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10,800 | 27,454,261 | OA can function as a non-opioid mediated assessment tool for endogenous pain inhibition , and activates brain regions such as periaqueductal gray ( PAG ) , dorsolateral prefontral cortex , insula , medulla , pons and cerebellum , indicating strong brain derived pain modulation .
The primary somatosensory cortex is , conversely , less activated during OA .
OA is decreased in neuropathic patients .
Nonetheless , evidence for the influence of individual factors on OA is limited .
OA and CPM seem to rely on different mechanisms .
This systematic review displays OA as a temporal filtering mechanisms that is more brain-derived compared to the spatial assessment method CPM . | BACKGROUND Offset analgesia ( OA ) is an increasingly described phenomenon to measure endogenous pain inhibition , in which a greater decrease in pain intensity is experienced than would be predicted by the decrease in painful stimulation .
The temporal filtering in this OA phenomenon differs from the spatial filtering in the commonly described conditioned pain modulation ( CPM ) .
Yet , the knowledge on the efficacy of OA in chronic pain patients is scarce , compared to CPM efficacy .
OBJECTIVE This systematic review has been conducted to provide an overview of the current knowledge regarding OA , and to compare it to CPM . | & NA ; Under specific experimental conditions , oxycodone seems to exert spinal ( temporal summation ) rather than supraspinal ( conditioned pain modulation ) analgesic effects in humans . & NA ; Opioid analgesia is mediated primarily by modulating ( inhibiting and enhancing ) pain mechanisms at the spinal and supraspinal levels . Advanced psychophysical paradigms of temporal summation ( TS ) and conditioned pain modulation ( CPM ) likely represent pain mechanisms at both levels . Therefore , the study of opioid effects on TS and CPM can shed light on their analgesic mechanisms in humans . The current r and omized , double‐blind study tested the effects of oxycodone on the magnitude of both TS and CPM in 40 healthy subjects . TS was tested by measuring increments in pain intensity in response to 10 repetitive painful phasic heat stimuli . CPM was assessed by subtracting the response to a painful phasic heat stimulus administrated simultaneously with a conditioning cold pain stimulus from a painful phasic heat stimulus alone . These paradigms were tested before and at 60 , 120 , and 180 minutes after administration of a single oral dose of either oxycodone or an active placebo . Repeated‐ measures analysis of variance revealed significant effects of oxycodone , but not placebo , on the magnitude of TS ( F = 7.196 , P < .001 ) . Pairwise comparisons revealed that relative to baseline , TS was significantly reduced at 60 minutes ( P = .008 ) and at 180 minutes ( P = .017 ) after oxycodone administration . In contrast , no significant effects of either oxycodone ( F = 0.871 , P = .458 ) or placebo ( F = 2.086 , P = .106 ) on the magnitude of CPM were found . These results suggest that under the current experimental conditions , oxycodone exerted spinal , rather than supraspinal , analgesic effects . Furthermore , compared with CPM , TS seems more suitable for study ing the mechanisms of opioid analgesia in humans Background Variation in the serotonin transporter ( 5-HTT ) gene ( SLC6A4 ) has been shown to influence a wide range of affective processes . Low 5-HTT gene-expression has also been suggested to increase the risk of chronic pain . Conditioned pain modulation ( CPM ) - i.e. ‘ pain inhibits pain ’ - is impaired in chronic pain states and , reciprocally , aberrations of CPM may predict the development of chronic pain . Therefore we hypothesized that a common variation in the SLC6A4 is associated with inter-individual variation in CPM . Forty-five healthy subjects recruited on the basis of tri-allelic 5-HTTLPR genotype , with inferred high or low 5-HTT-expression , were included in a double-blind study . A submaximal-effort tourniquet test was used to provide a st and ardized degree of conditioning ischemic pain . Individualized noxious heat and pressure pain thresholds ( PPTs ) were used as subjective test-modalities and the nociceptive flexion reflex ( NFR ) was used to provide an objective neurophysiological window into spinal processing . Results The low , as compared to the high , 5-HTT-expressing group exhibited significantly reduced CPM-mediated pain inhibition for PPTs ( p = 0.02 ) and heat-pain ( p = 0.02 ) . The CPM-mediated inhibition of the NFR , gauged by increases in NFR-threshold , did not differ significantly between groups ( p = 0.75 ) . Inhibition of PPTs and heat-pain were correlated ( Spearman ’s rho = 0.35 , p = 0.02 ) , whereas the NFR-threshold increase was not significantly correlated with degree of inhibition of these subjectively reported modalities . Conclusions Our results demonstrate the involvement of the tri-allelic 5-HTTLPR genotype in explaining clinical ly relevant inter-individual differences in pain perception and regulation . Our results also illustrate that shifts in NFR-thresholds do not necessarily correlate to the modulation of experienced pain . We discuss various possible mechanisms underlying these findings and suggest a role of regulation of 5-HT receptors along the neuraxis as a function of differential 5-HTT-expression & NA;Diffuse noxious inhibitory controls ( DNIC ) were tested for their effect on noxious only , non‐noxious and proprioceptive cells in the dorsal horn of the intact anaesthetized rat . Unlike convergent neurones , as described in the previous paper , there was no effect of DNIC on these neurones , It is concluded that convergent neurones are specifically inhibited by DNIC.The effect of DNIC could not be demonstrated for convergent neurones in the spinal animal . Thus the neuronal substrate for DNIC must involve supraspinal structures . Because of the level of firing in convergent neurones induced by hair and touch receptors , presumably constantly and r and omly activated in the freely moving animal , a noxious message arriving at higher centres may be partly masked by this background noise . On the basis of the known role of convergent neurones in nociception , we propose the following mechanism which may interpret this paradoxical convergence : two pools of convergent neurones are influenced by a painful peripheral stimulation , one segmental pool being activated whilst the remaining population of cells is inhibited ; the “ contrast ” between the messages from these two pools may well produce a significant pain signalling output from the convergent dorsal horn cells . These results and their theoretical implication s are discussed with regard to the concept of the “ analgesic system ” , certain clinical observations and the paradoxical pain relieving effects of counterirritation and some forms of acupuncture Attenuation of responses to repeated sensory events has been thoroughly studied in many modalities ; however , attenuation of pain perception has not yet benefitted from such extensive investigation . Described here are two psychophysical studies that examined the effects of repeated exposure to thermal stimuli , assessing potential attenuation of the perception of pain and its possible spatial specificity . Twenty-two subjects were presented thermal stimuli to the volar surface of the right and left forearms . Twelve subjects in study 1 received the same stimuli and conditions on each of five daily experimental sessions , whereas 10 subjects in study 2 received thermal stimuli , which were restricted to one side for four daily sessions and then applied to the other side on the fifth session . Ratings of warmth intensity , pain intensity , and pain unpleasantness were recorded while the subjects performed a thermal sensory discrimination task . Results of study 1 demonstrate that repeated stimulation with noxious heat can lead to long-term attenuation of pain perception ; results of study 2 extend these findings of attenuation to both pain intensity and unpleasantness and show that this effect is highly specific to the exposed body side for both aspects of the pain experience . We suggest that the functional plasticity underlying this attenuation effect lies in brain areas with a strong contralateral pattern of pain-related activation The subjective experience of one 's environment is constructed by interactions among sensory , cognitive , and affective processes . For centuries , meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events . To better underst and how meditation influences the sensory experience , we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants . After 4 d of mindfulness meditation training , meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57 % and pain intensity ratings by 40 % when compared to rest . A two-factor repeated- measures ANOVA was used to identify interactions between meditation and pain-related brain activation . Meditation reduced pain-related activation of the contralateral primary somatosensory cortex . Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions . Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula , areas involved in the cognitive regulation of nociceptive processing . Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation , an area implicated in reframing the context ual evaluation of sensory events . Moreover , reductions in pain unpleasantness also were associated with thalamic deactivation , which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas . Together , these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information & NA ; Inhibitory and facilitatory descending pathways , originating at higher central nervous system sites , modulate activity of dorsal horn nociceptive neurons , and thereby influence pain perception . Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain . The N‐methyl‐d‐aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients . This effect is due to desensitization of sensitized N‐methyl‐d‐aspartate receptors . Additionally , ketamine may modulate or enhance endogenous inhibitory control of pain perception . Diffuse noxious inhibitory control ( DNIC ) and offset analgesia ( OA ) are 2 mechanisms involved in descending inhibition . The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control . Ten healthy subjects ( 4 men/6 women ) received a 1‐hour placebo or S(+)‐ketamine ( 40 mg per 70 kg ) infusion on 2 separate occasions in r and om order . Upon the termination of the infusion , DNIC and OA responses were obtained . After placebo treatment , significant descending inhibition of pain responses was present for DNIC and OA . In contrast , after ketamine infusion , no DNIC was observed , but rather a significant facilitatory pain response ( P < 0.01 ) ; the OA response remained unchanged . These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation . The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC . Diffuse noxious inhibitory control responses following a 1‐hour low‐dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation The endogenous analgesia ( EA ) system is psychophysically evaluated using various paradigms , including conditioned pain modulation ( CPM ) and offset analgesia ( OA ) testing , respectively , the spatial and temporal filtering processes of noxious information . Though both paradigms assess the function of the EA system , it is still unknown whether they reflect the same aspects of EA and consequently whether they provide additive or equivalent data . Twenty-nine healthy volunteers ( 15 males ) underwent 5 trials of different stimulation conditions in r and om order including : ( 1 ) the classic OA three-temperature stimulus train ( ‘ OA ’ ) ; ( 2 ) a three-temperature stimulus train as control for the OA ( ‘ OAcon ’ ) ; ( 3 ) a constant temperature stimulus ( ‘ constant ’ ) ; ( 4 ) the classic parallel CPM ( ‘ CPM ’ ) ; and ( 5 ) a combination of OA and CPM ( ‘ OA + CPM ’ ) . We found that in males , the pain reduction during the OA + CPM condition was greater than during the OA ( P = 0.003 ) and CPM ( P = 0.07 ) conditions . Furthermore , a correlation was found between OA and CPM ( r = 0.62 , P = 0.01 ) at the time of maximum OA effect . The additive effect found suggests that the two paradigms represent at least partially different aspects of EA . The moderate association between the CPM and OA magnitudes indicates , on the other h and , some commonality of their underlying mechanisms BACKGROUND Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the µ-opioid receptor combined with inhibition of neuronal norepinephrine reuptake . Both mechanisms are implicated in activation of descending inhibitory pain pathways . In this study , we investigated the influence of tapentadol on conditioned pain modulation ( CPM , an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus ) and offset analgesia ( OA , a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation ) . METHODS Twenty-four patients with diabetic polyneuropathy ( DPN ) were r and omized to receive daily treatment with tapentadol sustained-release ( SR ) [ average daily dose 433 ( 31 ) mg ] or placebo for 4 weeks . CPM and OA were measured before and on the last day of treatment . RESULTS Before treatment , none of the patients had significant CPM or OA responses . At week 4 of treatment , CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses . CPM increased from 9.1 (5.4)% ( baseline ) to 14.3 (7.2)% ( placebo ) and 24.2 (7.7)% ( tapentadol SR , P<0.001 vs placebo ) ; relief of DPN pain was also greater in patients treated with tapentadol than placebo ( P=0.028 ) . Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses ( P=0.78 ) . CONCLUSIONS Tapentadol 's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses . CLINICAL TRIAL REGISTRATION The study was registered at trialregister.nl under number NTR2716 OBJECTIVE Temporal summation ( TS ) of pain , conditioned pain modulation ( CPM ) , and exercise-induced analgesia ( EIA ) are often investigated in chronic pain population s as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition , respectively , but interactions are not yet clear both in healthy controls and in chronic pain patients . Therefore , the present double-blind r and omized placebo-controlled study evaluates pains cores , TS , and CPM in response to exercise in healthy controls , patients with chronic fatigue syndrome and comorbid fibromyalgia ( CFS/FM ) , and patients with rheumatoid arthritis ( RA ) , both under placebo and paracetamol condition . METHODS Fifty-three female volunteers - of which 19 patients with CFS/FM , 16 patients with RA , and 18 healthy controls - underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions ( paracetamol vs. placebo ) , with an interval of 7 days . Before and after exercise , participants rated pain intensity during TS and CPM . RESULTS Patients with rheumatoid arthritis showed decreased TS after exercise , both after paracetamol and placebo ( P < 0.05 ) . In patients with CFS/FM , results were less univocal . A nonsignificant decrease in TS was only observed after taking paracetamol . CPM responses to exercise are inconclusive , but seem to worsen after exercise . No adverse effects were seen . CONCLUSION This study evaluates pain scores , TS , and CPM in response to submaximal exercise in 2 different chronic pain population s and healthy controls . In patients with RA , exercise had positive effects on TS , suggesting normal EIA . In patients with CFS/FM , these positive effects were only observed after paracetamol and results were inconsistent Summary The magnitude of offset analgesia is not altered by naloxone administration , by remifentanil analgesia , or during opioid‐induced hypersensitivity . Offset analgesia is therefore subserved by nonopioid mechanisms . ABSTRACT The mechanisms supporting temporal processing of pain remain poorly understood . To determine the involvement of opioid mechanisms in temporal processing of pain , responses to dynamic noxious thermal stimuli and offset analgesia were assessed after administration of naloxone , a μ‐opioid antagonist , and on a separate day , during and after intravenous administration of remifentanil , a μ‐opioid agonist , in 19 healthy human volunteers . Multiple end points were sample d from real‐time computerized visual analog scale ratings ( VAS , 1 to 10 ) to assess thermal sensitivity , magnitude and duration of offset analgesia , and painful after sensations . It was hypothesized that the magnitude of offset analgesia would be reduced by direct opioid antagonism and during states of acute opioid‐induced hypersensitivity ( OIH ) , as well as diminished by the presence of exogenous opioids . Surprisingly , the magnitude of offset analgesia was not altered after naloxone administration , during remifentanil infusion , or after the termination of remifentanil infusion . Because thermal hyperalgesia was observed after both drugs , 8 of the original 19 subjects returned for an additional session without drug administration . Thermal hyperalgesia and increased magnitude of offset analgesia were observed across conditions of remifentanil , naloxone , and no drug within this subset analysis , indicating that repeated heat testing induced thermal hyperalgesia , which potentiated the magnitude of offset analgesia . Thus , it is concluded that the mechanisms subserving temporal processing of nociceptive information are largely opioid‐independent , but that offset analgesia may be potentiated by heat‐induced thermal hyperalgesia in a proportion of individuals Inefficient endogenous pain inhibition , in particular impaired conditioned pain modulation ( CPM ) , may disturb central pain processing in patients with chronic whiplash-associated disorders ( WAD ) . Previous studies revealed that abnormal central pain processing is responsible for a wide range of symptoms in patients with chronic WAD . Hence , the present study aim ed at examining the functioning of descending pain inhibitory pathways , and in particular CPM , in patients with chronic WAD . Thirty-five patients with chronic WAD and 31 healthy controls were subjected to an experiment evaluating CPM . CPM was induced by an inflated occlusion cuff and evaluated by comparing temporal summation ( TS ) of pressure pain prior to and during cuff inflation . Temporal summation was provoked by means of 10 consecutive pressure pulses at upper and lower limb location . Pain intensity of first , fifth , and 10th pressure pulse was rated . During heterotopic noxious conditioning stimulation , TS of pressure pain was significantly depleted among healthy controls . In contrast , TS was quite similar prior to and during cuff inflation in chronic WAD , providing evidence for dysfunctional CPM in patients with chronic WAD . The present study demonstrates a lack of endogenous pain inhibitory pathways , and in particularly CPM , in patients with chronic WAD , and hence provides additional evidence for the presence of central sensitization in chronic WAD Abstract Expectation/placebo‐related mechanisms and specific effects of therapies show additive effects , such that a therapy is less effective if the placebo component is absent . So far , the placebo component has been disrupted experimentally by using covert administrations of treatments . Here , we show for the first time that disruption of expectation/placebo‐related analgesic mechanisms may occur in a clinical condition , Alzheimer ’s disease ( AD ) . In order to assess the placebo component of a therapy , we used the recently developed open – hidden paradigm . A local anesthetic was applied , either overtly or covertly , to the skin of AD patients to reduce burning pain after venipuncture . The placebo ( psychological ) component is represented by the difference between the analgesic effect after open ( expected ) and after hidden ( unexpected ) application . We correlated the placebo component with both cognitive status and functional connectivity among different brain regions . We found that AD patients with reduced Frontal Assessment Battery scores showed reduced placebo component of the analgesic treatment . We also found that the disruption of the placebo component occurred when reduced connectivity of the prefrontal lobes with the rest of the brain was present . Remarkably , the loss of these placebo‐related mechanisms reduced treatment efficacy , such that a dose increase was necessary to produce adequate analgesia . These findings highlight the active role of cognition and prefrontal lobes in the therapeutic outcome and underscore the need of considering a possible revision of the therapeutic approach in Alzheimer patients in order to compensate for the loss of the endogenous expectation and placebo mechanisms OBJECTIVE To examine possible deficiencies in endogenous pain modulating mechanisms in fibromyalgia patients compared with matched pain-free control subjects . DESIGN /SUBJECTS/ METHODOLOGY : Pain reduction was investigated in 25 female patients with fibromyalgia and 26 age-matched healthy women using the diffuse noxious inhibitory controls ( DNIC ) paradigm . Tonic thermal stimuli at painful and nonpainful intensities , tailored to individual heat pain thresholds , were employed to induce pain inhibition . The anticipated effect was assessed by measuring the electrical pain threshold and detection threshold , using a double staircase method . Only nontender control points were stimulated ( thermode on the foot , electrodes on the inner forearm ) . RESULTS The patients with fibromyalgia had significantly lower heat pain thresholds than the healthy subjects , but similar electrical detection and pain thresholds . The repeatedly applied electrical stimuli result ed in a degree of perceptual adaptation that was similar between the two groups . However , concurrent tonic thermal stimuli , at both painful and nonpainful levels , significantly increased the electrical pain threshold in the healthy subjects but not in the fibromyalgia patients . The electrical detection threshold was not affected in either group . CONCLUSIONS Pain modulation , produced by a concurrent tonic stimulus in healthy persons , was not seen in the fibromyalgia group . The patients either had deficient pain modulation or were unable to tolerate a tonic stimulus intense enough to engage a modulatory process . It remains to be established whether the pain reduction found in the healthy subjects was the conventional DNIC effect , another effect ( e.g. , distraction ) , or a combination of both UNLABELLED Genetic studies have become indispensable in underst and ing pain mechanisms , shedding light on the role of monoamine pathways in pain modulation . The present study was aim ed to explore the relationship between functional polymorphisms in serotonin and dopamine-related genes and pain modulation . Two paradigms of pain modulation were administered to 191 healthy participants in a r and om order : Conditioned Pain Modulation in response to painful stimuli ( CPM(painful ) ) tested by the coadministration of repeated short painful heat stimuli and a conditioning tonic cold pain stimulation ; and Conditioned Pain Modulation in response to nonpainful stimuli ( CPM(nonpainful ) ) tested similarly , except for using a painless conditioning stimulation . Using the Transmission Disequilibrium Test ( TDT ) , functional variable number of t and em repeat ( VNTR ) polymorphisms of the following c and i date genes were studied : 1 ) serotonin transporter ( 5-HTTLPR ) ; 2 ) dopamine transporter ( DAT1 ) ; 3 ) dopamine receptor 4 ( DRD4 ) ; and 4 ) monoamine oxidase A ( MAOA ) . DNA sample s from both participants and their parents were analyzed . A significant association was found between CPM(nonpainful ) and the 5-HTTLPR polymorphism ( P = .001 ) . More specifically , carriers of the long allele exhibited a significantly higher magnitude of CPM(nonpainful ) than carriers of the short allele . No associations were found between the dopamine-related genes and both types of pain modulation . These results highlight the importance of serotonin in endogenous analgesia . PERSPECTIVE This article presents an association between the serotonin transporter gene polymorphism ( 5-HTTLPR ) and pain modulation derived by nonpainful conditioned pain modulation ( CPM(nonpainful ) ) , rather than painful conditioned pain modulation ( CPM(painful ) ) . These findings emphasize the complex role of serotonin in pain modulation , and highlight the importance of genetic studies in the underst and ing of interindividual differences in sensitivity to pain OBJECTIVE Conditioned pain modulation ( CPM ) and offset analgesia ( OA ) are considered to represent paradigms of descending inhibitory pain modulation in humans . This study tested the effects of hydromorphone therapy on descending inhibitory pain modulation , as measured by changes from baseline in the magnitudes of CPM and OA . DESIGN Prospect i ve evaluation . SETTING Institute of Pain Medicine , Rambam Health Care Campus . SUBJECTS Patients with chronic radicular pain . METHODS Thirty patients received 4 weeks of oral hydromorphone treatment at an individually titrated dose ( mean ± st and ard deviation dose of 11.6 ± 4.8 mg/day ) . CPM and OA were assessed before and after hydromorphone treatment . CPM was assessed by subtracting the response to a painful phasic heat stimulus administered simultaneously with a conditioning cold pain stimulus , from the response to the same heat stimulus administered alone . The OA paradigm consisted of a three-temperature stimuli train ( T1 = 49 ° C [ 5 seconds ] , T2 = 50 ° C [ 5 seconds ] , and T3 = 49 ° C [ 20 seconds ] ) . The magnitude of OA was quantified by subtracting minimal pain scores obtained during T3 from the maximal pain scores obtained during T2 . RESULTS CPM scores changed from a baseline of 17.7 ± 20.6 to 21 ± 20.4 following treatment , and OA scores changed from 7.8 ± 20.5 to 9.7 ± 14.6 . Wilcoxon signed rank test indicated that these changes were not significant ( CPM : P = 0.22 ; OA : P = 0.44 ) . McNemar test revealed that the percentage of patients who exhibited a change in the direction of CPM or OA in response to hydromorphone treatment was not significant ( CPM : P = 0.37 ; OA : P = 0.48 ) . CONCLUSIONS These results suggest that the descending inhibitory pain modulation , as manifested in humans by CPM and OA , is unlikely to be mediated by hydromorphone therapy |
10,801 | 18,981,046 | Meta-analyses showed that when eccentric exercise was performed at higher intensities compared with concentric training , total strength and eccentric strength increased more significantly .
However , compared with concentric training , strength gains after eccentric training appeared more specific in terms of velocity and mode of contraction .
Eccentric training performed at high intensities was shown to be more effective in promoting increases in muscle mass measured as muscle girth .
In addition , eccentric training also showed a trend towards increased muscle cross-sectional area measured with magnetic resonance imaging or computerised tomography .
Subgroup analyses suggest that the superiority of eccentric training to increase muscle strength and mass appears to be related to the higher loads developed during eccentric contractions .
The specialised neural pattern of eccentric actions possibly explains the high specificity of strength gains after eccentric training . | The aim of this systematic review was to determine if eccentric exercise is superior to concentric exercise in stimulating gains in muscle strength and mass .
Meta-analyses were performed for comparisons between eccentric and concentric training as means to improve muscle strength and mass . | Thirty elite tennis players were r and omly assigned to three groups to evaluate shoulder isokinetic internal and external rotation training : an isokinetic concentric group , an isokinetic eccentric group , and a control group with no training . Subjects were tested before and after training both concentrically and eccentrically using an isokinetic dynamometer . Functional output before and after training was assessed by the average and peak velocity of six maximal serves . The effect of training on serve velocity endurance was also assessed . Statisti cally significant concentric and eccentric strength gains ( 11 % ) were obtained in both training groups when com pared with controls ( decreased total average strain of 2 % ) ( P < 0.0004 ) . Serve velocity increased by greater than 11 % in both training groups , which was a signifi ca nt increase from the average of 1 % in the control group ( P < 0.0001 ) . In the endurance study , training group subjects displayed a tendency to maintain their serve velocity ( loss of approximately 2 % ) greater than controls ( loss of 6.4 % ) ( P < 0.05 ) . Isokinetic training led to increases in objective and functional output in elite tennis players . This training regimen may have signifi cance in the final stages of the rehabilitation of injured shoulders as well as in improved performance and re duced injury risk The purpose of this study was to determine whether cross-education , defined as the increase in strength of an untrained limb after training of the contralateral homologous limb , is specific to low and high velocity eccentric training . Twenty-six subjects were r and omized into two groups ( n=13 each ) that performed unilateral eccentric training of the elbow flexors on an isokinetic dynamometer at velocities of either 30 ° s-1 ( 0.52 rad s-1 ) or 180 ° s-1 ( 3.14 rad s-1 ) . Subjects trained three times per week for 8 weeks . Ten subjects served as controls and did not train . Subjects were tested before and after training for peak torque of the elbow flexors during eccentric and concentric contractions at 30 ° s-1 and 180 ° s-1 . Eccentric peak torque at the velocity of 180 ° s-1 in the untrained arm increased only for the group that trained at that velocity ( P<0.05 ) . There were no other changes in untrained arms for any of the groups at velocities of 30 ° s-1 or 180 ° s-1 . For the trained arm , the increase in eccentric torque ( pooled over velocities ) was greatest for the group training at 180 ° s-1 , whereas the increase in concentric torque was similar for the groups training at 30 ° s-1 and 180 ° s-1 . For the trained arm , there was no specificity for velocity or contraction type . We conclude that cross-education was specific to contraction type and velocity when fast ( but not slow ) eccentric contractions were used during training ; whereas there was no specificity of training in the trained arm O2 uptake ( VO2 ) kinetics and electromyographic ( EMG ) activity from the vastus medialis , rectus femoris , biceps femoris , and medial gastrocnemius muscles were studied during constant-load concentric and eccentric cycling . Six healthy men performed transitions from baseline to high-intensity eccentric ( HE ) exercise and to high-intensity ( HC ) , moderate-intensity ( MC ) , and low-intensity ( LC ) concentric exercise . For HE and HC exercise , absolute work rate was equivalent . For HE and LC exercise , VO2 was equivalent . VO2 data were fit by a two- or three-component exponential model . Surface EMG was recorded during the last 12 s of each minute of exercise to obtain integrated EMG and mean power frequency . Only in the HC exercise did VO2 increase progressively with evidence of a slow component ( phase 3 ) , and only in HC exercise was there evidence of a coincident increase with time in integrated EMG of the vastus medialis and rectus femoris muscles ( P < 0.05 ) with no change in mean power frequency . The phase 2 time constant was slower in HC [ 24.0 + /- 1.7 ( SE ) s ] than in HE ( 14.7 + /- 2.8 s ) and LC ( 16.7 + /- 2.2 s ) exercise , while it was not different from MC exercise ( 20.6 + /- 2.1 s ) . These results show that the rate of increase in VO2 at the onset of exercise was not different between HE and LC exercise , where the metabolic dem and was similar , but both had significantly faster kinetics for VO2 than HC exercise . The VO2 slow component might be related to increased muscle activation , which is a function of metabolic dem and and not absolute work rate We compared the effects of concentric ( Con ) and eccentric ( Ecc ) isokinetic training on quadriceps muscle strength , cross-sectional area , and neural activation . Women ( age 20.0 + /- 0.5 yr ) r and omly assigned to Con training ( CTG ; n = 16 ) , Ecc training ( ETG ; n = 19 ) , and control ( CG ; n = 19 ) groups were tested before and after 10 wk of unilateral Con or Ecc knee-extension training . Average torque measured during Con and Ecc maximal voluntary knee extensions increased 18.4 and 12.8 % for CTG , 6.8 and 36.2 % for ETG , and 4.7 and -1.7 % for CG , respectively . Increases by CTG and ETG were greater than for CG ( P < 0.05 ) . For CTG , the increase was greater when measured with Con than with Ecc testing . For ETG , the increase was greater when measured with Ecc than with Con testing . The increase by ETG with Ecc testing was greater than the increase by CTG with Con testing . Corresponding changes in the integrated voltage from an electromyogram measured during strength testing were 21.7 and 20.0 % for CTG , 7.1 and 16.7 % for ETG , and -8.0 and -9.1 % for CG . Quadriceps cross-sectional area measured by magnetic resonance imaging ( sum of 7 slices ) increased more in ETG ( 6.6 % ) than in CTG ( 5.0 % ) ( P < 0.05 ) . We conclude that Ecc is more effective than Con isokinetic training for developing strength in Ecc isokinetic muscle actions and that Con is more effective than Ecc isokinetic training for developing strength in Con isokinetic muscle actions . Gains in strength consequent to Con and Ecc training are highly dependent on the muscle action used for training and testing . Muscle hypertrophy and neural adaptations contribute to strength increases consequent to both Con and Ecc training The quantification of the progression of muscle fatigue during a sustained contraction is a valuable tool in several clinical applications , ranging from the evaluation of functional impairment to the development of specific rehabilitative and training protocol s. In these fields , great importance is given to isokinetic contractions . The aim of this paper was twofold : first , to propose signal processing methods for assessing the spectral changes of the surface myoelectric signal due to fatigue during isokinetic concentric and eccentric knee flexion-extension movements at a given angular velocity ( 60/spl deg//s ) ; second , to analyze the electrical manifestations of muscle fatigue of four thigh muscles ( vastus lateralis , vastus medialis , rectus femoris , and biceps femoris ) in the two contraction modalities ( i.e. concentric versus eccentric ) . We demonstrated that , when considering concentric contractions , localized muscle fatigue can be assessed by computing the mean frequency of the frequency marginal of the time-frequency distribution derived from the surface myoelectric signal collected during each contraction cycle . Stronger nonstationarities were observed in the surface myoelectric data recorded within each cyclical movement of the studied eccentric exercise . Thus we propose the computation of the instantaneous mean frequency of the signal based on an original cross-time-frequency algorithm , which proved more sensitive than the frequency marginal in tracking the spectral changes associated with localized muscle fatigue . We derived the average fatigue pattern of the investigated muscles from experimental data recorded from a sample population consisting of twenty healthy subjects and we statistically compared the two contraction modalities . Our results showed that the electrical manifestations of muscle fatigue during concentric contractions were higher than those found during eccentric contractions , although in the latter modality the torque exerted and the mechanical work produced by the subjects were larger than those recorded during the concentric exercise . The results presented in this paper have potential clinical application and they could play an important future role in investigations of muscle behavior during dynamic , highly fatiguing contractions This research was supported by a Duke University Research Council Grant . The purpose of this study was to examine mode and speed specificity of strength training by comparing concentric and eccentric isokinetic exercise of the quadriceps . Forty-eight healthy men ( mean age = 23.9 years ) were r and omly assigned to one of three groups : concentric training ( C ) , eccentric training ( E ) , or control ( K ) . Average force ( in Newtons ) of 3 concentric and of 3 eccentric quadriceps contractions on the KIN-COM(R ) dynamometer at 60 , 120 , and 180 degrees /sec was evaluated prior to and following a 6 week period during which only the C and E groups trained . Training sessions ( 3/week ) included 4 submaximal and 1 maximal warm-up followed by 10 maximal effort isokinetic contractions of the quadriceps at 120 degrees /sec for each leg . Group C subjects trained concentrically only while Group E subjects trained eccentrically only . A t-test for independent means showed no significant right/left differences . ANOVA and Scheffe 's F-tests were then used to assess the differences in training effects among the 3 groups for the left leg only . Results showed that although Group C increased slightly in both concentric and eccentric force at all speeds , the gains were significant only for concentric force at 180 degrees /sec . Group E showed significant gains ( p < 0.05 ) in eccentric force at all speeds but not in concentric force . The K group had no significant change in concentric or eccentric force at any speed . We conclude that the eccentric mode of isokinetic exercise has highly specific strength training effects while the concentric mode has less specific training effects . In addition , speed of exercise does not appear to have specific training effects . J Orthop Sports Phys Ther 1989;11(2):70 - 75 The purpose of this study was to compare the short-term strength and neural adaptations to eccentric and concentric training at equal force levels . Forty-two sedentary women ( age = 21.5 yr ) were ranked based on the initial quadriceps strength score , and trios of subjects were r and omly assigned to either an eccentric ( n = 14 ) , a concentric ( n = 14 ) , or a nonexercising control group ( n = 14 ) . Training involved a total of 824 eccentric or concentric quadriceps actions at 1.05 rad.s-1 administered in four sets of 6 - 10 repetitions , four times per week for 6 wk . Before and after training , all subjects were tested for unilateral maximal isometric and eccentric and concentric actions at 1.05 rad.s-1 and for a 40-repetition eccentric and concentric fatigue series of the left and right quadriceps . Surface electromyographic activity of the vastus lateralis and medialis was monitored during testing . Concentric training increased concentric ( 36 % , P < 0.05 ) , isometric ( 18 % , P < 0.05 ) , and eccentric strength ( 13 % ) , and eccentric training increased eccentric ( 42 % , P < 0.05 ) , isometric ( 30 % , P < 0.05 ) , and concentric ( 13 % ) strength . Eccentric training improved eccentric and isometric strength more ( P < 0.05 ) than did concentric training . The electromyographic adaptations were greater with eccentric training . Cross-education was 6 % , and neither training mode modified fatigability . The data suggest that training of the quadriceps muscle with submaximal eccentric actions brings about greater strength adaptations faster than does training with maximal-level concentric actions in women . This greater adaptation is likely to be mediated by both mechanical and neural factors The purpose of this study was to estimate the efficiency of ATP utilization for concentric , eccentric , and isometric muscle action in the human tibialis anterior and extensor digitorum longus in vivo . A dynamometer was used to quantitate muscle work , or tension , while simultaneous 31P-nuclear magnetic resonance data were collected to monitor ATP , phosphocreatine , inorganic phosphate , and pH. The relative efficiency of the actions was estimated in two ways : steady-state effects on high-energy phosphates and a direct comparison of ATP synthesis rates with work . In the steady state , the cytosolic free energy dropped to the lowest value with concentric activity , followed by eccentric and isometric action for comparative muscle tensions . Estimates of ATP synthesis rates revealed a mechanochemical efficiency [ i.e. , ATP production rate/work ( both in J/s ) ] of 15.0 + /- 1.3 % in concentric and 34.7 + /- 6.1 % in eccentric activity . The estimated maximum ATP production rate was highest in concentric action , suggesting an activation of energy metabolism under these conditions . By using direct measures of metabolic strain and ATP turnover , these data demonstrate a decreasing metabolic efficiency in human muscle action from isometric , to eccentric , to concentric action The objectives of this study were to determine whether the occurrence of delayed onset muscle soreness ( DOMS ) for the vastus lateralis muscle was associated with elevated intramuscular pressure ( IMP ) ; and to assess , whether high eccentric forces occurred at an increased muscle length ( as determined by joint angle ) . Therefore , peak knee extension torque , peak IMP of the vastus lateralis muscle , and the joint angle at which peak torque ( JAPT ) occurred were determined in eight male subjects during repetitive eccentric and concentric activities until fatigue occurred . Peak torque was significantly higher for eccentric compared to concentric activity ( P < 0.01 ) and declined significantly for both activities ( P < 0.01 ) throughout the protocol s. When comparing the start ( prior to fatigue ) to the end ( fatigue state ) , mean torque for eccentric activity declined from 191 to 147 ( N · m ) and for concentric activity declined from 166 to 104 ( N · m ) . In contrast , peak IMP was not significantly different between the types of activity and did not change significantly with time . At the start and the end , the mean IMP remained constant for eccentric activity at 54 mmHg ( 7.2 kPa ) but for concentric activity was 78 mmHg ( 10.4 kPa ) and 96 mmHg ( 12.8 kPa ) , respectively . All the subjects , however , experienced DOMS of the vastus lateralis muscle exclusively for the eccentric activity leg . The JAPT was not different between activity types and did not change significantly with time ; however , a significant interaction between activity type and time was observed ( P = 0.01 ) . For eccentric activity JAPT ( 0 ° = fully extended leg ) was 81 ° ( 1.38 rad ) and 79 ° ( 1.34 rad ) and for concentric activity was 76 ° ( 1.29 rad ) and 83 ° ( 1.41 rad ) at the start and the end , respectively . From our studies we concluded that during eccentric activity the magnitude of IMP for the vastus lateralis muscle did not reflect the high muscles forces ; therefore it would appear that IMP was not an etiologic indicator of DOMS , and that JAPT measurements did not offer an explanation for the high forces which were associated with eccentric activity The effect of training with concentric and eccentric contractions on fiber hypertrophy and isometric torque production was investigated in 20 healthy subjects . One group ( eight female and two male subjects ) performed concentric contractions of their quadriceps femoris muscles at an intensity of 90 % of their maximal concentric power . The other group ( six female and four male subjects ) performed eccentric contractions at the same relative power level . Both groups exercised three times per week for 4 wk at a constant speed of 60 degrees.s-1 on a Kin-Com dynamometer . Needle biopsies were obtained from the vastus lateralis before and after the exercise program . Fiber-type differentiation was performed using a myosin ATPase stain at a preincubation of 10.5 . Maximal isometric knee extension torque was also measured before and after the exercise program . An analysis of covariance was used to determine whether there were significant differences between the exercise groups in : 1 ) the post-exercise fiber areas and 2 ) maximal isometric torque ( MIso ) , while controlling for initial differences . Results showed a significant difference between the Type II fiber areas ( P < 0.01 ) and the MIso ( P = 0.01 ) . These data indicate that , when exercising at the same relative power level , a subject performing concentric contractions will show greater muscle hypertrophy and improve in MIso production more than a subject training with eccentric contractions The purpose of this study was to determine the differences in cardiovascular response between high‐intensity eccentric ( ECC ) and concentric ( CON ) contractions , and to obtain the basic data applicable to resistance training in middle‐aged and elderly individuals . The subjects who participated in this study were nine healthy men ( age 24·1 ± 1·3 years ) . ECC and CON were r and omly selected , as each test consisted of a high‐intensity ( 80 % of peak torque ) bout of 60 s of ECC and CON isokinetic contractions of the flexor carpi radialis . Systolic pressure ( SBP ) , diastolic pressure ( DBP ) and heart rate ( HR ) during ECC and CON were measured using a Finometer . Mean arterial pressure ( MAP ) was calculated by SBP and DBP . Rate‐pressure product ( RPP ) was calculated by SBP and HR . SBP , DBP , MAP and RPP during ECC were significantly smaller compared with CON . It is clear that cardiovascular response by high‐intensity contraction is smaller in ECC than in CON . High‐intensity ECC has been suggested to exert only small stress to the cardiovascular system . Thus , being a contraction mode it may be applicable to resistance training Abstract The aims of this study were to assess changes in muscle architecture , isometric and dynamic strength of the leg extensor muscles , result ing from dynamic resistance training , and the relationships between strength and muscle architecture variables . The participants ( n = 30 ) were r and omly assigned to one of two groups . The training group ( n = 16 ; age 21.8 ± 2.3 years , body mass 74.8 ± 9.2 kg , height 1.75 ± 0.08 m ) performed dynamic resistance training for 13 weeks . The control group ( n = 14 ; age 19.9 ± 1.5 years , body mass 74.0 ± 8.5 kg , height 1.76 ± 0.05 m ) did not perform any resistance training . Maximal dynamic and isometric strength were tested in both groups , before and after the training period . The members of the training group used the free-weight squat lift ( 90 ° ) as their training exercise . The concentric phase of the squat was performed explosively . Skeletal muscle architecture of the vastus lateralis was visualized using ultrasonography . At the end of the study , significant increases in vastus lateralis muscle thickness ( + 6.9 % , P < 0.001 ) , fascicle length ( + 10.3 % , P < 0.05 ) , one-repetition maximum ( + 8.2 % , P < 0.05 ) , rate of force development ( + 23.8 % , P < 0.05 ) and average force produced in the first 500 ms ( + 11.7 % , P < 0.05 ) were seen only in the training group . Adaptations to the muscle architecture in the training group limited the loss of fibre force , and improved the capacity for developing higher velocities of contraction . The architectural changes in the training group were similar to those seen in studies where high-speed training was performed . In conclusion , dynamic resistance training with light loads leads to increases in muscle thickness and fascicle length , which might be related to a more efficient transmission of fibre force to the tendon The purpose of this study was to assess and compare eccentric ( ECC ) and concentric ( CONC ) torque output of the quadriceps and hamstring muscles and to analyze the effect of gravity effect torque ( GET ) correction on the calculation of the hamstring/quadriceps peak torque quotient ( H/Q quotient ) . Twenty female subjects performed maximal voluntary CONC and ECC contractions of the quadriceps and hamstring muscles at five isokinetic lever arm velocities from 60 degrees/s to 360 degrees/s . Peak torque was measured and corrected for GET . Mean ECC torque did not significantly change with increasing ECC velocity for either the quadriceps or hamstring muscles ( P greater than 0.05 ) . Mean CONC torques were significantly lower than the corresponding ECC torques ( P less than 0.05 ) and decreased with increasing CONC velocity . At each test velocity , the CONC H/Q quotient was significantly lower than the corresponding ECC H/Q quotient ( P less than 0.05 ) . Mean H/Q quotients did not significantly change with increasing velocity for either the CONC or ECC tests ( means : 0.46 and 0.57 ; P greater than 0.05 ) . Mean H/Q quotients not corrected for GET significantly increased with increasing velocity for the CONC ( 0.61 to 0.78 ; P less than 0.05 ) , but not ECC tests ( 0.66 to 0.71 ; P greater than 0.05 ) . The results indicate that the ECC torque-velocity curve is essentially level for both quadriceps and hamstring muscles . The present findings point strongly toward the necessity of correcting for GET when calculating both CONC and ECC H/Q quotients . