FDG PET bowel uptake artefacts and potential for recording inaccurate mean st and ardised uptake value ( SUV ) measurements in PET-CT scans . Accordingly , we investigate the influence of different SUV normalisations on FDG PET uptake of the bowel and assess which one(s ) have least dependence on body size factors in patients with and without the introduction of the anti-peristalsis agent N-butylscopolamine ( Buscopan ) . Methods This study consisted of 92 prospect i ve oncology patients , each having a whole body 18F-FDG PET scan . Correlations were investigated between height , weight , glucose , body mass index ( bmi ) , lean body mass ( lbm ) and body surface area ( bsa ) with maximum and mean SUV recorded for bowel normalised to weight ( SUVw ) , lbm ( SUVlbm ) , bsa ( SUVbsa ) and blood glucose corrected versions ( SUVwg , SUVlbmg , SUVbsag ) . Results St and ardised uptake value normalisations were significantly different between control and Buscopan groups with less variability experienced within individual SUV normalisations by the administration of Buscopan . Mean SUV normalisations accounted for 80 % of correlations in the control group and 100 % in the Buscopan group . Further , > 86 % of all correlations across both groups were dominated by mean SUV normalisations of which , about 69 % were accounted for by SUVbsa and SUVbsag . Conclusions We recommend avoiding mean SUVbsa and individual glucose normalisations especially , mean SUVbsag as these dominated albeit relatively weak correlations with body size factors in control and Buscopan groups . Mean and maximum SUVw and SUVlbm were shown to be independent of any body size parameters investigated in both groups and therefore considered suitable for monitoring FDG PET uptake in the normal bowel for our patient cohort 18F-FDG PET is often used to monitor tumor response in multicenter oncology clinical trials . This study assessed the repeatability of several semiquantitative st and ardized uptake values ( mean SUV [ SUVmean ] , maximum SUV [ SUVmax ] , peak SUV [ SUVpeak ] , and the 3-dimensional isocontour at 70 % of the maximum pixel value [ SUV70 % ] ) as measured by repeated baseline 18F-FDG PET studies in a multicenter phase I oncology trial . Methods : Double-baseline 18F-FDG PET studies were acquired for 62 sequentially enrolled patients . Tumor metabolic activity was assessed by SUVmean , SUVmax , SUVpeak , and SUV70 % . The effect on SUV repeatability of compliance with recommended image-acquisition guidelines and quality assurance ( QA ) st and ards was assessed . Summary statistics for absolute differences relative to the average of baseline values and repeatability analysis were performed for all patients and for a subgroup that passed QA , in both a multi- and a single-observer setting . Intrasubject precision of baseline measurements was assessed by repeatability coefficients , intrasubject coefficients of variation ( CV ) , and confidence intervals on mean baseline differences for all SUV parameters . Results : The mean differences between the 2 SUV baseline measurements were small , varying from −2.1 % to 1.9 % , and the 95 % confidence intervals for these mean differences had a maximum half-width of about 5.6 % across the SUV parameters assessed . For SUVmax , the intrasubject CV varied from 10.7 % to 12.8 % for the QA multi- and single-observer data sets and was 16 % for the full data set . The 95 % repeatability coefficients ranged from −28.4 % to 39.6 % for the QA data sets and up to −34.3 % to 52.3 % for the full data set . Conclusion : Repeatability results of double-baseline 18F-FDG PET scans were similar for all SUV parameters assessed , for both the full and the QA data sets , in both the multi- and the single-observer setting s. Central ized quality assurance and analysis of data improved intrasubject CV from 15.9 % to 10.7 % for averaged SUVmax . Thresholds for metabolic response in the multicenter multiobserver non-QA setting s were −34 % and 52 % and in the range of −26 % to 39 % with central ized QA . These results support the use of 18F-FDG PET for tumor assessment in multicenter oncology clinical trials UNLABELLED We previously reported that respiratory motion is a major source of error in quantitation of lesion activity using combined PET/CT units . CT acquisition of the lesion occurs in seconds , rather than the 4 - 6 min required for PET emission scans . Therefore , an incongruent lesion position during CT acquisition will bias activity estimates using PET . In this study , we systematic ally analyzed the range of activity concentration changes , hence SUV , for lung lesions . METHODS Five lung cancer patients were scanned with PET/CT . In CT , data were acquired in correlation with the real-time positioning . CT images were acquired , in cine mode , at 0.45-s intervals for slightly longer ( 1 s ) than a full respiratory cycle at each couch position . Other scanning parameters were a 0.5-s gantry rotation , 140 kVp , 175 mA , 10-mm couch increments , and a 2.5-mm slice thickness . PET data were acquired after intravenous injection of about 444 - 555 MBq of (18)F-FDG with a 1-h uptake period . The scanning time was 3 min per bed position for PET . Regularity in breathing was assisted by audio coaching . A commercial software program was then used to sort the acquired CT images into 10 phases , with 0 % corresponding to end of inspiration ( EI ) and 50 % corresponding to end of expiration ( EE ) . Using the respiration-correlated CT data , images were rebinned to match the PET slice locations and thickness . RESULTS We analyzed 8 lesions from 5 patients . Reconstructed PET emission data showed up to a 24 % variation in the lesion maximum st and ardized uptake values ( SUVs ) between EI and EE phases . Examination of all the phases showed an SUV variation of up to 30 % . Also , in some cases the lesion showed up to a 9-mm shift in location and up to a 21 % reduction in size when measured from PET during the EI phase , compared with during the EE phase . CONCLUSION Using respiration-correlated CT for attenuation correction , we were able to quantitate the