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Address reprint requests to Dr. J. R. Basford , Mayo Clinic , 200 First Street S.W. , Rochester , MN 55905 . The purpose of this study was to compare the effects of eccentric and concentric isokinetic training exercises on eccentric and concentric quadriceps performance in 63 healthy subjects during a six-week training period . The subjects were r and omly divided into three groups : eccentric training , concentric training , and no training . Members of the training groups exercised their right quadriceps only . Orientation , training , and testing were performed on a computer-assisted isokinetic dynamometer ( KIN-COM ) at 100 degrees /sec . All subjects were tested concentrically and eccentrically on both quadriceps ; and peak torque , total work , and position angle at peak torque were measured . Analysis of variance and post hoc analyses were performed on the mean changes ( pretest and posttest differences ) for all groups . The concentric training group demonstrated the most significant increases in concentric torque and work ; the eccentric training group demonstrated the most significant increases in eccentric torque and work . No significant changes were seen in the untrained left limbs of any group . These results support the concept of mode specificity in isokinetic exercise training . J Orthop Sports Phys Ther 1991;14(1):31 - 36 Abstract The purpose of this study was to compare pure eccentric and concentric isokinetic training with respect to their possible specificity in the adaptation of strength and morphology of the knee extensor muscles . Ten moderately trained male physical education students were divided into groups undertaking eccentric ( ETG ) and concentric ( CTG ) training . They performed 10 weeks of maximal isokinetic ( 90 ° · s−1 ) training of the left leg , 4 × 10 repetitions – three times a week , followed by a second 10-week period of similar training of the right-leg . Mean eccentric and concentric peak torques increased by 18 % and 2 % for ETG and by 10 % and 14 % for CTG , respectively . The highest increase in peak torque occurred in the eccentric 90 ° · s−1 test for ETG ( 35 % ) whereas in CTG strength gains ranged 8%–15 % at velocities equal or lower than the training velocity . Significant increases in strength were observed in the untrained contra-lateral leg only at the velocity and mode used in ipsilateral training . Cross-sectional area of the quadriceps muscle increased 3%–4 % with training in both groups , reaching statistical significance only in ETG . No major changes in muscle fibre composition or areas were detected in biopsies from the vastus lateralis muscle for either leg or training group . In conclusion , effects of eccentric training on muscle strength appeared to be more mode and speed specific than corresponding concentric training . Only minor adaptations in gross muscle morphology indicated that other factors , such as changes in neural activation patterns , were causing the specific training-induced gains in muscle strength Summary Women participated in 5 months of unilateral concentric ( n = 37 ) or eccentric ( n = 33 ) isokinetic resistance training of the legs and arms . Limb muscular strength increased as did total body , leg , and arm fat-free soft tissue mass , total body BMC , hip BMD , and forearm BMC and BMD . Isokinetic training benefits bone mineral acquisition . Introduction and hypothesisIsokinetic resistance training ( IRT ) is osteogenic ; however , it is not known if concentric or eccentric modalities of IRT produce differential effects on bone . We tested our hypothesis that high-load eccentric versus concentric mode of IRT would produce greater increases in muscular strength , fat-free soft tissue mass ( FFSTM ) , bone mineral density ( BMD ) and content ( BMC ) in trained legs and arms . Methods Participants were r and omized to 5 months of concentric ( n = 37 ) or eccentric ( n = 33 ) training . The non-dominant leg and arm were used during training ; dominant limbs served as controls . Muscular strength was measured with an isokinetic dynamometer ; body composition was measured by dual-energy X-ray absorptiometry . Results Muscular strength of the concentrically and eccentrically trained leg ( 18.6 % ; 28.9 % ) and arm ( 12.5 % ; 24.6 % ) significantly increased with training . Gains in total body ( TB ) BMC ( p < 0.05 ) and , in the trained limbs , total proximal femur BMD ( p < 0.05 ) and total forearm BMD ( p < 0.05 ) and BMC ( p < 0.05 ) occurred in both groups . FFSTM increased for the TB and trained leg and arm ( all p < 0.001 ) in both modes . Conclusion Regardless of the mode , high-intensity , slow-velocity IRT increases muscular strength and FFSTM of trained limbs and imparts benefits to TB BMC and site-specific BMD and BMC in young women This study assessed muscular torque and rate of torque development following concentric ( CON ) or eccentric ( ECC ) isokinetic training . Thirty-eight women were r and omly assigned to either CON or ECC training groups . Training consisted of knee extension and flexion of the nondominant leg three times per week for 20 weeks ( SD = 1 ) . Eccentric training increased ECC knee extension and flexion peak torque more than CON training . The ECC group improved acceleration time and time to peak torque with ECC movements versus the CON group . Slow-velocity ECC isokinetic training yielded greater ECC and similar CON torque development gains versus CON training over the course of 20 weeks in young women RATIONALE AND AIMS ' OTseeker ' is an online data base of r and omized controlled trials ( RCTs ) and systematic review s relevant to occupational therapy . RCTs are critically appraised and rated for quality using the ' PEDro ' scale . We aim ed to investigate the inter-rater reliability of the PEDro scale before and after revising rating guidelines . METHODS In study 1 , five raters scored 100 RCTs using the original PEDro scale guidelines . In study 2 , two raters scored 40 different RCTs using revised guidelines . All RCTs were r and omly selected from the OTseeker data base . Reliability was calculated using Kappa and intraclass correlation coefficients [ ICC ( model 2,1 ) ] . RESULTS Inter-rater reliability was ' good to excellent ' in the first study ( Kappas > or= 0.53 ; ICCs > or= 0.71 ) . After revising the rating guidelines , the reliability levels were equivalent or higher to those previously obtained ( Kappas > or= 0.53 ; ICCs > or= 0.89 ) , except for the item , ' groups similar at baseline ' , which still had moderate reliability ( Kappa = 0.53 ) . In study 2 , two PEDro scale items , which had their definitions revised , ' less than 15 % dropout ' and ' point measures and variability ' , showed higher reliability . In both studies , the PEDro items with the lowest reliability were ' groups similar at baseline ' ( Kappas = 0.53 ) , ' less than 15 % dropout ' ( Kappas < or= 0.68 ) and ' point measures and variability data ' ( Kappas < or= 0.68 ) . CONCLUSION The PEDro scale is a reliable instrument for rating the quality of RCTs . Revised rating guidelines are provided for scale items that are difficult to rate , and helped to improve inter-rater reliability Twenty-two male and female college varsity tennis players trained for 6 weeks , one group using eccentric isokinetic internal and external shoulder rotation , and the second group using concentric isokinetic internal and external shoulder rotation . Subjects pretested and posttested both concentrically and eccentrically , so that training overflow and specificity could be examined . Three maximally hit tennis serves made before and after training , which were analyzed by high speed cin ematography to obtain ball velocity , served as a func tional performance measurement . Statistical analysis of peak torque ( newton meters ) and peak torque to body weight ratio have revealed significant concentric strength gains ( P < 0.005 ) in the concentric as well as the eccentric training groups . Eccentric strength gains were demonstrated by the concentric training group at selected speeds ( P < 0.05 and P < 0.005 ) but were not generated in the eccentric group at the P < 0.05 significance level . Functional test analysis shows an increase in maximal serve velocity at a significance level of P < 0.005 in the concentric training group , with no significant ( P > 0.01 ) increases in the eccentric group The purpose of this study was to compare pure eccentric and concentric strength training regarding possible specific effects of muscle action type on neuromuscular parameters , such as a decreased inhibition during maximal voluntary eccentric actions . Two groups of young healthy adult men performed 10 weeks of either eccentric or concentric unilateral isokinetic knee extensor training at 90 degrees.s(-1 ) , 4 sets of 10 maximal efforts , 3 days a week . Knee extensor torque and surface EMG from the quadriceps and hamstring muscle groups were collected and quantified in a window between 30 and 70 degrees knee angle ( range of motion 90 - 5 degrees ) during maximal voluntary eccentric and concentric knee extensor actions at 30 , 90 , and 270 degrees.s(-1 ) . Changes in strength of the trained legs revealed more signs of specificity related to velocity and contraction type after eccentric than concentric training . No major training effects were present in eccentric to concentric ratios of agonist EMG or in relative antagonist ( hamstring ) activation . Thus , for the trained leg , the muscle action type and speed specific changes in maximal voluntary eccentric strength could not be related to any effects on neural mechanisms , such as a selective increase in muscle activation during eccentric actions . Interestingly , with both types of training there were specific cross-education effects , that is , action type and velocity specific increases in strength occurred in the contralateral , untrained , leg , accompanied by a specific increase in eccentric to concentric EMG ratio after eccentric training 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 . 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 The purpose of this investigation was to determine the effects of a concentric vs. eccentric resistance training program on single muscle fiber myosin heavy chain ( MHC ) adaptations in humans . Fifteen sedentary , healthy males were divided into three groups : concentric training ( CTG ) ( n = 6 , 24.2 + /- 1.7 y , 181 + /- 2 cm , 82.5 + /- 4.6 kg ) , eccentric training ( ETG ) ( n = 6 , 23.7 + /- 1.6 y , 178 + /- 3 cm , 90.4 + /- 6.1 kg ) , and control ( CTL ) ( n = 3 , 23 + /- 1.5 y , 181 + /- 2 cm , 97 + /- 13.2 kg ) . The subjects performed 4 sets of 8 unilateral repetitions starting at 80 % of concentric 1-RM , 3 days/week for a total of 4 weeks . Subjects were tested pre- and post-training for concentric 1-RM . Muscle biopsies were obtained from the vastus lateralis pre- and post-training for determination of single fiber MHC isoform distribution using SDS-PAGE/silver staining ( 100 fibers analyzed/subject pre- and post-training ) . Fibers expressing more than one MHC isoform ( i.e. , hybrid fibers ) were analyzed for relative MHC isoform proportions via densitometry . The training program result ed in a 19 % 1-RM strength gain for CTG ( p < 0.05 ) with no change in ETG or CTL . MHC-IIx fibers decreased by 7 % in CTG ( p < 0.05 ) and ETG had an 11 % increase in total hybrids ( MHC-I/IIa + MHC-IIa/IIx ) ( p < 0.05 ) . No other differences were noted in MHC distribution among the three groups . Densitometry analysis of hybrid fibers showed no change in relative MHC isoform proportions pre- to post-training for any group . These data suggest that the MHC distribution did not change dramatically as a result of 4 weeks of concentric vs. eccentric resistance training despite the increase in whole muscle strength from concentric muscle actions Heart rate ( HR ) , mean arterial blood pressure ( MAP ) , and rate-pressure product ( RPP ) responses to submaximal isokinetic concentric ( CON ) and eccentric ( ECC ) knee extension exercise were compared at the same absolute torque output in 20 young ( mean+/-SD=23.2+/-1.7 years ) and 20 older ( mean+/-SD=75.2+/-4.6 years ) adults . After determination of peak CON and ECC torques , subjects performed separate , r and omly ordered , 2-minute bouts of isokinetic CON and ECC exercise ( 90 degrees/s , exercise intensity : 50 % of CON peak torque ) . CON exercise elicited greater changes in HR , MAP , and RPP than ECC exercise ( p<.001 ) for both age groups . There were no age-related differences in HR , MAP , or RPP responses for either CON or ECC exercise . At the same absolute torque output , isokinetic CON knee extension exercise elicited significantly greater increases in cardiovascular stress than ECC exercise in both young and older adults . This result has implication s for determining appropriate fitness and rehabilitation programs |
10,802 | 26,167,737 | Furthermore , the current scientific evidence shows that the sodium hypochlorite-based ( Carisolv ) chemomechanical caries removal method was more time consuming when compared to the enzyme-based ( Papacarie ) chemomechanical and the conventional caries removal methods . | OBJECTIVES The aim of this review was to assess the method ologies used in previously published prospect i ve r and omized clinical trials on chemomechanical caries removal and to conduct a meta- analysis to quantify the differences in the excavation time between chemomechanical and conventional caries removal methods . | OBJECTIVE To determine the efficacy of chemo-mechanical caries removal using Carisolv and compare it to the conventional method of caries removal . DESIGN A quasi-experimental study . PLACE AND DURATION OF STUDY The Department of Operative Dentistry , Fatima Jinnah Dental College Hospital , Karachi , from October 2003 to March 2004 . PATIENTS AND METHODS Thirty patients with contralateral cariously involved m and ibular molars participated in the study . Patients were selected using convenience sampling . One side of each patient was r and omly selected for treatment with either Carisolv or the conventional method . In the study group , carious lesion was removed with Carisolv instruments , whereas in control group excavators and round steel burs were used . Single observer assessed all the treated lesions . Time required to remove caries and completeness of caries removal was observed for both techniques . Data was compared using ' Fisher 's exact test ' and ' Independent sample s t-test ' . RESULTS Time taken to remove caries using Carisolv was 12.19 ( SD 3.7 ) minutes , whereas time taken to remove caries by conventional method was 7.4 ( SD 3.21 ) minutes . The difference was statistically significant ( p-value<0.005 ) . Caries could not be removed in 3 teeth in the study group with Carisolv . Complete caries removal was , however , achieved in the control group . The difference was statistically insignificant ( p-value>0.005 ) . CONCLUSION Chemo-mechanical caries removal with Carisolv is as effective as conventional methods in removing dental caries , however , it is significantly more time-consuming OBJECTIVES The purpose of this study was to compare the chemomechanical caries-removal system ( Carisolv ) with high-speed excavation in cavitated occlusal caries of primary molars . Design and setting . The study was a r and omized controlled , clinical trial in which the two techniques were compared in each subject . Participants were chosen from public schools , in Maracaibo County , Zulia State , Venezuela . SAMPLE AND METHODS The sample consisted of 80 primary molars selected from 40 children ( mean age 7.7+/-0.7 years ) . Each patient had at least two contralateral primary molars with cavitated occlusal caries and approximately equal-size access to lesions . The outcome variables were : clinical ly complete caries removal , size of the opening of the cavity , volume of carious tissue removed , pain during caries removal , anaesthesia requested by the patient , caries-removal time , and behaviour and preference of patients . RESULTS All treated molars were clinical ly caries free whichever caries-removal procedure was used . When Carisolv ' was used the final cavity entrance sizes were smaller ( P<0.001 ) and the estimated volume of tissue removed was less ( P<0.001 ) . The time taken for caries removal was three times longer ( 7.51+/-1.83 min , P<0.001 ) . Some pain was reported by seven ( 17.5 % ) participants when Carisolv was used , compared with 16 ( 40 % ) when high-speed excavation was used ( P<0.05 ) . Using the Carisolv method there was a higher proportion of patients with positive behaviour ( P<0.01 ) , and 71.0 % ( P<0.05 ) preferred this treatment . CONCLUSION Carisolv is an effective clinical alternative treatment for the removal of occlusal dentinal caries in cavitated primary molars ; it is more conservative of dental tissue and appeared to be more comfortable for most patients , although the clinical time spent is longer than when using high-speed excavation PURPOSE The purpose of this controlled clinical trial was to compare the working time for caries removal in primary teeth , the need for local anesthesia and patient cooperation , when the chemomechanical Carisolv or the conventional mechanical method were used . METHODS The sample consisted of primary teeth of children who had occlusal or buccal carious lesions into dentin . High speed and /or low speed were used as the conventional mechanical method of caries removal . The efficiency in caries removal was judged on the basis of clinical criteria . Length of working time , need of local anesthesia , and level of patient cooperation were recorded for both methods . Statistical analysis was performed using the student 's t test and chi-square test . RESULTS Working time with the chemomechanical method was much more prolonged than with the mechanical method ( P < .001 ) , but it did not negatively affect children 's cooperation . Furthermore , the chemomechanical method reduced the need for administration of local anesthesia for Class V cavity preparations . CONCLUSIONS The chemomechanical method , although more prolonged , is effective in caries removal in primary teeth , does not influence children 's cooperation and may reduce the need of local anesthesia in Class V restorations Carisolv is a minimally invasive method for softening and removing dentine caries . A new , modified Carisolv gel has been developed in order to optimise the efficiency if its chemical caries dissolution . The aim of the present study was to compare the caries removal efficiency of the original gel with that of the new gel , which contains almost double the concentration of sodium hypochlorite . Ten dentists treated 202 cavities in 170 patients ; 104 cavities were r and omised to the new gel and 98 to the original gel . Their mean treatment times for caries removal were 6.7±4.1 min and 7.6±4.2 min , respectively ( P>0.05 ) . In close-to-pulp lesions , constituting 32 % of the cavities , the mean times for caries removal were 9.0±7.0 min and 11.6±4.4 min for the new and original gels , respectively ( P<0.01 ) . Question naires revealed that 81 % of the patients preferred chemomechanical treatment to drilling . In conclusion , the improved efficiency of the modified Carisolv gel did reduce the time for caries removal in deep lesions . However , it still needs more time than conventional drilling The purpose of this study was to evaluate the clinical performance of glass ionomer cement ( GIC ) restorations comparing two minimally invasive methods in permanent teeth after 12 months . Fifty pregnant women ( second trimester of pregnancy ) , mean age 22 ± 5.30 years , were treated by two previously trained operators . The treatment approaches tested were : chemomechanical method ( CarisolvTM ; MediTeam ) and atraumatic restorative treatment ( ART ) . A split-mouth study design was used in which the two treatments were r and omly placed in 50 matched pairs of permanent teeth . The chemomechanical method ( CM ) was the test group and the ART was the control group . The treatments were performed in Public Health Centers . The tested restorative material was a high-strength GIC ( Ketac Molar ; 3M/ESPE ) . The restorations were placed according to the ART guidelines . Two calibrated independent examiners evaluated the restorations in accordance with ART criteria . The interexaminer kappa was 0.97 . Data were analyzed using 95 % confidence interval on the binomial distribution and Fisher 's exact test at 5 % significance level . In a 12-month follow-up , 86 % of the restorations were evaluated . In the test group ( CM ) , 100 % ( CI=93.3 - 100 % ) of the restorations were considered successful . In the control group ( ART ) 97.6 % ( CI=87.4 - 99.9 % ) of the restorations were considered successful and 2.4 % unsuccessful ( marginal defect > 0.5 mm ) . There was no statistically significant difference between the 12-mounth success rate for both groups ( Fisher 's exact test : P=0.49 ) and between the two operators ( Fisher 's exact test : P=1.00 ) . Both minimally invasive methods , chemomechanical method and ART , showed a similar clinical performance after 12 months of follow up UNLABELLED The change in the concepts of cavity preparation and the development of reliable adhesive material s lead to the development of alternative methods of caries removal . Chemo-mechanical caries removal ( CMCR ) involves the chemical softening of carious dentin , followed by its removal with gentle excavation . OBJECTIVE The present study was conducted to evaluate clinical ly the efficiency of caries removal using a new chemo-mechanical agent ( Papacarie ) compared to the conventional drilling method including the need for local anesthesia , the need for drill , duration of the treatment and the pain reaction . STUDY DESIGN This study was split mouth design . The study was performed on thirty seven bilateral open carious lesions . They were divided into two equal groups according to method of caries removal . In Group I , caries was removed using the Papacarie system and in Group II , caries was removed with the conventional drill . RESULTS The results showed that the Papacarie was as efficient as the drill in caries removal from open carious lesions with no significant difference in the operating time . The new CMCR agent also reduced significantly the need for local anesthesia and the use of drill . In addition , Papacarie was also more comfortable than the traditional rotatory instruments . CONCLUSIONS It was concluded that Papacarie could be an effective caries removal method to treat children , particularly those who present with early childhood caries or management problems Objective . The purpose of this study was to make a clinical comparison of the chemomechanical method for caries removal and the conventional rotary instruments technique when used in children and adolescents . Material and Methods . The study comprised 120 patients aged 3–17 years r and omized into two groups : caries were removed chemomechanically in 60 patients and 60 patients received conventional treatment with rotary instruments . The outcome variables were : clinical ly complete caries removal , pain during caries removal , need for local anesthesia , treatment time , preferences of patients , and clinical success of the restorations during the 12-month evaluation period . Results . Complete caries removal was achieved in 92 % of chemomechanically treated teeth and in all teeth treated with rotary instruments ( p>0.05 ) . The chemomechanical method significantly reduced the need for local anesthesia ( p<0.001 ) . Eighty-five percent of patients treated with Carisolv and 47 % treated with rotary instruments were satisfied with the treatment ( p<0.05 ) . The mean time for chemomechanical caries removal was 11.2±3.3 min and 5.2±2.8 min for caries removal with rotary instruments ( p<0.001 ) . At the end of the 12-month evaluation period , there was no observed influence of the caries removal method on the survival of the restorations . Conclusions . The chemomechanical caries removal technique is an adequate alternative to the conventional rotary instruments method and is advantageous in pediatric dentistry 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 Dental fear is often associated with experience of pain , unpleasant sounds and uncomfortable vibrations caused by dental drills . Therefore patients welcome alternative , less painful excavating methods such as lasers , s and blasters and chemomechanical systems . The aim of this study was to compare a chemomechanical caries removal system ( Carisolv ) to traditional drilling with regard to patient acceptance and time consumption as well as the six-month success rate of fillings . Ninety-two primary teeth in 46 children were included in the study . From this study , the following conclusions can be drawn : patient acceptance of Carisolv-treatment compared to drilling is excellent , since 65 % would choose Carisolv and no one drilling when treated next time . The dentists rated patients ' degree of pain significantly lower in Carisolv situations than in drill situations . Time consumption is significantly higher when excavating with Carisolv ( 6.7 min . ) than with drill ( 3.3 min . ) . The durability of fillings six months after treatment is equal in the two groups AIM To test the null hypothesis that Carisolv is no more effective than 1 % sodium hypochlorite in cleaning uninstrumented , immature root canals . METHODOLOGY A total of 240 uniform , immature ovine incisors were decoronated at the CEJ level and r and omly divided into four groups of 60 . After gross pulp extirpation , canals were flooded with normal saline ( negative control ) , 1 % NaOCl , Carisolv or 5 % NaOCl ( positive control ) and incubated for 10 min ( group 1 ) , 20 min ( group 2 ) , 30 min ( group 3 ) or 30 min , refreshing irrigant at 10 and 20 min ( group 4 ) . SEM photomicrographs of canal wall debris in the apical , middle and coronal thirds were scored against a 5-point scale . Internal consistency was assessed by kappa statistics . Debris scores for different irrigant regimes at different canal levels were analysed by non-parametric tests ( P < 0.05 ) . RESULTS Canals were consistently cleaner in the coronal and middle than apical thirds . NaOCl ( 5 % ) was consistently most effective . Carisolv and NaOCl ( 1 % ) were no more effective than normal saline in group 1 ( P > 0.05 ) , but significantly more effective than normal saline in groups 2 ( middle and apical 1/3 ) , 3 and 4 ( P < 0.05 ) . Carisolv and NaOCl ( 1 % ) had comparable activity in groups 1 , 2 ( middle and apical thirds ) and 3 , but NaOCl ( 1 % ) was significantly more effective than Carisolv in group 4 ( coronal and middle thirds ) . CONCLUSIONS 1 . The ovine incisor model presents opportunities to investigate irrigation regimes under controlled ex-vivo conditions . 2.NaOCl ( 5 % ) remains the most effective irrigant for rapid debris removal in immature root canals . 3 . Carisolv cleans pulp debris from the walls of immature root canals as effectively as NaOCl ( 1 % ) during static , unrefreshed wall contact for between 20 and 30 min . 4 . Refreshment of NaOCl ( 1 % ) enhances its cleaning ability above that of Carisolv PURPOSE This study 's purpose was to evaluate complete caries removal time ( CCR ) and patient acceptance of the chemomechanical caries removal agent and papain gel Papacárie in disabled patients . METHODS Fifty-one consecutive patients entered a prospect i ve , controlled , r and omized , open study . Patients were divided into 2 groups : ( 1 ) group 1=28 children 3 to 10 years old with or without visual or hearing impairments , motor disability on upper limbs , and inability to respond to simple orders ; and ( 2 ) group 2=23 children , without visual or hearing impairments , with motor disability on the upper limbs and the ability to respond to simple orders . CCR time was measured in both groups . Patients ' acceptance was assessed only in group 2 by using the visual analogy of face scale . The visual scale was presented in phase A -- after the radiography with the child sitting on the dental chair before the beginning of the treatment , phase B -- during the treatment , after total removal of the carious tissue and phase C -- after the restoration was complete ( treatment was finished ) . RESULTS The total CCR average time was 8 minutes for each tooth when groups 1 and 2 were considered . Group 2 patients ' acceptance in the first treatment was not statistically significant in all stages . CONCLUSIONS Papacárie gel had a completed caries removal time of 8 minutes per tooth and is well accepted by the patients in all phases and in the first and subsequent visits The purpose of this study was to evaluate the effectiveness of subgingival application of Carisolv gel as an adjunctive therapy to scaling and root planing ( SRP ) on calculus removal compared to conventional instrumentation . Forty-five teeth requiring extraction due to severe periodontal disease were r and omized to the following treatments : 1 ) SRP alone ; 2 ) placebo gel + SRP ; 3 ) Carisolv gel + SRP . Either test or placebo gel was applied subgingivally for 1 min and then the root were instrumented until a smooth and calculus-free surface was achieved . Instrumentation time and the number of strokes required were recorded . After extraction , the efficacy of root surface instrumentation was measured by percentage of remaining calculus . There was no statistically significant difference ( p>0.05 ) between the treatment groups regarding either time required for instrumentation or the percentage of residual calculus . The subgingival application of Carisolv gel prior to SRP did not provide any additional benefit to root instrumentation compared to scaling and root planing alone OBJECTIVE Carisolv is a relatively new chemomechanical method for caries removal . The aim of this clinical study was to compare Carisolv with the conventional drilling technique . METHOD AND MATERIAL S Forty-five volunteers , ages 18 to 55 years , each with two contralateral primary coronal mesio-occlusal or disto-occlusal carious lesions , similar in extent , participated in the study . Two calibrated operators treated all lesions . One operator treated both lesions in one visit ( one lesion with Carisolv and the other with conventional drilling ) . Following the filling procedure , the opinion of each patient regarding each caries removal method was recorded . The need for drilling in addition to the Carisolv application , the time required for caries removal , the need for anesthesia , and the gingival reaction to the Carisolv gel were recorded by each operator for each case . RESULTS The patients found Carisolv treatment more pleasant ( 82 % ) and preferable ( 88 % ) to drilling . Of the patients treated with drilling , 40 % required anesthesia compared to the 8 % treated with Carisolv . Additional drilling for complete caries removal was needed in 10 % of Carisolv-treated lesions . Carisolv induced no gingival reaction . Significantly longer times were required for caries removal with Carisolv ( 12.2 + /- 4.1 minutes ) compared to drilling ( 6.8 + /- 2.8 minutes ) . CONCLUSIONS The Carisolv technique was : ( a ) accepted by the majority of patients , ( b ) efficient for caries removal , ( c ) considered a time-consuming technique for the dentists , and ( d ) considered less dependent on local anesthesia BACKGROUND This study compared the chemical , morphological and microhardness changes in carious dentine following application of NaOCl-based ( Carisolv ) , papain-based ( Papacarie ) chemomechanical caries removal agents with conventional rotary method . METHODS Thirty-two carious and eight non-carious human permanent molars were used . The carious molars were r and omly distributed into four groups : Group 1 ( positive control ) - molars were left without caries removal ; Group 2 - caries excavated with rotary method ; Group 3 - caries excavated with Carisolv ; Group 4 - caries excavated with Papacarie . Group 5 ( negative control ) consisted of eight sound molars . After caries excavation , all specimens were prepared for chemical , morphological analysis and Vickers hardness testing . RESULTS EDX analysis showed no significant difference in Ca wt% , P wt% and Ca/P ratio among Groups 2 to 5 . Vickers hardness of dentine from Groups 3 and 4 was significantly lower ( p < 0.05 ) than for Groups 2 and 5 . The use of Papacarie result ed in a dentine surface without smear layer and patent tubules , while Carisolv result ed in a dentine surface exhibiting two patterns : ( 1 ) the presence of smear layer or ( 2 ) patent tubules with partial smear layer formation . CONCLUSIONS Papain-based ( Papacarie ) chemomechanical caries removal method is a reliable alternative to conventional rotary and NaOCl-based ( Carisolv ) caries removal BACKGROUND The chemical-mechanical removal of caries involves the chemical softening of the infected dentin , following by the mechanical removal of the softened tissue using non-cutting manual instruments . Papacárie ( Fórmula&Açāo , Sao Paulo , Brazil ) is a product in gel form used for the chemical-mechanical softening of the affected tissue . OBJECTIVE The purpose of the present study was to evaluate the effectiveness of Papacárie . METHODS Clinical and radiographic evaluations were performed on 14 young permanent molars treated with Papacárie and restored with glass ionomer cement ( VitroMolar DFL Ind. Com LTDA , Rio de Janeiro , Brazil ) 24 months following intervention . RESULTS Success was achieved in 13 of the 14 cases . CONCLUSION Papacárie was effective in the treatment of carious lesions and constitutes a conservative alternative that offers benefits to patients |
10,803 | 24,594,804 | This meta- analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics .
These data suggest that BRAFV600E mutation could be used to supplement st and ard clinical and pathological staging for the better management of individual CRC patients , and could be considered as a poor prognostic marker for CRC | BACKGROUND Colorectal cancer ( CRC ) is a heterogeneous disease with multiple underlying causative genetic mutations .
The B-type Raf proto-oncogene ( BRAF ) plays an important role in the mitogen-activated protein kinase ( MAPK ) signaling cascade during CRC .
The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy .
However , the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial .
We performed a systematic review and meta- analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC . | PURPOSE Mutations affecting the KRAS gene are established predictive markers of outcome with anti-epithelial growth factor receptor ( EGFR ) antibodies in advanced colorectal cancer ( CRC ) . The relevance of these markers for anti-vascular endothelial growth factor ( VEGF ) therapy is controversial . This analysis was performed to assess the predictive and prognostic impact of KRAS and BRAF gene mutation status in patients receiving capecitabine with bevacizumab ( CG ) or capecitabine without bevacizumab in the phase III AGITG MAX ( Australasian Gastrointestinal Trials Group MAX ) study . PATIENTS AND METHODS Mutation status was determined for 315 ( 66.9 % ) of the original 471 patients . Mutation status was correlated with efficacy outcomes ( response rate , progression-free survival [ PFS ] , and overall survival [ OS ] ) , and a predictive analyses was undertaken . RESULTS Mutations in KRAS and BRAF genes were observed in 28.8 % and 10.6 % of patients , respectively . KRAS gene mutation status ( wild type [ WT ] v mutated [ MT ] ) had no prognostic impact for PFS ( hazard ratio [ HR ] , 0.89 ; CI , 0.69 to 1.14 ) or OS ( HR , 0.97 ; CI , 0.73 to 1.28 ) . BRAF mutation status ( WT v MT ) was not prognostic for PFS ( HR , 0.80 ; CI , 0.54 to 1.18 ) but was prognostic for OS ( HR , 0.49 ; CI , 0.33 to 0.73 ; P = .001 ) . By using the comparison of capecitabine versus capecitabine and bevacizumab ( CB ) and CB plus mitomycin ( CBM ) , KRAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .95 and 0.43 , respectively ) . Similarly , BRAF gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .46 and 0.32 , respectively ) . CONCLUSION KRAS gene mutation status was neither prognostic for OS nor predictive of bevacizumab outcome in patients with advanced CRC . BRAF gene mutation status was prognostic for OS but was not predictive of outcome with bevacizumab PURPOSE Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer . We took advantage of PETACC-3 , an adjuvant trial with 3,278 patients with stage II to III colon cancer , to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting . PATIENTS AND METHODS Formalin-fixed paraffin-embedded tissue blocks ( n = 1,564 ) were prospect ively collected and DNA was extracted from tissue sections from 1,404 cases . Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction . Survival analyses were based on univariate and multivariate proportional hazard regression models . RESULTS KRAS and BRAF tumor mutation rates were 37.0 % and 7.9 % , respectively , and were not significantly different according to tumor stage . In a multivariate analysis containing stage , tumor site , nodal status , sex , age , grade , and microsatellite instability ( MSI ) status , KRAS mutation was associated with grade ( P = .0016 ) , while BRAF mutation was significantly associated with female sex ( P = .017 ) , and highly significantly associated with right-sided tumors , older age , high grade , and MSI-high tumors ( all P < 10(-4 ) ) . In univariate and multivariate analysis , KRAS mutations did not have a major prognostic value regarding relapse-free survival ( RFS ) or overall survival ( OS ) . BRAF mutation was not prognostic for RFS , but was for OS , particularly in patients with MSI-low ( MSI-L ) and stable ( MSI-S ) tumors ( hazard ratio , 2.2 ; 95 % CI , 1.4 to 3.4 ; P = .0003 ) . CONCLUSION In stage II-III colon cancer , the KRAS mutation status does not have major prognostic value . BRAF is prognostic for OS in MS-L/S tumors Purpose : Colon tumors with defective DNA mismatch repair ( dMMR ) have a well-characterized phenotype and accounts for ∼15 % to 20 % of sporadic colon cancer as well as those colon cancer patients with Lynch syndrome . Although the presence of dMMR seems to be a favorable prognostic marker , data suggest that these patients do not respond as well to adjuvant chemotherapy . Experimental Design : In this study , we examined the prognostic significance of tumor MMR deficiency and the presence of a specific mutation in BRAF ( V600E ) in a group of patients ( n = 533 ) who participated in a r and omized prospect i ve clinical trial through the North Central Cancer Treatment Group . Results : Tumors with dMMR were found to be associated with higher tumor grade ( P = 0.001 ) , proximal location ( P < 0.0001 ) , and improved overall and disease-free survival ( P = 0.05 and 0.04 , respectively ) . Among all cases examined , evaluation of the BRAF V600E mutation status revealed no statistically significant differences in either disease-free or overall survival . Patients were then grouped into four categories for further analysis : dMMR/BRAF(− ) , dMMR/BRAF(+ ) , pMMR/BRAF(− ) , and pMMR/BRAF(+ ) . The dMMR/BRAF(− ) group had a significantly improved overall survival ( 5-year overall survival of 100 % versus 73 % , P = 0.002 ) compared with all others . The remaining three groups had very similar survival outcomes . An additional cohort of tumors previously classified as having dMMR were also tested for the BRAF V600E alteration . Results remained significant ( P = 0.006 ) when the two groups were combined for analysis . Conclusions : Overall , these data suggest that the underlying molecular etiology of those tumors having dMMR may influence the disease outcome in these patients Purpose : Alterations in the RAS-RAF-MAP2 K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis . In colorectal cancer , BRAF mutation is associated with microsatellite instability ( MSI ) , and typically predicts inferior prognosis . We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer . Methods : We assessed status of BRAF c.1799T > A ( p . V600E ) mutation and MSI in 506 stage III colon cancer patients enrolled in a r and omized adjuvant chemotherapy trial [ 5-fluorouracil and leucovorin ( FU/LV ) vs. irinotecan ( CPT11 ) , FU and LV ( IFL ) ; CALGB 89803 ] . Cox proportional hazards model was used to assess the prognostic role of BRAF mutation , adjusting for clinical features , adjuvant chemotherapy arm , and MSI status . Results : Compared with 431 BRAF wild-type patients , 75 BRAF-mutated patients experienced significantly worse overall survival [ OS ; log-rank P = 0.015 ; multivariate HR = 1.66 ; 95 % CI : 1.05–2.63 ] . By assessing combined status of BRAF and MSI , it seemed that BRAF-mutated MSS ( microsatellite stable ) tumor was an unfavorable subtype , whereas BRAF wild-type MSI-high tumor was a favorable subtype , and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes . Among patients with BRAF-mutated tumors , a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm ( multivariate HR = 0.52 ; 95 % CI : 0.25–1.10 ) . Among patients with BRAF wild-type cancer , IFL conferred no suggestion of benefit beyond FU/LV alone ( multivariate HR = 1.02 ; 95 % CI : 0.72–1.46 ) . Conclusions : BRAF mutation is associated with inferior survival in stage III colon cancer . Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy . Clin Cancer Res ; 18(3 ) ; 890–900 . © 2011 AACR Background BRAF and K-ras proto-oncogenes encode components of the ERK signalling pathway and are frequently mutated in colorectal cancer . This study investigates the associations between BRAF and K-ras mutations and clinicopathological , lifestyle and dietary factors in colorectal cancers . Methods 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for BRAF and K-ras mutations . Diet and lifestyle data were collected prospect ively using seven day food diaries . Results BRAF V600E mutation was found in 15.6 % of colorectal cancers but at higher frequencies in cancers with proximal location , poor differentiation and microsatellite instability ( MSI ) ( all p < 0.001 ) . K-ras mutation ( mostly in codons 12 and 13 ) was found in 22.0 % of colorectal cancers but at higher frequencies in cancers of more advanced Dukes ' stage ( p = 0.001 ) , microsatellite stable ( MSS ) status ( p = 0.002 ) and in individuals with lower blood high-density lipoprotein concentrations ( p = 0.04 ) . Analysis of dietary factors demonstrated no link between BRAF mutation and any specific dietary constituent , however , K-ras mutation was found at higher frequencies in individuals with higher white meat consumption ( p < 0.001 ) . Further analysis of specific mutation type demonstrated that G to A transitions in K-ras were observed at higher frequencies in individuals consuming lower amounts of fruit ( p = 0.02 ) . Conclusion These data support the model of BRAF and K-ras mutations arising in distinct colorectal cancer subsets associated with different clinicopathological and dietary factors , acting as mutually exclusive mechanisms of activation of the same signalling pathway The aim of this study was to identify KRAS and BRAF gene mutations in colorectal cancer patients and to assess whether they are linked with clinicopathological features . The results of KRAS and BRAF mutation analysis could be used in the selection of patients for anti-EGFR therapy . All specimens were obtained during routine surgery of patients with colorectal carcinoma . The diagnoses were established by st and ard procedures and confirmed histopathologically . After DNA extraction , KRAS mutations were analyzed using quantitative real-time PCR and BRAF mutations were analyzed using real-time PCR by fluorescence melting curve analysis . Our results show that KRAS gene mutations were detected in 35.6 % sample s and the most frequent mutation was Gly12Val . BRAF gene mutation Val600Glu was detected in 8.5 % sample s. Statistical analysis revealed a significant association between the KRAS mutation and Dukes ' stage ( p=0.034 ) , with the lowest frequency in Dukes'A , and between the KRAS mutation and histological grade ( p=0.044 ) , with no KRAS mutation found in poor differentiated tumors . The first data about KRAS and BRAF mutational status in the sample of Croatian population with colorectal cancer shows that the incidence of KRAS and BRAF mutations is within generally valid limits . Prospect i ve studies are to be continued in order to determine whether these mutations contribute to progression of colorectal cancer |
10,804 | 24,959,104 | There was weak evidence for IACIs decreasing clinical signs and symptoms in the lower leg , improving joint range of motion , decreasing leg length discrepancy , and for imaging techniques detecting the effects of IACIs .