fluctuations in PET SUVs . Because those changes may lead to estimates of lower SUVs , the respiratory phase during CT transmission scanning needs to be measured or lung motion has to be regulated for imaging lung cancer in routine clinical practice UNLABELLED Our objective was to derive the best glucose sensitivity factor ( g-value ) and the most discriminating st and ardized uptake value ( SUV ) normalized to glucose for classifying indolent and aggressive lymphomas . METHODS The maximum SUV obtained from (18)F-FDG PET over the area of biopsy in 102 patients was normalized by serum glucose ( [ Glc ] ) to a st and ard of 100 mg/dL. Discriminant analysis was performed by using each SUV(100 ) ( SUV x {100/[Glc]}(g ) , calculated using various g-values ranging from -3.0 to 0 , one at a time ) as a variable against the lymphoma grade s , and plotting the percentage of correct classifications against g ( g-plot ) to search for the best g-value in normalizing SUV(100 ) for classifying grade s. To address the influence of the extreme glucose conditions , we repeated the same analyses in 12 patients with [ Glc ] < or = 70 mg/dL or [ Glc ] > or = 110 mg/dL. RESULTS SUV(100 ) correctly classified lymphoma grade s ranging from 62 % to 73 % ( P < 0.0005 ) , depending on the g-value , with a maximum at a g-value of -0.5 . For the subgroup with extreme glucose values , the g-plot also revealed higher and more optimal discrimination at a g-value of -0.5 ( 92 % ) than at a g-value of 0 ( 83 % ) ( P = 0.03 ) . The discrimination deteriorated at g < -1 in both analyses . The box plot for all cases using a g-value of -0.5 showed little overlap in classifying lymphoma grade s. For a visually selected threshold SUV(100 ) of 7.25 , the sensitivity , specificity , and accuracy of identifying aggressive grade s were 82 % , 79 % , and 81 % , respectively . CONCLUSION The results suggest that metabolic discrimination between lymphoma grade s using a glucose-normalized SUV from (18)F-FDG PET is improved by introducing g-value as an extra degree of freedom PURPOSE To reevaluate the relationships between st and ardized uptake values ( SUVs ) and body weight by using positron emission tomography ( PET ) with 2-[fluorine 18]fluoro-2-deoxy-D-glucose ( FDG ) . MATERIAL S AND METHODS FDG PET scanning was performed in 138 female patients with known or suspected primary breast cancers . SUVs in blood and tumor ( n = 79 ) were calculated by using body weight ( SUVbw ) , ideal body weight ( SUVibw ) , lean body mass ( SUVlbm ) , and body surface area ( SUVbsa ) on images obtained 50 - 60 minutes after the injection of FDG . RESULTS There was a strong positive correlation between the blood SUVbw and body weight ( r = 0.705 , P < .001 ) . The blood SUVibw reduced the weight dependence but showed a negative correlation with body weight ( r = -0.296 , P < .001 ) . Both the blood SUVibm and SUVbsa eliminated the weight dependence and showed no correlation with body weight ( r = -0.010 , P = .904 and r = 0.106 , P = .215 , respectively ) . Although there was a wide variance in the tumor SUVbw , it showed a weak but significant positive correlation with body weight ( r = 0.207 , P = .033 ) . Plots of the tumor SUVlbm and SUVbsa versus body weight showed relatively flat slopes . CONCLUSION SUVlbm and SUVbsa are weight-independent indices for FDG uptake , and SUVlbm appears to be more appropriate for quantifying FDG uptake to avoid overestimation of glucose utilization in obese patients |
11,398 | 15,681,586 | Acetaminophen administration was not associated with a decrease in the incidence of morphine-related adverse effects or an increase in patient satisfaction .
Adding acetaminophen to PCA was associated with a morphine-sparing effect of 20 % ( mean , -9 mg ; CI -15 to -3 mg ; P=0.003 ) over the first postoperative 24 h. CONCLUSION Acetaminophen combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period | BACKGROUND Acetaminophen is commonly used for the management of perioperative pain .
However , there is a marked discrepancy between the extent to which acetaminophen is used and the available evidence for an analgesic effect after major surgery .
The aim of this systematic review is to determine the morphine-sparing effect of acetaminophen combined with patient-controlled analgesia ( PCA ) with morphine and to evaluate its effects on opioid-related adverse effects . | The efficiency and safety of postoperative use of propacetamol was estimated in 30 patients by means of double blind placebo controlled method . The first group consisted of 15 patients to whom propacetamol was introduced intravenously in single dose of 2 g along with patient controlled anesthesia with promedol . Placebo in combination with patient control anesthesia were used in 15 patients from the 2nd group . Intravenous introducing of propacetamol in dose of 2 g in 15 minutes provides relief of pain intensity in postoperative period . So it permits to consider propacetamol as basic non-opioid analgesic . In early postoperative period combination of propacetamol and opioid analgesic ( promedol ) reduces dem and s in the latter by 44 % BACKGROUND Propacetamol is widely used in the management of postoperative pain . It decreases morphine requirements but its effect on the incidence of morphine-related adverse effects remains unknown . METHODS Patients ( 550 ) were r and omly assigned to receive propacetamol or a placebo over the first 24 h after operation in a blinded study . Intravenous morphine titration was performed , after which morphine was administered s.c . every 4 h according to their pain score . Pain was assessed using a visual analogue scale ( VAS ) . The primary end-point was the incidence of morphine-related adverse effects . The main secondary end-points were morphine requirements and VAS score . RESULTS After morphine titration , the VAS score and the number of patients with pain relief did not differ between groups . Morphine requirements were decreased in the propacetamol group ( 21 vs 14.5 mg , P<0.001 ) but the incidence of morphine-related adverse effects did not differ between groups ( 42 vs 46 % , not significant ) . In patients with moderate pain ( n=395 ) , morphine requirements decreased by 37 % ( P<0.001 ) and the percentage of patients requiring no morphine was greater ( 21 vs 8 % , P=0.002 ) in the propacetamol group . In patients with severe pain ( n=155 ) , morphine requirements decreased by 18 % ( P=0.04 ) in the propacetamol group and the number of patients who did not require morphine ( 3 vs 8 % ) did not differ significantly . CONCLUSIONS Although propacetamol induced a small morphine-sparing effect , it did not change the incidence of morphine-related adverse effects in the postoperative period . Moreover , no benefit could be demonstrated in patients with severe postoperative pain In order to compare the morphine‐sparing effect , analgesic efficacy and tolerance of nefopam and propacetamol given at their highest recommended doses , 120 patients undergoing elective hepatic resection were r and omly assigned to receive postoperative intravenous patient‐controlled analgesia with morphine alone , or in combination with nefopam ( 20 mg.4 h‐1 ) or propacetamol ( 2 g.6 h‐1 ) . Compared with the control group ( 43 [ 7–92 ] mg ) , median [ range ] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group ( 21 [ 3–78 ] mg , p < 0.001 ) and 20 % lower in the propacetamol group ( 35 [ 6–84 ] mg , p = 0.15 ) . Analgesia was superior in the nefopam group despite the lower morphine consumption . Adverse effects were comparable in the three groups , except for significantly more nausea in the control group ( 39 % vs. 17 and 26 % in the nefopam and propacetamol groups , respectively ) and more sweating in the nefopam group ( 17 % vs. 0 and 3 % in the control and propacetamol groups , respectively ) . Overall patient satisfaction was better ( p < 0.001 ) in patients given nefopam ( 97 % ) than those receiving morphine alone ( 82 % ) or propacetamol ( 74 % ) Purpose The concept of balanced analgesia suggests that a combination of analgesic drugs may enhance analgesia and reduce side effects after surgery . This study evaluated the effect of the combination of propacetamol ( Prodafalgan ) and ketoprofen ( Profenid ) after surgery of a hemiated disc of the lumbar spine . Methods After r and omization . 60 patients received : placebo ( group 1 ) ; 2 g propacetamol ( group 2 ) ; 50 mg ketoprofen ( group 3 ) ; or a combination of 2 g propacetamol and 50 mg ketoprofen ( group 4 ) . Drugs were administered every six hours for two days after surgery . The patients used morphine with patient controlled analgesia pumps ( bolus 1 mg ; lock out time 10 min ) and were evaluated with a visual analogue scale ( VAS ) at rest and movement every six hours for two days . Side effects were noted . Results The patient characteristics and surgery were identical for each of the four groups . The VAS scores throughout the study were lower in group 4 than in groups 1 , 2 and 3 both at rest ( P < 0.05 ) and on movement ( P < 0.01 ) . The cumulative dose of morphine at 48 hr was lower in group 4 than in group 1 ( 23.4 ± 5 mg vs 58.9 ± 9 mg ; P < 0.01 ) or group 2 ( 23.4 ± 5 mg vs 43.4 ± 6.6 mg ; P < 0.05 ) and similar to that in group 3 ( 34.2 ± 4.5 mg ) . The incidence of side effects was similar in all groups . Conclusion The combination of propacetamol and ketoprofen reduced pain scores both at rest and on movement . The drug combination did not reduce the morphine consumption and incidence of side effects . RésuméButLe concept d’analgésie balancée suggère que I’association de drogues analgésiques en postopératoire peut permettre d’améliorer I’analgésie et réduire les effets secondaires . Cette étude a évalué I’intérêt d’une association de propacetamol ( Prodafalgan ) et de ketoprofen ( Profenid ) pour I’analgésie après chirurgie d’une hernie discale lombaire . MéthodesAprès r and omisation 60 patients ont reçu : un placebo ( groupe 1 ) ; 2 g de propacetamol ( groupe 2 ) ; 50 mg de ketoprofen ( groupe 3 ) ; où I’association de 2 g de propacetamol et 50 mg de ketoprofen ( groupe 4 ) . Les produits analgésiques ont été administrés toutes les six heures pendant 48 h. Les patients utilisaient de la morphine grâce à une pompe d’analgésie autocontrôlée pendant 48 h ( bolus 1 mg ; période réfractaire 10 mm ) et la douleur était évaluée par échelle visuelle analogique toutes les six heures au repos et au mouvement . Les effets secondaires étaient notés toutes les six heures . Result atsLes patients et la chirurgie étaient similaires dans les quatre groupes . Les scores d’EVA etaient plus bas pendant les 48 heures de I’étude dans le groupe 4 par rapport à ceux des groupes 1 , 2 et 3 au repos ( P < 0.05 ) comme au mouvement ( P < 0.01 ) . Les doses cumulées de morphine étaient significativement plus basses à 48 h dans le groupe 4 par rapport au groupe 1 ( 23.4 ± 5 mg vs 58.9 ± 9 mg ; P < 0.01 ) . groupe 2 ( 23.4 ± 5 mgvs 43.4 ± 6.6 mg ; P < 0.05 ) et pas significativement différentes de celles du groupe 3 ( 34.2 ± 4.5 mg ) . L’incidence des effets secondaires était similaire dans tous les groupes . Conclusion L’association de propacetamol et ketoprofen a réduit les scores de douleur au repos et au mouvement par rapport aux groupes traités par une seule drogue analgésique . Lassociation propacetamol-ketoprofen n’a pas significativement réduit la consommation de morphine et les effets secondaires Iiés à la morphine We assessed the analgesic efficacy of IV propacetamol and ketorolac in a double-blinded , placebo-controlled study involving patients undergoing total hip or knee replacement procedures . On the first morning after major joint replacement surgery , 164 patients experiencing moderate-to-severe pain were r and omly assigned to receive an IV infusion of propacetamol ( 2 g ) , ketorolac ( 15 or 30 mg ) , or placebo ( saline ) . Patient-controlled analgesia with morphine was made available as a “ rescue ” analgesic on patient ’s request during the 6-h postdosing evaluation period . The median time to onset of analgesia with propacetamol ( 8 [ 95 % confidence interval 6,10 ] min ) was shorter than ketorolac 15 mg ( 14 [ 7,16 ] min ) , and placebo ( 16 [ 8 ; not estimable ] min ) although the differences did not reach statistical significance . However , compared with ketorolac 30 mg , propacetamol had a shorter duration of analgesia ( 3.5 [ 2;5.4 ] vs 6 [ 3.3 ; not estimable ] h ) . Analysis of pain intensity and pain relief scores demonstrated that propacetamol produced a significantly greater improvement in pain relief than saline from 45 min until 5 h after the injection . Propacetamol was not significantly different from ketorolac 15 mg and 30 mg with respect to the main analgesic efficacy variables during the 6-h assessment period . The most frequently reported adverse event with propacetamol was injection site pain ( 28 % vs 19 % for ketorolac 15 mg , 29 % for ketorolac 30 mg , and 10 % for placebo , respectively ) . In conclusion , propacetamol ( 2 g IV ) possesses a similar analgesic efficacy to ketorolac ( 15 or 30 mg IV ) after total hip or knee replacement surgery We have evaluated the morphine-sparing effect of rectal paracetamol during the first 24 h after abdominal hysterectomy in a placebo-controlled , double-blind study . We studied 72 patients receiving patient-controlled analgesia ( PCA ) with i.v . morphine after a st and ardized anaesthetic , allocated r and omly to receive rectal paracetamol 1.3 g , diclofenac 50 mg or placebo , after wound closure and at 8 and 16 h. Suppositories were blinded by the hospital pharmacy . Study violations excluded data from seven patients . Patient data , morphine doses during anaesthesia and recovery , and sedation and nausea scores were comparable . Mean morphine consumption during PCA was 35.0 ( SD 20.4 ) mg , 32.7 ( 27.4 ) mg and 54.9 ( 28.3 ) mg in the paracetamol ( n = 24 ) , diclofenac ( n = 20 ) and placebo ( n = 21 ) groups , respectively ( P < 0.05 ) . Morphine sparing during PCA for paracetamol and diclofenac ( 36 % vs 40 % over 24 h ) was significant from 4 h. Global scores of average pain over 24 h were lower after diclofenac compared with paracetamol ( P < 0.01 ) and placebo ( P = 0.08 ) . We conclude that rectal paracetamol was an efficacious adjuvant analgesic after regular dosing UNLABELLED We assessed the relative morphine consumption in a combined analgesic regimen ( on-dem and morphine plus the nonopioids propacetamol or ketorolac ) after gynecologic surgery . Two hundred women r and omly received two i.v . doses of propacetamol 2 g or ketorolac 30 mg in a double-blinded , double-dummy trial . Patients were monitored for 12 h , and the following efficacy variables were assessed : total dose of morphine , pain intensity , and global efficacy . Safety and tolerability were evaluated by the occurrence of adverse events , especially the presence and intensity of gastrointestinal symptoms . Hemostatic variables were measured 30 and 60 min after the first infusion ; arterial blood pressure , heart and respiratory rates , sedation scores , and renal and hepatic function were also assessed . Total morphine requirements were not significantly different between the propacetamol ( 10.6 + /- 4.8 mg ) and ketorolac ( 10.2 + /- 4.4 mg ) groups . The evolution of pain intensity and the global efficacy also showed similar patterns in the two groups : 70.2 % of patients in the propacetamol group rated the efficacy as " good/ excellent " compared with 68.2 % in the ketorolac group . There were no clinical ly significant changes in vital signs or laboratory values and no observed differences between the two groups , although ketorolac slightly , but not significantly , prolonged the bleeding time . Epigastric pain was present in 9 % and 15 % of patients receiving propacetamol and ketorolac , respectively . There were two adverse events in the propacetamol group and four in the ketorolac group . Propacetamol demonstrates an efficacy similar to that of ketorolac and has an excellent tolerability after gynecologic surgery . IMPLICATION S Propacetamol and ketorolac , combined with patient-controlled analgesia morphine , show similar analgesic efficacy after gynecologic surgery . Morphine consumption and pain scores were comparable in the two studied groups . Propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic surgery We studied 80 children , aged 5 - 13 yr , who received PCA with morphine after appendicectomy using a st and ardized tracheal general anaesthetic . All patients received morphine 0.1 mg kg-1 before surgical incision and all had wound infiltration with bupivacaine 1 mg kg-1 at the end of surgery . Patients were allocated r and omly to receive postoperative analgesia with PCA morphine alone , morphine plus diclofenac 1 mg kg-1 , morphine plus paracetamol 15 - 20 mg kg-1 or morphine plus a combination of both diclofenac and paracetamol . Cumulative morphine consumption was significantly reduced by concurrent administration of diclofenac but no additive effect of paracetamol was demonstrable with the doses used in the study . Analgesia , as assessed by movement pain scoring , was significantly improved by the addition of diclofenac despite lower morphine consumption . Adverse effects and duration of PCA were comparable in the four groups Background : Combined analgesic regimens have been suggested to improve the treatment of postoperative pain . The aim of our study was to evaluate the analgesic efficacy and tolerability of propacetamol , in combination with morphine We compared the efficacy and side effects of propacetamol ( P ) , an injectable prodrug of acetaminophen , 2 g and tramadol ( T ) , a weak synthetic opioid , 1.5 mg.kg-1 , given intravenously following thyroidectomy . 80 patients were r and omly assigned to blindly receive one dose of P or T on request in the PACU . Residual pain was treated with i.v . PCA morphine . Pain and patient satisfaction were assessed with Visual Analog Scales . Demographic and peroperative data were comparable in both groups . Although the morphine consumption was comparable ( p = 0.71 ) , the decrease in VAS pain scores was significantly higher following tramadol ( p = 0.03 ) . More patients complained of nausea and vomiting ( p = 0.01 ) during the first two hours following injection of tramadol , but there was no difference throughout the whole study . Oversedation was not observed in any group . We conclude that a single dose of tramadol provides a better quality of analgesia than propacetamol during the first six hours after thyroidectomy , but fails to ensure optimal analgesia , since VAS pain scores failed to fall below 3 despite the use of supplemental morphine Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids . However , because opioids have numerous side effects , coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose . In this prospect i ve , r and omized , double-blinded study , we evaluated the efficacy of propacetamol , an IV administered prodrug of acetaminophen ( paracetamol ) , as an adjunctive analgesic after cardiac surgery . Seventy-nine patients scheduled for elective coronary artery bypass grafting were r and omized to receive either propacetamol 2 g ( n = 40 ) or placebo ( n = 39 ) IV in 6-h intervals for 72 h. From the time of extubation , patients had access to an opioid ( oxycodone ) via a patient-controlled analgesia device . Pain was evaluated on a visual analog scale four times daily , whereas respiratory function tests ( forced vital capacity , forced expiratory volume in 1 s , peak expiratory flow , and arterial blood gas measurements ) were performed once a day . The prespecified primary efficacy variable ( cumulative oxycodone consumption at the end of the 72-h postoperative period ) was 123.5 mg ( 51.3 mg ) ( mean [ sd ] ) in the propacetamol group and 141.8 mg ( 57.5 mg ) in the placebo group ( difference in mean , 18.3 mg = 13 % ; 95 % confidence interval , 6.1–42.7 mg;P = 0.15 ) . Pain scores did not differ between the groups at rest ( P = 0.65 ) or during a deep breath ( P = 0.72 ) . The groups were also similar in terms of pulmonary function tests , postoperative bleeding , and hepatic function tests , and no significant differences were noted in the incidences of adverse effects . After completion of the study , a post hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals . This analysis showed a significantly ( P = 0.036 ) smaller consumption of oxycodone in the propacetamol group at 24 h ( 47.1 mg [ 20.7 mg ] versus 57.9 mg [ 23.9 mg ] ; difference in mean , 10.8 mg ; 95 % confidence interval , 0.7–20.9 mg ) . In conclusion , propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients , nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery . However , post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group The analgesic efficacy and safety of propacetamol ( Pro-Dafalgan ) , an injectable prodrug of acetaminophen , in combination with morphine administered by patient-controlled analgesia ( PCA ) were studied in 60 patients ( 56 men , 4 women ; age 18 - 40 years ; mean age , 26 years ) after knee ligamentoplasty . Using a double-blind , r and omized , parallel-group design , the effects of four ( every 6 hr ) intravenous injections of 2 g propacetamol (= 1 g acetaminophen ) were compared with four injections of placebo ( PL ) in the recovery room immediately after surgery . Efficacy was assessed over 24 hr by automatic recording on the PCA device of the cumulative dose of morphine and the number of boluses requested . It was also assessed on pain scores rated on a five-point verbal scale and a visual analogue scale before administration , at 1 , 2 , 3 , and 4 hr , and then every 2 hr until the 24th hr after administration . A five-point global efficacy scale was also administered . Any side effects were recorded throughout the duration of the study , and the ability to tolerate the drug was assessed by recording arterial pressure , cardiac and respiratory frequency , and sedation at the same assessment times as the pain scores . The 24-hr morphine consumption was significantly decreased in the propacetamol group ( number of 1 mg boluses : 14.7 + /- 11.3 versus 23.2 + /- 13.8 , P = 0.01 ; PCA usage : 26.4 + /- 12.3 mg versus 34.6 + /- 15.4 mg , P = 0.03 ; PCA usage + titration : 34.5 + /- 12.7 mg versus 43.1 + /- 15.9 mg , P = 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Purpose In 1994 , we developed a practice guideline which stated that ketoprofen should be used in every adult patient after surgical procedures for which at least moderate pain was anticipated . The dose recommended was 50 mg every six hours iv in the operating room followed by oral administration as soon as possible for three days . The purpose of this study was to evaluate the success of the guideline implementation . Methods In 1995 , an audit performed by a research pharmacist assistant under the supervision of the authors analysed prospect ively the files of patients scheduled for orthopedic or general surgery during a one-month period . The compliance of the nurses was also recorded . Results Of 185 patients operated upon during the period , seven were transferred to the ICU and were not evaluated . Ketoprofen was not prescribed to 112 ( 63 % ) of the 177 remaining patients , either because minor pain was expected ( n = 55 ) or because one or several contra-indications to its use were detected . In cases where ketoprofen was used although theoretically contraindicated ( 11 % ) , review of the medical records and interviews of anesthesiologists showed that prescription was guided by a risk/benefit analysis . In 18 % of cases , nurses did not administer at least one dose of ketoprofen although medical prescription requested regular administration . Conclusion Although the use of NSAIDs is still controversial , implementation by anesthesiologists of a practice guideline introducing ketoprofen for postoperative analgesia was successful and the nursing non-compliance rate to follow written orders was modest . RésuméObjectifEn 1994 , nous avons instauré des recomm and ations de pratique clinique ( RPC ) concernant la douleur post-opératoire qui incluaient des directives sur le kétoprofène : l’administration de kétoprofène ( 50 mg·6 heures ) devait être systématique pour tout opéré chez lequel une douleur au moins modérée était prévue . L’administration intraveineuse devait être relayée par la voie orale dès que