Conclusions There is some weak evidence for the efficacy of IACIs improving certain outcome measures . | Background Juvenile Idiopathic Arthritis ( JIA ) commonly affects joints of the lower limb including the knee , ankle , subtalar and other foot joints .
Intra-articular corticosteroid injections ( IACIs ) are considered to be effective for short-term relief of synovitis , however , there appears to be a significant lack of published evidence from comparative effectiveness studies .
The aim of this study was to identify and critically appraise the evidence for the efficacy of lower limb IACIs in children/adolescents with JIA . | The use of intraarticular triamcinolone hexacetonide in the management of persistent arthritis of the knee joint that is unresponsive to nonsteroidal anti-inflammatory drugs was prospect ively evaluated in 40 children with chronic arthritis . Of 49 knees that were injected , 63.3 % maintained complete resolution of effusion and other signs of inflammation at the 6-month followup . This favorable outcome correlated with a young age , a short disease duration , and a higher dose of triamcinolone hexacetonide . At the 12-month followup , 45 % of the injected knees remained in remission Background Children with arthritis may endure a lifetime of disfigurement , dysfunction , and pain if acute inflammation progresses to chronic changes in the joint cartilage and underlying bone . Intraarticular steroids have become an integral component of treatment , but at times are difficult to deliver to joints , such as the subtalar joint , that have complex anatomies . Objective We describe our technique and outcomes using fluoroscopically guided intraarticular subtalar steroid injection in patients with active symptoms of juvenile idiopathic arthritis ( JIA ) . Material s and methods Fluoroscopically guided subtalar joint injections were performed in 38 children ( mean age 6.7 years ) . Medical records were review ed retrospectively and improvement was evaluated clinical ly by the degree of foot movement in eversion and inversion . Results Subtalar joint injection was technically successful in 100 % of the JIA patients with improvement in physical symptoms in 34/38 ( 89 % ) . Of the 38 children , 32 were followed up within 13 weeks of the initial injection and , therefore , satisfied the eligibility criteria for resolution of arthritis . Of these 32 children , 14 showed clinical resolution ( 44 % ) . The mean duration of improvement was 1.2 ± 0.9 years . Children with a longer interval ( > 1 year ) from diagnosis to treatment had significantly less resolution ( P = 0.04 ) . Local subcutaneous atrophy or hypopigmentation were observed in 53 % of the children after steroid injection ( 20/38 ) . These minor complications were associated with a greater volume of steroid injected into the site per child ( P = 0.02 ) . Conclusion Fluoroscopically guided subtalar joint injection is an effective treatment for subtalar arthropathy . Prompt referral for intraarticular steroid treatment in the acute phase improves response . Skin changes often occur at the injection site , and specific pre caution s should be employed to reduce this risk . Prospect i ve study is indicated to determine the most effective treatment strategy to prevent long-term pain and disability OBJECTIVE To compare the efficacy and safety of intra-articular triamcinolone hexacetonide ( TH ) and triamcinolone acetonide ( TA ) in children with oligoarticular juvenile idiopathic arthritis ( JIA ) . METHODS One hundred and thirty joints of 85 patients undergoing intra-articular injections were r and omly treated with either TH or TA depending on the availability of the drug . The efficacy of both treatments was evaluated prospect ively in a blinded fashion . A good response was defined as a decrease in the articular score of > or = 60 % from baseline . Clinical , laboratory and immunological variables were noted in order to examine possible factors , other than treatment , predictive of the result . RESULTS Seventy injections were performed using TH and 60 with TA . The two groups were comparable for clinical , immunological and laboratory characteristics . The rate of response was significantly higher with TH than with TA : 81.4 % vs 53.3 % ( P = 0.001 ) at 6 months , 67.1 vs 43.3 % ( P = 0.006 ) at 12 months , and 60 vs 33.3 % ( P = 0.002 ) at 24 months . CONCLUSION At comparable doses TH appeared to be much more effective than TA for intra-articular use , in both short- and long-term follow-up . This result was not affected by disease duration or degree of local and systemic inflammation OBJECTIVE Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide ( TA ) is equivalent to that of triamcinolone hexacetonide ( TH ) , if used at double the dosage . In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints , in children with juvenile idiopathic arthritis ( JIA ) . METHOD Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study . The symmetry was assessed by both clinical examination and synovial fluid analysis . The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA . The identity of injected compound was blinded to the patient and to the physician . RESULTS Thirty-seven patients , 30 female , seven male , with JIA , entered the study . A total of 86 joints were injected . Twenty-one ( 53.8 % ) of the joints injected with TA relapsed first compared with only six ( 15.4 % ) of the joints injected with TH . In three ( 7.7 % ) relapse occurred simultaneously . Nine ( 23 % ) were still in remission after 24-month follow-up . The percentage of joints with lasting remission was higher with TH than with TA ( 80 vs 47.5 % after 12 months and 63.6 vs 32.4 % after 24 months , respectively ; log rank test P = 0.003 ) . CONCLUSION Even when TA is given at higher doses , TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA Intraarticular steroid therapy in juvenile chronic arthritis ( JCA ) is performed because of high local efficacy with few side effects . Imaging is used for initial evaluation and for monitoring of treatment response . The aim of this study was to compare imaging findings in diseased hips and knees before and after therapy . A prospect i ve study was performed on 10 patients ( 15 joints ) scheduled for intraarticular therapy . Pretherapeutic assessment included clinical work-up , radiographs , ultrasound ( US ) , and magnetic resonance imaging ( MRI ) of affected joints . Following therapy , clinical and sonographic examinations were performed at 1 week and 1 month . MRI was repeated at 1 month . MRI and US demonstrated pannus formation and effusion , but differentiation was less distinct on US . Popliteal cysts and lymph nodes were visible in both modalities . MRI additionally revealed articular cartilage loss and subchondral cysts , not shown by US . Epiphyseal overgrowth and osteopenia were best seen radiographically . At present MRI is the best tool to assess the inflammatory changes of the joints in JCA . Initial staging of the joints may be done with plain films and MRI . US is useful to assess effusion and pannus and may be used to monitor treatment response OBJECTIVE To determine in a prospect i ve analysis whether baseline demographic , clinical , and laboratory variables predict the outcome of intraarticular corticosteroid ( IAC ) injection of the knees in children with juvenile idiopathic arthritis ( JIA ) . METHODS We studied consecutive patients who met the criteria for the diagnosis of JIA and received their initial injection of triamcinolone hexacetonide in one or both knees . Predictor variables included sex , age , age at onset of JIA , onset subtype , disease duration , drug therapy at the time of IAC injection , physician and parent global assessment of disease status , Childhood Health Assessment Question naire disability index , erythrocyte sedimentation rate ( ESR ) , C-reactive protein , involvement of other joints besides knees , amount of fluid aspirated , and dose of IAC injected . The primary outcome measure was persistence of complete clinical response at 6 months , i.e. , no evidence of synovitis clinical ly . RESULTS Ninety-four patients were available for analysis . At 6 months after the IAC injection , 65 ( 69 % ) patients showed a sustained complete clinical response , whereas 29 ( 31 % ) had had a recurrence of joint inflammation . Univariate statistical analyses showed that patients who had a sustained clinical response had a significantly higher ESR than those who did not ( p = 0.023 ) . The ESR was the only variable that remained in the best-fit model from multivariate logistic regression analysis ( OR 2.61 , p = 0.049 ) . CONCLUSION Our findings indicate that patients with JIA who have a higher ESR are more likely to benefit from IAC injection of the knees OBJECTIVE To determine if intraarticular ( i.a . ) injection of triamcinolone hexacetonide ( steroids ) used early in the course of pauciarticular juvenile rheumatoid arthritis ( pauci JRA ) is associated with less leg length discrepancy ( LLD ) or thigh circumference discrepancy ( TCD ) . METHODS Children with pauci JRA who had asymmetric lower-extremity arthritis diagnosed before age 7 years in Seattle , Washington ( WA ; n = 16 ) and in Chapel Hill and Durham , North Carolina ( NC ; n = 14 ) were retrospectively identified . WA children were given i.a . steroids within 2 months of diagnosis ; the injections were repeated if synovitis recurred in the same joint or in a different joint . These children were compared with NC children who were not treated with i.a . steroids . Thigh circumference was measured at 10 cm above the patella , and leg length was measured from the anterior superior iliac spine to the mid-medial malleolus , by a single observer . LLD and TCD are reported as the percentage of difference between leg measurements in each subject . RESULTS The WA and NC subjects had comparable disease severity and duration of followup ( in months ) . Twelve WA children had subsequent i.a . steroid injections ( mean 3.25 injections per child over mean + /- SD 42 + /- 11 months ) . The WA subjects had significantly less LLD ( P = 0.005 , by Student 's 2-sided t-test ) and prescriptions for shoe lifts ( P = 0.002 , by Fisher 's 2-sided exact test ) . There was not a significant difference in TCD between the 2 groups ( P = 0.139 , by Student 's 2-sided t-test ) . Similar findings were obtained when the analysis was limited to children with monarticular knee arthritis . CONCLUSION Early and continued use of i.a . steroids may be associated with less LLD in young children with pauci JRA . This may indicate decreased duration of synovitis The use of intra-articular steroids in one or both knees was evaluated in 21 children with type 1 pauciarticular juvenile chronic arthritis ( JCA ) . The beneficial effect of the injection was noted within 3 days with no significant adverse reactions . Remission exceeding 6 months was seen in 70 % of the knees and the arthritis remained inactive during the follow up period in 37 % . The beneficial effect of the injection did not correlate with sex , age of onset or the presence of antinuclear antibodies or HLA-B27 antigen and there was no relationship with the size of involved joints at onset , the ESR at onset , or the presence of uveitis . Intra-articular corticosteroids in this type of JCA may provide prompt relief of swelling and pain and reduce the need for other forms of therapy . Remission was long lasting in the majority of the children Both pragmatic and explanatory r and omised controlled trials have a useful role to play in the evaluation of health care interventions . In this descriptive article , the key steps in conducting a pragmatic trial are described . The strengths and limitations of pragmatic trials are also discussed . The main strength of pragmatic trials is that they can evaluate a therapy as it is used in normal practice . Comparisons are made between pragmatic and explanatory trials , on the underst and ing that trials may have aspects to them that make the trial more of a hybrid . A case is made for the appropriate use and relevance of pragmatic trials in the evaluation of alternative and complementary medicine OBJECTIVE To describe radiographic findings at disease onset and 3-year followup in patients with juvenile rheumatoid arthritis ( JRA ) and juvenile spondyloarthropathy ( JSpA ) , to assess radiographic progression and its predictors , and to prospect ively assess clinical outcome and predictors of persistent disease at 3-year followup . METHODS A total of 197 patients with JRA/JSpA were examined every 6 months for 3 years . Radiographic examination was performed at baseline and 3-year followup of knees and ankles ( all patients ) and of other joints on clinical indication . Remission was defined as minimum 6 months without medication and no clinical signs of active disease . RESULTS Radiographic abnormalities were found in 88 % of the patients at onset and in 81 % after 3 years . Frequency of swelling/osteoporosis decreased and frequency of abnormal growth increased from baseline to followup . Knees , h and s , and wrists had most frequently radiographic abnormalities . Radiographic progression occurred in 38 % of the patients . Joints with swelling/osteoporosis on radiographs , young age , and a large number of mobility-restricted joints at baseline were predictors of radiographic progression . At 3 years , 26 % of the patients were in remission and 75 % had been treated with disease-modifying antirheumatic drugs . Reduced well-being , a large number of active joints and negative antinuclear antibody at baseline were predictors of persistent disease after 3 years . CONCLUSION After 3 years most patients had radiographic abnormalities and persistent disease . Young age , many affected joints , reduced well-being , and negative antinuclear antibody at onset increased the risk of radiographic progression and persistent disease after 3 years In adult rheumatology it is common practice to give intra-articular steroid medication for the suppression of chronic synovitis in various inflammatory joint diseases . However , few data exist ( 1 , 2 ) on the correct place of this treatment in the management of children suffering from juvenile chronic arthritis ( JCA ) . In our experience of the pauciarticular form of JCA , chronic synovitis in a single joint does not respond sufficiently to conventional nonsteroid anti-inflammatory agents but can be suppressed by the administration of intra-articular steroids . The beneficial effect and duration of a single dose injection of intra-articular steroid highly depends on the preparation selected . According to several authors ( 1 , 3 - 7 ) , the preparation with the longest lasting effect is triamcinolone hexacetonide . This study compares the long-term effects of triamcinolone hexacetonide and betamethasone given intra-articularly to patients with the pauciarticular form of JCA OBJECTIVE Etanercept monotherapy has been studied and approved for treatment of polyarticular juvenile idiopathic arthritis ( JIA ) . The following study evaluates the safety and efficacy of combination therapy of etanercept and methotrexate compared to etanercept monotherapy in JIA . METHODS We perfomed an open , non-r and omised study on patients who had previously failed to respond to at least one disease-modifying antirheumatic drug ( DMARD ) . A total of 722 patients with JIA in whom at least 1 item of follow-up data was recorded were identified ; of these , 118 patients treated with further slow acting drugs were excluded . In all , 504 patients were treated with a combination of etanercept and methotrexate . A total of 100 patients treated with etanercept only were in the control group . Efficacy was calculated using the American College of Rheumatology paediatric scores for 30 , 50 and 70 % improvement ( PedACR30/50/70 ) . Adverse events ( AEs ) and serious adverse events ( SAEs ) were reported . RESULTS After 12 months 55 patients in the monotherapy group and 376 patients in the etanercept and methotrexate group were available for comparison . For the intention to treat analysis , 65 patients discontinuing treatment prematurely were included . All activity parameters decreased significantly in both treatment groups . After 12 months 81%/74%/62 % of patients of the etanercept and methotrexate group and 70%/63%/45 % of patients of the etanercept monotherapy group achieved PedACR30/50/70 scores , respectively ( p<0.05 for PedACR30 , p<0.01 for PedACR70 ) . The likelihood of achieving a PedACR70 increased with combination therapy with an odds ratio of 2.1 ( 95 % CI 1.2 to 3.5 ) . In total , 25 infectious and 23 non-infectious SAEs including 3 malignancies occurred in the etanercept and methotrexate group , and 1 infectious and 3 non-infectious SAEs occurred in the single etanercept group . CONCLUSIONS The patients ' disease activity improved during etanercept monotherapy and etanercept and methotrexate combination therapy . Tolerability in both treatment groups was comparable |
10,805 | 11,869,677 | No significant difference was found between the two groups when comparing functioning ( ADL and IADL ) , mental status , attitudes to perceived health , life satisfaction or mortality .
REVIEW ER 'S CONCLUSIONS There is insufficient evidence to estimate the likely benefits , harms and costs of institutional or at-home care for functionally dependent older people | BACKGROUND An increasing number of functionally dependent older people require care and medical treatment .
Increasingly governments are shifting re sources into community care expecting both reduction in costs and improvement in the quality of care .
However , it is difficult to establish the costs and benefits of institutional and the alternative at-home care .
OBJECTIVES To assess the effects of institutional versus at-home care for functionally dependent older people on health outcomes , satisfaction ( of functionally dependent older people , relatives and health care professionals ) , quality of care and costs . | Abstract Objectives : To examine the cost of providing hospital at home in place of some forms of inpatient hospital care . Design : Cost minimisation study within a r and omised controlled trial . Setting : District general hospital and catchment area of neighbouring community trust . Subjects : Patients recovering from hip replacement ( n=86 ) , knee replacement ( n=86 ) , and hysterectomy ( n=238 ) ; elderly medical patients ( n=96 ) ; and patients with chronic obstructive airways disease ( n=32 ) . Interventions : Hospital at home or inpatient hospital care . Main outcome measures : Cost of hospital at home scheme to health service , to general practitioners , and to patients and their families compared with hospital care . Results : No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement , or elderly medical patients . Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy ( ratio of geometrical means 1.15 , 95 % confidence interval 1.04 to 1.29 , P=0.009 ) and for those with chronic obstructive airways disease ( Mann-Whitney U test , P=0.01 ) . Hospital at home significantly increased general practitioners ' costs for elderly medical patients ( Mann-Whitney U test , P<0.01 ) and for those with chronic obstructive airways disease ( P=0.02 ) . Patient and carer expenditure made up a small proportion of total costs . Conclusion : Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial , and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease . There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease . Key messages Hospital at home schemes are a popular alternative to st and ard hospital care , but there is uncertainty about their cost effectiveness In our r and omised controlled trial we compared the cost of hospital at home care with that of inpatient hospital care for patients recovering from hip replacement , knee replacement , and hysterectomy ; elderly medical patients ; and those with chronic obstructive airways disease There were no major differences in health service costs between the two arms of the trial for patients recovering from hip or knee replacement and elderly medical patients Hospital at home care increased healthcare costs for patients recovering from hysterectomy and for those with chronic obstructive airways disease Hospital at home care result ed in some costs shifting to general practitioners for elderly medical patients and those with chronic obstructive airways This paper reports the results of a r and omized experiment that tested the effects and costs of providing so-called homemaker services to a chronically ill population . The concept of homemaker services , as dis ? tinct from professional home health and ther ? apeutic nursing services , originally was de ? veloped for children by welfare agencies in the early part of the century . Later , the focus of such services changed from children to adults , with special emphasis on the chronically ill elderly . In the view of some long-term care specialists , homemaker or home health aide services for the elderly now should be regard ? ed as an accepted supplement to family health care , deserving a legitimate position in a con ? tinuum of care.1'2 Medicare policy has not shared this view . Regulations currently authorize a home health aide to perform personal care and only certain limited household services , which include changing the bed , light cleaning , food shop ? ping , and help in cooking.3 For a patient to receive home health aide services , he or she simultaneously must be receiving skilled nurs ? ing or another skilled service . State Medicaid programs are not required to follow these restrictive regulations , but by choice most state programs do . Separation of professional and therapeutic services from those provided by homemaker-home health aides has been advocated by some research ers and practitioners.4,5 Regrettably , little has been reported on the outcomes and costs of homemaker services , although there has been abundant literature on the efficacy and costs of home health care.6 - This study is part of a project that aim ed to increase the participation of informal caregivers in the hospital care for elderly patients . The staff who worked in the wards that were studied created activity programmes for caregivers and changed their ward policies to encourage the participation of the caregivers . In addition , quality assurance programmes were developed and primary nursing was introduced to ensure individualized , need-based and family centered care . In order to explore the changes in perceived quality of care , and to test the differences in care quality between the study and the control wards ( i.e. two wards in a university hospital , two wards in a geriatric unit and two wards of a nursing home ) , the interrupted time series with a non-equivalent control group time series design was used . During periods of 2 months in 1991 , 1992 and 1993 the data were collected from elderly patients ( n = 97 ) and their informal caregivers ( n = 369 ) using a structured question naire based on need theories . The results indicated that the quality of care was improved , especially in the study wards of the university hospital and of the nursing home . This care quality measure was found to be a useful tool for getting feedback from patients and their caregivers concerning care given . Aspects of nursing practice that needed to be improved were identified ( i.e. poor communication between the patient , their caregiver and staff , and lack of support to the patient and caregiver by staff ) Abstract Objective : To investigate the efficacy of intervention by a psychogeriatric team in the treatment of depression in elderly disabled people receiving home care from their local authority . Design : R and omised controlled trial with blind follow up six months after recruitment . Setting : Community of south east London . Subjects : 69 people aged 65 or over who received home care and were depressed according to criteria of the st and ardised automatic geriatric examination for computer assisted taxonomy ( AGECAT ) . 33 were r and omly allocated to an intervention group and 36 to a control group . Intervention : Members of the intervention group received an individual package of care that was formulated by the community psychogeriatric team in their catchment area and implemented by a research er working as a member of that team . The control group received normal general practitioner care . Main outcome measures : Recovery from depression ( AGECAT case at recruitment but non-case at follow up ) . Results : Data were analysed on an intention to treat basis . 19 ( 58 % ) of the intervention group recovered compared with only nine ( 25 % ) of the control group , a difference of 33 % ( 95 % confidence interval 10 % to 55 % ) . This powerful treatment effect persisted after controlling for possible confounders in logistic regression analysis , with members of the intervention group more likely than members of the control group to have recovered at follow up ( odds ratio 9.0 ( 2.0 to 41.5 ) ) . This did not seem to be a simple effect of antidepressant prescription : use of antidepressants at follow up did not have a significant effect ( multiply adjusted odds ratio 0.3 ( 0.0 to 1.9 ) ) . Conclusions : Depression is treatable in elderly people receiving home care . Therapeutic nihilism based on an assumed poor response to treatment in these socially isolated , disabled elderly people in the community is not supported . Key messages This r and omised controlled trial evaluated whether intervention by a psychi- atric team would improve depression in elderly people receiving home care Overall , 58 % of those receiving the intervention had recovered from their depression six months later compared with only 25 % of those receiving unsup- plemented general practitioner care These results should be achievable by other community old age psychiatry services The current comparative inaction on the part of health and social services needs to be This study compared the functional ability and perceived health status of stroke patients treated by a domiciliary rehabilitation team or by routine hospital-based services after discharge from hospital . Patients discharged from two acute and three rehabilitation hospitals in Nottingham were r and omly allocated in three strata ( Health Care of the Elderly , General Medical and Stroke Unit ) to receive domiciliary or hospital-based care after discharge . Functional recovery was assessed by the Extended Activities of Daily Living ( ADL ) scale three and six months after discharge and perceived health at six months was measured by the Nottingham Health Profile . A total of 327 eligible patients of 1119 on a register of acute stroke admissions were recruited over 16 months . Overall there were no differences between the groups in their Extended ADL scores at three or six months , or their Nottingham Health Profile scores at six months . In the Stroke Unit stratum , patients treated by the domiciliary team had higher household ( p = 0.02 ) and leisure activity ( p = 0.04 ) scores at six months than those receiving routine care . In the Health Care of the Elderly stratum , death or a move into long-term institutional care at six months occurred less frequently in patients allocated to the routine service , about half of whom attended a geriatric day hospital . Overall there was no difference in the effectiveness of the domiciliary and hospital-based services , although younger stroke unit patients appeared to do better with home therapy while some frail elderly patients might have benefited from day hospital attendance This paper describes a program ( Community Care Program ) in which some elderly hospital patients who were c and i date s for nursing home placement were placed in foster homes . Caregivers were carefully trained and supervised . A total of 112 elderly in patients were r and omly assigned to placement in a nursing home or a foster care home . Patients and caregivers were interviewed at 3 , 6 , 9 , and 12 months after placement . Community Care Program patients were more likely to maintain or improve ADL ( activities of daily living ) and mental status scores . They also had better nursing outcomes and were more likely to get out of the house than were nursing home patients . Nursing home patients had higher life satisfaction , and participated in more social and recreational activities . The Community Care Program was 17 per cent less costly than nursing home care . The results suggest that foster care may be a viable alternative for a segment of the nursing home population Abstract Objective : To compare effectiveness and acceptability of early discharge to a hospital at home scheme with that of routine discharge from acute hospital . Design : Pragmatic r and omised controlled trial . Setting : Acute hospital wards and community in north of Bristol , with a catchment population of about 224 000 people . Subjects : 241 hospitalised but medically stable elderly patients who fulfilled criteria for early discharge to hospital at home scheme and who consented to participate . Interventions : Patients ' received hospital at home care or routine hospital care . Main outcome measures : Patients ' quality of life , satisfaction , and physical functioning assessed at 4 weeks and 3 months after r and omisation to treatment ; length of stay in hospital and in hospital at home scheme after r and omisation ; mortality at 3 months . Results : There were no significant differences in patient mortality , quality of life , and physical functioning between the two arms of the trial at 4 weeks or 3 months . Only one of 11 measures of patient satisfaction was significantly different : hospital at home patients perceived higher levels of involvement in decisions . Length of stay for those receiving routine hospital care was 62 % ( 95 % confidence interval 51 % to 75 % ) of length of stay in hospital at home scheme . Conclusions : The early discharge hospital at home scheme was similar to routine hospital discharge in terms of effectiveness and acceptability . Increased length of stay associated with the scheme must be interpreted with caution because of different organisational characteristics of the services . Key messages Pressure on hospital beds , the increasing age of the population , and high costs associated with acute hospital care have fuelled the search for alternatives to inpatient hospital care There were no significant differences between early discharge to hospital at home scheme and routine hospital care in terms of patient quality of life , physical functioning , and most measures of patient satisfaction Length of stay for hospital patients was significantly shorter than that of hospital at home patients , but , owing to qualitative differences between the two interventions , this does not necessarily mean differences in effectiveness Early discharge to hospital at home provides an acceptable alternative to routine hospital care in terms of effectiveness and patient A survey was conducted on 1035 persons constituting a semi-r and om age-structured sample of the population s of three areas in the west of Scotl and . The object was to attempt to estimate the needs of this population for domiciliary services . A method was developed of classifying the subjects into 12 ' care groups ' based on two characteristics , those of ' potential need ' and ' solitude ' . ' Potential need ' was a measure of disability and its severity was grade d according to the intervals that elapsed between necessary periods of help . ' Solitude ' was a measure of the time during each day when potential sources of help were spontaneously available . ' Potential need ' was found to be related linearly to age but to be independent of the other variables studied . ' Solitude ' was commonest in the 75 - 84-year age group and varied in the three areas studied , but no relationship with any other variable was detected . An estimate was made of the domiciliary services which would be required to ensure a satisfactory st and ard of care for the subjects in the sample . Assuming present or slightly better levels of hospital provision and slightly lower provision of residential homes there is still a need for a very great increase in domiciliary services if satisfactory st and ards of community care are to be attained The purpose of this study was to compare health status outcomes in three alternative long-term care setting s in the Veterans Administration : 1 ) home care ; 2 ) community-based nursing home care ; and 3 ) hospital-based nursing home care . Patients were measured on a behavioral index of health status , at two points in time : when transferred from the acute care hospital to one of the three treatment programs ( pretest and three months later ( posttest ) . Since patients could not be r and omly distributed to programs , two methods were employed to control for potential sample selection bias : the choice of a nonequivalent control group design , and multivariate analytic techniques . First , within each program type , patients were r and omly selected from both a hospital that offered only that program as a long-term care alternative and from a hospital that provided all three treatment setting s. Second , multiple regression analysis was used to control for pretest differences among patients . Patients placed in the home care program displayed the greatest mean improvement in functional health status , holding all other variables constant . This treatment effect was not uniform , however ; patients showed differential rates of improvement across the three programs , based upon both initial health status and prognosis OBJECTIVE To study the effect of outpatient geriatric evaluation and management on physical function , mental status , and subjective well-being . DESIGN Prospect i ve r and omized controlled trial with a 1-year study period . SETTING Large medical school-affiliated public hospital in an urban community . SUBJECTS Patients at least 70 years old admitted to the medicine service were screened , r and omized , and completed a 1-year follow-up interview . INTERVENTIONS Comprehensive geriatric evaluation and an outpatient care management program . MAIN OUTCOME MEASURES Mental status ( SPMSQ ) , ADL ( Katz Index ) , IADL ( Five-Item OARS Scale ) , Life satisfaction ( LSI-Z ) , and self-perception of health status ( physical health section of OARS ) . RESULTS No significant differences were found for cognitive status , ADL functioning , life satisfaction , nursing home placement , or mortality . The experimental patients reported significantly higher function in IADL and more favorable self-perception of health status compared with controls . CONCLUSION Outpatient comprehensive geriatric evaluation and management appears to be a useful model for providing care to medically frail elderly patients Health screening for old people who live at home has been the subject of debate for 30 years or so . It has come to the fore again in the UK with the new emphasis on annual assessment s by general practitioners ( GPs ) of those aged 75 or more . Screening in the elderly has implication s for manpower . How can it best be done ? We describe here a r and omised , controlled study of case finding and surveillance in patients aged 65 and over in a general practice in South Wales . Problem identification was by a postal question naire , focusing on function , that was sent at r and om to 369 eligible patients with subsequent verification and intervention by a specially appointed nurse . The 356 controls had no question naires and no contact with that nurse . The study lasted 3 years , and end-points included mortality , self-ratings of quality of life , and health status , and use of all services ( GP contacts , hospital admission , home help , and so on ) . Mortality was significantly lower in the intervention group ( 18 % ) than in the controls ( 24 % ) ( difference 6.0 % [ 95 % CI 0.1 - 11.9 % ] , p less than 0.05 ) . Total number of hospital admissions did not differ between intervention and control groups , but duration of hospital stay of patients aged 65 to 74 years was significantly shorter in the intervention group ( difference 4.6 days [ 95 % CI 1.6 - 7.6 ] , p less than 0.01 ) . An increase in visits to a GP was largely offset by a lower number of home visits by a GP . Quality -of-life measures revealed no between-group differences , but self-rated health status was superior in the intervention group . We conclude that the use of a postal screening question naire with selective follow-up and intervention can favourably influence outcome and use of health care re sources by elderly people living at home Multidisciplinary clinical programs for frail el derly people have emerged since the 1980 's in the form of in-hospital and post-hospital geriatric assessment units , and physician-led home health care teams ( 1 - 3 ) . The present work was occa sioned by a crisis of bed availability in the hospitals of Stockholm , Sweden , which occurred due to re tention of large numbers of frail elderly patients oth erwise ready for discharge . We developed a physi cian-led primary home care intervention program for chronically ill , dependent patients after short term hospital care . In collaboration with home services assistance , a multidisciplinary team as sessed each patient 's needs for medical , function al and social care in the home . This service was compared with usual hospital and post-hospital care in terms of 6-month health outcomes and cost , in a prospect i ve , r and omized controlled trial described in greater detail elsewhere ( 4 - 6 ) . The study was conducted from May 1988 to Octobe r 1990 . Patients awaiting hospital discharge , but at risk for long-stay hospital care were recruit ed in St. Gorans , a county general hospital . Pa tients were required to be medically stable , but chronically ill , and dependent in 1 - 5 Katz ADLs . Demented and aphasic patients , and those from service hotels , were excluded . Over 23 months , 745 in patients were screened , with 255 meeting the study criteria . Consenting patients were ran domly assigned either to receive " team " ( N=150 ) or " st and ard " care ( N=99 ) . Following r and omization , " team " subjects were discharged home to the care of the team , comprised of the project and team physicians , a secretary , district nurse , physiother apist , occupational therapist , and nurse assistant . " Sta ndard " care could consist of continued treat ment in an acute or long-stay hospital , followed by st and ard district nurse-administered care at home . At r and omization , team and control patients were found very comparable in most assessed characteristics , including age , gender , and other demographic and functional measures ( Table 1 ) . Team patients had significantly more medical di agnoses at baseline ( p=0 .003 ) . Both team and control patients were moderately impaired in cog nition and basic ADLs . Patients in each group were taking over 4 prescribed medications ( 4 , 5 ) . By six months , 27 % of team and 26 % of con trol patients had died ( NS ) . Survivors in both groups tended to recover in terms of basic and in strumental ADLs , cognitive status , mobility , and social activities ( 4 ) . From r and omization to 6 month follow-up , team patients had improved significantly more than controls in instrumental ADLs and outdoor mobility status ( Table 2 ) . Also , changes in the number of active diagnoses and medications favored team patients . Analysis of service utilization and associated costs demonstrated that surviving team patients used less long-term institutional care ( p < O .OOl ) and more home care ( p = O.OOl ) , than surviving controls ( Table 3 ) . Further , among survivors , total health-care costs were significantly less for the team group , with a reduction of 20.2 % ( 5 ) . Among decedents , team patients spent more days at home ( p < O.OOl ) and used less inpatient and more outpatient care than controls ( Table 4 ) . Total costs did not differ significantly . In summary , this multidisciplinary in-home team care program was found to be cost-effective for se lected elderly , chronically ill , dependent hospital patients . We determined that these patients can live a fairly normal life at home in spite of their health problems and daily assistance needs . The level of psychiatric symptomatology was assessed with the General Health Question naire and the Present State Examination in a r and om community sample of women . Subsequently it was ascertained which of the women had been the victims of sexual or physical abuse , in either childhood or adult life . Women with a history of being abused were significantly more likely to have raised scores on both measures of psychopathology and to be identified as psychiatric cases . 20 % of women who had been exposed to sexual abuse as a child were identified as having psychiatric disorders , predominantly depressive in type , compared with 6.3 % of the non-abused population . Similar increases in psychopathology were found in women who had been physically or sexually assaulted in adult life . These findings indicate that the deleterious effects of abuse can continue to contribute to psychiatric morbidity for many years OBJECTIVES To investigate whether care of elderly and disabled patients could be more cost-effective after a short-term hospital stay , we examined the impact of a primary home care intervention program on functional status , use and costs of care after 6 months . METHODS When clinical ly ready for discharge from the hospital , chronically ill patients with dependence in one to five functions in personal activities of daily living were r and omized to physician-led primary home care with a 24-hour service , and the controls were offered ordinary care . Physical , cognitive , social , and medical functions were assessed in 110 team subjects and 73 controls . Data regarding inpatient days and outpatient visits were collected and converted to costs . RESULTS Team patients demonstrated better instrumental activities of daily living and outdoor walking and significantly fewer diagnoses and drugs at 6 months . They used less inpatient and more outpatient care compared with the control patients . Significant cost reductions were found in the team group . CONCLUSIONS This primary home care intervention program is cost-effective , at least for a selection of patients at risk for long-term hospital care |
10,806 | 17,943,790 | These results suggest that calcium channel blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation . | BACKGROUND The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large dem and for cadaveric kidneys necessitating the use of kidneys from marginal donors .
Calcium channel blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis ( ATN ) if given in the peri-operative period .
However , there is controversy surrounding their use in this situation with no consensus as to their efficacy .
OBJECTIVES To evaluate the benefits and harms of using calcium channel blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation . | Of 113 cyclosporine-treated primary renal allograft recipients , 60 were r and omized to receive st and ard therapy without diltiazem ( ND ) and 53 received st and ard therapy plus diltiazem ( D ) . There was no difference in CsA blood levels between ND and D at all intervals between 3 and 24 months follow-up , yet the D group required 35 % less CsA than the ND group ( measured at 12 months ) . At all intervals to 24 months there was no difference in blood pressure , renal function ( as measured by serum creatinine ) , or in the number of grafts lost between the 2 groups ( ND , 4 lost ; D , 3 lost ) . There was no significant difference in the total number of rejection episodes in the 2 groups ( ND , 89 episodes ; D , 71 episodes ) . However , the severity of rejection episodes was greater in the ND group as evidence d by a significant difference in the usage of OKT3 ( ND , 17 courses ; D , 8 courses of OKT3 , P<0.06 ) . Of the biopsy-proven episodes of rejection , there were more episodes of vascular rejection in the ND group ( ND , 14 episodes ; D , 3 episodes , P=0.005 ) . The incidence of primary nonfunction was less in the D group ( ND , 16 patients ; D , 5 patients , P=0.05 ) . It was concluded that the use of diltiazem was associated with a markedly reduced requirement for CsA without any adverse effect on graft function or graft outcome . Diltiazem with CsA was associated with fewer episodes of primary nonfunction and less-severe rejection episodes and in particular fewer episodes of vascular rejection BACKGROUND Hypertension and hyperuricaemia are common side-effects of cyclosporin A ( CsA ) treatment in renal transplant recipients . While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population , recent evidence suggests amlodipine might also reduce hyperuricaemia . The present study was design ed to compare the effects of the calcium channel blocker amlodipine ( 5 - 10 mg/day ) and the beta-adrenoceptor antagonist tertatolol ( 5 - 10 mg/day ) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension . METHODS Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were r and omized in a double-blind , parallel-group manner to receive either amlodipine ( n = 24 ) or tertatolol ( n = 24 ) for 60 days . The primary outcome measure was the change from baseline in serum uric acid concentration . Secondary analyses of efficacy were based on changes in renal function and blood pressure . RESULTS Amlodipine significantly decreased serum uric acid levels from 483 + /- 99 to 431 + /- 110 microM/l ( P < 0.001 ) , while tertatolol significantly increased uric acid from 450 + /- 98 to 476 + /-84 microM/l ( P = 0.006 ) . Amlodipine also significantly increased glomerular filtration rate ( P = 0.0048 ) and the clearance rate of uric acid ( P = 0.023 ) and it reduced the fractional proximal tubular reabsorption of sodium ( P < 0.001 ) , compared with tertatolol . Renal plasma flow and filtered fraction were unaffected by both treatments , as was trough CsA blood concentration . Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol ( P = 0.007 ) . The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups . Both drugs were well tolerated . CONCLUSIONS Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients BACKGROUND After successful kidney transplantation patients may suffer from the adverse effects due to the use of calcineurin inhibitors . Calcium channel blockers are effective in the treatment of hypertension and may ameliorate cyclosporine- ( CsA ) induced impairment of renal function after kidney transplantation . Calcium channel blockers may also modulate the immune-system which may result in reduction of acute rejection episodes . PATIENTS AND METHODS From June 1995 till 1997 the effect of isradipine ( Lomir ) on renal function , incidence and severity of delayed graft function ( DGF ) , and acute rejection after kidney transplantation , was studied in 210 renal transplant recipients , who were r and omized to receive isradipine ( n=98 ) or placebo ( n=112 ) after renal transplantation in a double-blind fashion . RESULTS In the isradipine group renal function was significantly better at 3 and 12 months ( P=0.002 and P=0.021 ) compared with the placebo group . DGF was present in both groups : isradipine : (28 + 6)/98 ( 35 % ) ; placebo : (35 + 9)/112 ( 40 % ) , P=0.57 . Severity of DGF was comparable in both groups ( isradipine : 9.1+/-8.7 vs. placebo : 9.3+/-8.1 days ) . No statistical difference was found in incidence or severity of biopsy-proven acute rejection [ isradipine : (42 + 6)/98 ( 49 % ) versus placebo : (46 + 9)/112 ( 49 % ) , P=1.00 ] . Renal vein thrombosis was observed in eight patients . This proved to be associated with the route of administration of the study medication [ 6/45 ( 13 % ) on i.v . medication versus 2/165 ( 1 % ) on oral medication , P<0.001 ] . CONCLUSIONS Addition of isradipine results in a better renal function after kidney transplantation , without effect on incidence or severity of DGF or acute rejection Intrarenal vasoconstriction is a characteristic feature of CsA nephrotoxicity . The influence of nifedipine , a dihydropyridine calcium channel blocker and potent renal vasodilator , on renal haemodynamics was investigated in 11 cyclosporin A (CsA)- and 9 azathioprine (Aza)-treated normotensive long-term renal allograft recipients . Baseline Cr51-EDTA clearance and effective renal plasma flow ( ERPF ) were similar in both groups . Nifedipine 20 mg twice daily for 28 days significantly increased Cr51-EDTA clearance ( + 14.8 % ) in the CsA group ; however , ERPF , renal vascular resistance ( RVR ) , and filtration fraction did not change . Nifedipine did not influence renal haemodynamics in the azathioprine group . The increase in Cr51-EDTA clearance in the CsA group did not correlate with baseline renal function , CsA dose or whole blood levels , donor age , duration of graft , or renal functional reserve capacity . This study suggests that nifedipine confers a beneficial effect on renal haemodynamics in long-term CsA-treated renal allograft recipients and appears to improve renal function by a non-haemodynamic mechanism Verapamil has proven effective in preventing acute renal failure in animal models if given prior to the insult and hence possibly has a role in the preservation of cadaveric renal tissue for transplantation . Twenty renal donors were r and omly assigned to treatment ( receiving verapamil 20 mg intravenously ) and control groups . Recipients were monitored for renal failure by urine output and serum creatinines on days 1 and 7 and dialysis requirement to one week . Early urine outputs and serum creatinines ( day 1 ) were significantly better in the treated than control group ( p greater than 0.01 , 0.05 respectively ) . We conclude therefore that verapamil may prevent post-transplant acute renal failure , but its optimal dosage and route of administration remain to be determined The purpose was to study whether the calcium entry blocker , felodipine , could reduce the nephrotoxic and hypertensive effect of cyclosporine . The effect of felodipine on glomerular filtration rate ( GFR ) , renal plasma flow ( RPF ) , fractional excretion of sodium , lithium clearance and blood pressure was measured in three r and omized , placebo-controlled studies of cyclosporine treated patients . In study one , 10 renal transplant recipients were examined within the first six months after transplantation in a cross-over design . Renal hemodynamics were determined after the acute ingestion of felodipine or placebo , with an interval of less than one week between the two examinations . In study two , 79 renal transplant recipients were r and omized to a treatment with felodipine or placebo just before transplantation , and renal hemodynamics were determined after twelve weeks . In study three , 18 patients , who were treated with cyclosporine due to dermatological diseases , were examined in a cross-over design to determine their renal hemodynamics after four weeks of treatment with felodipine or placebo . Felodipine increased renal hemodynamics in study one ( GFR 16 % , RPF 33 % , P < 0.01 for both ) , in study two ( GFR 23 % , RPF 28 % , P < 0.05 for both ) , and in study three ( GFR 13 % , RPF 26 % , P < 0.01 for both ) . FE(Na ) was significantly increased by felodipine in studies one and three , but not in study two . Lithium clearance was significantly increased and blood pressure significantly reduced by felodipine in all three studies . It can be concluded that felodipine counteracts both the cyclosporine induced impairment in renal hemodynamics and the increase in blood pressure in acute and short-term studies Background . Studies have provided conflicting results as to the protective role of calcium channel blockers ( CCB ) in cyclosporine-treated patients with regard to blood pressure control and preservation of renal graft function . Lacidipine is a dihydropyridine CCB that possesses antioxidative , anti-atherosclerotic , and anti-adhesion properties and was shown to prevent cyclosporine-induced nephrotoxicity in a rat model . Methods . We conducted a multicenter prospect i ve , r and omized , placebo-controlled study in 131 de novo recipients of a cadaveric renal allograft on cyclosporine therapy . The aim of this 2-year study was to assess the effects of lacidipine on graft function ( plasma iohexol clearance ) , renal plasma flow , anastomotic arterial blood flow , deterioration of renal function , blood pressure , acute rejection , and hospitalization rate . Results . A total of 118 recipients were available for intention-to-treat analysis on efficacy ( lacidipine : n=59 ; placebo : n=59 ) . Graft function assessed by serum creatinine concentration and glomerular filtration rate measured as plasma iohexol clearance , was persistently better in lacidipine-treated patients from 1 year onwards ( respectively , P<0.01 and P<0.05 ) . Renal plasma flow and anastomotic blood flow were not significantly higher in lacidipine-treated patients . Three patients on lacidipine therapy and four on placebo experienced treatment failure defined as an increase in serum creatinine from baseline of more than 60 % ( log-rank test : P=0.57 ) . Study groups did not differ in acute rejection rate , trough blood cyclosporine concentrations , blood pressure , number of antihypertensive drugs , hospitalization rate , and adverse event rate . Conclusions . The use of calcium channel blockers in cyclosporine-treated renal recipients results in a significantly better allograft function at 2 years and this effect is independent of blood pressure lowering A local measurement of the partial pressure of oxygen in the renal cortex was performed during renal transplantation in 40 patients aged between 10 and 62 years . During the measurement , 20 of the patients received the calcium channel blocker diltiazem . Accurate knowledge of the renal microcirculation in the postischemic phase became possible when PO2 tissue polarography was performed . Moreover , measurement in four live donors before removal of the kidneys allowed an exact comparison between the postischemic microcirulation and the native in situ perfusion . A good postischemic baseline histogram ( similar to the situation in a live donor ) or quick stabilization of the histogram during the course was found to correlate with a prompt initial renal function . Intra-arterial administration of diltiazem led to an insignificant improvement of the primary function rate . In the case of kidneys with longer cold ischemic periods and initially indifferent baseline histograms there was an especially pronounced benefit of diltiazem administration . Not only macroscopic examination , but also polarographic measurements revealed an improvement in the renal microcirculation throughout , with higher mean values for PO2 and homogeneity of all PO2 values measured after administration of diltiazem . In keeping with this , in such cases the incidence of primary renal function was distinctly higher . In cases with improved cortical circulation the a-v oxygen difference was less pronounced , so that evaluation of the avDO2 determinations suggests distinct perfusion improvement following diltiazem Calcium antagonists ( CATs ) have a role in the management of certain types of renal insufficiency . These include prophylaxis against post-transplant-associated acute renal failure and cyclosporine A (CsA)-induced renal dysfunction . For the transplanted kidney , CATs may be beneficial in several setting s. First , a CAT during organ procurement protects the kidney during ischemic periods . Second , CATs given perioperatively protect the kidney during reperfusion and early after transplantation . Third , CATs also offer protection against CsA nephrotoxicity Calcium entry blockers have a protective effect on experimental postischemic acute renal failure ( ARF ) . Since delayed graft function ( DGF ) in cadaver kidney transplants is in part due to an ischemic damage to the kidney , we initiated two prospect i ve , r and omized clinical trials of human kidney transplants . Study I ( control : n = 22 ; diltiazem : n = 20 ) : Diltiazem ( D ) was added to Eurocollin 's solution at a dose of 20 mg/l . If the donor had been treated with D , the graft recipient got a bolus injection of 0.28 mg/kg D and a continuous infusion of 0.002 mg/min/kg D for the first two days . A dose of 60 mg D was then given orally twice daily . Study II ( control : n = 11 ; diltiazem : n = 10 ) : We used the same regimen without donor pretreatment . All patients had immunosuppression with cyclosporine A ( CsA ) and low-dose steroids . Primary graft function ( PGF ) was defined as vital kidney function without hemodialysis ( HD ) during the first week . In both studies the incidence of PGF was higher in the D groups ( I : 90 % vs. 59 % , p less than 0.05 ; II : 70 % vs. 55 % ) . In the control groups , 3.6 + /- 0.4 ( I ) and 4.9 + /- 0.7 ( II ) HD per patient was necessary , compared to 0.6 + /- 0.2 ( I ) , p less than 0.05 ) and 1.9 + /- 0.4 ( II ) HD in the treatment groups . ( ABSTRACT TRUNCATED AT 250 WORDS Acute postischemic renal failure ( ARF ) is a major complication in surgery and in particular in renal transplantation . Calcium channel blockers ( CCBs ) are able to prevent or ameliorate ARF in different experimental models when given before ischemic injury . Because ARF , which is observed in 20–60 % of graft recipients , carries the risk of undetected rejections and nephrotoxic injury and is also expensive , we tested the hypothesis , suggested by animal experiments , that there is also a beneficial effect of CCBs when given after ischemic injury . A total of 134 recipients of first or second cadaver grafts were r and omly assigned to a diltiazem pretreatment ( DZ ) or control ( C ) group . Kidney grafts were pretreated immediately prior to transplantation by reperfusion with 500 ml Euro-Collins ( preservation fluid ) , with or without DZ . The DZ patients also received a 74-h infusion of DZ ( 0.12 mg/kg/h ) , starting 2 h prior to surgery . DZ was continued ( 90 mg b.i.d . p.o . ) until day 30 . Immunosuppression consisted of low-dose steroids and cyclosporine A ( CSA ) ( 10 mg/kg p.o . ) . CSA was instituted 6 h after surgery and later adjusted to achieve whole-blood trough levels of 300–600 ng/ml [ by polyclonal radioimmunoassay ( RIA ) ] . A total of 129 patients were available for efficacy analysis . There were no significant differences concerning donor demographics , human lymphocyte antigen ( HLA ) match , or ischemic times . ARF was defined as a need for dialysis in the first week . Our data show a significant reduction in ARF in grafts pretreated with DZ . Because of comparable study conditions for all grafts , an important role of calcium-mediated mechanisms , such as vasoconstriction and calcium influx in ischemic cells in the genesis of post-transplant ARF , is suggested . The number of rejection episodes and early graft survival were not affected by DZ treatment BACKGROUND Acute tacrolimus toxicity is manifest by oliguria and elevated serum creatinine . Various vasoregulatory molecules have been implicated in calcineurin inhibitor-mediated nephrotoxicity , including calcium , adenosine and endothelin . Theophylline ( THEO ) , a non-specific adenosine-receptor antagonist prevents renal dysfunction from various nephrotoxins which mediate vasoconstriction . In the setting of acute tacrolimus toxicity , we demonstrated that administration of THEO along with a loop diuretic ( LD ) enhanced diuresis . This r and omized , controlled trial was undertaken to confirm these earlier findings under more rigorous conditions . METHODS Children with non-renal visceral transplant(s ) and evidence of tacrolimus nephrotoxicity oliguria with a 25 % increase in serum creatinine concentration from baseline , a whole blood tacrolimus concentration > 20 ng/dl and oliguria resistant to therapy with a LD were r and omized to receive either THEO ( n = 10 ) or normal saline placebo ( n = 8) . Using pre and post ( 6 h ) timed urine collection s and coincident plasma concentrations the following were measured or calculated : urine flow rate , net fluid balance , creatinine clearance , fractional excretion of chloride , free water clearance and distal delivery of chloride . RESULTS These patients had markedly impaired creatinine clearance at the onset of tacrolimus toxicity . Urine flow increased in the LD + THEO group by 110 % over baseline , but was unchanged in the LD + NS group . An increase in creatinine clearance did not reach statistical significance ( P = 0.09 ) . Fractional excretion of chloride and distal solute delivery increased after THEO treatment . CONCLUSIONS THEO induced a solute diuresis during furosemide-resistant oliguric tacrolimus toxicity in paediatric patients with a trend towards improved renal function ABSENCE OF , or poor , graft function in the early postoperative period following kidney transplantation remains a serious problem . To date , infusion of lowdose dopamine or administration of calcium channel blockers ( CCB ) has been used to reduce the incidence of acute tubular necrosis . The aim of this study was to investigate the effects of diltiazem and dopamine infusions on early graft function in renal transplant recipients , and to compare these effects with outcome in graft recipients who did not receive these agents Calcium channel blockers have immunomodulating effects in vitro and may be effective in preventing cyclosporine nephrotoxicity . We studied the effect of verapamil following renal transplantation on the incidence of rejection and cyclosporine nephrotoxicity in a double-blind , placebo-controlled trial . Patients were r and omly assigned to placebo ( n = 28 ) or verapamil ( n = 32 ) at doses of 80 mg twice a day . There was no difference in the incidence of rejection or cyclosporine toxicity in the two study arms . Recipients r and omized to verapamil had lower mean cyclosporine doses at all intervals during a 1-year follow-up . Although cyclosporine doses were lower in the placebo group , the mean cyclosporine levels were equivalent in the two groups . Recipients in the verapamil-treated group had a higher mean serum creatinine at the end of the study --1.7 mg/dL versus 1.4 mg/dL in the placebo group . Actual 1-year graft survival was 89 % for the placebo recipients versus 91 % in the verapamil-treatment group . When compared with placebo , the concomitant use of low-dose verapamil results in lower cyclosporine doses but equivalent cyclosporine blood levels . Reduction in the incidence of rejection or cyclosporine nephrotoxicity were not observed To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function , we conducted three separate , prospect i ve , r and omized trials . In these trials , we investigated the effects of diltiazem and those of the prostacycline analogue iloprost . In the first study , 22 control patients and 20 diltiazem patients received grafts perfused with either vehicle or diltiazem 20 mg/L in the Euro-Collins solution . Subsequently , the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg , followed by a continuous infusion of 0.002 mg/min/kg for the following 2 days . Thereafter , diltiazem 60 mg was given to the treated subjects orally for up to 4 years . In the second study , 11 control subjects and 10 diltiazem subjects received the same postoperative regimen , but all grafts were harvested without addition of diltiazem to the perfusion solution . In the third protocol , four groups were studied as follows : 19 control subjects who received no specific treatment , 16 subjects who received diltiazem , 16 subjects who were given iloprost , and 14 subjects who received both iliprost and diltiazem . The donor kidney of treated patients was perfused with either diltiazem , iloprost , or both drugs . Primary graft function occurred more commonly in the groups receiving diltiazem . Further , in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function . Fewer rejection episodes occurred in patients receiving diltiazem . Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment . Moreover , renal biopsies showed less severe signs of cyclosporin-A ( CyA ) nephrotoxicity in diltiazem-treated patients compared to controls , even though these patients also exhibited higher CyA trough levels . ( ABSTRACT TRUNCATED AT 250 WORDS Pretreatment with calcium antagonists such as verapamil ( VP ) and isradipine prevents CsA-induced decrease in renal microcirculation in mice . Recently , in posttransplant cadaver renal transplant ( CRT ) recipients , we demonstrated a CsA-induced 70 % reduction in renal parenchymal diastolic blood flow velocity ( PDBFV ) . Using duplex Doppler scanning , this r and omized study of forty CRT patients examines the effect of pretreatment with VP on renal blood flow velocity and posttransplant function . Patients with initially low PDBFV ( less than 8.0 cm/sec ) who received VP therapy prior to administration of CsA experienced prompt restoration of flow , and continued to improve during CsA administration . With CsA alone , PDBFV diminished from 8.9 + /- 2.4 ( SD ) to 5.3 + /- 2.7 cm/sec ( P less than 0.002 ) . Although blood CsA levels were significantly higher at 1 , 4 , and 7 days ( 68 , 184 , and 235 ng/ml , respectively ) , after CsA induction , during VP treatment than in control patients ( 39 , 105 , and 156 ng/ml , respectively ) ( P less than 0.001 ) , with the same daily doses of CsA , serum creatinines at day 7 were lower during VP treatment ( 1.28 + /- 0.44 vs. 1.66 + /- 0.44 mg% ) than in controls ( P less than 0.01 ) . When the glomerular filtration rate was less than 45 ml/min on day 1 . VP-treated patients showed greater improvement in GFR at day 7 by 34.1 + /- 10.9 ml/min compared with the 18 + /- 13 ml/min in controls ( P less than 0.02 ) . Only 3 of the 22 VP patients had rejection episodes within 4 weeks , versus 10 of the 18 recipients r and omized to no drug ( P less than 0.005 ) . We conclude that VP is beneficial in CRT because it improves renal blood flow characteristics and prevents CsA-induced inhibition of blood flow . VP also ameliorates CsA-induced acute nephrotoxicity , and is associated with improved immunosuppression and fewer early rejections Primary nonfunction in renal allografts makes the diagnosis of allograft dysfunction more difficult and may effect long-term graft survival . The prevention of primary nonfunction by a reperfusion technique has been assessed in a prospect i ve analysis of 145 consecutive renal transplants performed in a single center . All kidneys were retrieved using an in situ perfusion method , and all but 13 recipients received a st and ardized immunosuppressive protocol with cyclosporine . The first 106 transplants were performed without the benefit of any additional perfusion , and the incidence of primary nonfunction was 57.5 % in these patients . The last 39 kidneys received additional perfusion with kidney perfusion fluid immediately prior to implantation ( late perfusion ) . In the latter group , the incidence of primary nonfunction was 30.8 % ( P = 0.007 ) . Using logistic regression analysis , only three factors were found to be associated with primary nonfunction : immunosuppression with cyclosporine ( P = 0.01 ) , a second warm ischemia time of greater than 35 min ( P = 0.002 ) , and late perfusion ( P = 0.003 ) . In this study , the use of late perfusion alone has reduced the incidence of primary nonfunction by almost one half . The technique is simple , safe , inexpensive , and effective . Its routine use is now advocated in all renal transplants BACKGROUND The area-under-the-curve ( AUC ) of cyclosporine ( CsA ) reflects exposure to the drug , but this monitoring strategy is time-consuming and not cost-effective . Recently , it has been suggested that the concentration at 2 hours after dosing ( C2 ) shows the best correlation with AUC . The C2 has been replacing the trough measurement ( C0 ) to monitor CsA therapy , but in patients receiving diltiazem there is not much information about this issue . We investigated the correlations between C2 and C0 with absorption AUC over the first 4 hours ( AUC(0 - 4 ) ) in renal stable transplant patients receiving CsA therapy with or without diltiazem . PATIENTS AND METHODS Ten patients ( five men ) of ages 23 to 68 years and 6 to 84 months after transplantation , were r and omly assigned to an 8-week initial period of either diltiazem washout or controlled treatment with diltiazem . Time-concentration curves of cyclosporine were performed at the end of this period using a specific RIA measurement of blood sample s. Thereafter , a crossover of the groups was performed and after another 8 weeks , a second curve was obtained . Drugs that change the pharmacokinetics of cyclosporine or diltiazem were not allowed . RESULTS The cyclosporine daily dose was lower with diltiazem ( 173 + /- 4 mg vs 213 + /- 4 mg , P = .002 ) , but despite a dose reduction of only 19 % + /- 1.5 % , there was a trend to a larger AUC/dose ( 28 + /- 5 ng x h/mL x mg vs 17 + /- 2 ng x h/mL x mg , P = .1 ) and a trend to an increased C2 when treatment included diltiazem ( 1035 + /- 156 ng/mL vs 652 + /- 126 ng/mL , P = NS ) . Moreover , we confirmed that C2 showed the best correlation with AUC(0 - 4 ) , ( r = 0.7 , P = .04 ) , a correlation that improved with diltiazem ( r = 0.9 , P < .002 ) . CONCLUSION C2 is the point that correlates best with AUC(0 - 4 ) with or without diltiazem . C2 in the presence of diltiazem was associated with a stronger , more significant correlation with AUC(0 - 4 ) Background . Cardiovascular disease is the dominant cause of death in renal transplant recipients . Left ventricular hypertrophy ( LVH ) is a known risk factor . After renal transplantation , persistent hypertension is an important determinant for the further evolution of LVH . The aim of the present study was to compare the effect of an angiotensin converting enzyme ( ACE ) inhibitor ( lisinopril ) with a calcium channel blocker ( CCB ) ( controlled release nifedipine ) in treatment of posttransplant hypertension focusing on changes in LVH . Methods . One hundred fifty-four renal transplant recipients presenting with hypertension ( diastolic BP≥95 mmHg ) during the first 3 weeks after transplantation were r and omized to receive double-blind 30 mg nifedipine or 10 mg lisinopril once daily . Results . One hundred twenty-three patients completed 1 year of treatment . Good quality echocardiographic data were available in 116 recipients ( 62 nifedipine/54 lisinopril ) 2 and 12 months posttransplant . Blood pressure was equally well controlled in the two groups throughout the study ( mean systolic/diastolic±SD after 1 year : 140±16/87±8 mmHg with nifedipine and 136±17/85±8 mmHg with lisinopril ) . Left ventricular mass index was reduced by 15 % ( P < 0.001 ) in both groups ( from 153±43 to 131±38 g/m2 with nifedipine and from 142±35 to 121±34 g/m2 with lisinopril ) . There were no statistically significant differences between the two treatment groups at baseline or at follow-up . Conclusions . In hypertensive renal transplant recipients with well-controlled blood pressure , there is a regression of left ventricular mass after renal transplantation . The regression of left ventricular mass index is observed to a similar extent in patients treated with lisinopril or nifedipine A double-blind , r and omized , placebo-controlled study was conducted to determine the effect of nifedipine on early renal allograft function when added to a triple therapy immunosuppression regime comprising low-dose cyclosporin ( CsA ) , prednisolone and azathioprine . Fifty adult cadaveric renal allograft recipients were r and omized to placebo ( group P n = 17 ) , nifedipine 10 mg preoperatively and 20 mg b.d . postoperatively for 48 h , followed by matching placebo for 3 months ( group NS n = 16 ) or nifedipine 10 mg preoperatively and 20 mg b.d . postoperatively for 3 months ( group NL n = 17 ) . Donor and recipient exclusion criteria included recent calcium antagonist treatment . At 3 months after transplantation mean GFR adjusted for graft loss was significantly higher in group NL than in NS ( mean + /- SD 61 + /- 28 versus 34 + /- 25 ml/min/1.73 m2 ; P < 0.05 ) , group P being intermediate ( 45 + /- 34 ml/min/1.73 m2 ) . Similarly , effective renal blood flow ( ERBF ) at 3 months was higher in group NL than in groups P and NS ( mean + /- SD 351 + /- 175 versus 216 + /- 166 and 220 + /- 162 ml/min/1.73 m2 ; P < 0.05 ) . The differences were not significant by 6 months post-transplantation . This study suggests that oral nifedipine commenced preoperatively and continued for 3 months following transplantation has beneficial effects on early renal allograft function when incorporated as part of an immunotherapy regimen based on cyclosporin In a prospect i ve , r and omized and placebo-controlled study we evaluated the influence of treatment with the calcium-channel blocker diltiazem on the course and results of cadaveric kidney transplantation in 39 graft recipients . The grafts were reperfused with Euro-Collins solution containing diltiazem 20 mg/l . All recipients except those in chronic treatment with a calcium-channel blocker received preoperatively a bolus of diltiazem or placebo 0.3 mg/kg and in all an infusion of diltiazem or placebo 3 mg/kg/24 h was started preoperatively . After that , diltiazem or placebo was given orally for 3 months . Donors were not treated . Immunosuppressive therapy consisted of prednisone , azathioprine and CsA. There were no significant differences between the groups concerning donor or recipient characteristics , HLA-mismatching , and ischaemic time . Thrombosis leading to graft loss occurred in 3 recipients ( diltiazem:2 , placebo:1 ) and one graft was lost due to septicaemia ( diltiazem ) . For the remaining 35 grafts no beneficial effect of treatment with diltiazem was found for the rate of delayed graft function , the rate of rejections , time to first rejection , whole blood CsA concentration , or graft function . The CsA dose needed to reach target whole blood concentration was significantly less in the diltiazem group . In conclusion , our results do not indicate any beneficial effects of treatment with diltiazem in cadaveric kidney transplantation , except a reduction of costs because of a significant reduction of the CsA dosage BACKGROUND Treatment of posttransplant hypertension is still a matter of debate . Calcium antagonists may ameliorate renal side effects of cyclosporin . Angiotensin converting enzyme- ( ACE ) inhibitors may be more effective in sustaining renal function in native chronic renal disease . We prospect ively compared the effect of controlled release nifedipine and lisinopril on long-term renal function in hypertensive kidney transplant patients treated with cyclosporin . METHODS A total of 154 renal transplant patients presenting with hypertension ( diastolic blood pressure > or=95 mmHg ) during the first 3 weeks after transplantation were r and omised to receive double-blind nifedipine 30 mg or lisinopril 10 mg once daily . A total of 123 patients completed 1 year of treatment ( 69 nifedipine , 54 lisinopril ) and 64 patients completed 2 years of double-blind treatment ( 39 nifedipine , 25 lisinopril ) . Baseline glomerular filtration rate was measured as 99 mTc-diethylene-triaminepentaacetate clearance in a stable phase 2 to 5 weeks after inclusion and repeated at 1 and 2 years . RESULTS Baseline glomerular filtration rates were similar ( 46+/-16 ml/min with nifedipine , 43+/-14 ml/min with lisinopril ) . The changes in glomerular filtration rates from baseline were statistically significant between the groups after 1 year ( 9.6 ml/min mean treatment difference ( 95 % confidence interval [CI]s 5.5 - 13.7 ml/min , P=0.0001 ) and remained statistically significant also after 2 years ( 10.3 ml/min mean difference ( 95 % CIs 4.0 - 16.6 ] , P=0.0017 ) . After 1 year glomerular filtration rates averaged 56+/-19 ml/min in the nifedipine group and 44+/-14 ml/min in the lisinopril group . CONCLUSIONS Both nifedipine and lisinopril were safe and effective in treatment of hypertension in renal transplant patients treated with cyclosporin . Patients receiving nifedipine but not lisinopril improved kidney transplant function over a period of 2 years To investigate the effect of oral nifedipine , a calcium channel blocker known not to modify cyclosporin A ( CyA ) pharmacokinetics , on immediate transplant function and CyA nephrotoxicity , 68 adult renal transplant recipients were pre-operatively r and omized to one of three regimes : A ( high-dose CyA , initial dose 17 mg/kg per day , maintenance dose 7 mg/kg per day ) ; B ( regime A plus oral nifedipine ) ; C low-dose CyA , initial dose 10 mg/kg per day , maintenance 4 mg/kg per day plus azathioprine 1 mg/kg per day ) . All three groups received identical steroid regimes . Calcium channel blockers of all types were avoided in groups A and C. Delayed graft function ( dialysis dependence by day 4 ) was seen least frequently in group B ( P < 0.02 ) . Group B had improved graft function at 6 months compared with group A , identified by differences in serum creatinine ( P < 0.05 ) , GFR ( P < 0.01 ) and ERPF ( P < 0.05 ) . Similar differences in serum creatinine ( P < 0.05 ) and GFR ( P < 0.05 ) were also identified at 12 months . Group C also had better 6- and 12-month GFR values than group A ( P < 0.05 each ) . The three groups did not differ in donor or recipient age , HLA matching , ischaemic or anastomosis times , frequency of early rejection or whole-blood CyA levels . These results indicate that nifedipine significantly improves immediate and medium-term graft function BACKGROUND Usage of cyclosporin ( the Hong Kong Hospital Authority 's single largest item of drug expenditure ) continues to increase , mainly due to increasing numbers of renal allograft patients taking it as long-term antirejection therapy . Diltiazem , an antihypertensive agent , interferes with the first pass extraction of oral cyclosporin , thus serving to conserve its dosage . AIMS In renal transplant patients , to assess whether diltiazem co-treatment could achieve worthwhile dosage conservation of Neoral ( a relatively new microemulsified cyclosporin formulation ) , safely . METHODS A r and omized , placebo-controlled , double-blind clinical trial was undertaken at three local hospitals . Renal transplant recipients receiving Neoral as prophylactic immunosuppression were r and omized to two treatment arms . Active treatment consisted of diltiazem tablets 30 or 60 mg twice daily for patients weighing < 60 or > or= 60 kg , respectively . One hundred and ten eligible patients gave their informed consent , and were followed up for at least six months . The mean difference in the dollar cost in the sixth month was the primary outcome . Secondary /ancillary outcomes included changes in cyclosporin dosage and blood level , and untoward clinical events including rejection . Outcomes were evaluated by intention to treat analyses . RESULTS During weeks 23 - 26 ( sixth month ) post r and omization , diltiazem co-treatment yielded an estimated average cost saving per patient on drugs of 15%[the 95 % confidence interval ( CI ) of the difference being HK dollars 609 + /- 517 or pound 50 + /- 42 ] , with no apparent excess of untoward or adverse events , complications , hospitalization , outpatient visits , or inferior quality of life . CONCLUSIONS This diltiazem co-treatment regime applied to the nearly 1800 surviving renal allograft patients followed up in Hospital Authority hospitals could have saved approximately HK dollars 14.3 million ( pound 1.17 million ) annually , without adverse sequelae The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients . One hundred and forty-seven patients were r and omised to one of three regimens . Group A received CyA , 7 mg/kg per day , and prednisolone ; group B followed the same regimen as group A plus oral nifedipine and group C received CyA , 4 mg/kg per day , prednisolone and azathioprine . Calcium channel blockers were avoided in groups A and C. The crude 2-year ( P=0.0223 ) and 4-year ( P=0.0181 ) graft survival was significantly better in group B ( 86 % and 81 % , respectively ) than in group A ( 75 % and 63 % , respectively ) . Delayed initial function was seen least frequently in group B ( 10.2 % ) compared to groups A ( 31 % ) and C ( 28 % ; P<0.01 ) . Group B also experienced fewer rejection episodes than groups A and C ( P<0.05 ) . We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function , rejection frequency and long term graft survival Due to a shortage of suitable kidneys for transplantation there has been an increase in the use of kidneys taken from old and marginal donors , which has led to a high incidence of acute tubular necrosis . Several reports suggest that the administration of calcium channel blockers improves the initial function after renal transplantation . We conducted a r and omized , double-blind placebo-controlled trial to study the effect of the calcium channel blocker gallopamil on the incidence and course of acute tubular necrosis following cadaveric renal transplantation . A trend developed showing a decrease in episodes of acute tubular necrosis in gallopamil versus placebo , and became statistically significant when the outcome of kidneys from donors older than 50 years was analyzed separately [ gallopamil 6/14 ( 42 % ) vs. placebo 10/11 ( 91 % ) , P < 0.01 corrected chi2 ] . We conclude that pre-transplantation renal graft perfusion and post-transplantation recipient treatment with gallopamil reduces the incidence of post-transplantation acute tubular necrosis , particularly in kidney taken from older donors To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function , we conducted three separate , prospect i ve , r and omized trials . In these trials , we investigated the effects of diltiazem and those of the prostacyclin analogue iloprost . In the first study , 22 control patients and 20 diltiazem patients received grafts perfused with either vehicle or diltiazem 20 mg/liter in the Euro-Collins solution . Subsequently , the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg , followed by a continuous infusion of 0.002 mg/min/kg for the following two days . Thereafter , diltiazem 60 mg was given to the treated subjects orally for up to four years . In the second study , 11 control subjects and 10 diltiazem subjects received the same postoperative regimen , but all grafts were harvested without addition of diltiazem to the perfusion solution . In the third protocol , four groups were studied as follows : 19 control subjects who received no specific treatment , 16 subjects who received diltiazem , 16 subjects who were given iloprost , and 14 subjects who received both iloprost and diltiazem . The donor kidney of treated patients was perfused with either diltiazem , iloprost , or both drugs . Primary graft function occurred more commonly in the groups receiving diltiazem . Further , in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function . Fewer rejection episodes occurred in patients receiving diltiazem . Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment . Moreover , renal biopsies showed less severe signs of Cyclosporin A ( CsA ) nephrotoxicity in diltiazem-treated patients compared to controls , even though these patients also exhibited higher CsA trough levels . ( ABSTRACT TRUNCATED AT 250 WORDS Cyclosporin is a powerful stimulator of oxidative stress signaling , leading to TGFbeta production , NO degradation , endothelial dysfunction , hypertension and post-transplant nephropathy . Carvedilol , alpha1-beta-blocker with strong antioxidant activity , may interfere with this chain of events . Therefore , we measured monocyte ecNOS , TGFbeta and heme oxygenase-1 ( HO-1 ) mRNA level and plasma nitrite/nitrate , 3-nitrotyrosine , an estimate of peroxynitrite , and total plasma antioxidant power in kidney-transplanted patients with post-transplant hypertension , before and after treatment with carvedilol , 25 - 50 mg o.d . orally for 4 months ( n = 15 ) . The dihydropyridine calcium channel blocker nifedipine ( n = 10 ) was used as comparator antihypertensive drug . Blood pressure fell to a similar extent with both drugs . Carvedilol increased plasma antioxidant power and HO-1 mRNA and reduced 3-nitrotyrosine and TGFbeta mRNA levels , while the same was not observed with nifedipine . Monocyte ec NOS mRNA levels and plasma nitrite/nitrate were higher in the patients than in a normotensive healthy control group and were unaffected by either treatment . In conclusion , carvedilol reduces the oxidative stress and corrects the altered cellular signaling mediated by oxidative stress in CsA-induced post-transplant hypertension . Therefore , it may prevent long-term complications , such as endothelial dysfunction , fibrogenesis and post-transplant nephropathy by decreasing NO degradation and production of TGFbeta , a key fibrogenic cytokine , and by activating HO-1 production The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a r and omized , double-blind crossover fashion . Ten patients were studied after a 2-week placebo run-in and , after 8 weeks of active treatment , allowing a 2-week placebo washout between treatments . At the end of each period , glomerular filtration rate ( GFR ) and effective renal plasma flow ( ERPF ) were measured as 51Cr-EDTA and 123I-hippuran clearance , respectively , and tubular function evaluated by the lithium clearance technique was determined . Both drugs maintained GFR and ERPF and lowered mean arterial pressure ( MAP , mm Hg ) to a similar extent ( time x treatment , P = 0.466 ) : amlodipine from 126.9 + /- 2.5 to 115.9 + /- 2.2 ; perindopril from 126.9 + /- 2.5 to 117.9 + /- 3.9 ( time effect of all treatments together , P = 0.003 ) . Accordingly , renal vascular resistance ( RVR , mm Hg/mL/min/1.73 m2 ) was equally reduced ( time x treatment , P = 0.955 ) : amlodipine from 0.36 + /- 0.03 to 0.30 + /- 0.02 ; perindopril from 0.36 + /- 0.03 to 0.32 + /- 0.01 ( time effect all treatments together , P = 0.043 ) . Sodium clearance and fractional excretion of sodium were not affected by either drug . Output of fluid from the proximal tubules measured as clearance of lithium ( CLi , mL/min ) and uric acid ( CUr , mL/min ) was higher after amlodipine than after perindopril ( CLi 19.1 + /- 2.1 v 16.5 + /- 1.7 , P = 0.036 and CUr 7.0 + /- 0.6 v 5.9 + /- 0.4 , P = 0.007 ) . As a consequence , after amlodipine , distal absolute reabsorption of sodium was higher ( DARNa 2.57 + /- 0.28 v 2.19 + /- 0.22 mEq/min , P = 0.027 ) and serum uric acid was lower ( 5.9 + /- 0.3 v 6.7 + /- 0.4 mg/dL , P = 0.001 ) in comparison with perindopril . In cyclosporine-treated renal allograft hypertensives , amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent . Overall sodium excretion is not affected by either agent . Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril Calcium channel blockers and angiotensin converting enzyme‐inhibitors are commonly used in the treatment of hypertensive renal transplant recipients . The purpose of this study was to investigate if the response rate to treatment differs with these drugs in this setting . A single centre , prospect i ve , r and omised , double‐blinded , comparative study to address the efficacy of controlled release nifedipine or lisinopril in the treatment of hypertension ( diastolic blood pressure ≥95 mmHg ) in cyclosporin (CsA)‐treated renal transplant recipients was performed . Recipients were r and omised to receive either lisinopril ( 10 mg once daily ) or controlled release nifedipine ( 30 mg once daily ) . The dose was doubled on indication . The number of responders ( diastolic blood pressure < 90 mmHg on monotherapy ) were addressed during the early post‐transplant phase ( first 3 months ) and during a late post‐transplant phase ( from 3 to 12 months after renal transplantation ) in the same patient population . One hundred and fifty‐four patients ( nifedipine=78 , lisinopril=76 ) with untreated hypertension ( diastolic blood pressure≥95 mmHg ) were r and omised within 3 wk after renal transplantation . One hundred and twenty‐tree patients ( nifedipine=69 , lisinopril=54 ) completed the study . Fourteen ( 20 % ) nifedipine‐treated recipients responded during the early , and 26 ( 38 % ) during the late post‐operative phase ( months 4–12 after renal transplantation ) . Eleven ( 20 % ) lisinopril‐treated recipients responded during the early , and 18 ( 33 % ) during the late post‐transplant phase . Non‐responders were , on average , 8.5±1.5 kg heavier both in the early phase and after 1 yr of treatment ( p<0.01 ) , and 6.1±0.9 yr older than responders ( p<0.05 ) . In conclusion , these results indicate that both controlled release nifedipine and lisinopril are equally efficient in the treatment of post‐transplant hypertension . As monotherapy , both drugs show a ‘ response rate ’ of 20–38 % , depending on time interval after transplantation BACKGROUND Due to their vasodilatory effect , calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure ( BP ) seen in renal transplantation . METHODS In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment , 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a r and omized , double-blind , placebo-controlled study with two parallel groups . Felodipine ( ER tablets , 10 mg ) or placebo was given prior to transplantation and each day during the study period . The patients were assessed twice , i.e. at 4 - 6 weeks and at 10 - 12 weeks after transplantation . Renal plasma flow ( RPF ) and glomerular filtration rate ( GFR ) were measured by constant infusion technique . Tubular function was estimated from clearance of lithium . RESULTS At 6 weeks after transplantation , felodipine caused a significantly higher RPF [ felodipine : 219 + /- 70 ml/min ; placebo : 182+/-56 ml/min ( mean+/-1 SD ) ; P=0.03 ] . No differences were found in GFR , filtration fraction ( FF ) , tubular sodium h and ling , or sodium excretion . Felodipine lowered BP significantly . At 12 weeks after transplantation , felodipine caused a significantly higher GFR ( felodipine : 49+/-18 ml/min ; placebo : 40+/-16 ml/min ; P=0.05 ) and RPF ( felodipine : 225+/-77 ml/min ; placebo : 175+/-48 ml/min ; P<0.01 ) . No difference was found in FF . Felodipine lowered BP significantly . No differences were found with regard to duration of primary anuria , hospitalization time , number of rejection episodes , plasma creatinine day 7 post-transplant , or treatment doses of CsA. CONCLUSIONS It is concluded that in renal transplant recipients treated with CsA , felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo , despite a concomitant lowering of BP . A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested The objective of this work was to study the possible protective effect of verapamil against the ischaemic acute tubular necrosis in kidney transplantation In a prospect i ve r and omized trial we evaluated the influence of the calcium antagonist diltiazem ( Dil ) on the development of acute tubular necrosis ( ATN ) in cadaveric kidney transplantation . Dil was added to Eurocollin 's solution ( 20 mg/l ) at donor nephrectomy . The graft recipient received a preoperative bolus injection of Dil ( 0.28 mg/kg ) which was followed by an infusion of Dil ( 0.0022 mg/min/kg ) for 2 days . Thereafter , Dil was applied orally . Immunosuppressive therapy consisted of ciclosporin ( CS ) and low-dose steroids . There were no significant differences between the groups with respect to donor characteristics , HLA matching and ischemic periods . In the control group ( n = 22 ) , 9 patients ( 41 % ) developed ATN compared to 2 patients ( 10 % ) in the Dil group ( p less than 0.05 ) . In the control group , 3.5 + /- 0.4 HD per patient were necessary compared to 0.6 + /- 0.2 in the Dil group ( p less than 0.05 ) . Although CS blood levels were significantly higher in the Dil group ( 1st week 1,150 vs. 728 ng/ml ; p less than 0.01 ) , the GFR of grafts with primary function was significantly higher in the Dil group ( day 7:39 vs. 24 ml/min ; p less than 0.05 ) . A significant reduction of the CS dose by 30 % ( p less than 0.01 ) led to comparable CS levels . In the Dil group , significantly fewer rejection episodes occurred during the first month . Our data indicate that the application of the calcium antagonist Dil lowered the incidence of posttransplant ATN . In addition , there is a possibility that Dil not only ameliorates ischemic damage in the kidney , but also reduces CS nephrotoxicity |
10,807 | 26,365,608 | In this largest and up-to- date review on intra-arterial vasodilators use to reduce RAS , we have found that the verapamil at a dose of 5 mg or verapamil in combination with nitroglycerine are the best combinations to reduce RAS | OBJECTIVES The aim of this study is to review the available literature on the efficacy and safety of agents used for prevention of RAS .