possible pour une durée totale de 3 jours . Le but de cette étude était de savoir si cet antalgique était bien prescrit ( audit des pratiques médicales ) et bien administré ( audit des pratiques infirmières).MéthodeEn 1995 , un audit réalisé par un pharmacien assistant de recherche supervisé par les auteurs a étudié prospect ivement tous les dossiers des patients opérés de chirurgie abdominale ou orthopédique pendant un mois . RésultatsParmi les 185 patients , 7 n’ont pas été étudie car ils ont été transférés en réanimation avec ventilation post-opératoire . Le kétoprofène n’a pas été prescrit chez 112 patients ( 63 % ) soit parce qu’une douleur mineure était attendue ( n = 55 ) soit parce qu’une contre-indication avait été détectée . Dans 11 % des cas , le kétoprofène avait été utilisé bien que théoriquement contre-indiqué . Dans tous ces cas , l’analyse du dossier avec le praticien suggérait un rapport risque/bénéfice acceptable . L’adhésion des infirmères était bonne avec la nonadministration d’au moins une dose chez 18 % des patients . Conclusion La mise en oeuvre de ces RPC a été un succès et bien que l’emploi des AINS soit controversé , ces produits sont bien prescrits et l’adhésion des infirmières est satisfaisante We sought to determine the analgesic efficacy , opioid-sparing effects , and tolerability of propacetamol , an injectable prodrug of acetaminophen , in combination with morphine administered by patient-controlled analgesia ( PCA ) after spinal fusion surgery . Forty-two patients undergoing spinal stabilization surgery were r and omized into two groups , which were given either an IV placebo or an IV injection of 2 g propacetamol every 6 h for 3 days after surgery . The postoperative opioid analgesic requirement was assessed with a PCA device used to self-administer morphine . Pain relief was evaluated by a visual analog pain scale and by verbal rating scores of pain relief at 8-h intervals for up to 72 h after surgery . The cumulative dose of morphine at 72 h was smaller in the Propacetamol group than in the Placebo group ( 60.3 ± 20.5 vs 112.2 ± 39.1 mg;P < 0.001 ) . The pain scores were significantly lower in the Propacetamol group measured at two intervals of the study , although visual analog scale pain intensity scores were smaller than 3 in both groups . Most patients in the Placebo group obtained a greater degree of sedation on postoperative Day 3 ( P < 0.05 ) . This study demonstrates the usefulness of propacetamol as an adjunct to PCA morphine in the treatment of postoperative pain after spinal fusion Background and Objectives A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery . This study evaluates the postoperative analgesic effects of propacetamol and /or diclofenac in parturients undergoing elective cesarean delivery under spinal anesthesia . Methods After r and omization , 80 healthy parturients received the following : placebo ( group M ) , 100 mg diclofenac rectally every 8 hours ( group MD ) , 2 g propacetamol intravenously every 6 hours ( group MP ) , or a combination of 2 g propacetamol and 100 mg diclofenac ( group MDP ) as described above . Drugs were administered for 24 hours after surgery . Postoperative pain was controlled with a patient controlled analgesia pump , using morphine . The visual analog scale ( VAS ) at rest and on coughing , as well as the morphine consumption , were evaluated at 2 , 6 , and 24 hours postoperatively . Also , the side effects experienced after undergoing the different regimens were compared . Results The patients ’ characteristics did not differ significantly between the 4 groups . VAS score at 2 hours , both at rest and on coughing were lower in group MDP and MD compared with group M ( P < .05 ) . At 24 hours , there was still a tendency toward lower pain scores in the groups MDP and MD ; however , this difference was only statistically significant at rest between the MDP group and the MP and M groups . Morphine consumption at 2 , 6 , and 24 hours was lower in the MDP and MD groups compared with the MP and M groups ( P < .05 ) . The morphine-sparing effect was higher in groups MDP and MD compared with group MP ( 57 % and 46 % , respectively , v 8.2 % , P < .05 ) . The incidence of side effects was similar in all groups . However , the power of the study was too low to permit an evaluation of potential side effects . Conclusion Diclofenac after cesarean delivery improves analgesia and has a highly significant morphine-sparing effect . We were unable to demonstrate significant morphine-sparing effect of propacetamol or additive effect of propacetamol and diclofenac in this group of patients Background : Paracetamol is widely used for postoperative analgesia . The effect is well documented in minor and moderate extensive surgery , but the effect of paracetamol as an adjunct to opioids in major abdominal surgery is less examined We compared the ketoprofen-propacetamol combination relative to propacetamol alone in thyroid and parathyroid surgery in terms of postoperative analgesic efficacy , bleeding , and incidence of nausea and vomiting to determine whether ketoprofen results in any benefit in this type of surgery . Patients were distributed in two parallel groups to be managed by anesthesiologists habitually prescribing ( Ketoprofen group ) or not prescribing ( Control group ) ketoprofen in this situation . The same anesthetic technique was used for all patients . Postoperative analgesia consisted of 2 g of propacetamol every 6 h and morphine boluses if the pain score measured by the numerical rating scale pain exceeded 40 ( 3 mg IV every 10 min in the recovery room , then 5 mg SC every 4 h in the ward ) . The Ketoprofen group received 100 mg of ketoprofen IV during surgery ( starting on resection of specimen ) and 8 h later . In the recovery room , patients received oxygen if the Spo2 while they were breathing room air was < 95 % on admission and at 1 and 2 h. Pain scores , opioid consumption , the volume of the cervical draining fluid , and the concentration and mass of hemoglobin in this fluid collected over 24 h were recorded . The 214 patients were distributed into