BACKGROUND Different vasodilator agents have been used to prevent radial artery spasm ( RAS ) in patients undergoing transradial cardiac catheterization . | BACKGROUND Radial artery spasm is one of the most common complications during coronary angiography via the transradial approach , causing patient discomfort or sometimes interrupting the procedure . This study was design ed to compare the spasmolytic effect between nicor and il and a cocktail during transradial coronary angiography . METHODS A r and omized study to compare 4 mg of nicor and il and a cocktail ( mixture of normal saline , 200 microg of verapamil ) was performed in 150 patients . We examined vasospasms of the radial artery that were expressed as stenosis of the radial artery vessel diameter after the procedure . RESULT The reductions of systolic and diastolic blood pressures showed no significant differences between the two groups ( 15.4+/-11.5/7.7+/-7.8 mmHg for nicor and il and 16.3+/-13.4/6.2 mmHg for cocktail ) . Both agents induced a significant radial artery vasodilation after transradial administration at proximal and mid segments ( P < 0.001 for all ) . Nicor and il showed a significant increase of the mean change of the radial artery diameter compared to the cocktail at mid-segment ( 0.32+/-0.23 mm for nicor and il and 0.24+/-0.15 mm for a cocktail , P < 0.05 ) . There was no statistically significant difference between the two groups in radial artery spasm ( 50.7 % vs. 52.0 % in nicor and il and a cocktail , respectively ) after catheterization . CONCLUSION Nicor and il with vasodilator effects by a dual mechanism was effective as the cocktail in preventing radial artery spasm during transradial coronary angiography Background Verapamil is traditionally applied prophylactically in transradial procedures to prevent radial artery spasm . However , verapamil may have side effects and is contraindicated in some clinical setting s. Methods and Results During an investigator‐initiated , r and omized , double‐blind trial , we evaluated the need for preventive verapamil administration . After vascular access was established , patients received either 5 mg verapamil ( n=297 ) or placebo ( n=294 ) . We compared the rate of access site conversions as primary end point using a superiority margin of 5 % . Occurrence of code breaks ( composite of conversions and unplanned use of verapamil ) , overall verapamil use , procedural and fluoroscopic times , contrast volume , and subjective pain were investigated as secondary end points . The rate of access site conversions was not different in the 2 arms ( placebo 1.7 % versus verapamil 0.7 % , P=0.28 , difference 1.0 % , 95 % CI for the difference −1.1 % to 3.3 % ) . Proportion of code breaks was similar in the 2 groups ( 3.4 % versus 1.3 % , P=0.11 ) , whereas overall verapamil use was markedly lower in the placebo arm ( 2.0 % versus 100 % , P<0.0001 ) . Procedural time ( median [ IQR ] 16.0 minutes [ 9.0 to 30.0 minutes ] versus 17.0 minutes [ 10.0 to 31.0 minutes ] , P=0.37 ) , fluoroscopic time ( 4.4 minutes [ 2.1 to 9.6 minutes ] versus 4.8 minutes [ 2.4 to 10.7 minutes ] , P=0.28 ) , contrast volume ( 72.5 mL [ 48.0 to 146.0 mL ] versus 75.5 mL [ 47.0 to 156.5 mL ] , P=0.74 ) , and pain score ( P for trend=0.12 ) were comparable in the 2 groups . Conclusions The preventive use of verapamil may be unnecessary for transradial procedures . The omission of prophylactic verapamil may not only reduce the rate of potential complications related to the drug but also allow the safe extension of the transradial method to those with contraindications to verapamil . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT01402427 OBJECTIVES This study sought to estimate the economic impact of same-day home discharge compared with overnight hospitalization after transradial percutaneous coronary intervention ( PCI ) . BACKGROUND Same-day home discharge after transradial PCI and a bolus-only abciximab regimen was found to be clinical ly noninferior to the abciximab st and ard therapy and overnight hospitalization in patients with various forms of acute coronary syndromes . METHODS In the EASY ( Early Discharge After Transradial Stenting of Coronary Arteries ) trial , 1,005 patients were r and omized after a bolus of abciximab and uncomplicated transradial coronary stenting , either to same-day home discharge and no infusion ( outpatient group ) or to overnight hospitalization and 12-h abciximab infusion ( overnight-stay group ) . We estimated post-PCI health care cost ( in Canadian dollars ) of trial subjects and short-term economic impact of same-day home discharge . As r and omization was done after the procedure , outcomes were similar , and PCI re source use showed minimal and nonsignificant differences , a post-PCI cost-minimization analysis was conducted . Detailed per-patient information of health care re sources used immediately after PCI up to 30 days was collected . RESULTS Mean post-PCI hospital stay was 8.9 h for out patients versus 26.5 h for overnight-stay patients ( p < 0.001 ) . At 30-day follow-up , the mean cumulative medical cost per outpatient was $ 1,117 ± $ 1,554 versus $ 2,258 ± $ 1,328 for overnight-stay patients . The mean difference of $ 1,141 ( 95 % confidence interval : $ 962 to $ 1,320 ) was mainly due to the extra night for overnight hospital stay . CONCLUSIONS In a real-world setting , same-day home discharge after uncomplicated transradial PCI and a bolus-only abciximab regimen result ed in a 50 % relative reduction in medical costs . Extension of this outpatient strategy would be welcomed by the hospitals and reimbursement systems in a context of increasing dem and for health care cost reduction . ( Early Discharge After Transradial Stenting of Coronary Arteries [ EASY ] ; NCT00169819 ) We examined the response of the radial artery to vasoactive agents ( isosorbide dinitrate , ISDN , 1 mg , 3 mg , and 5 mg ; verapamil , 1 mg , 3 mg , and 5 mg ; and lidocaine , 10 mg , 30 mg , and 50 mg ) in 100 consecutive patients admitted for elective coronary angiography . The drug solutions were directly injected into the radial artery from the puncture site . As a result , 5 mg of ISDN increased the diameter of the radial artery by 31 % and 28.8 % at the proximal and distal sites , respectively . Similarly , 5 mg of verapamil increased it by 9 % and 10.8 % at the proximal and distal site , respectively . But 10 mg of lidocaine decreased it by −15.6 % and −12.1 % at the proximal and distal site , respectively . At the doses utilized , ISDN was the most potent vasodilator for the radial artery and lidocaine caused paradoxical vasoconstriction . Cathet . Cardiovasc . Intervent . 49:253–256 , 2000 . © 2000 Wiley‐Liss , OBJECTIVE Radial artery spasm remains a major complication of transradial coronary interventions . The aim of this study was to compare the efficacy of three different intra-arterial vasodilating cocktails in reducing the incidence of radial artery spasm in patients undergoing transradial coronary angiography . The secondary goal was to assess the predictors of arterial spasm in this large group of patients . METHODS A total of 379 patients undergoing the procedure were r and omly enrolled in 1 of 3 groups . Every patient in each of the 3 groups received intra-arterial heparin , lidocaine and diltiazem . Along with that , patients in Group A received nitroglycerin ; patients in Group B received nitroprusside instead of nitroglycerin ; and patients in Group C received both nitroglycerin and nitroprusside . A single experienced operator , blinded to the study drug , subjectively determined the presence of spasm . RESULTS Of 379 patients , a total of 44 patients ( 11.6 % ) experienced spasm . The occurrence of spasm was similar , independent of the vasodilator cocktail used ( Group A : 12.2 % , Group B : 13.4 % , Group C : 9.5 % ; p = 0.597 ) . After multivariate analysis , the following variables were found to be independent predictors of spasm : radial artery diameter (RD)/height index ( p = 0.005 ) , RD/BSA index ( p = 0.012 ) , and sheath outer diameter (OD)/RD index ( p = 0.024 ) . CONCLUSION In this prospect i ve , r and omized trial , the addition of a direct nitric oxide donor to nitroglycerin in an antispastic cocktail did not reduce the risk of spasm , and the use of nitroglycerin was found to be as effective as nitroprusside . Also , morphometric and mechanical factors play a significant role in predicting the occurrence of radial spasm . The sex of the patient , presence of diabetes , body surface area and smoking history appeared to play no role in predicting the occurrence of radial spasm OBJECTIVE To evaluate the impact of the use , prior to the procedure , of injectable diltiazem to prevent complications . METHODS Between September 2000 and July 2001 , 50 patients underwent transradial coronary angiography and were r and omized to receive placebo ( GI ) or diltiazem ( GII ) through a catheter inserted into the radial artery . All patients received isosorbide mononitrate . Ultrasound analyses of the radial artery were performed before examination , 30 minutes afterwards , and 7 days afterwards to evaluate the flow , the diameter , and the artery output . RESULTS The radial artery diameter of GI was 2.4d + /- 0.5 mm before the procedure and 2.3 + /- 0.5 mm after 30 minutes ( NS ) , whereas in GII the diameter was 2.2 + /- 0.3 mm before the examination and + /- 2.5 0.4 mm 30 minutes after it ( P<0.001 ) . Radial artery output in group 1 was 7.3 + /- 5.l2 mL/min before the examination and 6.1 + /- 3.5 mL/min 30 minutes after the examination ( NS ) , and GII had an increase of 5.9 + /- 2.5 mL/min before examination to 9.05 + /- 7.78 mL/min after the examination ( P=0.04 ) . Complications ( spasm , occlusion , and partial obstruction ) occurred in 4 patients ( 17.4 % ) in GI and did not occur in GII ( P=0.04 ) . CONCLUSION The study suggests a decrease in vascular complications through the transradial access for coronary angiography with the use of diltiazem as an antispasmodic drug , result ing in the significant increase in the diameter of the radial artery and radial artery output OBJECTIVES This study sought to determine the relationships among access site practice , clinical presentation , and procedural outcomes in a large patient population . BACKGROUND Transradial access ( TRA ) has been associated with improved patient outcomes in selected population s in r and omized trials . It is unclear whether these outcomes are achievable in clinical practice . METHODS Using the BCIS ( British Cardiovascular Intervention Society ) data base , we investigated outcomes for percutaneous coronary intervention procedures undertaken between 2007 and 2012 according to access site practice . Patients were categorized as stable , non-ST-segment elevation acute coronary syndrome ( NSTEACS ) and ST-elevation acute coronary syndrome ( STEACS ) . The impact of access site on 30-day mortality , major adverse cardiac events , bleeding , and arterial access site complications was studied . RESULTS Data from 210,260 TRA and 229,687 transfemoral access procedures were analyzed . Following multivariate analysis , TRA was independently associated with a reduction in bleeding in all presenting syndromes ( stable odds ratio [ OR ] : 0.24 , p < 0.001 ; NSTEACS OR : 0.35 , p < 0.001 ; STEACS OR : 0.47 , p < 0.001 ) as well as access site complications ( stable OR : 0.21 , p < 0.001 ; NSTEACS OR : 0.19 ; STEACS OR : 0.16 , p < 0.001 ) . TRA was associated with reduced major adverse cardiac events only in patients with unstable syndromes ( stable OR : 1.08 , p = 0.25 ; NSTEACS OR : 0.72 , p < 0.001 ; STEACS OR : 0.70 , p < 0.001 ) . TRA was associated with improved outcomes compared with a transfemoral access ( TFA ) with a vascular closure device in a propensity matched cohort . CONCLUSIONS In this large study , TRA is associated with reduced percutaneous coronary intervention-related complications in all patient groups and may reduce major adverse cardiac events and mortality in ACS patients . TRA is superior to transfemoral access with closure devices . Use of TRA may lead to important patient benefits in routine practice . TRA should be considered the preferred access site for percutaneous coronary intervention OBJECTIVE To assess the effect of intra-arterial magnesium on the radial artery during transradial cardiac catheterization . BACKGROUND Transradial coronary angiography has become popular in the last decade and offers several advantages over transfemoral angiography . Radial artery spasm is a major limitation of this approach , and a vasodilatory cocktail is usually given . The aim of this study was to examine the effect of magnesium sulphate on the radial artery during cardiac catheterization . METHODS This was a prospect i ve , double-blind , r and omized trial of 86 patients undergoing radial catheterization . Patients were r and omized to receive magnesium sulphate ( 150 mg ) or verapamil ( 1 mg ) into the radial sheath . Radial dimensions were assessed using Doppler ultrasound . The primary endpoint of the study was a change in radial artery diameter following administration . Secondary endpoints included operator-defined radial artery spasm and patient pain . RESULTS Following administration of the study drug , there was an increase in radial artery diameter in both groups ( p < 0.01 ) , although the increase seen was greater in the group receiving magnesium ( magnesium 0.36 + /- 0.03 mm ; verapamil 0.27 + /- 0.03 mm ; p < 0.05 ) . Administration of verapamil result ed in a fall in mean arterial pressure ( MAP ) ( change in MAP -6.6 + /- 1.4 mmHg ; p < 0.01 ) , whereas magnesium did not have a hemodynamic effect . Severe arm pain ( pain score > 5 ) was observed in 14 ( 30 % ) patients receiving verapamil and 9 ( 27 % ) receiving magnesium ( p = NS ) . CONCLUSION This study demonstrates that magnesium is a more effective vasodilator when compared to verapamil , with a reduced hemodynamic effect , and is equally effective at preventing radial artery spasm . As such , the use of this agent offers distinct advantages over verapamil during radial catheterization Background : Bleeding and transfusion after percutaneous coronary intervention ( PCI ) are known predictors of mortality . Transradial arterial access reduces bleeding and transfusion related to femoral access complications , although its association with mortality is unknown . Objective : To determine the association of arterial access site ( radial or femoral ) with transfusion and mortality in unselected PCIs . Design , setting and patients : By data linkage of three prospect ively collated provincial registries , 38 872 procedures in 32 822 patients in British Columbia were analysed . The association between access site , transfusion and outcomes was assessed by logistic regression , propensity score matching and probit regression . Main outcome measures : 30-Day and 1-year mortality . Results : 1134 ( 3.5 % ) patients had at least one blood transfusion . Transfused patients had a significantly increased 30-day and 1-year mortality , adjusted odds ratio ( 95 % CI ) 4.01 ( 3.08 to 5.22 ) and 3.58 ( 2.94 to 4.36 ) , respectively . By probit regression the absolute increase in risk of death at 1 year associated with receiving a transfusion was 6.78 % . The number needed to treat was 14.74 ( prevention of 15 transfusions required to “ avoid ” one death ) . Radial access halved the transfusion rate . After adjustment for all variables , radial access was associated with a significant reduction in 30-day and 1-year mortality , odds ratio = 0.71 ( 95 % CI 0.61 to 0.82 ) and 0.83 ( 0.71 to 0.98 ) , respectively ( all p<0.001 ) . Conclusions : In a registry of all comers to PCI , transradial access was associated with a halving of the transfusion rate and a reduction in 30-day and 1-year mortality Radial artery spasm occurs frequently during the transradial approach for coronary catheterization . Premedications with nitroglycerin and verapamil have been documented to be effective in preventing radial spasms . Verapamil is relatively contraindicated for some patients with left ventricular dysfunction , hypotension and bradycardia . We would like to know whether nitroglycerin alone is sufficient for the prevention of radial artery spasm . We conducted a r and omized controlled trial to compare the spasmolytic effect between heparin alone , heparin plus nitroglycerin and heparin plus nitroglycerin and varapamil during transradial cardiac catheterization . In this study , a total of 406 patients underwent transradial cardiac catheterization and intervention . After successful cannulation and sheath insertion of radial arteries , 133 patients in group A received 3,000 units of heparin , 100 µg of nitroglycerin and 1.25 mg of verapamil via sheath , 135 patients in group B received 3,000 units of heparin and 100 µg of nitroglycerin , and 93 patients in group C received 3,000 units of heparin . Five patients in group A ( 3.8 % ) , 6 patients in group B ( 4.4 % ) and 19 patients in group C ( 20.4 % ) showed radial spasms . There is no statistically significant difference between groups A and B ( p = 0.804 ) , but there are strong statistically significant differences between groups A and C ( p = 0.001 ) and groups B and C ( p = 0.003 ) . Intra-arterial premedication with 100 µg nitroglycerin and 3,000 units of heparin is effective in preventing radial spasms during transradial cardiac catheterization OBJECTIVES This study used intravascular ultrasound ( IVUS ) to evaluate radial artery volume changes after intraarterial administration of nitroglycerin and /or verapamil . BACKGROUND Radial artery spasm , which is associated with radial artery size , is the main limitation of the transradial approach in percutaneous coronary interventions ( PCI ) . METHODS This prospect i ve , r and omized study compared the effect of two intra-arterial vasodilator regimens on radial artery volume : 0.2 mg of nitroglycerin plus 2.5 mg of verapamil ( Group 1 ; n = 15 ) versus 2.5 mg of verapamil alone ( Group 2 ; n = 15 ) . Radial artery lumen volume was assessed using IVUS at two time points : at baseline ( 5 minutes after sheath insertion ) and post-vasodilator ( 1 minute after drug administration ) . The luminal volume of the radial artery was computed using ECOC R and om Fields ( ECOC-RF ) , a technique used for automatic segmentation of luminal borders in longitudinal cut images from IVUS sequences . RESULTS There was a significant increase in arterial lumen volume in both groups , with an increase from 451 ± 177 mm³ to 508 ± 192 mm³ ( p = 0.001 ) in Group 1 and from 456 ± 188 mm³ to 509 ± 170 mm³ ( p = 0.001 ) in Group 2 . There were no significant differences between the groups in terms of absolute volume increase ( 58 mm³ versus 53 mm³ , respectively ; p = 0.65 ) or in relative volume increase ( 14 % versus 20 % , respectively ; p = 0.69 ) . CONCLUSIONS Administration of nitroglycerin plus verapamil or verapamil alone to the radial artery result ed in similar increases in arterial lumen volume according to ECOC-RF IVUS measurements Aims : Radial artery spasm remains the major limitation of transradial approach for percutaneous coronary interventions . The aim of our study was to evaluate the efficacy of vasodilators in the prevention of radial artery spasm during percutaneous coronary interventions . Methods and results : 1,219 patients were consecutively r and omized to receive placebo ( n = 198 ) , molsidomine 1 mg ( n = 203 ) , verapamil 2.5 mg ( n = 409 ) , 5 mg ( n = 203 ) or verapamil 2.5 mg and molsidomine 1 mg ( n = 206 ) . All drugs were administered through the arterial sheath . The primary end point was the occurrence of a radial artery spasm defined by the operator as severe limitation of the catheter movement , with or without angiographic confirmation . Main characteristics including age , sex , wrist and arterial sheath diameters and procedure duration were identical across the groups . The rate of radial artery spasm was lowest in patients receiving verapamil and molsidomine ( 4.9 % ) , compared to verapamil 2.5 mg or 5 mg ( 8.3 and 7.9 % ) , or molsidomine 1 mg ( 13.3 % ) ; and placebo ( 22.2 % ) ( P < 0.0001 ) . Conclusion : Radial artery spasm during transradial percutaneous interventions was effectively prevented by the administration of vasodilators . The combination of verapamil 2.5 mg and molsidomine 1 mg provided the strongest relative risk reduction of spasm compared to placebo and should therefore be recommended during percutaneous coronary interventions through the radial approach . © 2006 Wiley‐Liss , OBJECTIVES The aim of this study was to assess the impact of length and hydrophilic coating of the introducer sheath on radial artery spasm , radial artery occlusion , and local vascular complications in patients undergoing transradial coronary procedures . BACKGROUND Radial artery spasm is common during transradial procedures and the most common cause for procedural failure . METHODS We r and omly assigned , in a factorial design , 790 patients scheduled for a transradial coronary procedure to long ( 23-cm ) or short ( 13-cm ) and hydrophilic-coated or uncoated introducer sheaths . The primary outcome measure was clinical evidence of radial artery spasm , and secondary outcome measures were patient discomfort and local vascular complications . RESULTS Procedural success was achieved in 96 % of the cases , and radial artery spasm accounted for 17 of 33 failed cases . There was significantly less radial artery spasm ( 19.0 % vs. 39.9 % , odds ratio [ OR ] : 2.87 ; 95 % confidence interval [ CI ] : 2.07 to 3.97 , p < 0.001 ) and patient reported discomfort ( 15.1 % vs. 28.5 % , OR : 2.27 ; 95 % CI : 1.59 to 3.23 , p < 0.001 ) in patients receiving a hydrophilic-coated sheath . No difference was observed between long and short sheaths . Radial artery occlusion was observed in 9.5 % of the patients and was not influenced by sheath length or coating . A local large hematoma or arterial dissection was seen in 2.6 % of the patients with no difference in groups allocated at r and omization . Younger age , female sex , diabetes , and lower body mass index were identified as independent predictors of radial artery spasm . CONCLUSIONS Hydrophilic sheath coating , but not sheath length , reduces the incidence of radial artery spasm during transradial coronary procedures The objective of this study was to evaluate phentolamine as radial artery spasmolytic in transradial catheterization procedures . Radial artery spasm is a relatively frequent complication during transradial approach , causing patient discomfort or even making it impossible to continue the procedure . As radial artery spasm is mediated by the stimulation of α‐adrenoreceptors , the use of the α‐blocker phentolamine could make sense as spasmolytic . We design ed a r and omized double‐blind study to compare phentolamine vs. verapamil , the st and ard spasmolytic agent . Five hundred patients ( 250 in each arm ) su bmi tted to a transradial cardiac catheterization were consecutively included and r and omly assigned to receive 2.5 mg of verapamil or 2.5 mg of phentolamine after sheath insertion . Both vasodilator agents induced a significant radial artery diameter increase ( from 2.22 ± 0.53 to 2.48 ± 0.57 mm , P < 0.001 for verapamil , and from 2.20 ± 0.53 to 2.45 ± 0.53 mm , P < 0.001 for phentolamine ) . However , verapamil was more efficacious to prevent radial artery spasm ( 13.2 % compared with 23.2 % in phentolamine‐treated patients ; P = 0.004 ) . Follow‐up ( 20 ± 18 days ) evaluation of the radial artery patency by plestismography and pulse oximetry showed no differences between the two groups in the rate of radial occlusion ( 3.0 % vs. 3.2 % in verapamil and phentolamine treated patients , respectively ) . Phentolamine was an effective radial vasodilator agent , although it showed less ability to prevent radial artery spasm than verapamil . Radial artery occlusion rate was almost identical for both vasodilators . Thus , phentolamine could be a valid alternative to verapamil as a radial artery spasmolytic agent . © 2005 Wiley‐Liss , BACKGROUND Transradial access is a recently developed alternative for diagnostic cardiac catheterization . Its effects on quality of life after the procedure , patient preference , and cost are unknown . METHODS AND RESULTS We performed a r and omized single-center trial in which 99 patients underwent transfemoral and 101 underwent transradial diagnostic cardiac catheterization . Quality of life was measured with the SF-36 and visual analog scales at baseline , 1 day , and 1 week . Patients were examined at 1 day and at 1 week after for complications . Costs were measured prospect ively . One patient in the femoral group and 2 in the radial group crossed over to the alternative access site . There were no major access site complications . One patient in the transfemoral group had a minor stroke . Transradial catheterization significantly reduced median length of stay ( 3.6 vs 10.4 hours , P < .0001 ) . Over the first day after the procedure , measures of bodily pain , back pain , and walking ability favored the transradial group ( P < .05 for all comparisons ) . Over the week after the procedure , changes in role limitations caused by physical health , bodily pain , and back pain favored the transradial group ( P < .05 for all comparisons ) . There was a strong patient preference for transradial catheterization as well ( P < . 0001 ) . Transradial catheterization led to significant reductions in bed , pharmacy , and total hospital costs ( $ 2010 vs $ 2299 , P < .0001 ) . CONCLUSIONS Among patients undergoing diagnostic cardiac catheterization , transradial access leads to improved quality of life after the procedure , is strongly preferred by patients , and reduces hospital costs |
10,808 | 23,320,933 | The majority of COC users report no significant change in libido although in most studies a decline in plasma levels of free testosterone and an increase in those of sex hormone binding globulin were observed | OBJECTIVES To determine the relationship between the use of combined oral contraceptives ( COCs ) and sexual desire based on a systematic review of the literature . | We prospect ively estimated the prevalence of the polycystic ovary syndrome ( PCOS ) , as defined by the NIH/NICHHD 1990 endocrine criteria , in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation . Anthropometric data ; the presence of hirsutism , acne , and and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels . PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , and 3 ) exclusion of hyperprolactinemia , thyroid disorders , and nonclassic 21-hydroxylase deficiency . Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more , acne was considered as a sign of hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen index above the 95th percentile of the control values derived from the nonhirsute , nonacneic women having regular menses who were not receiving hormonal therapy . PCOS was present in 10(6.5 % ) , hirsutism was present in 11 ( 7.1 % ) , and acne was present in 19 ( 12.3 % ) of the 154 women . Our results demonstrate a 6.5 % prevalence of PCOS , as defined , in a minimally biased population of Caucasian women from Spain . The polycystic ovary syndrome , hirsutism , and acne are common endocrine disorders in women BACKGROUND Oral contraceptive is the most commonly used method of fertility control . Yasmin is a combination of a novel progestogen with anti- and rogenic and anti-mineralcorticoid activities ( 3 mg Drospirenone ( DRSP ) and 30 microg ethinylestradiol ( EE ) ) . It has been shown in many clinical trials that Yasmin is an efficacious oral contraceptive , lacking undesired effects as with other oral contraceptives such as weight gain . However the effects of Yasmin on sexual desire and libido have not been intensively investigated so far OBJECTIVE Investigate the effects of Yasmin on sexual desire , libido and changes in the free and rogen index ( FAI ) compare to Meliane ( 75 microg gestodene + 20 microg ethinylestradiol ) . MATERIAL AND METHOD The authors ' report the results of a double blind r and omized controlled study using a translated version of the Female Sexual Function Index question naire ( FSFI ) for the assessment of the sexual function . The free and rogen index was calculated from measurements of testosterone and sexual hormone binding globulin . RESULT The result shows statistically significant improvements regarding sexual desire , arousal and overall satisfaction in the Yasmin group . Additionally , an increased frequency of orgasms in the Meliane group was reported . Statistically significant differences between the two treatments regarding changes in the FSFI score and changes in the free and rogen index have not been observed . CONCLUSION The novel oral contraceptive containing drospirenone ( Yasmin ) and the non-anti- and rogenic progestin containing oral contraceptive ( Meliane ) do not show unfavorable effects on sexual response and libido The relationships between plasma free testosterone ( FT ) and measures of sexual attitude , sexual behavior , and gender role behavior were assessed in 55 oral contraceptive-using and 53 nonusing female undergraduates . Plasma FT and other measures of and rogenicity were substantially lower in the oral contraceptive ( OC ) group . Correlations between FT and certain behavioral and attitudinal measures were found in the OC users but not the nonusers . In the OC users , FT was positively associated with frequency of sexual intercourse but not with frequency of masturbation . It was negatively associated with restrictive sexual morality . Correlations between FT and measures of gender role behavior were negligible , and FT was unrelated to proceptivity , homosexual interest , or the use of sexual fantasy . The occurrence of some predicted correlations among pill-using women but not the nonusers requires explanation , particularly in view of the substantially lower levels of FT in the pill-using group . It is suggested that and rogen — behavior relationships in women are easily obscured by psychosocial influences and in this sample of young women such influences may have been more powerful among those not using OCs . Such psychosocial influences are likely to differ at different stages of women 's life cycles . The importance of controlling for such influences in any study of hormone — sexual behavior relationships in women is emphasized , and the need for prospect i ve studies of women before and after starting on steroidal contraception is recognized The aim of this study was to examine whether changes in plasma and rogen levels ( total testosterone ( T ) , free testosterone ( FT ) , and dehydro-epi and rosterone-sulfate ( DHEA-S ) ) induced by oral contraceptive ( OC ) use were related to changes in sexual interest or response or in mood . Sixty-one women provided blood sample s and were assessed , using interviews and st and ardized question naires , prior to starting , and after 3 months on OCs ( Ortho-Tricyclen , Ortho-Tricyclen-Lo , or Ortho-Cyclen , all containing the same progestagen , norgestimate ) . Significant decreases in T , FT , and DHEA-S were found after 3 months , although the extent of reduction was variable across women . There was some support for a relationship between the degree of reduction in total T and FT and the frequency of sexual thoughts after 3 months on OCs . However , some women had no loss of sexual interest in spite of substantial reduction in FT , and there was overall no evidence that reduction in FT affected enjoyment of sexual activity with a partner . The findings are consistent with the idea that some women may be more sensitive to changes in T than others . No relationship was found between negative mood , as assessed by the Beck Depression Inventory , and changes in T , FT , or The relationship between plasma testosterone ( T ) secretion and patterns of sexual behavior was examined in 18 women using oral contraceptives ( OCs ) and 13 nonusers matched for partner availability . Retrospective assessment s of perimenstrual symptoms , sexual attitudes , and sexual experience were obtained and women completed daily ratings of the frequency of sexual activities and the level of well-being for 1 month . Plasma levels of sex hormone binding globulin ( SHBG ) , progesterone , Total T , Free T , and non-SHBG bound T were determined by radioimmunoassay at four phases of the pill or menstrual cycle . Overall , women not using OCs had higher plasma levels of Total , Free , and non-SHBG bound T and lower plasma levels of SHBG than those of OC users . Further , only nonusers had perimenstrual decreases in plasma levels of Total and Free T. The two groups were comparable on most retrospective measures . However , OC users reported more satisfaction with their sexual partners than did nonusers and prospect i ve monitoring revealed that they engaged in sexual interactions more frequently than did nonusers across the cycle . In contrast , both groups reported a similar frequency of autosexual activities across the cycle . There were no correlations between average levels of T and levels of sexual desire , sexual interactions , or autosexuality . Moreover , only nonusers reported a decrease in levels of sexual desire during the perimenstrual period that was associated with the changes in Free T over the menstrual cycle BACKGROUND The ovaries provide approximately half the circulating testosterone in premenopausal women . After bilateral oophorectomy , many women report impaired sexual functioning despite estrogen replacement . We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause . METHODS Seventy-five women , 31 to 56 years old , who had undergone oophorectomy and hysterectomy received conjugated equine estrogens ( at least 0.625 mg per day orally ) and , in r and om order , placebo , 150 microg of testosterone , and 300 microg of testosterone per day transdermally for 12 weeks each . Outcome measures included scores on the Brief Index of Sexual Functioning for Women , the Psychological General Well-Being Index , and a sexual-function diary completed over the telephone . RESULTS The mean ( + /-SD ) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter ( 4.2+/-2.8 pmol per liter ) during placebo treatment to 3.9+/-2.4 pg per milliliter ( 13.5+/-8.3 pmol per liter ) and 5.9+/-4.8 pg per milliliter ( 20.5+/-16.6 pmol per liter ) during treatment with 150 and 300 microg of testosterone per day , respectively ( normal range , 1.3 to 6.8 pg per milliliter [ 4.5 to 23.6 pmol per liter ] ) . Despite an appreciable placebo response , the higher testosterone dose result ed in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women ( P=0.03 for both comparisons with placebo ) . At the higher dose the percentages of women who had sexual fantasies , masturbated , or engaged in sexual intercourse at least once a week increased two to three times from base line . The positive-well-being , depressed-mood , and composite scores of the Psychological General Well-Being Index also improved at the higher dose ( P=0.04 , P=0.03 , and P=0.04 , respectively , for the comparison with placebo ) , but the scores on the telephone-based diary did not increase significantly . CONCLUSIONS In women who have undergone oophorectomy and hysterectomy , transdermal testosterone improves sexual function and psychological well-being INTRODUCTION Women may use new oral contraceptives ( OC ) having flexible extended-cycle regimens with a reduced hormone-free interval . AIM To study the changes of the quality of sexual life in users of the traditional 21/7 or extended-cycle 24/4 OC regimens both containing 3 mg drospirenone and 20 µg ethinyl estradiol . METHODS One hundred fifteen women ( age range 18 - 37 years ) were enrolled . Fifty-four women were r and omly placed on traditional OC st and ard regimen , administered for 21 days , followed by a 7-day hormone-free interval ( group A ) ; and 61 women were placed on extended-cycle OC regimen covering 24 days of the cycle with a 4-day hormone-free interval ( group B ) . The Short Form-36 ( SF-36 ) vali date question naire to assess quality of life ( QoL ) and the Short Personal Experience Question naire ( SPEQ ) to measure the changes of sexual behavior were administered before starting OC intake and at the 3rd and 6th cycle follow-ups . MAIN OUTCOME MEASURE The SF-36 and the SPEQ question naires . RESULTS Group A women reported QoL improvement during the 6th cycle on all the scales ( P < 0.05 ) . Group B women reported QoL improvement during the 3rd and 6th cycle ( P < 0.05 ) . Satisfaction with sexual activity , arousal , orgasm , and desire increased during the 3rd cycle in women on the group B ( P < 0.05 ) . Group A women did not report any change in all SPEQ items . At the 6th cycle , group B women reported better sexual experience than baseline in all SPEQ items ( P < 0.05 ) . All subjects who were affected by dyspareunia before OC intake reported decreased genital pain associated with intercourse at the 3rd and 6th cycle of both OC regimens ( P < 0.05 ) . CONCLUSION Women could use OCs in a subjective flexible modality . The extended-cycle OC might produce positive effects on the quality of sexual life , enforcing the concept of tailoring an OC to a woman The purpose of the study was to explore predictors of discontinuation of oral contraceptives ( OC ) including pre-OC use characteristics and adverse physical , emotional , and sexual effects of OCs . Women aged 18 + years in committed , sexually active relationships were assessed before starting OC and reassessed at 3 , 6 , and 12 months or shortly after discontinuation . Assessment included pre-OC use attitudes and expectations about the pill ; self-reported side effects and perimenstrual symptoms including premenstrual syndrome ( PMS ) ; physical and emotional well-being ; and sexual interest , enjoyment , and frequency of sexual activity . Seventy-nine women completed the study , 38 % continued OCs , 47 % discontinued , and 14 % switched to another OC . Emotional side effects , worsening of PMS , decreased frequency of sexual thoughts , and decreased psychosexual arousability correctly categorized 87 % of cases by using logistic regression . Emotional and sexual side effects were the best predictors of discontinuation/switching , yet such OC effects have been largely ignored in the research literature An open , r and omized , multicenter study was carried out to compare two oral contraceptives as regards their therapeutic efficacy in and rogenization symptoms such as acne , seborrhea and hirsutism in women . The preparations used were the combination of 2 mg cyproterone acetate ( CPA ) with 0.035 mg ethinyl estradiol ( EE ) ( Diane35 ® , Schering AG , Berlin‐West ) and 0.150 mg desogestrel ( DG ) with 0.03 mg ethinyl estradiol ( Marvelon ® , Organon , Oss , The Netherl and s ) BACKGROUND Data relating to the influence of hormonal contraception on sexual life are conflicting and mostly they refer to oral contraceptives . In this r and omized , controlled , prospect i ve study we compared the effect of an intravaginal hormonal contraceptive with the effect of a combined oral contraceptive on sexual function . METHODS Fifty-one healthy women with a permanent partner and an active sexual life were r and omly divided in two groups according to a computer-generated r and omization list : 26 women ( group A ) used an intravaginal contraceptive releasing 120 microg/day of etonogestrel and 15 microg/day of ethinylestradiol ( EE ) and 25 women ( group B ) used an oral contraceptive containing 20 microg di EE and 150 microg of desogestrel . Twenty-five women participated in the study as control group ( group C ) . A specific question naire was completed by the patients and their partners at the start of the study and after cycles 3 and 6 of contraceptive use . RESULTS Within 3 months of contraceptive use , women from both groups A and B reported a global improvement in sexual function . A statistically significant increase in sexual fantasy was reported only by patients of group A. Whereas partners of the women in both groups A and B reported an improvement in sexual function after 3 months of contraceptive intake , only patients ' partners of group A reported a significant increase in sexual interest , complicity and sexual fantasy . CONCLUSIONS Both hormonal contraceptives tested were seen to have a positive effect on some aspects of sexual function . The intravaginal contraceptive ring seems to exert a further positive effect on the psychological aspect of both women and their partners , which is evident from an improved complicity and sexual satisfaction INTRODUCTION A new oral contraceptive containing the natural estrogen estradiol and a 19-nortestosterone derivate dienogest ( DNG ) in a four-phasic 28-day regimen may be used by women . AIM To investigate the quality of sexual life of healthy women on estradiol valerate and DNG ( E2V/DNG ) oral contraceptive . METHODS Fifty-seven women ( age range 18 - 48 years ) were enrolled . The Short Form-36 ( SF-36 ) question naire to assess quality of life ( QoL ) was administered at baseline and at the 26th day of both the 3rd and 6th cycles of oral contraceptive ( OC ) intake . The Short Personal Experience Question naire ( SPEQ ) to measure the change of sexual behavior was used at the 2nd , 7th , 14th , 21st , 26th , and 28th days of the baseline cycle , as well as at the same days of both the 3rd and 6th cycle of contraceptive intake . MAIN OUTCOME MEASURE The SF-36 and the SPEQ question naires . RESULTS Women reported QoL improvement at the 3rd ( P < 0.05 ) and at the 6th cycles ( P < 0.01 ) . By SPEQ , improvement of sexuality during the 3rd and the 6th cycle with respect to baseline experience was observed ( P < 0.05 ) . The frequency of sexual activity remained basically unchanged ( P = NS ) . Enjoyment and desire improved at the 6th cycle with respect to the 3rd cycle ( P < 0.05 ) . All women reported decreased dyspareunia at the 3rd and 6th cycles ( P < 0.05 ) . Interestingly , desire , arousal , orgasm , enjoyment , and sexual activity improved , reaching a peak around the 14th day of the menstrual cycle ( P < 0.05 ) . At the 3rd and 6th cycle , women on OCs were sexually cyclic , but the peak improvement of desire , arousal , orgasm , enjoyment , and sexual activity appeared around the 7th day of OC intake ( P < 0.05 ) . CONCLUSION Reduced hormone-free interval is a new concept in low-dose OC regimens . Moreover , the E2V/DNG multiphasic extended regimen has been found to positively modify the sexuality of users OBJECTIVE The objective of this study was to compare cycle control , tolerability and sexual well-being with the use of three hormonal contraceptives . METHODS In this prospect i ve r and omized study , the effects of two combined oral contraceptives [ 20 microg of ethinylestradiol (EE)/100 microg of levonorgestrel and 15 microg of EE/60 microg of gestodene ] were compared with those of the vaginal ring ( 15 microg of EE/120 microg of etonogestrel ) . One-year data from 280 women were obtained . We investigated the pattern of menstrual cycle and the incidence of weight gain , nausea , headache , breast tenderness , irritability , depression and vaginal dryness . Moreover , desire and sexual satisfaction were evaluated . Finally , the cumulative rate of discontinuation in the three groups was estimated . CONCLUSION The analysis of adverse events revealed two crucial points for acceptability , compliance and continuation : poor cycle control and disturbance of sexual intercourse due to vaginal dryness and loss of desire The objective of this prospect i ve study was to assess the effects of a low-dose oral contraceptive ( OC ) containing 15 microg ethinylestradiol and 60 microg gestodene on sexuality . Forty-eight healthy volunteers ( age range , 18 - 35 years ) , having regular menstrual cycles with ovulation , participated in the study . Sexual behavior was assessed using the self-administered Personal Experience Question naire , at baseline , and at 3 , 6 and 9 months of pill use . Women reported decreased sexual desire ( p < 0.005 ) and sexual activity ( p < 0.05 ) at the 9th month of pill use , and diminished sexual arousal at the 3rd month of pill intake ( p < 0.05 ) , with respect to baseline . The frequency of orgasm did not change during OC use ( p = NS ) . Moreover , sexual enjoyment was worse at the 3rd , 6th and 9th month with respect to baseline ( p < 0.001 ) . The low dose of ethinylestradiol could cause decreased vaginal lubrication , and diminished sexual arousal could be due to hypo and rogenism . Women may expect increased sexual performance when they take the pill , as compared to before starting contraception . Consequently , they could have an unexpected effect with pill use , though sexuality may remain the same OBJECTIVE To assess sexual function of first-time users of the contraceptive ring and contraceptive patch . DESIGN Open-label r and omized trial . SETTING Multicenter study . PATIENT(S ) A total of 500 healthy , premenopausal , nonpregnant women who had recently used combined oral contraceptives . INTERVENTION(S ) Contraceptive ring vs. contraceptive patch . MAIN OUTCOME MEASURE(S ) Subjects completed the Female Sexual Function Index ( FSFI ) before r and omization to the study product and after 3 months . Unadjusted and adjusted changes in total and domain FSFI scores from baseline to exit were compared between treatment groups using linear regression ( intention-to-treat approach ) . RESULT ( S ) Final adjusted mean total FSFI scores increased by 0.32 points in the patch group and decreased by 0.74 points in the ring group . Subjects in the ring group had worsening scores in the areas of arousal ( score change -0.169 ring vs 0.010 patch ) , lubrication ( score change -0.202 ring vs. 0.031 patch ) , and pain ( score change -0.162 ring vs. 0.182 patch ) . CONCLUSION ( S ) Among recent combined oral contraceptive users , slight decrements in sexual function scores were noted with contraceptive ring use overall and in several domains of sexual functioning , whereas slight increases were noted with patch use . However , for both products , these changes are not likely to be clinical ly significant A placebo-controlled , double-blind study was carried out to assess the direct hormonal effects of combined and progestogen-only oral contraceptives on well-being and sexuality of women in two contrasting cultures . One-hundred-fifty women , who had been sterilised or whose partners had been vasectomised , were recruited from two centres-Manila , Philippines , and Edinburgh , Scotl and . After one month pretreatment assessment , women were r and omly assigned to one of three treatments ( combined oral contraceptive ( COC ) , progestogen-only pill ( POP ) , or placebo ; 50 within each treatment group , 25 per centre ) and continued on treatment for four months . Assessment was by daily ratings , question naires and interviews . The COC adversely affected sexuality in the Edinburgh women , with 12 of the 25 women in this group also reporting the side effect of reduced sexual interest . There were modest negative effects of the combined pill on mood , more noticeable in the Edinburgh women . The POP was associated with no adverse effects on sexuality and some improvement in well-being in both centres . Possible explanations for the apparent lack of adverse effects in the Manila women are discussed . The negative effects reported may be less evident in women using the COC for contraceptive purpose s but may lead to discontinuation in some women and warrant further investigation BACKGROUND This study was conducted to compare the effects of two contraceptive pills with different doses of the same components , on plasma and rogen levels and female sexual function among women without previous sexual dysfunction . STUDY DESIGN The participants were r and omized into two groups , to receive pills containing ethynylestradiol ( EE ) 30 mcg and levonorgestrel ( LNG ) 150 mcg or EE 20 mcg and LNG 100 mcg , for six cycles . Sexual function was assessed using a st and ardized question naire [ Female Sexual Function Index ( FSFI ) ] . Hormone assays were performed at baseline and after the sixth cycle . RESULTS Forty-nine women were included in the EE30/LNG150 group and 48 in the EE20/LNG100 group . EE30/LNG150 group presented 54 % and 67 % decreases of total testosterone and free and rogen index , respectively , with statistical significance . EE20/LNG100 presented reductions of 20 % and 42 % , respectively , but without statistical significance . Both groups showed improvements in the FSFI " desire " score , but with statistical significance only for EE20/LNG100 group . CONCLUSIONS EE30/LNG150 decreased plasma and rogen levels , but there was no impairment in sexual desire , on the other h and , sexual desire score increased with EE20/LNG100 formulation PURPOSE This study compared two oral contraceptives ( OCs ) with the same triphasic regimen of progestin ( norgestimate 0.18 , 0.215 and 0.25 mg ) but differing doses of ethinyl estradiol ( EE ) - 25 and 35 microg EE - in their effects on and rogens , mood and sexual interest in women starting on OCs . METHODS Total testosterone ( T ) , free testosterone ( FT ) , sex-hormone-binding globulin ( SHBG ) and dehydroepi and rosterone sulphate ( DHEA-S ) , together with measures of mood [ Beck Depression Inventory ( BDI ) ] , sexual interest [ Dyadic and Solitary subscales of the Sexual Desire Inventory ( SDI ) ] and self-reported side effects were assessed before starting on the OC and again after 3 months of use . RESULTS Sixty women , all university students , were r and omized to receive either the 25 microg EE ( N/EE25 ) or the 35 microg EE ( N/EE35 ) pill ; 12 women discontinued , leaving 48 who completed the 3-month study . Their mean age was 19.7 years ( 18 - 30 ) and they were predominantly white and single . Both OCs produced reductions in mean T [ N/EE35 : from 1.33 to 0.60 nmol/L , p<.001 ; N/EE25 : from 1.12 to 1.02 nmol/L ; nonsignificant ( NS ) ] and FT ( N/EE35 : from 41.3 to 4.4 pmol/L , p<.001 ; N/EE25 : from 25.4 to 7.9 pmol/L , p<.01 ) , but the reduction in both T and FT was significantly greater with the higher EE dose ( N/EE35 ) ( p=.05 and p=.03 , respectively ) . DHEA-S was also reduced with both formulations ( N/EE35 : from 7.26 to 5.22 micromol/L ) ; N/EE25 : from 7.50 to 5.39 micromol/L ) , although the reduction was only significant in the N/EE35 group ( p<.02 ) . Considerable variability in changes in mood was evident with both OCs , with some women showing predominantly negative effects ( 10 in N/EE35 , 5 in N/EE25 ) ; others , positive effects ( 9 in N/EE35 , 17 in N/EE25 ) and some , no change ( four in each group ) . Women using N/EE25 were significantly more likely to show improvement in premenstrual mood than those in the N/EE35 group ( p<.02 ) , although there was no correlation between changes in BDI and FT or DHEA-S. Sexual interest scores did not change significantly from baseline to posttreatment with either OC ( N/EE35 : dyadic , from 40.5 to 39.6 , NS ; solitary , from 5.9 to 6.4 , NS ; N/EE25 : dyadic , from 36.7 to 37.0 , NS ; solitary , from 5.0 to 4.2 , NS ) . CONCLUSION The lower EE pill reduced FT less and was associated with greater improvement in premenstrual mood . A causal relation between these two effects is uncertain The aim of the study was to determine the changes , if any , on the sexual behavior of women using an oral contraceptive containing 30 microg ethinylestradiol ( EE ) and 3 mg drospirenone ( DRSP ) . Eighty healthy volunteer women ( age range , 19 - 31 years ) , with regular menstrual cycle length ( mean 27.6+/-3.1 ) and ovulation , participated in this prospect i ve study . Sexual behavior was assessed using the self-administered Personal Experience Question naire , at baseline and at 3 , 6 and 9 cycles of pill use . Women reported increased ( i ) sexual enjoyment ( p < .001 ) , ( ii ) orgasm frequency ( p < .05 ) and ( iii ) satisfaction with sexual activity ( p < .05 ) during all periods of pill intake with respect to baseline . Both arousal and frequency of sexual activity improved at the sixth and ninth cycle of pill use ( p < .05 ) with respect to baseline . Moreover , women reported decreased genital pain associated with intercourse during pill intake ( p < .05 ) . Desire did not change during the use of the pill ( p = NS ) . The mild dose of EE may have improved vaginal lubrication , sexual arousal and decreased dyspareunia . Consequently , women may have experienced increased sexual performance . In addition , improved sexual activity could have been the result of the effects of DRSP , with its antimineralocorticoid effects which could improve pill compliance , with a more satisfied sexual life Two multicenter , double-blind , placebo-controlled studies were conducted to evaluate the effectiveness of triphasic norgestimate/ethinyl estradiol ( Ortho Tri-Cyclen ) for the treatment of acne vulgaris . To our knowledge , these studies were the first double-blind , placebo-controlled trials to evaluate the efficacy of an oral contraceptive ( OC ) in the treatment of acne ; in fact , they are probably the first placebo-controlled trials ever completed using modern OC . This article examines the conduct and feasibility of these studies including discussion s on study planning enrollment , maintenance of the blind , continuation rates , and pregnancy prevention . Subjects were between the ages of 15 and 49 years , with moderate acne vulgaris , no contraindications to oral contraceptive use , and were willing to use a nonsteroidal method of birth control during the 6 months of the trial . More than 500 participants were enrolled in 1 year . Discontinuation rates between groups were similar . To explore the reasons for the similar and low discontinuation rates , OC-related side effects were evaluated in comparison to placebo . This analysis revealed that the OC exhibited a side effect profile that was similar , in many cases , to that of placebo . Although pregnancies occurred in the placebo arm , the incidence was consistent with expected failure rates for users of nonsteroidal methods in the general population The combined oral contraceptive ( COC ) pills , injectables , intrauterine contraceptive device ( IUCD ) and female sterilization are the most common contraceptive methods used by women . Women 's choice , compliance and satisfaction with specific contraceptive methods are influenced by any impact of the method on their quality of life and sexual function . Anxiety regarding possible adverse effects of the contraceptive methods on their quality of life and sexual function is one of the common concerns . The aim of this prospect i ve observational study was to determine the impact of the abovementioned contraceptive methods on the quality of life and sexual function of the users . A sample of 361 Hong Kong Chinese women who were first-time users of the following contraceptive methods completed the study : COC pills ( n=87 ) , injectables ( n=67 ) , IUCD ( n=96 ) and female sterilization ( n=111 ) . Quality of life and sexual function of the subjects were assessed before and 3 - 4 months after use of the method by a st and ardized question naire . The questions were adopted from the vali date d Chinese versions of the World Health Organization Quality of Life ( WHOQOL ) question naire and the Derogatis Sexual Functioning Inventory ( DSFI ) . In the female sterilization group , we found a significantly higher score for sexual satisfaction ( p=.004 ) and sexual drive ( p=.003 ) 3 - 4 months after sterilization , as well as an improved WHOQOL social domain score ( p=.009 ) . However , the other DSFI subscale scores and WHOQOL domain scores were not significantly different ( p>.05 ) . No significant difference was demonstrated in all the WHOQOL domain scores and DSFI subscale scores after use of COC pills , injectables and IUCD ( p>.05 ) . We conclude that the COC pills , injectables , IUCD and female sterilization all do not have significant adverse impact on quality of life and sexual function . After female sterilization , there is a significant improvement in sexual satisfaction and sexual drive OBJECTIVE This study was conducted to assess the long-term efficacy and safety of a low-dose monophasic combined oral contraceptive ( COC ) containing 0.02 mg ethinylestradiol ( EE ) and 2 mg chlormadinone acetate ( CMA ) in a novel regimen administered daily for 24 days followed by a 4-day placebo interval . STUDY DESIGN In this multicenter , uncontrolled , Phase III trial , 1665 subjects took the COC 0.02 mg EE/2 mg CMA for up to 21 cycles . The overall Pearl Index was the primary end point ; cycle control , safety , effect on acne and seborrhea , and changes in body weight and libido were secondary end points . RESULTS Contraceptive efficacy was analyzed for 1653 subjects completing 21,495 cycles . Six pregnancies occurred during trial duration with one attributable to method failure . The overall Pearl Index for the first year of use was 0.33 ( 95 % confidence interval , 0.09 - 0.85 ) . The mean number of bleeding/spotting days during six 90-day reference periods ( RPs ) decreased from 17.0 ( RP 1 ) to 11.7 ( RP 6 ) , and the number of bleeding episodes per RP decreased from 3.8 ( RP 1 ) to 2.7 ( RP 6 ) . Among subjects who presented with acne at the baseline visit , a decrease of papules/pustules and comedones was observed during the course of the trial . The most common " at least possibly related " adverse events were headache , breast discomfort and nausea . The tolerability and well-being was reported as being excellent or good in the majority of trial subjects ( 84.6 % and 80.2 % , respectively ) . CONCLUSIONS The low-dose COC 0.02 mg EE/2 mg CMA administered daily for 24 days followed by a 4-day placebo interval provides high contraceptive efficacy combined with an adequate cycle control and safety profile , beneficial effects on acne , and is well tolerated INTRODUCTION Oral contraceptives ( OCs ) have been the preferred method of birth control because of their high rate of effectiveness . OC use , however , has been associated with women 's sexual health complaints and and rogen insufficiency . OC use is associated with a decrease of and rogen ovarian synthesis and an increase in the production of sex hormone-binding globulin ( SHBG ) . There have been limited studies assessing SHBG values after discontinuation of OC use . AIM To retrospectively investigate SHBG levels before and after discontinuation of OC use . MAIN OUTCOME MEASURE Sex hormone-binding globulin values were compared at baseline , while on the OC , and well beyond the 7-day half-life of SHBG at 49 - 120 ( mean 80 ) days and > 120 ( mean 196 ) days after discontinuation of OCs . METHODS A total of 124 premenopausal women with sexual health complaints for > 6 months met inclusion /exclusion criteria . Three groups of women were defined : ( i ) " Continued-Users " ( N = 62 ; mean age 32 years ) had been on OCs for > 6 months and continued taking them ; ( ii ) " Discontinued-Users " ( N = 39 ; mean age 33 years ) had been on OCs for > 6 months and discontinued them ; and ( iii ) " Never-Users " ( N = 23 ; mean age 36 years ) had never taken OCs . RESULTS Sex hormone-binding globulin values in the " Continued-Users " were four times higher than those in the " Never-User " group ( mean 157 + /- 13 nmol/L vs. 41 + /- 4 nmol/L ; P < 0.0001 ) . Despite a decrease in SHBG values after discontinuation of OC use , SHBG levels in " Discontinued-Users " remained elevated in comparison with " Never-Users " ( N = 26 ; P < 0.0001 for > 120 days ) . CONCLUSION In women with sexual dysfunction , SHBG changes in " Discontinued-Users " did not decrease to values consistent with " Never-Users . " Long-term sexual , metabolic , and mental health consequences might result as a consequence of chronic SHBG elevation . Does prolonged exposure to the synthetic estrogens of OCs induce gene imprinting and increased gene expression of SHBG in the liver in some women ? Prospect i ve research is needed In a clinical multicenter observational study including 584 women attended by 99 participating gynaecologists the quality of life changes after 3 month use of an oral contraceptive preparation containing 30 mcg ethinylestradiol ( EE ) and 3 mg drospirenone was evaluated through the use of a self developed question naire using 20 items with a 5 scale answer scheme . We found a mean positive change of life quality of 7.3 % . Significant changes were observed regarding subjective experiences of weight , skin , hair , cycle , attractivity , libido and mental wellbeing |
10,809 | 31,641,922 | Substance use prevention programs for Indigenous youth led to reductions in substance use frequency and intention to use ; improvements in substance-related knowledge , attitudes and resistance strategies ; and delay in substance use initiation .
Prevention programs have the potential to reduce substance use among Indigenous adolescents , especially when they are developed in partnership with Indigenous people . | This systematic review assessed the current evidence base of substance use prevention programs for Indigenous adolescents in the USA , Canada , Australia and New Zeal and . | PURPOSE The purpose of this study was to examine the relationship between age at drinking onset and the development of DSM-IV alcohol abuse and dependence in a 12-year prospect i ve study of youth in the United States . METHODS Logistic regression analyses were used to quantify the relationship between age at drinking onset and the development of alcohol abuse and dependence controlling for sociodemographic factors and problem indicators . RESULTS The odds of alcohol dependence decreased by 5 % in 1989 and 9.0 % in 1994 for each year drinking onset was delayed . In 1994 , the odds of alcohol abuse increased by 7.0 % with each decreasing year of age at drinking onset , while age at drinking onset was not related to alcohol abuse in 1989 . Several other risk factors were found to be strong and consistent predictors of abuse and dependence in 1989 and 1994 , including being male , divorced , separated or never married , younger , and having an early history antisocial behaviors and marijuana use . IMPLICATION S Implication s of the results of this study are discussed in terms of other factors that may impact on the onset-abuse and onset-dependence relationship and the need to focus future prevention efforts This article describes a small efficacy trial of the Living in 2 Worlds ( L2W ) substance use prevention curriculum , a culturally adapted version of keepin ’ it REAL ( kiR ) re design ed for urban American Indian ( AI ) middle school students . Focused on strengthening resiliency and AI cultural engagement , L2W teaches drug resistance skills , decision making , and culturally grounded prevention messages . Using cluster r and om assignment , the research team r and omized three urban middle schools with enrichment classes for AI students . AI teachers of these classes delivered the L2W curriculum in two schools ; the remaining school implemented kiR , unadapted , and became the comparison group . AI students ( N = 107 ) completed a pretest question naire before they received the manualized curriculum lessons , and a posttest ( 85 % completion ) 1 month after the final lesson . We assessed the adapted L2W intervention , compared to kiR , with paired t tests , baseline adjusted general linear models , and effect size estimates ( Cohen ’s d ) . Differences between the L2W and kiR groups reached statistically significant thresholds for four outcomes . Youth receiving L2W , compared to kiR , reported less growth in cigarette use from pretest to posttest , less frequent use of the Leave drug resistance strategy , and less loss of connections to AI spirituality and cultural traditions . For other substance use behaviors and antecedents , the direction of the non-significant effects in small sample tests was toward more positive outcomes in L2W and small to medium effect sizes . Results suggest that evidence -based substance use prevention programs that are culturally adapted for urban AI adolescents , like L2W , can be a foundation for prevention approaches to help delay initiation and slow increases in substance use . In addition to study limitations , we discuss implementation challenges in delivering school-based interventions for urban AI population ABSTRACT Background : Early substance use threatens many American Indian/Alaska Native ( AI/AN ) communities , as it is a risk factor for maladaptive use and adverse health outcomes . Marijuana is among the first substances used by AI/AN youth , and its use becomes widespread during adolescence . Interventions that delay or reduce marijuana use hold the promise of curbing substance disorders and other health risk disparities in AI/AN population s. Objectives : We evaluated the effectiveness of the Circle of Life ( COL ) program in reducing marijuana use among young AI adolescents . COL is a culturally tailored , theory-based human immunodeficiency virus ( HIV ) and sexually transmitted disease ( STD ) intervention shown to delay sexual initiation among AI youths . Methods : We conducted secondary analyses of data from a school-based group r and omized trial conducted between 2006 and 2007 in all 13 middle schools on a rural , Northern Plains reservation ( N = 635 , 47 % female ) . We used discrete-time survival analysis ( DTSA ) to assess COL effectiveness on risk of marijuana initiation among AI youths and latent growth curve modeling ( LGCM ) to evaluate effects on frequency of marijuana use over time . Results : DTSA models showed that the overall risk of marijuana initiation was 17.3 % lower in the COL group compared to the control group . No intervention effect on frequency of marijuana use emerged in LGCM analyses . Conclusion : COL is a multifaceted , culturally tailored , skills-based program effective in preventing marijuana uptake among AI youth This paper reports on the evaluation of a culturally grounded prevention intervention targeting substance use among urban middle-school students . The curriculum consists of 10 lessons promoting antidrug norms and teaching resistance and other social skills , reinforced by booster activities and a media campaign . Three versions were delivered : Mexican American , combined African American and European American , and Multicultural . Thirty-five middle schools were r and omly assigned to 1 of the 3 versions or the control . Students completed baseline and follow-up question naires over a 2-year period ( total 6,035 respondents ) . Analyses utilizing a generalized estimating equations approach assessed the overall effectiveness of cultural grounding and the cultural matching hypothesis . Support was found for the intervention 's overall effectiveness , with statistically significant effects on gateway drug use as well as norms , attitudes , and resistance strategies but with little support for the cultural matching hypothesis . Specific contrasts found the Mexican American and Multicultural versions impacted the most outcomes PURPOSE Toward developing attractive and effective means to reduce cancer risks faced by Native American people , this study developed and tested interactive computer software to improve dietary choices and prevent tobacco use among Native American adolescents . METHODS Based on a legend of the Seneca Nation , a cancer prevention lesson was developed and programmed for software . A sample of 368 Native American adolescents were divided r and omly into intervention and control arms . Youths in both arms were pre-tested , youths in the intervention arm interacted with the software , and all youths were post-tested . Pre-test and post-test measures covered information and attitudes about cancer risks from dietary practice s and tobacco use . RESULTS Pre-test scores differed between the two arms on youths ' age and on one outcome variable . Relative to their counterparts in the control arm , youths in the intervention arm increased their post-test scores on 8 of 12 outcome measurement variables . Process data gathered during intervention delivery indicated that nearly all youths were involved with the interactive software and lesson . CONCLUSION Interactive computer software holds promise for delivering cancer risk reduction intervention aim ed at modifying dietary habits and preventing tobacco use among Native American youth Background The rate of smoking commercial tobacco products among American Indian youth is double the rate for white youth . Interventions are needed to reduce this disparity . Objective To test the feasibility of a Web-based intervention to influence attitudes toward and intentions about smoking cigarettes among American Indian youth who attended a Native summer camp in the Northern Plains . Methods The study website , the SmokingZine , was originally developed and tested in Canadian youth , then adapted to be appropriate for American Indian youth . We conducted a r and omized controlled trial to test the influence of exposure to the adapted SmokingZine website on smoking attitudes and behaviors among American Indian youth 12–18 years of age . Participants assigned to the intervention group were given access to the website for 1 hour per day during their camp experience and asked to sign in to the site and use it . Control group participants were not given access to the site . Results A total of 52 % of intervention youth signed in to the website at least once . Among nonsmokers , intentions to try a cigarette in the intervention group declined from 16 % to 0 % , and increased from 8 % to 25 % in the control group ( P < .05 ) . Compared with the control group , youth in the intervention group were more likely to help others quit ( 21 percentage point change in intervention versus no change in control ; P < .05 ) and had less positive attitudes about the drug effects of smoking ( –0.19 change in intervention versus 0.67 in control ; P < .05 ) . Conclusion These data indicate that SmokingZine needs more long-term , rigorous investigation as a way to keep American Indian youth from becoming regular smokers . Because the intervention group could use computers only 1 hour per day , increasing access might result in more visits and a greater effect of the website on smoking behaviors This article examines changes in the drug resistance strategies used by urban American Indian ( UAI ) middle school students during a pilot test of a substance use prevention curriculum design ed specifically for UAI youth , Living in 2 Worlds ( L2W ) . L2W teaches four drug resistance strategies ( refuse , explain , avoid , leave [ R-E-A-L ] ) in culturally appropriate ways . Data come from 57 UAI students ( 53 % female ; mean age = 12.5 years ) who participated in L2W during an academic enrichment class for Native youth at two Phoenix schools . Students completed a pre-test question naire before the L2W lessons and a post-test 7 months later . Questions assessed the use of R-E-A-L and alternative strategies commonly reported by UAI youth ( change the subject , use humor ) . Tests of mean differences from pre-test to post-test showed significant increases in use of refuse , explain , and leave , and an exp and ing R-E-A-L repertoire . Use of more passive strategies ( avoid , use humor ) did not change significantly , except for change the subject , which increased . Changes in the use of strategies did not differ significantly by gender , age , school grade s , parental education , or length of urban residence . The L2W curriculum appears effective in teaching culturally relevant communication strategies that exp and UAI youths ' repertoire of drug resistance skills This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth . After completing pretest measurements , 1,396 third- through fifth- grade Native American students from 27 elementary schools in five states were divided r and omly by school into two intervention arms and one control arm . Following intervention delivery , youths in all arms completed posttest measurements and three annual follow-up measurements . Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention . One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth . Outcome assessment batteries measured youths ' reported use of smoked and smokeless tobacco , alcohol , and marijuana . Over the course of the 3.5-year study , increased rates of tobacco , alcohol , and marijuana use were reported by youths across the three arms of the study . Though cigarette use was unaffected by intervention , follow up rates of smokeless tobacco , alcohol , and marijuana use were lower for youths who received skills intervention than for youths in the control arm . Community intervention components appeared to exert no added beneficial influence on youths ' substance use , beyond the impact of skills intervention components alone . Finally , gender differences were apparent across substances , measurements , and study arms , with girls smoking more cigarettes and boys using more smokeless tobacco , alcohol , and marijuana Objectives To evaluate the effectiveness of a multilevel intervention design ed to prevent underage alcohol use among youths living in the Cherokee Nation . Methods We r and omly assigned 6 communities to a control , Communities Mobilizing for Change on Alcohol ( CMCA ; a community-organizing intervention targeting alcohol access ) only , CONNECT ( a school-based universal screening and brief intervention ) only , or a combined condition . We collected quarterly surveys 2012 - 2015 from students starting in 9th and 10th grade s and ending in 11th and 12th grade s. Response rates ranged from 83 % to 90 % ; 46 % of students were American Indian ( of which 80 % were Cherokee ) and 46 % were White only . Results Students exposed to CMCA , CONNECT , and both showed a significant reduction in the probability over time of 30-day alcohol use ( 25 % , 22 % , and 12 % reduction , respectively ) and heavy episodic drinking ( 24 % , 19 % , and 13 % reduction ) compared with students in the control condition , with variation in magnitude of effects over the 2.5-year intervention period . Conclusions CMCA and CONNECT are effective interventions for reducing alcohol use among American Indian and other youths living in rural communities . Challenges remain for sustaining intervention effects |
10,810 | 23,426,599 | Results show that , for many aspects of the h and -sewn colorectal anastomosis technique , evidence is lacking .
A single-layer continuous technique using inverting sutures with slowly absorbable monofilament material seems preferable .
However , in contrast to stapled and compression colorectal anastomoses , the technique for h and -sewn colorectal anastomoses is nonst and ardized with regard to intersuture distance , suture distance to the anastomotic edge , and tension on the suture . | Many different techniques of colorectal anastomosis have been described in search of the technique with the lowest incidence of anastomotic leak .