two groups ( n = 107 in each group ) that were comparable in terms of age , weight , sex , duration of surgery , type of endocrinopathy , surgeon involvement , and the intraoperative dose of sufentanil ( P > 0.2 ) . The Ketoprofen group had lower numerical rating scale ( P < 0.05 ) , received less morphine during the first 24 h after surgery ( 7.4 ± 5 vs 11.7 ± 6 mg , P < 0.05 ) , had fewer nausea and vomiting episodes ( 21 vs 38 , P < 0.05 ) , and were less likely to require oxygen breathing after 1 h in the recovery room ( 33 vs 59 patients , P < 0.05 ) . The two groups had the same 24-h volume of cervical draining fluid ( 72.5 ± 43 vs 70 ± 42 mL , P > 0.2 ) and the same concentration ( 5.9 ± 3.4 vs 6.4 ± 2.8 g per 100 mL , P > 0.1 ) and mass of hemoglobin ( 3.9 ± 2.8 vs 4.2 ± 2.5 g , P > 0.2 ) in this collected fluid . Two cervical hematomas necessitating reintervention occurred in the Control group , compared with none in the Ketoprofen group . Ketoprofen reduces the pain score after thyroid and parathyroid surgery , as well as morphine requirements and related adverse effects , without increasing the risk of cervical bleeding In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies The analgesic and antipyretic efficacy of propacetamol is identical to paracetamol . Because the propacetamol is injectable and its side effects are uncommon and mild , it is the drug commonly used in France for postoperative pain relief . The aim of this prospect i ve study was to compare the analgesic efficacy of propacetamol after breast surgery or thyroidectomy when it was administered either systematic ally or on the patients dem and . After informed consent , 119 patients having undergone breast surgery or thyroidectomy , having received the same general anaesthesia and scheduled for receiving propacetamol postoperatively , were included in the study . Two groups of patients were compared , those who received propacetamol on dem and ( D Group ) and those who received propacetamol systematic ally ( S Group ) . During the first 24 hours , analgesia was evaluated on a visual analogical scale grade d from 0 to 100 mm , at rest and during mobilization ; the efficacy was also evaluated by the amount of additional analgesic drug injected . Side effects were also compared between the 2 treatment groups . In the 2 groups , demographic data , type of anaesthesia and type of surgery were identical . Postoperative pain relief and supplemental injection of morphine were not statistically different between the 2 groups . Propacetamol doses were statistically higher in the S group than in the D group ( 7.8 + /- 0.7 g and 3.9 + /- 2.3 g respectively , p < 0.05 ) . Pain during propacetamol infusion was more frequent in the D group than in the S group ( 30 % and 13 % respectively , p < 0.05 ) . No other adverse effects were observed during the study . Propacetamol alone is sufficient for pain relief after peripheral surgery ; more than 90 % of patients need no supplemental analgesic , and adverse effects are rare Opioids play a fundamental role in the management of postoperative pain , but their use is associated with a number of side effects , including nausea and vomiting , sedation , and respiratory depression . Co-administration of a nonopioid has been proposed as a method of reducing opioid intake and minimizing side effects . Sixty-one ASA physical status I and II patients were enrolled in a double-blind , r and omized , placebo-controlled , parallel study to investigate the effect of a combination of acetaminophen and morphine after open reduction and internal fixation of acute limb fractures . Patients were r and omized to receive either oral acetaminophen ( 1 g every 4 h ) or placebo as an adjuvant to morphine by patient-controlled analgesia ( PCA ) postoperatively . They were assessed daily for 72 h or until the PCA was discontinued according to st and ardized guidelines . The outcome variables collected were pain scores ( 11-point scale ) , amount of morphine self-administered , duration of PCA use , compliance with study design , incidence of nausea and sedation , and overall patient satisfaction . The acetaminophen group had lower pain scores on Day 1 ( 2.1 vs 3.3 ; P = 0.03 ) and a shorter average duration of PCA use ( 35.8 vs 45.5 h ; P = 0.03 ) . Overall patient satisfaction was also significantly greater in the acetaminophen group ( 8.7 vs 7.9 ; P = 0.04 ) . These data suggest that acetaminophen is a useful adjunct to morphine PCA . Implication s : This study assesses the benefit of combining two analgesics for the treatment of postoperative pain . Such a combination improves the quality of pain relief and patient satisfaction . ( Anesth Analg 1998;87:368 - 72 Background : Despite the widespread use of paracetamol for many years , the analgesic serum concentrations of paracetamol are unknown . Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied In 12 healthy volunteers , paracetamol pharmacokinetics were compared following administration of 1 g propacetamol HCl given intravenously over a 15-min period and 500 mg paracetamol given orally . Mean + /- SD total AUC ( microgram/ml.h ) following the iv formulation was significantly ( P < 0.01 ) greater than following oral paracetamol ( 25.53 + /- 4.27 vs 21.04 + /- 4.49 ) corresponding to a mean oral bioavailability of paracetamol of 82.2 + /- 9.4 % . Between 1 and 2 h after administration , paracetamol plasma concentrations became very similar following both formulations . In another study , 2 g propacetamol HCl was given both as a 15-min infusion and as a 2-min bolus injection to six healthy volunteers . Contrary to mild to moderate local discomfort experienced during the 2-min bolus injection , the 15-min infusion was well tolerated without any complaints reported |
11,399 | 28,285,148 | Our meta‐ analysis found decreased IL‐2 and IL‐6 post‐treatment levels in FEPOur meta‐ analysis found decreased IL‐2 and IL‐6 post‐treatment levels in FEP.IL‐6 and IL‐2 , and possibly IL‐1&bgr ; , could be considered as state markers .
TNF‐&agr ; , IL‐17 , and IFN‐&ggr ; might represent trait markers in drug‐naïve FEP .