A systematic review of leak rates of techniques of h and -sewn colorectal anastomosis was conducted to provide a guideline for surgical residents and promote st and ardization of its technique . | A controlled evaluation of a single‐layer everting technique of suture versus a conventional two‐layer inverting technique has been attempted in clinical large‐bowel surgery . Thirty‐five patients suffering from carcinoma or other diseases of the large intestine were allocated r and omly to each technique in the conduct of various forms of colonic resection with anastomosis or closure of a transverse colostomy . There were 3 operative deaths after everting suture and 1 after inverting suture , all attributable mainly to anastomotic failure . A higher proportion of patients developed wound infection or peritonitis after everting than inverting suture—51 as against 35 per cent . Overt faecal fistulation was observed in no less than 43 per cent of the patients having everting suture , but in only 8·6 per cent of those treated by inverting suture . Late stricture formation was noted in 2 cases after everting suture , but in none after inverting suture BACKGROUND AND AIMS Sphincter-saving procedures for resection of mid and , in some cases , of distal rectal tumors have become prevalent as their safety have been established . Increased anastomotic leak rate , associated with the type of anastomosis and the distance from the anal verge , has been reported . To compare surgical outcomes of end-to-end and end-to-side anastomosis after anterior resection for T1-T2 rectal cancer . METHODS During the study period , a total of 298 rectal cancer patients were treated . Patients with T1-T2 rectal cancer ( i.e. , tumor level < or = 15 cm from the anal verge ) fit for surgery were asked to participate in the study . Patients were r and omized to receive either an end-to-end anastomosis or an end-to-side anastomosis using the left colon . Surgical results and complications were recorded . RESULTS Seventy-seven patients were r and omized . Thirty-seven end-to-end anastomoses and 40 end-to-side anastomoses were performed . Anastomotic leakage after end-to-end anastomosis was 29.2 % , while after end-to-side anastomosis was 5 % ( P = 0.005 ) . In the end-to-end group 11 patients had anastomotic leaks : nine patients needed a re-intervention with colostomy creation subsequently closed in seven cases . Two patients of the end-to-side group experienced anastomotic leakage and were successfully treated conservatively . CONCLUSIONS Regarding postoperative surgical complications , end-to-side anastomosis is a safe procedure Abstract . This study represents a European prospect i ve clinical multicenter trial and was undertaken to evaluate the applicability of the biofragmentable anastomosis ring ( BAR ) as a routine anastomotic tool in teaching hospitals . The trial results analyzed consisted of 1666 BAR anastomoses performed in 1360 patients from March 1989 to May 1996 in the upper ( 1042 anastomoses ) and lower ( 624 anastomoses ) gastrointestinal ( GI ) tract . Only patients selected for elective procedures and having previously undergone ortho grade bowel cleansing were entered into the trial . In the upper GI tract six anastomoses ( 0.58 % ) developed clinical ly relevant and radiologically detectable leaks with indications for reoperation . In the lower GI tract 42 ( 6.73 % ) anastomoses showed a radiologically detectable leak with clinical manifestations in 28 cases ( 4.48 % ) . Reoperation was performed in 18 cases ( 2.80 % ) . The overall leakage rate with clinical relevance was 2.04 % . Three gastrojejunostomy episodes of bleeding were observed ( 0.18 % ) at the BAR anastomotic site . During the early postoperative course there was no ileus due to obstruction of a BAR anastomosis . Re introduction of diet after the operation was not delayed . In two centers a follow-up evaluation reported no BAR-related late anastomotic stenoses . There were no intraoperative deaths , but 54 patients died postoperatively . Peritonitis following anastomotic leakage was responsible for postoperative deaths in four cases ; three of them were related to BAR anastomoses . In conclusion , the BAR anastomotic procedure is an established , rapid , simple to learn , highly st and ardized , safe technique with the advantage of no persistent foreign material in the anastomotic region and therefore no induction of stenosis . At present , the application of anastomoses in various segments of the GI tract , from the stomach to the middle third of the rectum , can be recommended Objective The authors compared both the initial and the long-term outcomes of patients undergoing stapled and sutured colorectal anastomoses . Summary Background Data Summary Background Data and stapled large bowel anastomoses are perceived to be equally safe , but concern has been raised about increased rates of tumor recurrence with the use of stapling instruments . Methods The outcome of patients with sutured and stapled colorectal anastomoses were compared in a prospect i ve , multicenter , r and omized study . Factors affecting long-term outcomes were assessed by both univariate and multivariate analysis . Results Results hundred thirty-two patients were recruited . There was a significant increase in radiologic leakage in the sutured group ( 14.4 % vs. 5.2 % , p < 0.05 ) , but there was no difference in clinical anastomotic leak rates , morbidity , or postoperative mortality . Tumor recurrence and cancer-specific mortality were higher in the sutured patients ( 7.5 % and 6.7 % , respectively ) and in patients with anastomotic leaks . Conclusions Conclusions study shows that suturing or stapling are equally safe in large bowel surgery . However , it also shows a long-term benefit of stapling in colorectal cancer patients OBJECTIVE To find out if there were any differences in postoperative complications and anastomotic leak rate between sutured and stapled anastomoses after bowel resection in patients exposed to the same preoperative management programme . DESIGN Prospect i ve observational non-r and omised study . SETTING Colorectal unit , Sweden . PATIENTS Between 1996 and 2000 bowel resections with anastomosis were done for 42 consecutive patients with Crohn 's disease . 20 patients had their anastomoses sutured ( sutured group ) and 22 had their anastomosis stapled ( stapled group ) over two successive periods . MAIN OUTCOME MEASURES Postoperative complications and anastomotic leak rate . RESULTS None of the patients were on immunosuppressive treatment and about half in each group had had several weeks of preoperative enteral nutrition . No anastomotic-related complications and few other postoperative complications were noted , irrespective of the anastomotic technique used . CONCLUSION A strategy to operate on Crohn patients without steroids and , if indicated , treated preoperatively with enteral nutrition and percutaneous drainage of abscesses result ed in no anastomotic leaks and few postoperative complications . These results were independent of the anastomotic technique used INTRODUCTION Although intestinal anastomoses are mainly made by staplers , manual anastomoses are still in use worldwide . In previous studies , single layer anastomosis has shown better results compared to double layer techniques . PURPOSE To test experimentally some aspects of three different single layer anastomotic techniques in order to identify advantages and disadvantages of each . MATERIAL AND METHODS The study was done on Sprague Dawley rats . Animals were r and omly divided into four groups . Three experimental groups consisted of 21 animals each , and the fourth sham group contained 10 animals . By 7 animals of each group were sacrificed on the 4th and the rest of 14 animals on the 7th postoperative day . In all groups the resected distal part of the colon was anastomosed using Halsted , Gambee and Gambee-Halsted technique . To evaluate each specific technique the following were used : postoperative complication frequency , biomechanical measurements , adhesion density , condition of intestinal lumen and histological parameters of the healing process . RESULTS The complication frequency was not significantly different between the tested techniques . The average bursting pressure and tensile strength were higher on both the 4th and 7th postoperative days with the Gambee technique . In the colon segments removed on the 4th postoperative day 97 % of pressure induced ruptures occurred in the anastomotic line , whereas on the 7th postoperative day 76 % of ruptures occurred about 1 cm distal to the anastomotic line . CONCLUSION The Gambee technique had significantly better biomechanical and histological results compare to the other two anastomotic techniques . Adhesion density was significantly lower in the control group ( p<0.001 ) 272 patients underwent r and omly 133 h and sewn anastomosis and 139 stapled anastomosis ( 159 proximal and 119 distal ) after elective colorectal resection for 194 carcinomas , and 78 sigmoid diverticulosis and benign tumors . Both groups were comparable with regard to mortality ( 3.3 p. cent ) , wound abcesses ( 3 p. cent ) extra abdominal post operative complications ( 20 p. cent ) . There were however more reoperations in the stapled group ( 10 versus 6 ) , and also more low intestinal anastomotic bleeding ( 9 versus 5 ) . Stapled anastomosis were associated with less clinical fistulas ( 8 p. cent versus 12 p. cent ) and only after low colorectal anastomosis ( 9 p. cent versus 20 p. cent ) . Stapling devices decrease the duration of the anastomosis by 8 mn , but this gained time does not influence the total duration of the operation . These advantages must be weighed against the risks inherent to their uses , mishaps ( 14 p. cent ) , hemorrhages ( 6.5 p. cent ) , strictures ( 8 p. cent ) , and their higher cost ( 15 times as much ) In a r and omized prospect i ve clinical trial one layer and two layer techniques have been compared in 92 patients undergoing colorectal anastomosis . The results were assessed radiologically by barium studies on the tenth postoperative day . There was no significant difference in the incidence of anastomotic breakdown with either technique when the anastomosis was performed above the pelvic peritoneal reflection . When the anastomosis was situated below the pelvic peritoneum the incidence of dehiscence was significantly greater when a two layer technique was used BACKGROUND Although used widely for supraperitoneal anastomoses , circular stapled anastomoses have never been proved better than h and -sewn anastomoses . In the one prospect i ve controlled trial that studied these anastomoses specifically , the only significant difference found was that there were more clinical ly obvious leakages with the circular stapled variety , but not in the overall clinical and roentgenologic leakage rates . METHODS One hundred fifty-nine consecutive patients ( 88 men and 71 women , mean age 65.8 + /- 12.1 years ) were r and omized to undergo h and -sewn ( n = 74 ) or circular stapled ( n = 85 ) supraperitoneal colorectal anastomosis after left colectomy . RESULTS Patient demographics were similar in both groups . Overall mortality was 1.3 % ( 2 of 159 ; one in each group ) . No statistically significant difference ( NS ) was found in the rate of early complications , including anastomotic leakage ( 4 of 74 versus 6 of 85 ) in the h and -sewn and stapled anastomoses , respectively ) . Mishaps ( n = 10 ) and hemorrhage ( n = 5 ) occurred in the stapled group only . Stapled anastomoses took an average of 8 minutes less to perform ( p < 0.001 ) , but this time gain did not significantly influence the overall duration of operation ( identical median times ) . The median duration of hospitalization was 13 and 14 days , respectively ( NS ) . At 8 months there were 2 of 74 strictures in the h and -sewn group and 4 of 85 strictures in the stapled group ( NS ) . CONCLUSIONS According to these results , there seems to be no advantage of routine or regular use of stapling instruments for supraperitoneal colorectal anastomosis Anastomotic leakage is a major complication of rectal cancer surgery . The aim of this study was to investigate risk factors associated with symptomatic anastomotic leakage after total mesorectal excision ( TME ) The aim of this retrospective non‐r and omized study was to evaluate the short‐term functional outcome following elective resectional surgery for complicated sigmoid diverticular disease , and to compare results of patients having h and ‐sewn or stapled end‐to‐end colonic anastomosis to the proximal rectum The merits of stapled versus h and sewn anastomosis were evaluated in a prospect i ve r and omized study of 60 patients undergoing resection for rectal cancer . The analysed factors included the time required for construction of anastomosis , post operative complications , local recurrence , disease free state and survival . H and sewn anastomosis was performed in two layers with 3/0 silk in 30 cases and the stapled anastomosis with EEA staplers in 30 cases . The anastomosis time averaged 24 minutes in the suture group and 16 minutes in the stapling group . Five post-operative complications occurred in each group . Six patients of the h and sewn group developed local recurrence as a first sign of treatment failure compared to four patients in the stapled group . The average time of study was 41 months . No significant difference was found in the overall survival pattern of the two groups BACKGROUND Controversy still exists concerning the impact of patient and tumor characteristics on anastomotic dehiscence after resection for rectal cancer . METHODS Between January 1986 and July 2006 , 472 patients underwent curative rectal resection . Patient and tumor characteristics , details of treatment , and postoperative results were recorded prospect ively . Univariate and multivariate analysis were applied to identify risk factors for anastomotic leakage . RESULTS In our patients , the anastomotic leak rate was 10.4 % ( 49 of 472 patients ) , and mortality was 2.2 % ( 1 of 49 patients ) . In univariate analysis , tumor diameter and absence of a protective stoma were associated with increased anastomotic leak rate , whereas American Society of Anesthesiologists ( ASA ) score and tumor localization showed borderline significance . In multivariate analysis , tumor diameter , tumor localization , and absence of a protective stoma were significantly associated with anastomotic leakage . CONCLUSIONS Patients with large and low lying rectal tumors are at high risk for anastomotic leakage . A protective stoma significantly decreases the rate of clinical leaks and subsequent reoperation after low anterior resection Pre clinical animal studies have clearly indicated that dyed and undyed polydioxanone monofilament absorbable sutures have prolonged breaking strength retention , a reliable absorption profile and minimal tissue reaction . The suture provides wound support throughout extended postoperative periods and is most useful in those situations in which prolonged suture integrity is desirable . Based upon these clinical studies , polydioxanone monofilament absorbable sutures must be considered as a reliable , easy to use suture material which fulfills all performance criteria . The over-all clinical results were excellent . Polydioxanone was rated as significantly superior to gut in every category evaluated . The results of this study support the cl aim that polydioxanone monofilament absorbable sutures are the suture of choice for general surgical use as well as in a variety of other clinical applications in which an absorbable suture is required One hundred and eighteen patients undergoing low colorectal anastomoses were r and omly allocated to reconstitution by either single layer interrupted extramucosal sutures or circular staple gun . In the 60 patients undergoing sutured anastomosis there were 2 ( 3 per cent ) clinical leaks and 4 ( 7 per cent ) radiological leaks , and no failures of the 58 patients who underwent stapled anastomosis there were 4 failures , 7 ( 12 per cent ) clinical leaks , 14 ( 24 per cent ) radiological leaks and 1 death . Stapled anastomoses were more than ten times as expensive as sutured anastomoses and there were no savings in time or numbers of associated colostomies . An interrupted extramucosal suture technique remains the ultimate st and ard for low colorectal anastomosis BACKGROUND Disagreement continues among several studies as to the relative advantages and disadvantages of stapled versus sutured colorectal anastomoses . METHODS One hundred and thirteen consecutive patients ( 48 men and 65 women , mean age : 67 + /- 12 years ) were r and omized to either h and -sewn ( n = 59 ) or stapled ( n = 54 ) infraperitoneal colorectal anastomosis . Both groups had similar patient demographics except that fewer patients ( 4 versus 15 ) had chronic disease ( p < 0.02 ) and were undergoing side-to-end ( 11 versus 39 ) and more patients were undergoing end-to-end ( 37 versus 20 ) anastomosis in the stapled group ( p < 0.001 ) . RESULTS Overall mortality was 6 % ( 7 of 113 patients ) , with no difference found between the two types of anastomosis . Fewer anastomotic leaks occurred in the stapled group ( 11 versus 7 ) , with an a posteriori gamma error of 11 % , whereas the other early postoperative complications occurred with similar frequency in the two groups . Nine mishaps occurred in the stapled group . Stapled anastomoses took less time ( median , 42 versus 30 minutes ) to perform ( p < 0.02 ) . At 8 months , two strictures occurred in the h and -sewn group ( n = 52 ) compared with eight strictures in the stapled group ( n = 50 ) ( p < 0.001 ) . CONCLUSIONS It was not possible to prove that lower anastomosis can be achieved with the stapling device . Routine or regular use of stapling instruments for infraperitoneal colorectal anastomosis can not be advocated because of higher incidence of mishaps and strictures , even though the operation takes less time to perform and anastomotic leakage occurs less often Two hundred and fifty patients undergoing elective surgical treatment involving anastomoses of the left side of the colon or colon and rectum have been studied in a r and omized trial in which the EEA ( U. S. Surgical Corp. ) circular stapler has been compared with single layer sutured anastomoses . Only patients in whom either technique was feasible were included in the analysis . The operative techniques were largely st and ardized . Patients were studied by means of a limited barium enema on the ninth or tenth postoperative day . The data have been analyzed for leakage rate ( clinical and roentgenologic ) , other complications and degree of experience of the surgeon . Eleven patients were excluded from the analysis because the selected technique could not be carried out ; of these , eight were in the stapled group in which it was possible to perform a sutured anastomosis . There were no instances in which it was possible to staple but not possible to suture . The remaining three exclusions were patients in whom either a coloanal anastomosis or a Hartmann procedure was performed . There was no over-all difference in the leakage rate -- roentgenologic , clinical or total -- between the two groups . However , when analyzed by the surgeon , the clinical leakage rate for surgeons in training was greater for sutured anastomoses than for stapled anastomoses ( p = 0.053 ) . Thus , it appears that the benefits of experience are more pronounced for sutured anastomoses but that , in experienced h and s , neither technique is superior Objective : The aim of this r and omized multicenter trial was to assess the rate of symptomatic anastomotic leakage in patients operated on with low anterior resection for rectal cancer and who were intraoperatively r and omized to a defunctioning stoma or not . Summary Background Data : The introduction of total mesorectal excision surgery as the surgical technique of choice for carcinoma in the lower and mid rectum has led to decreased local recurrence and improved oncological results . Despite these advances , perioperative morbidity remains a major issue , and the most feared complication is symptomatic anastomotic leakage . The role of the defunctioning stoma in regard to anastomotic leakage is controversial and has not been assessed in any r and omized trial of sufficient size . Methods : From December 1999 to June 2005 , a total of 234 patients were r and omized to a defunctioning loop stoma or no loop stoma . Loop ileostomy or loop transverse colostomy was at the choice of the surgeon . Inclusion criteria for r and omization were expected survival > 6 months , informed consent , anastomosis ≤7 cm above the anal verge , negative air leakage test , intact anastomotic rings , and absence of major intraoperative adverse events . Results : The overall rate of symptomatic leakage was 19.2 % ( 45 of 234 ) . Patients r and omized to a defunctioning stoma ( n = 116 ) had leakage in 10.3 % ( 12 of 116 ) and those without stoma ( n = 118 ) in 28.0 % ( 33 of 118 ) ( odds ratio = 3.4 ; 95 % confidence interval , 1.6–6.9 ; P < 0.001 ) . The need for urgent abdominal reoperation was 8.6 % ( 10 of 116 ) in those r and omized to stoma and 25.4 % ( 30 of 118 ) in those without ( P < 0.001 ) . After a follow-up of median 42 months ( range , 6–72 months ) , 13.8 % ( 16 of 116 ) of the initially defunctioned patients still had a stoma of any kind , compared with 16.9 % ( 20 of 118 ) those not defunctioned ( not significant ) . The 30-day mortality after anterior resection was 0.4 % ( 1 of 234 ) and after elective reversal a defunctioning stoma 0.9 % ( 1 of 111 ) . Median age was 68 years ( range , 32–86 years ) , 45.3 % ( 106 of 234 ) were females , 79.1 % ( 185 of 234 ) had preoperative radiotherapy , the level of anastomosis was median 5 cm , and intraoperative blood loss 550 mL , without differences between the groups . Conclusion : Defunctioning loop stoma decreased the rate of symptomatic anastomotic leakage and is therefore recommended in low anterior resection for rectal cancer A polyglycolic acid device has been design ed for the performance of sutureless colonic anastomoses . The use of this biofragmentable anastomosis ring ( BAR ) was compared with conventional techniques in a prospect i ve , r and omized study of 59 patients ( x age , 49 years ) undergoing ileocolostomy ( n = 23 ) or colocolostomy ( n = 36 ) . The anastomotic technique was determined at surgery by r and omization ( BAR , 27 patients ; suture , 16 patients ; staple , 16 patients ) . Performance of an anastomosis with the BAR required an average of 22 minutes , a stapled anastomosis required 33 minutes , and the suture technique required 37 minutes . Learning curve error contributed to the six intraoperative complications that occurred with performance of the anastomosis ( BAR , three ; end-to-end anastomosis [ EEA ] instrument , three ) . The two postoperative deaths were unrelated to the anastomosis . Length of hospitalization in uncomplicated patients was the same among the three groups . The 17 patients with prolonged hospitalization had complications unrelated to anastomotic technique . All patients were followed for a minimum of 6 weeks ; no additional complications were identified . We concluded that 1 ) the BAR is a rapid , safe method for performance of sutureless anastomoses ; 2 ) perioperative mortality and morbidity rates of the BAR are comparable to conventional techniques of suture and staple ; and 3 ) long-term follow-up of BAR patients is warranted to determine the incidence of complications , such as structure and /or stenosis BACKGROUND Single-layer intestinal anastomoses have been constructed conventionally using an interrupted suture technique . It is however , increasingly popular to perform such anastomosis using a continuous suture . METHODS One hundred and eighty consecutive patients with 254 continuous single-layer anastomoses performed over a 4 year period were included in the study . Sixty-one patients underwent oesophagectomy , oesophageal bypass or gastrectomy , 32 underwent biliary bypass , hepatic , biliary or pancreatic resection and 88 had colorectal operations . The median age was 67 years . RESULTS There were 254 anastomoses of which four leaked ( 1.6 % ) . Fifteen patients ( 8.3 % ) died in hospital . CONCLUSION These results show that the single-layer continuous suture technique is safe in gastrointestinal anastomoses Abstract Several studies have shown a lower rate of anastomotic leakages in patients with coloanal J-pouch reconstruction than in those with straight coloanal anastomosis following anterior resection of the rectum . This study investigated whether this difference is due to a better anastomotic microcirculation . Thirty-two healthy , adult Göttinger mini-pigs underwent anterior rectal resection . They were subsequently r and omized to following four groups ( eight pigs per group ) : straight end-to-end , side-to-end , small pouch ( 4 cm ) , and large pouch ( 8 cm ) coloanal anastomosis . Bowel perfusion was measured before and after vessel ligature at predefined locations using laser Doppler flowmetry . After completion of the anastomosis microcirculation was investigated 1 cm above , below , and directly at the anastomotic site . Following vessel ligature there was a 25 % drop in blood flow . After completion of the anastomosis there was a further decrease of 25 % in the distal segment , while no changes were observed above the anastomosis . There were no statistical differences either before or after completion of the anastomosis between the various groups . It is concluded that anastomotic blood flow does not depend on the type of coloanal reconstruction in healthy pigs Purpose : Anastomotic leaks are among the most dreaded complications after colorectal surgery . However , problems with definitions and the retrospective nature of previous analyses have been major limitations . We sought to use a prospect i ve data base to define the true incidence and presentation of anastomotic leakage after intestinal anastomosis . Methods : A prospect i ve data base of two colorectal surgeons was review ed over a 10-year period ( 1995–2004 ) . The incidence of leak by surgical site , timing of diagnosis , method of detection , and treatment was noted . Complications were entered prospect ively by a nurse practitioner directly involved in patient care . St and ardized criteria for diagnosis were used . A logistic regression model was used to discriminate statistical variation . Results : A total of 1223 patients underwent resection and anastomosis during the study period . Mean age was 59.1 years . Leaks occurred in 33 patients ( 2.7 % ) . Diagnosis was made a mean of 12.7 days postoperatively , including four beyond 30 days ( 12.1 % ) . There was no difference in leak rate by surgeon ( 3.6 % vs. 2.2 % ; P = 0.08 ) . The leak rate was similar by surgical site except for a markedly increased leak rate with ileorectal anastomosis ( P = 0.001 ) . Twelve leaks were diagnosed clinical ly versus 21 radiographically . Contrast enema correctly identified only 4 of 10 leaks , whereas CT correctly identified 17 of 19 . A total of 14 of 33 ( 42 % ) patients had their leak diagnosed only after readmission . Fifteen patients required fecal diversion , whereas 18 could be managed nonoperatively . Conclusions : Anastomotic leaks are frequently diagnosed late in the postoperative period and often after initial hospital discharge , highlighting the importance of prospect i ve data entry and adequate follow-up . CT scan is the preferred diagnostic modality when imaging is required . More than half of leaks can be managed without fecal diversion PURPOSE : Functional outcome after low anterior resection with side-to-end anastomosis is comparable with that after a colonic J-pouch construction . The optimum size of the side limb has yet to be determined . This prospect i ve r and omized trial compared a 3-cm ( short ) and 6-cm ( long ) side limb . METHODS : Forty-four patients with a mid or low rectal cancer undergoing low anterior resection were r and omly assigned to each group . Physiologic and clinical assessment s were performed preoperatively and at 3 , 6 , and 12 months after ileostomy closure . Defecography was performed at six months after ileostomy closure . RESULTS : Twenty patients in each group completed the study . Among them , one patient with a short limb and two others with a long limb developed leakage . Sphincter function and reservoir function were similar between the groups . Bowel function or incontinence scoring was similar between the groups . The incidence of incomplete evacuation assessed by defecography in the long limb group was significantly greater than in the short limb group ( 13/20 long and 5/20 short , P = 0.025 ) . One patient in the long limb group experienced fecal impaction . CONCLUSION : The study showed similar clinical results in patients with either a short limb or a long limb but seemed to be underpowered . A long limb may be associated with fecal impaction in patients undergoing low anterior resection with side-to-end anastomosis INTRODUCTION Anastomotic leakage is a major complication of colorectal surgery causing a significant increase in 30-day mortality . The long-term prognosis of anastomotic leakage is poorly documented . This study was design ed to assess whether anastomotic leakage affects five-year survival and local recurrence . METHODS A total of 5,173 patients were recruited to the Wessex Colorectal Cancer Audit during the period September 1991 to August 1995 ( prospect i ve data , 5-year follow-up ) . The effect of anastomotic leakage on five-year survival and local recurrence was analyzed using Kaplan-Meier curves and the log-rank test . RESULTS A total of 1,834 patients underwent a curative resection with an anastomosis ( anastomotic leak = 71 ; 3.9 percent ) : 30-day mortality : 18.3 percent in the leak group , and 3.5 percent in the nonleak group ( P < 0.001 ) ; local recurrence : 19 percent in the leak group , and 9.8 percent in the nonleak group ( P = 0.018 ) . A total of 1,201 patients underwent colonic anastomosis ( anastomotic leak = 31 ; 2.6 percent ) . There was no significant difference in local recurrence or five-year survival between the leak and nonleak groups . A total of 633 patients underwent rectal anastomosis ( anastomotic leakage = 40 ; 6.3 percent ) : 30-day mortality : 10 percent in the leak group , and 2 percent in the nonleak group ( P = 0.014 ) ; cumulative five-year estimate of local recurrence : 25.1 ( 95 percent confidence interval , 9.6–40.5 ) percent in the leak group , and 10.4 ( 95 percent confidence interval , 7.7–13 ) percent in the nonleak group ( P = 0.007 ) . Cumulative five-year estimate of overall survival : 52.8 ( 95 percent confidence interval , 36.1–69.4 ) percent in the leak group , and 63.9 ( 95 percent confidence interval , 59.9–67.9 ) percent in the nonleak group ( P = 0.19 ) . CONCLUSIONS After rectal anastomosis , an anastomotic leak is associated with a significant increase in local recurrence We present results obtained in a group of patients included in a r and omized study from 1979 to 1985 for evaluation of mechanical anastomosis after anterior resection for cancer of the rectum ; 113 patients were operated on , 58 with manual and 55 with instrumental anastomosis . There was no significant difference in morbidity or mortality between the groups . The incidence of anastomotic fistulas ( clinical and sub clinical ) was similar ( 12 % vs. 15 % ) , although a large number of tumors in the lower third of rectum was treated by manual anastomosis . Concerning late complications , more stenoses , although mainly asymptomatic , were detected after instrumental anastomosis ( 15 % vs. 6 % ) . The incidence of local recurrence within 3 years was quite similar in the 2 groups ( about 15 % ) , and usually occurred in patients who already had generalized disease There are scant experimental data directly comparing the healing of the circular-stapled ( CS ) anastomotic technique with the st and ard Czerny-Lembert two-layer h and sewn ( HS ) anastomotic technique during the acute and chronic phases of healing . The purpose of this study , therefore , was toseriallyevaluate wound healing in CS and HS anastomoses in the normal porcine colorectum . Forty-two adult female mixed-breed pigs r and omly under-went either HS or CS anastomosis at the sacral promontory . Laser Doppler velocimetry ( LDV ) was used to measure perianastomotic blood flow . Groups of animals under-went a second surgery at 3 , 5 , 11 , 60 , or 120 days postoperatively , and anastomoses were restudied using LDV , gross and microscopic grading of inflammation , bursting pressures , and hydroxyproline content . Additionally , the 60-day and 120-day groups of animals under-went preoperative biplanar barium enemas to identify leaks or stenoses . No significant differences in perianastomotic blood flow between the HS and CS techniques were obtained over the entire 120-day study period . Serial evaluation of wound healing revealed no significant differences between the two anastomotic techniques with respect to bursting pressures , gross or microscopic inflammatory scores , or hydroxyproline content . There were no leaks or stenoses with either technique . Despite earlier reports to the contrary , there appears to be no fundamental difference in the mode of healing in the porcine colorectum comparing the HS technique with the CS technique BACKGROUND The fear of anastomotic complications prevents the spread of the use of the biofragmentable anastomosis ring ( BAR ) in intestinal surgery . PATIENTS AND METHODS A total of 453 patients underwent intestinal resection and anastomosis with the BAR . RESULTS In all , 514 anastomoses have been carried out , 424 ( 83 % ) in elective setting s , and 90 ( 18 % ) in emergency . Fifty-one patients had multiple anastomoses . Reoperation was performed in 4 patients ( 1 % ) who had a complete anastomotic leakage . In 13 patients ( 3 % ) , anastomotic leakage was partial , and only 1 patient required reoperation . No postoperative intestinal obstruction occurred . Four patients ( 1 % ) developed late anastomotic strictures , which have been treated by endoscopic dilation . CONCLUSIONS The results of our experience and those of other large clinical series definitely confirm the effectiveness of the BAR method , which seems to be a st and ard , easy , rapid , and safe technique either in elective or emergency surgery Mortality rates from the Large Bowel Cancer Project are presented with special reference to patients older than 70 years . The in-hospital mortality rate among those who underwent curative resection for colorectal carcinoma was 7 % . Unlike long-term prognosis , which is influenced by pathological features , in-hospital mortality is influenced largely by clinical factors . Age was an adverse factor ( 78 % of deaths occurred among those aged over 70 , who formed 46 % of the study population ) , as was obstruction or perforation . 55 % of deaths were due to cardiopulmonary complications . Educating patients to seek treatment early , careful preoperative assessment and postoperative monitoring of cardiopulmonary function , and , in selected patients , use of local treatments rather than wide resections may help to reduce mortality in elderly patients A r and omized , prospect i ve study should be done to evaluate any new procedure or instrument . Our experience with the end-to-end anastomosis ( EEA ) stapler suggests that an anastomosis can be created in a shorter time than is required for the traditional h and -sewn technique . This difference is even greater when the anastomosis is technically difficult and located deep within the pelvis . There appears to be little difference in the security of a h and -sewn anastomosis compared with that of stapled anastomosis . Postoperative complications appear similar . With the stapler , however , there is an increased risk of intraoperative complications that are not apparent with the traditional h and -sewn technique . These include rectal tears and anastomotic defects . It appears that the EEA stapler can save as many as 12 percent of rectums that otherwise might have to be removed because of technical inability to perform an anastomosis Background Biofragmentable anastomosis ring ( BAR ) has been proven to be a safe anastomotic device in elective surgery . The use of this anastornotic ring in high‐risk patients has not been established Performance of low , anterior colorectal anastomosis by means of stapled end-to-end anastomoses and h and sutures was achieved in 51 patients . Among the 26 stapled anastomoses , leakage and external fistula were observed in two cases , but subsequent surgery has never been necessary . Conversely , h and sutures were associated with external fistula again in two cases , but leakage and peritonitis were observed in two other cases . It is suggested that stapled anastomoses are at least as reliable as sutured , colorectal anastomoses . Moreover , the stapling device enables the surgeon not only to extend the range of anterior resection to lower tumors but also to extend the level of resection below the tumor The merits of mechanical versus manual anastomosis were evaluated in a prospect i ve study of 48 patients undergoing resection of colonic or rectal cancer . The analyzed factors included the time required for construction of the anastomosis , the length of hospital stay , the cost/benefit ratio and complications . The anastomosis was manually performed with monolayer polyglactin 910 sutures in 24 cases and mechanically with an E.E.A. stapler in 24 . The anastomosis time averaged 14 min in the suture group and 14.3 min in the stapling group , and the respective hospitalization times were 16 and 17 days . The mean cost was 48,000 lire in the manual , and 200,000 lire in the mechanical group . Four complications occurred in each group . Apart from the cost , no intergroup difference was statistically significant PURPOSE Anastomotic configuration may influence anastomotic leak rates . The aim of this study was to determine whether a side-to-side stapled ileocolonic anastomosis produces lower anastomotic leak rates than those with a h and sewn end-to-end ileocolonic anastomosis after ileocecal or ileocolonic resection for Crohn ’s disease . METHODS A series of 122 consecutive patients underwent elective ileocecal or ileocolonic resection with ileocolonic anastomosis for Crohn ’s disease from January 1998 to June 2003 : 71 had h and sewn end-to-end anastomosis and 51 had side-to-side stapled anastomosis . The choice between the two anastomoses was left to the surgeon ’s preference . A retrospective analysis was performed to assess if there was any difference in anastomotic leak rates . RESULTS The two groups were comparable in terms of age , gender , preoperative presence of abscess or fistula , history of smoking , and albumin levels . More patients were taking steroids in the h and sewn group than in the stapled group . In the h and sewn group there were 10 anastomotic leaks ( 14.1 percent ) and in the stapled group there was 1 anastomotic leak ( 2.0 percent ) ( risk difference , + 12.1 percent ; 95 percent confidence interval , 1.7–22.2 ; P = 0.02 ) . Anastomotic configuration was the sole variable that influenced anastomotic leak rates at univariate analysis . Mortality was 1.4 percent in the h and sewn group and 0 percent in the stapled group . Complications other than anastomotic leak developed in 11 patients in the h and sewn group and in 6 patients in the stapled group . Mean postoperative hospital stay was 12.3 days in the h and sewn group and 9.7 days in the stapled group ( P = 0.03 ) . Excluding those patients who had an anastomotic leak , the difference was still present ( h and sewn group , 10.1 days ; stapled group , 9.1 days ; P = 0.04 ) . CONCLUSION Although confirmation from r and omized , controlled trials is required , side-to-side stapled anastomosis seems to substantially decrease anastomotic leak rates in surgical patients with Crohn ’s disease , compared with h and sewn end-to-end anastomosis . Postoperative hospital stay decreased in the stapled anastomosis group , and this was not entirely a result of decreased anastomotic leak rates Objective : The objective of this study was to investigate prophylactic pelvic drainage and other factors that might be associated with anastomotic leakage after elective anterior resection of primary rectal cancer . Summary Background Data : Anastomotic leak after anterior resection for primary rectal cancer leads to significant postoperative morbidity and mortality . The role of pelvic drainage in the prevention of anastomotic leakage is controversial . Methods : We investigated 978 consecutive patients undergoing elective anterior resection for primary rectal cancer between February 1995 and December 1998 in a single institution . Use of a drain and type of drainage were at the surgeon 's preference . Data were prospect ively collected during hospitalization . Twenty-five independent tumor- , patient- , and treatment-related variables were analyzed . The dependent variable was clinical anastomotic leakage . A binary logistic regression analysis was used to assess the independent association of variables with the dependent variable . Results : The clinical anastomotic leakage rate was 2.8 % . Independent risk factors for anastomotic leakage were use of an irrigation – suction drain ( odds ratio [ OR ] , 9.13 ; 95 % confidence interval [ CI ] , 1.16–71.76 ) , blood transfusion , poor colon preparation ( OR , 2.58 ; 95 % CI , 1.10–5.88 ) , and anastomotic level 5 cm or less from the anal verge ( OR , 2.38 ; 95 % CI , 1.03–5.46 ) . Conclusions : Routine use of pelvic drainage is not justified and should be discouraged . In cases in which pelvic drainage is required such as in difficult operations or to prevent pelvic hematoma , pelvic drainage other than irrigation – suction should be considered The Biofragmentable Anastomosis Ring ( BAR ) is a device , which originally has been design ed for sutureless large bowel anastomoses . In this study , the method is evaluated in comparison with sutured and stapled anastomoses through experimental surgery . Clinical results of colonic BAR anastomoses are compared to those gained by sutured anastomoses . New applications of the anastomosis ring : small bowel anastomoses and cholecystojejunostomies are introduced in clinical trials . Fourteen dogs had a laparotomy with three consequent colonic transections . These were anastomosed ; one by manual suture , one with a circular stapler and one with the BAR . On day 1 , 3 , 5 , 7 , or 40 , postoperatively , the animals were sacrificed , and each operated colonic segment was removed for examination . In four animals dilation of the bowel was seen proximal to the BAR anastomosis . No clinical obstruction had been noted in them , however . Up to the seventh postoperative day , edematous and inflamed mucosa was observed with the BAR , and the least reaction was connected to the stapled anastomoses . Forty days after the operation all the three types of anastomoses had healed equally well both macroscopically and histologically . One hundred and fifty patients undergoing colonic surgery were r and omized into two groups : 71 underwent h and -suture and 79 were fitted with the BAR . Five patients , two treated using the BAR and three by suturing , developed anastomotic leakage . During follow up , one patient in each group underwent reoperation for anastomotic stricture . Recovery of the gastrointestinal tract and the hospital stay were similar in the two groups . The late results after colonic anastomoses performed with the BAR were evaluated in 26 patients who had undergone a left sided colonic or rectosigmoid anastomosis . One had been operated on for an anastomotic stricture 22 months after the initial operation , which was a sigmoid resection . One had been operated during the study for reasons not related to the anastomosis . 24 patients underwent the study scheme . In 16 of the patients , the anastomosis could not be radiologically identified , and in seven not even during endoscopy . Histologically there was mild to moderate fibrosis and scarring in 17 anastomoses and in the seven that could not be identified , only normal colonic mucosa was found . Of one hundred and seventy patients undergoing upper gastrointestinal surgery , 81 had the jejunojejunal enteroanastomosis done with the BAR and 89 patients received sutures . Both end-to-side ( 101 patients ) and side-to-side reconstructions ( 69 patients ) were done . Neither ruptures nor obstructions of the enteroanastomosis occurred . ( ABSTRACT TRUNCATED AT 400 WORDS Introduction Provided technique is faultless , the major determinants of anastomotic dehiscence are old age , malnutrition , disseminated cancer , low anterior resection , the presence of peritoneal sepsis and poor mechanical cleansing of the bowel ( Irvin & Goligher 1973 ) . Good technique is essential . Certain aspects are self-evident : an adequate blood supply to the ends being joined ; lack of tension on the anastomosis ; and the use of an appropriate suture material . Some technical refinements , however , are controversial , and we are unaware of any study of the effect on anastomotic integrity of varying the suture distance from the edges of the bowel . Cadaver studies ( Leaper et al. 1977 ) showed that the suture-holding capacity of incised abdominal wall depends largely on the distance at which the sutures are inserted from the cut edges , and it seemed logical to extend this concept of the ' deep bite ' . We have , therefore , compared colonic anastomoses made by a single layer of interrupted inverting sutures placed at either 5 mm or 10 mm from the cut edges of the bowel Abstract 440 patients were prospect ively enrolled in a r and omized , multicenter trial to compare 4 types of manual ( 84 interrupted end-to-end , 77 continuous end-to-side ) 82 interrupted end-to-side , and 91 continuous end-to-side ( polyglycolic derived suture ) and 1 type of stapled ( 106 side-to-side with GIA + TA devices ) ileocolonic anastomosis after right hemicolectomy for carcinoma . The trial was design ed according to Schwartz ' pragmatic formulation . All 5 groups were well-matched , except for a lower rate of intraoperative sepsis in the stapled group ( P<0.02 ) . The main end point was anastomotic leakage detected clinical ly or by routine sodium diatrizoate enema on the 8–10th postoperative day . Results showed that stapled ileocolonic anastomosis was associated with less anastomotic leakages ( 2.8 % ) than all the other techniques combined ( 8.3 % ) . In spite of the fact that staples are approximately ten times more expensive , our results suggest performing side-to-side ( GIA + TA ) mechanical anastomosis after right resection for carcinoma . Résumé440 malades ont été inclus prospect ivement dans un essai multi-centrique r and omisé afin de comparer 4 types de sutures manuelles avec un fil lentement résorbable ( 84 sutures termino-terminales à points séparés , 77 termino-terminales par sujet , 82 latéro-terminales à points séparés et 91 termino-latérales par sujet ) et une variété d'anastomoses mécaniques ( 106 sutures latéro-latérales aux pinces GIA + TA ) . Il s'agissait d'anastomoses iléo-coliques après hémicolectomie droite pour cancer . L'essai a été réalisé selon la formulation pragmatique de Schwartz . Tous les 5 groupes étaient bien appareillés à l'exception du plus petit taux de suppuration dans le groupe par anastomose mécanique ( P<0.02 ) . Le principal résultat était le lachâge d'anastomose détecté cliniquement ou par un lavement de routine aux produits hydrosolubles au 8–10ème jour post-opératoire . Les résultats montraient que les anastomoses mécaniques étaient associées avec moins de lachage d'anastomose ( 2,8 % ) que toutes les autres techniques ( 8,3 % ) . En dépit du fait que les anastomoses mécaniques sont approximativement 10 fois plus chères , nos résultats suggèrent qu'il faut réaliser des anastomoses latéro-larérales ( GIA + TA ) mécaniques après hémi-colectomie droite pour cancer OBJECTIVE To determine the suitability of a single-layer continuous technique for intestinal anastomosis in a surgical training program . SUMMARY BACKGROUND DATA Several recent reports have advocated the use of a continuous single-layer technique for intestinal anastomosis . Purported advantages include shorter time for construction , lower cost , and perhaps a lower rate of anastomotic leakage . The authors hypothesized that the single-layer continuous anastomosis could be safely introduced into a surgical training program and that it could be performed in less time and at a lower cost than the two-layer interrupted anastomosis . METHODS The study was conducted during a 3-year period ending September 1999 . All adult patients requiring intestinal anastomosis were considered eligible . Patients who required anastomosis to the stomach , duodenum , and rectum were excluded . Patients were also excluded if the surgeon did not believe either technique could be used . Patients were r and omly assigned to one- or two-layer techniques . Single-layer anastomoses were performed with a continuous 3 - 0 polypropylene suture . Two-layer anastomoses were constructed using interrupted 3 - 0 silk Lembert sutures for the outer layer and a continuous 3 - 0 polyglycolic acid suture for the inner layer . The time for anastomosis began with the placement of the first stitch and ended when the last stitch was cut . Anastomotic leak was defined as radiographic demonstration of a fistula or nonabsorbable material draining from a wound after oral administration , or visible disruption of the suture line during reexploration . RESULTS Sixty-five single-layer and 67 two-layer anastomoses were performed . The groups were evenly matched according to age , sex , diagnosis , and location of the anastomosis . Two leaks ( 3.1 % ) occurred in the single-layer group and one ( 1.5 % ) in the two-layer group . Two abscesses ( 3.0 % ) occurred in each group . A mean of 20.8 minutes was required to construct a single-layer anastomosis versus 30.7 minutes for the two-layer technique . Mean length of stay was 7.9 days for single-layer patients and 9.9 days for two-layer patients ; this difference did not quite reach statistical significance . Cost of material s was $ 4.61 for the single-layer technique and $ 35.38 for the two-layer method . CONCLUSIONS A single-layer continuous anastomosis can be constructed in significantly less time and with a similar rate of complications compared with the two-layer technique . It also costs less than any other method and can be incorporated into a surgical training program without a significant increase in complications AIM To compare the long-term outcome of patients after right hemicolectomy for colorectal cancer undergoing ileocolonic reconstruction either by a sutured technique or by side-to-side stapled anastomosis . METHODS Single surgeon series from 1992 to 2001 comprising 100 consecutive patients , 59 with h and sutured reconstruction and 41 undergoing TLC 55 mm stapled side-to-side anastomosis . Details of gender , patient age , and elective versus emergency presentation , Dukes stage , and curative versus palliative resection were recorded prospect ively . In addition , post-operative hospital stay and subsequent survival were determined by prospect i ve protocol follow-up . RESULTS Overall 24 % of the patients studied presented as emergencies and underwent a palliative procedure . There were no anastomotic leaks in either the stapled or sutured groups . Hospital mortality was also not significantly different -- stapled reconstruction , 7 % , sutured reconstruction , 10 % ( p value 0.624 ) . Overall long-term cancer outcome was the same for both anastomotic techniques , both stapled and sutured groups having a median survival of 2.9 years . CONCLUSIONS Stapled ileocolonic reconstruction after right hemicolectomy for colonic carcinoma is a safe and reliable surgical technique associated with long-term cancer outcomes comparable with those obtained by the sutured anastomotic technique OBJECTIVE To evaluate the merits of continuous and interrupted colonic anastomoses . DESIGN Prospect i ve non-r and omised study . SETTING District hospital , UK . SUBJECTS 53 Patients ( 24 male and 29 female ) of whom 26 underwent continuous and 27 interrupted sutured colonic anastomoses . MAIN OUTCOME MEASURES Mortality at 30 days , time taken to complete anastomosis , anastomotic dehiscence and anastomotic stricture . RESULTS No patient died within 30 days . There were no significant differences in ( median , range ) time taken to complete the anastomosis ( continuous : 15 ( 7 - 23 ) minutes ; interrupted : 26 ( 10 - 34 ) minutes , p = 0.27 ) ; anastomotic leak rate ( continuous 1 ; interrupted 1 ) and anastomotic stricture ( continuous 1 and interrupted 1 ) . Patients were followed up for a mean of 15 months after continuous and 18 months after interrupted colonic anastomoses . CONCLUSION As both techniques were equally safe , it is probable that the type of colonic anastomosis done will remain a matter of individual preference Sutureless colonic anastomosis using a biofragmentable anastomosis ring ( BAR ) has been evaluated in a prospect i ve r and omized comparison with sutures and staples for elective colorectal surgery . One hundred and one patients underwent BAR anastomosis , 85 a sutured anastomosis , and 16 a stapled anastomosis . There were two anastomotic leaks in the patients undergoing BAR anastomosis , seven in patients having a sutured anastomosis , and one in a patient who had a stapled anastomosis . Wound infection occurred in ten BAR patients , ten sutured patients and no stapled patient . There was no statistically significant difference in these or in other postoperative complications between the groups . The BAR was easy to use and is a safe alternative to sutures and staples for large bowel anastomosis Bowel anastomoses are conventionally performed using a h and sewn technique or a stapling device . Each has potential benefits and disadvantages . The most clinical ly significant complications of the bowel anastomosis are anastomotic leakage and stricture formation . The indices of healing and tissue cohesion were compared dynamically over time in 24 dogs r and omized to undergo either a st and ard two-layer h and sewn anastomosis or a stapled anastomosis with the Premium CEEATM(United States Surgical Corporation , Norwalk , CT ) . Animals were sacrificed at 1 , 4 , 7 , and 28 days postoperatively . Each anastomosis was evaluated for anastomotic index , burst pressure , collagen content , and histologic appearance . The anastomotic index was similar on postoperative day ( POD ) 1 , 4 , and 7 ; but on day 28 all h and sewn anastomoses had larger diameters than the widest CEEATManastomosis . Burst pressure was higher in h and sewn anastomoses at all intervals . Collagen content tended to be higher on POD 7 in the CEEATManastomoses . Histological evaluation showed more complete epithelialization and less inflammation in h and sewn anastomoses on POD 28 . The higher level of collagen in the CEEATManastomoses on POD 7 may be implicated in the tendency toward stricture formation found with this type of anastomosis . This study demonstrates that the greater speed and ease of the stapled anastomosis is offset by the greater strength , reduced tendency to stricture , and more complete healing of the h and sewn anastomosis One hundred patients undergoing elective left‐sided colonic or rectal resections were r and omly allocated to have an anastomosis performed either with the EEA stapling gun or by h and suture using a single layer of interrupted sutures . In six patients the anastomosis could not be performed with the stapling gun . Clinical leakage occurred in two of the remaining 94 cases ; both had h and ‐sutured anastomoses . Radiological leakage was demonstrated in 13 further cases ( 7 stapled , 6 sutured ) ; there was no statistical difference in leakage rate with stapled and h and ‐sutured anastomoses One hundred and fifty consecutive patients undergoing colonic surgery were r and omized into two groups : 71 underwent h and ‐suture with a two‐layer anastomosis of resorbable suture material ( 3/0 Dexon ) and 79 were fitted with the biofragmentable anastomotic ring ( Valtrac – BAR ) . Five patients , two treated using the BAR and three by suturing , developed anastomotic leakage which required a Hartmann‐type reoperation . This was successful in four ; one patient in the suture group died after reoperation . One patient who underwent suture had an early anastomotic stricture with fatal sequelae . Three other patients ( one in the BAR group and two in the suture group ) died after operation from other causes . Thus the mortality rate was 6 per cent in the suture group and 1 per cent in the BAR group . During follow‐up , one patient in each group underwent reoperation for anastomotic stricture . Recovery of the gastrointestinal tract was similar in the two groups regarding duration of nasogastric drainage , intravenous fluid therapy and ileus . There was no difference between the groups in duration of hospital stay . The BAR seems to be a safe and reliable alternative to conventional suture anastomosis in colonic surgery In a r and omized , prospect i ve study of 438 patients , the safety and efficacy of the Valtrac biofragmentable anastomotic ring ( BAR ) was compared with stapling and with conventional suture techniques . There was no significant difference in the morbidity , mortality , and clinical course of the patients . The BAR can effect reestablishment of intestinal continuity somewhat more rapidly , but its major advantage is its uniform applicability to all areas of the intestinal tract , except the low rectum We r and omly allocated 100 patients undergoing colonic or rectal resections to have their anastomoses made either by a single layer of braided polyester interrupted sutures , or by the SPTU circular stapling instrument . Twelve anastomoses leaked , 4 being detected only by contrast enema . There was no difference in leak rate between the two anastomotic methods , but patients in the stapled group had a significantly higher incidence of minor wound infection , and spent significantly more days in hospital after operation . The stapling instrument is no safer than sutures for colonic and rectal anastomoses , but considerably facilitates the performance of a low anterior resection |
10,811 | 27,996,083 | It is uncertain whether covering surgical wounds healing by primary intention with wound dressings reduces the risk of SSI , or whether any particular wound dressing is more effective than others in reducing the risk of SSI , improving scarring , reducing pain , improving acceptability to patients , or is easier to remove . | BACKGROUND Surgical wounds ( incisions ) heal by primary intention when the wound edges are brought together and secured , often with sutures , staples , or clips .