Relevant sensitivity analysis confirmed these findings .
IL‐1&bgr ; had high between‐ study heterogeneity .
IL‐6 and IL‐2 , and possibly IL‐1&bgr ; , could be considered state markers , decreasing after antipsychotic treatment , whilst TNF‐&agr ; , IL‐17 , and IFN‐&ggr ; might be considered trait markers . | HighlightsPrevious research on the acute effect of antipsychotics on cytokines is inconclusive .
First episode psychosis ( FEP ) is an ideal population to study this topic .
ABSTRACT Schizophrenia is likely to be associated with immunological abnormalities .
However , antipsychotics may induce immunomodulatory effects , by influencing plasma cytokines . | BACKGROUND C-reactive protein ( CRP ) , intercellular adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , and E-selectin are systemic inflammatory markers ( IM ) that positively correlate with cardiovascular ( CV ) risk . Despite the known CV effects of atypical antipsychotics , there is limited prospect i ve data on IM changes during treatment . METHODS The IM outcomes were compared between antipsychotic treatment groups in the CATIE ( Clinical Antipsychotic Trials of Intervention Effectiveness ) schizophrenia trial phase 1 with subjects with laboratory assessment s at baseline and 3 months ( n = 789 ) . RESULTS There were significant treatment differences in CRP , E-selectin , and ICAM-1 at 3 months , with a differential impact of baseline values on the CRP and ICAM-1 results . In overall comparisons , quetiapine and olanzapine had the highest median levels for CRP , and olanzapine for E-selectin and ICAM-1 . Olanzapine was significantly different after baseline adjustment than perphenazine ( p = .001 ) for E-selectin , and in those with low baseline CRP ( < 1 mg/L ) , olanzapine was significantly different than perphenazine ( p < .001 ) , risperidone ( p < .001 ) , and ziprasidone ( p = .002 ) for CRP . Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median , but the differences were not statistically significant versus olanzapine ( p = .010 ) , quetiapine ( p = .010 ) , and risperidone ( p = .006 ) after controlling for multiple comparisons . The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP . CONCLUSIONS This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation . C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients Objective The present study aim ed to examine the changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve , first-episode schizophrenia . Methods Sixty-two drug naïve , first-episode schizophrenia ( SZ group ) and 60 healthy individuals ( control group ) were enrolled in the study . Serum interleukin-1β ( IL-1β ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) levels , and body weight were measured at baseline for both groups , and repeated for the SZ group at five different time points during 6-month risperidone treatment . Results At baseline , serum IL-1β , IL-6 , and TNF-α levels in the SZ group ( 53.28 ± 12.62 , 33.98 ± 14.13 , 50.08 ± 12.86 pg/mL , respectively ) were significantly higher than those in the control group ( 23.49 ± 15.27 , 15.53 ± 7.16 , 32.12 ± 15.23 pg/mL , respectively ) ( p 's < 0.001 ) . Within the SZ group , serum IL-1β levels decreased significantly at 2 weeks ( 48.02 ± 16.00 pg/mL , p < 0.01 ) and 1 month ( 44.70 ± 16.63 pg/mL , p < 0.001 ) , but then gradually increased at 2 months ( 48.49 ± 18.87 pg/mL ) , 3 months ( 50.59 ± 18.48 pg/mL ) and 6 months ( 53.64 ± 16.22 pg/mL ) to the levels comparable to baseline ; serum IL-6 levels changed significantly over the course of treatment ( p = 0.001 ) , but reached the levels comparable to baseline at 6 months ( 37.13 ± 13.23 pg/mL ) ; serum levels of TNF-α increased significantly at 3 months ( 55.02 ± 16.69 pg/mL , p < 0.01 ) and 6 months ( 58.69 ± 13.57 pg/mL , p < 0.001 ) ; steady and significant weight gain was observed at each follow-up time point ( p 's < 0.001 ) , from 56.71 ± 9.25 kg at baseline to 62.72 ± 9.53 kg at 6 months . Conclusions Risperidone treatment is associated with changes in serum pro-inflammatory cytokines levels and weight . There is an initial anti-inflammatory effect that reduces with treatment , potentially due to its weight gain side effect The second generation antipsychotics clozapine and olanzapine are known to cause weight gain . However , only clozapine is associated with drug-induced fever . Cytokines have been linked to the induction of both weight gain and drug-induced fever . We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion . Thirty patients suffering from schizophrenia , schizophreniform disorder or schizoaffective disorder were treated with either clozapine ( mean modal dose : 266.7+/-77.9 mg ) or olanzapine ( 21.2+/-2.5 mg ) in a r and omized , double-blind , 6-week study . Body mass index ( BMI ) , tympanic temperature , and plasma levels of leptin and cytokines ( tumor necrosis factor-alpha ( TNF-alpha ) , soluble TNF receptor 1 and 2 ( sTNFR-1/2 ) , soluble interleukin-2 receptors ( sIL-2R ) , interleukin-6 ) were determined weekly . BMI , leptin and cytokines significantly increased over time , except interleukin-6 and sTNFR-1 in the olanzapine group . All cytokines numerically increased compared to baseline already during the first week of treatment in both groups . Leptin , TNF-alpha , sTNFR-1 , sTNFR-2 and sIL-2R levels correlated with the BMI . Five patients who received clozapine ( 33 % ) developed drug-induced fever ( > /=38 degrees C ) . In these , interleukin-6 peak levels were significantly ( p<0.01 ) higher than in those patients treated with clozapine who did not develop fever . In conclusion , increase of BMI appears to be related to clozapine 's and olanzapine 's similar effects on cytokine systems , whilst drug-induced fever appears to be related to clozapine 's differential effects on interleukin-6 |
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