Wound dressings applied after wound closure may provide physical support , protection and absorb exu date .
There are many different types of wound dressings available and wounds can also be left uncovered ( exposed ) .
Surgical site infection ( SSI ) is a common complication of wounds and this may be associated with using ( or not using ) dressings , or different types of dressing .
OBJECTIVES To assess the effects of wound dressings compared with no wound dressings , and the effects of alternative wound dressings , in preventing SSIs in surgical wounds healing by primary intention . | Topical silicone gel sheeting and intralesional steroids are the only evidence -based recommendable forms of treatment to control the quality of a scar . The advantages and disadvantages of both are well known . This study was undertaken to verify the efficacy of a new topical silicone treatment : a self-drying spreadable gel that needs no means of fixation and can not be seen because of complete transparency . Fresh surgical scars treated with the tested product showed significantly better outcomes than those untreated in a prospect i ve trial involving a group of 160 patients . Patient compliance was particularly good , especially for scars on exposed areas such as the face , where the traditional gel sheeting is frequently discontinued at an early stage by patients who object to its visibility . The results of the self-drying silicone gel have indeed been satisfactory . Considering the effective results obtained and the good patient compliance , the authors currently rate this concept of treatment as the first choice for preventing hypertrophy of recent scars Purpose The purpose of this study was to determine if the use of antibiotic-impregnated fibrin sealant ( AFS ) was effective in preventing surgical site infections ( SSI ) associated with spinal instrumentation . Methods In a preliminary study , five pieces of vancomycin-impregnated fibrin sealant , five nuts that were not treated with the sealant , and five nuts that were treated with the sealant were subjected to agar diffusion testing . In a clinical study , the rates of deep SSI were compared between 188 patients who underwent procedures involving spinal instrumentation without AFS ( group 1 ) and 196 patients who underwent procedures involving spinal instrumentation with AFS ( group 2 ) . Results All five pieces of vancomycin-impregnated fibrin sealant and the five nuts treated with the sealant exhibited antimicrobial efficacy , while the five untreated nuts did not exhibit antimicrobial efficacy in the agar diffusion test . In the clinical study , 11 ( 5.8 % ) of the 188 patients in group 1 acquired a deep SSI , while none ( 0 % ) of the 196 patients in group 2 acquired a deep SSI . Conclusion The present study demonstrated that the application of AFS to spinal instrumentation yielded good clinical outcomes in terms of the prevention of postoperative spinal infections . It is hoped that limiting AFS use to patients requiring spinal instrumentation and those with risk factors for SSI will reduce the overall costs while preventing SSIs This study reports the results of a prospect i ve r and omised controlled trial that compared three non-adherent wound dressings applied to h and surgery wounds . Paraffin-impregnated gauze ( Jelonet ) was compared with a cellulose , acetate fibre dressing coated with a petrolatum emulsion ( Adaptic ) and a polyamide net dressing impregnated with silicone gel ( Mepitel ) . The dressings were assessed for their ease of application and removal , pain on removal and wound appearance . Results from 99 patients were available for analysis . Adaptic was significantly easier to remove ( p < 0.01 ) , required less soaking ( p < 0.05 ) , was less painful to remove ( p < 0.05 ) and caused less wound maceration ( p < 0.05 ) than Jelonet , but was significantly more difficult to apply ( p < 0.05 ) . Mepitel was also easier to remove but this did not reach statistical significance . It was also more difficult to apply than Jelonet ( p < 0.05 ) . We recommend that Adaptic should be used routinely as the non-adherent dressing for incisions or traumatic wounds on the h and . The slight increased difficulty in applying the dressing is outweighed by the major advantages associated with its removal BACKGROUND Topical 2-octylcyanoacrylate tissue adhesive is an alternative to traditional devices for closing short surgical incisions . METHODS An open-label , r and omized study compared a new high-viscosity formulation of 2-octylcyanoacrylate with commercially available devices , including low-viscosity 2-octylcyanoacrylate , for epidermal closure of incisions > or = 4 cm requiring subcutaneous and /or deep-dermal suturing . RESULTS Of patients with 1 to 3 wounds , 106 were treated with high-viscosity 2-octylcyanoacrylate and 103 with commercially available devices . The day-10 rates of healing by wound were 96 % and 97 % for study versus control treatment and 97 % and 95 % for new and old 2-octylcyanoacrylate formulations versus other controls , respectively . Day-10 infection rates by wound were 4 of 145 versus 7 of 131 for study versus control treatment and 6 of 207 and 5 of 69 for new and old 2-octylcyanoacrylate versus other controls , respectively . CONCLUSIONS The new tissue adhesive formulation provides epidermal wound closure equivalent to commercially available devices with a trend to decreased incidence of wound infection Forty-five surgical wounds were closed by suture technic and then treated with either a polyethylene oxide gel ( POG ) dressing or a povidone-iodine-impregnated polyethylene oxide gel ( PVPI-POG ) dressing . In the control group with the POG dressing alone , three wound infections , representing 25 % of those patients , were encountered . In the PVPI-POG dressing group no wound infections were encountered . Wound healing , in terms of reduced inflammation and faster epidermal approximation , appeared better in the PVPI-POG dressing group The aim of this study was to assess the feasibility of using Leptospermum honey in a r and omised trial to reduce the incidence of wound infection after microvascular free tissue reconstruction for cancer of the head and neck . During the one-year study period 70 consecutive patients were admitted to the regional maxillofacial ward for free tissue reconstruction . Of these , 56 ( 80 % ) consented to be r and omised and 49 ( 70 % ) were actually r and omised , 25 into the honey dressings group , and 24 into the conventional dressings group ( control ) . Six patients were missed when consent was required , 8 did not consent , and 7 who had given consent were missed at the r and omisation stage in theatre . Results of wound swabs were positive in 36 % of the honey group and 38 % of the control group . Methicillin-resistant Staphylococcus aureus ( MRSA ) was found in 28 % and 25 % , respectively . Of these , 38 % were deemed to require intervention . Honey dressings were acceptable to both patients and nurses . There was a reduction ( p<0.05 ) in duration of hospital stay in the honey group ( median 12 days , IQR 10 - 21 ) compared with the control ( median 18 days , IQR 13 - 28 ) . The cost of st and ard and honey dressings was similar . This feasibility study has shown that a r and omised controlled trial ( RCT ) is possible and that several hundreds of patients would be required to show a clinical benefit for honey . Further research is needed to confirm a shorter duration of hospital admission and if so , whether this is due to more rapid healing Purpose We prospect ively compared two types of dressing ( conventional gauze-based versus absorbing hydrofibre ) after primary total hip ( THA ) or knee ( TKA ) arthroplasties . Methods Eighty c and i date s for THA ( n = 40 ) or TKA ( s = 40 ) were r and omized : gauze-based versus hydrofibre absorbing ( Aquacel ® , ConvaTec ) . The two groups were comparable at baseline . Results There was a statistically significant decrease of dressing changes in the hydrofibre group ( p = 0.0006 ) . Two patients from the conventional group presented minor wound complications . Nurses ’ satisfaction was significantly higher in the hydrofibre group considering the adherence ( p = 0.04 ) and flexibility ( p = 0.03 ) . Patients experienced a higher satisfaction with respect to ease of movement ( p = 0.01 ) in the hydrofibre group . The cosmetic appearance of the scars six weeks after surgery was found to be similar between groups . Conclusions Our findings support an overall improved comfort for the patients and the medical staff by using hydrofibre dressings after primary THA and TKA . The reduction of required dressing changes was observed also A blinded r and omized clinical trial was undertaken to evaluate the effect of applying ointment to a wound before occlusive dressing , in comparison with no ointment or sterile paraffin OBJECTIVE To compare the performance of Hydrofiber and alginate dressings used in the treatment of primary hip arthroplasty wounds . METHOD Patients were r and omised into one of two groups , receiving either a Hydrofiber or an alginate dressing . Outcome measures , assessed by daily observations , included skin damage ( erythema , blisters and skin injuries ) and the dressing 's ability to h and le exu date s. Photos of the dressing and the skin area around wounds were taken . Patients noted skin problems , discomfort at mobilisation and pain at dressing removal . RESULTS In the alginate group , there were fewer blisters in the wound area compared with the Hydrofiber group ( 7 % versus 18 % , p=0.03 ) . During dressing removal , fewer patients in the alginate group reported pain than patients in the Hydrofiber group ( 2.1 % versus 15 % , p=0.01 ) CONCLUSION We recommend the use of both dressings following total hip arthroplasty , although the alginate would be our first choice , as we found fewer blisters when using alginate dressings as opposed to Hydrofiber dressings . CONFLICT OF INTEREST None BACKGROUND : Patients who undergo colorectal surgery have up to a 30 % chance of developing a surgical site infection postoperatively . Silverlon is a silver nylon dressing design ed to prevent surgical site infections , but only anecdotal evidence has previously supported its efficacy . OBJECTIVE : The aim of this study was to evaluate the effect of silver nylon dressings in patients undergoing colorectal surgery . DESIGN : We performed a prospect i ve , r and omized , controlled trial comparing a silver nylon dressing with gauze dressings in patients undergoing elective colorectal surgery . SETTING : The study was performed at a university-based , tertiary referral center . PATIENTS : We studied patients undergoing elective colorectal surgery with an abdominal skin incision of at least 3 cm . INTERVENTION : Patients were r and omly assigned to receive either a silver nylon or a gauze dressing . MAIN OUTCOME MEASURES : The primary end point was surgical site infection occurring within 30 days of surgery . RESULTS : One hundred ten patients were enrolled in the study and were r and omly assigned to 1 of 2 treatment groups . After a 30-day follow-up period , the incidence of surgical site infection was lower in the silver nylon group compared with the control group ( 13 % vs 33 % , P = .011 ) . Twenty-five patients in the study developed superficial surgical site infections , 5 in the silver nylon group and 14 in the control group ( P = .021 ) . Two patients in the study group developed deep wound infections compared with 4 in the control group ( P = .438 ) . Multivariate analysis revealed that patients in the control group had a 3-fold increase in risk of infection compared with patients in the silver nylon group ( P = .013 ) . LIMITATIONS : A limitation of this study is that the members of the surgical team were not blinded to the treatment groups . CONCLUSION : Silver nylon is safe and effective in preventing surgical site infection following colorectal surgery BACKGROUND 4 methods are used in pediatric laparoscopic surgery to close trocar wounds . While tissue adhesives or adhesive strips have been shown to produce fewer wound complications and a better cosmetic result compared to trans- or only subcutaneous sutures , the choice of technique is still often based on the surgeon 's personal experience . Thus , the objective of this trial was to assess the impact of tissue adhesives ( Dermabond ™ ) compared to adhesive strips ( Steri-Strip ™ ) on potential complications of wound healing , wound pain , cosmetic outcome , and patient satisfaction after laparoscopic appendectomy in children . METHODS 49 patients undergoing laparoscopic appendectomy were enrolled in this prospect i ve r and omized trial . In every patient , two 5-mm and one 10-mm port-site incision was closed either with Dermabond ™ or Steri-Strip ™ after placing subcuticular absorbable sutures ( 4 - 0 Vicryl ™ ) . Postoperative complications , pain , and patient satisfaction with scars were evaluated at follow-up on day 10 and day 90 after the operation using a question naire and a visual analogue scale ( VAS ) . Photographs of scars taken on day 90 were evaluated on a VAS by 2 pediatric surgeons blinded to the closure method used . RESULTS According to the surgeons ' evaluation of the cosmetic outcome , a significant difference between the 2 groups with regard to the cosmetic score was found on day 90 of follow-up , favoring Steri-Strip ™ wound closure ( p < 0.05 ) . On day 10 and 90 there were no statistical differences between the 2 methods as regards the result of patient evaluations ( p > 0.05 ) . Only one wound infection ( 4 % ) was observed in the Steri-Strip ™ group ( n = 25 ) on day 10 . At follow-up on day 90 two patients ( 9.1 % ) in the Dermabond ™ group and one ( 4.8 % ) in the Steri-strip ™ group complained of wound pain ( p = 0.52 ) . CONCLUSIONS Both tissue adhesives and adhesive strips are excellent " no needle " alternatives for the closure of laparoscopic port-site incisions in children . As regards cosmetic outcome , Steri-Strip ™ wound closure seems to be the most suitable and is also the less expensive technique PURPOSE To examine the effectiveness of two methods of preventing blister formation under the taped portion of postoperative hip surgical dressings . DESIGN Comparative intervention study . SAMPLE Convenience sample of 148 consecutive hip surgery patients in two Connecticut community hospitals . METHODS Patients were preoperatively assigned to one of two postoperative surgical hip dressing taping methods or to the control group . The experimental group had the surgical dressing taped to either a hydrocolloid barrier or a nonhydrocolloid barrier 1-inch circumferentially around the surgical incision with the control group having the dressing taped directly to the skin . FINDINGS The research results found that taping the surgical dressing to a hydrocolloid barrier prevented blister formation . There were no blisters in either experimental group , but evidence of nonblanchable erythema on two patients in the nonhydrocolloid barrier group . CONCLUSION Taping of postoperative surgical hip dressings to a hydrocolloid barrier is superior to taping directly to skin or to a nonhydrocolloid barrier . IMPLICATION S FOR NURSING RESEARCH A larger scale study to examine potential factors that might place patients at high risk for blister formation is needed . This would aid in identification of patients that would benefit from different surgical dressing taping methods OBJECTIVE To compare the effect of occlusive ( Comfeel ) and conventional ( Mepore ) dressings on the healing of incisional wounds after abdominal operations . DESIGN Prospect i ve r and omised study . SETTING Laboratory and teaching hospital , Denmark . SUBJECTS 73 patients who underwent clean operations requiring incisions longer than 5 cm between August 1993 and August 1995 were r and omised to have their wounds dressed with either Comfeel or Mepore . INTERVENTIONS Comfeel was left on until the sutures were removed , and Mepore was removed 2 days postoperatively . MAIN OUTCOME MEASURES Infection , adherence , leakage , and cosmetic appearance three months later . RESULTS 36 patients were r and omised to have Comfeel and 37 to have Mepore . 29 patients were withdrawn from the study ( 20 having Mepore and 9 having Comfeel ) leaving 26 , and 17 for analysis , respectively . Wound infections developed in 1 patient in the Comfeel group and 5 in the Mepores group ( p = 0.2 ) . There were no differences between the groups regarding the need for dressings to be changed , the incidence of leakage , or loosening of the dressing from the skin . Comfeel adhered securely to the skin and remained more or less transparent until sutures were removed . It remained totally transparent in 23 ( 64 % ) , and no dressing became totally opaque . There were no differences in cosmetic appearance after three months . We had the impression that patients who had Comfeel were more comfortable and found it easier to mobilise and carry out their daily activities . CONCLUSION Occlusive dressings stay in place and stay transparent , and do not increase the risk of wound infection . They may even be more comfortable . they are a reasonable alternative to conventional dressings The need for dressings on clean and clean contaminated surgical wounds was investigated . A total of 1202 patients with 1202 clean or clean contaminated surgical wounds were r and omized into two groups : 633 wounds were covered by dressings up until the time of suture removal , and 569 wounds were treated without dressings after the first postoperative day . In the group characterized by long dressing time , the rate of postoperative wound infections was 4·9 per cent . The rate was 4·7 per cent in the group represented by short dressing time . Using short dressing time not only reduces the number of nursing hours but also limits the need for costly dressing material . In addition , both wound observation and patients ' personal hygiene are made easier Background An antimicrobial dressing containing ionic silver was found effective in reducing surgical-site infection in a preliminary study of colorectal cancer elective surgery . We decided to test this finding in a r and omized , double-blind trial . Methods Adults undergoing elective colorectal cancer surgery at two university-affiliated hospitals were r and omly assigned to have the surgical incision dressed with Aquacel ® Ag Hydrofiber dressing or a common dressing . To blind the patient and the nursing and medical staff to the nature of the dressing used , scrub nurses covered Aquacel ® Ag Hydrofiber with a common wound dressing in the experimental arm , whereas a double common dressing was applied to patients of control group . The primary end-point of the study was the occurrence of any surgical-site infection within 30 days of surgery . Results A total of 112 patients ( 58 in the experimental arm and 54 in the control group ) qualified for primary end-point analysis . The characteristics of the patient population and their surgical procedures were similar . The overall rate of surgical-site infection was lower in the experimental group ( 11.1 % center 1 , 17.5 % center 2 ; overall 15.5 % ) than in controls ( 14.3 % center 1 , 24.2 % center 2 , overall 20.4 % ) , but the observed difference was not statistically significant ( P = 0.451 ) , even with respect to surgical-site infection grade 1 ( superficial ) versus grade s 2 and 3 , or grade 1 and 2 versus grade 3 . Conclusions This r and omized trial did not confirm a statistically significant superiority of Aquacel ® Ag Hydrofiber dressing in reducing surgical-site infection after elective colorectal cancer surgery . Trial registration Clinical trials.gov : OBJECTIVE To investigate the effect of three postoperative dressings on orthopaedic wound healing . METHOD Three hundred orthopaedic patients were divided into three treatment groups and allocated to management with one of three dressings : Primapore , Tegaderm with pad , and OpSite Post-Op . Staff completed a question naire to evaluate the wound progression . Outcome measures were the presence of infection , blistering and the number of dressing changes required . RESULTS There was a significantly lower incidence of blistering with OpSite Post-Op ( 6 % ) than Tegaderm with pad ( 16 % ) and Primapore ( 24 % ) ( p<0.001 ) . Patients in the OpSite Post-Op group had the lowest exu date levels . CONCLUSION Dressings that employ a clear film and have a high moisture vapour transmission rate have been shown to reduce both the rate of blistering and wound discharge . The additional expense inherent in using such dressings may , in reality , prove cost-effective because of the reduced need for dressings changes and the subsequent earlier discharge of these patients from hospital with an uncomplicated wound Abstract Background : Surgical site infections ( SSI ) occur in 1.8%–9.2 % of women undergoing cesarean section ( CS ) and lead to greater morbidity rates and increased treatment costs . The aim of the study was to evaluate the efficacy and cost-effectiveness of dialkylcarbamoyl chloride ( DACC ) impregnated dressings to prevent SSI in women subject to CS . Methods : R and omized , controlled trial was conducted at the Mazovian Bródno Hospital , a tertiary care center performing approximately 1300 deliveries per year , between June 2014 and April 2015 . Patients were r and omly allocated to receive either DACC impregnated dressing or st and ard surgical dressing ( SSD ) following skin closure . In order to analyze cost-effectiveness of the selected dressings in the group of patients who developed SSI , the costs of ambulatory visits , additional hospitalization , nursing care , and systemic antibiotic therapy were assessed . Independent risk factors for SSI were determined by multivariable logistic regression . Results : Five hundred and forty-three women undergoing elective or emergency CS were enrolled . The SSI rates in the DACC and SSD groups were 1.8 % and 5.2 % , respectively ( p = 0.04 ) . The total cost of SSI prophylaxis and treatment was greater in the control group as compared with the study group ( 5775 EUR vs. 1065 EUR , respectively ) . Independent risk factors for SSI included higher pre-pregnancy body mass index ( adjusted odds ratio [ aOR ] = 1.08 ; [ 95 % confidence interval [ CI ] : 1.0–1.2 ] ; p < 0.05 ) , smoking in pregnancy ( aOR = 5.34 ; [ 95 % CI : 1.6–15.4 ] ; p < 0.01 ) , and SSD application ( aOR = 2.94 ; [ 95 % CI : 1.1–9.3 ] ; p < 0.05 ) . Conclusion : The study confirmed the efficacy and cost-effectiveness of DACC impregnated dressings in SSI prevention among women undergoing CS BACKGROUND Several pre- and intraoperative factors have been associated with incisional surgical site infection ( SSI ) , but little is known about the influence of postoperative wound care and especially , the use of different dressings on incisional SSI . The aim of this study was to compare 3 methods of wound dressings ( conventional dressing , silver-containing dressing , and mupirocin ointment dressing ) for their ability to prevent SSI , as measured by SSI rates , in patients with colorectal cancer undergoing elective open surgery . STUDY DESIGN A prospect i ve , r and omized study was performed . Inclusion criteria were diagnosis of colorectal neoplasms and plans to undergo elective surgery with curative aims . Patients were r and omized using a 1:1:1 allocation into 3 groups : patients receiving an ionic silver-containing dressing ( ISD ) ( group 1 ) , a mupirocin ointment application ( MOA ) ( group 2 ) , and a conventional dressing ( group 3 or st and ard dressing ) . The primary outcomes variable was occurrence of incisional SSI . Follow-up was 30 days postoperatively . RESULTS A total of 147 patients were included , 49 in each group . Incisional SSI occurred in 9 patients ( 18.4 % ) in the ISD group , 2 ( 4.1 % ) in the MOA group , and 10 ( 20.4 % ) in the st and ard dressing group ( p = 0.028 ) . Adjusting for multiple comparisons , there were no significant differences between ISD and st and ard dressing groups ; a significant difference was observed between ISD and MOA ( relative risk [ RR ] 4.5 ; 95 % CI ( 1.1 to 19.8 ) ; p = 0.046 ) and between the st and ard group and the MOA group ( RR 5 ; 95 % CI ( 1.2 to 21.7 ) ; p = 0.031 ) . CONCLUSIONS Topical application of mupirocin ointment achieves better results for the prevention of SSI than ionic silver-containing dressing or st and ard dressing in patients undergoing elective open colorectal surgery Background The aim of this multicenter , r and omized , prospect i ve study was to reveal a difference in terms of a guided healing period in the case of stoma orifices after reestablishing digestive continuity by comparing an alginate mesh with a polyvidone iodine mesh . Methods Between April 2004 and September 2005 , a total of 73 patients were r and omized into two groups : A ( alginate mesh ) and M ( polyvidone iodine mesh ) . The groups were comparable for demographic data , indications for and the type of stoma , and perioperative data . The main evaluation criterion was percentage healing at the 28th postoperative day ( D28 ) ; and the secondary criteria were healing time , rate of infectious complications , and number of dressing changes applied . Results The mean percentage healing at D28 was 91 % in group A and 87 % in group M ( p = 0.49 ) . The mean healing time was 31 days in group A and 32 days in group M ( p = 0.80 ) . One parietal abscess ( 3 % ) occurred in group A ( p = 0.37 ) . The mean number of meshes used was 13 ± 5 in group A and 18 ± 8 in group M ( p < 0.005 ) . Conclusion The use of an alginate mesh for guided healing of stoma orifices after reestablishing digestive continuity allows effective healing within a normal period of time with a lower number of meshes BACKGROUND / PURPOSE The covering of the sutured surgical wound with a sterile dressing is usually considered a routine conclusion to an aseptic operation . The wound is usually left dressed for a minimum of 3 to 5 days . The main purpose of dressing is protection of the wound against bacterial contamination that remains a significant source of postoperative morbidity . The aim of this study was to compare the infectious local risk when the clean pediatric surgical wounds were dressed or left exposed without dressing after the completion of wound closure . METHODS Four hundred fifty-one patients with clean surgical wounds were r and omized prospect ively to receive dressing ( n = 216 ) or have their wounds left exposed without any dressing ( n = 235 ) after the completion of wound closure . RESULTS In the group that received wound dressing , wound infection developed in 3 patients ( 1.4 % ) , whereas in the group that had wounds exposed without any dressing , 4 patients ( 1.7 % ) developed wound infection . CONCLUSIONS In children , there was no significant difference in terms of wound infection after applying dressing or leaving the clean surgical wounds exposed without any dressing after completion of wound closure . Dressing clean surgical wounds may be unnecessary OBJECTIVE To compare occlusive hydrocolloid dressing ( OHD ; Karayahesive ) and gauze dressing ( GD ) with regard to the cost and incidence of wound infection after abdominal surgery . METHODS A total of 134 patients who underwent incisions were r and omized to have their wounds dressed with either OHD or GD . OHD was left on until the sutures were removed , and GD was changed everyday postoperatively . The cost calculations represent the number of dressings required for each treatment group as determined by the frequency of required dressing changes and cost per dressing . RESULTS There were no differences between the groups regarding the need for dressings to be changed or the incidence of infection . OHD was less expensive and complicated than GD , which needed to be changed everyday ( p < 0.0001 ) . CONCLUSION The results suggest that OHD is less expensive to use than GD , and the risk of wound infection is not increased compared to GD Fifty patients underwent a variety of h and operations and were r and omized for wound closure either with tissue adhesive ( Indermil ) or sutures . The two treatment groups had similar demographic characteristics and similar outcomes at the 2 and 6 week postoperative assessment s which were performed by a design ated tissue viability nurse blinded to the method of closure . Five minor wound dehiscences occurred : three in the adhesive group and two in the suture group . No infection occurred in either group . In conclusion , the study demonstrates tissue adhesive is as effective as suture in this type of h and surgery This study was a r and omized-controlled trial comparing the st and ard type of dry dressing , Mepore , with moist wound healing , using a hydrofiber dressing , Aquacel , in primary closed wounds after vascular surgery . The endpoints were patient comfort , cost-effectiveness , infections , wound complications , and length of hospital stay . One hundred and sixty patients were r and omized to receive either Mepore or Aquacel dressing . There was no significant difference in patient comfort between the two groups , but a higher cost in the Aquacel group despite significantly fewer changes of dressings in these patients . No difference in the infection rate ( 13 % vs. 11 % , p=0.73 ) , length of hospital stay , or wound complications was noted between the two groups . We conclude that although the Aquacel dressing needed significantly fewer changes than the conventional dressing , this did not influence the patient comfort . Moreover , the traditional dressing scheme was significantly less expensive Introduction : Wound blisters are formed in the epidermis adjacent to surgicalincisions and are a significant cause of morbidity following hipsurgery . This study was design ed to compare two commonly used primary dressings , namely a nonadherent absorbable ( NAA ) dressing and paraffintulle gras ( PTG ) . Monitoring for the subsequent development of woundblisters in the epidermis adjacent to the surgical incision wasthen undertaken Purpose This prospect i ve and semi-r and omized study was conducted to clarify the effectiveness of a new hydrocolloid dressing placed over median sternotomy wounds using an occlusive dressing technique . Methods The subjects were 253 patients undergoing coronary artery bypass grafting ( CABG ) , who were r and omized to receive either the new hydrocolloid dressing ( Karayahesive , n = 117 ) or a polyurethane foam dressing ( Tegaderm plus Pad , n = 136 ) immediately after sternal wound closure . Karayahesive was left in place for 7 days , whereas the Tegaderm plus Pad was removed on postoperative day ( POD ) 2 and replaced with an adhesive wound dressing until POD 7 . Results In the Karayahesive group , complete integrity of the wound was achieved in 91 % of the patients , with an infection developing in 3.4 % : as a superficial surgical site infection ( SSI ) in three and as a deep SSI in one . On the other h and , in the Tegaderm plus Pad group , an infection developed in 10.3 % ( 14 patients ) of the patients : as a superficial SSI in nine and as a deep SSI in five ( P < 0.05 ) . The total treatment costs from the application of the dressing until completion of treatment was 699 yen for the Karayahesive and 910 yen for the Tegaderm plus Pad ( P < 0.001 ) . Conclusions The new hydrocolloid dressing , applied with an occlusive dressing technique to median sternotomy wounds , prevented SSI and was cost effective The majority of wound infections after median sternotomy in obese patients are triggered by the breakdown of skin suture and subsequent seepage of skin flora into the deeper tissue layers . In a prospect i ve study , 90 patients ( body mass index ≥30 ) who had cardiac surgery via median sternotomy were enrolled . In 45 patients , skin closure was performed according to the Donati technique ( vertical interrupted mattress suture ) and sealed with octylcyanoacrylate ( group A ) . In 45 patients , intracutaneous running technique without sealed was performed ( group B ) . The endpoint was wound infection within 90 days . Degree of obesity and other risk factors for wound infection were equally distributed between groups A and B ( all P>0.05 ) . In group A only two superficial infections occurred , whereas in group B there were nine wound infections including two deep infections ( P=0.026 ) . In 10 of 11 infections ( both groups ) coagulase-negative staphylococci were isolated . In eight of 11 wound infections the caudal third of the incision was affected . Intertrigo in inframammary skin folds was found in 20.0 % ( 18/90 ) of all patients but in 63.6 % ( seven of 11 ) of cases with infection . We conclude , that cyanoacrylate-sealed Donati suture is superior to intracutaneous suture technique since it offers tension-resistant closure with immediate microbial barrier properties BACKGROUND Infection in the saphenous vein harvest site is a common problem . We developed an occlusive circumferential wrap dressing technique that reduces skin edge tension , eliminates dead space , and prevents external contamination . We compared the surgical site infection rate using the wrap dressing technique with that of st and ard longitudinal dressings . METHODS . One hundred fifty-two consecutive patients were r and omly assigned to receive either st and ard dressings or the wrap dressing . Data were collected in the hospital and then 4 to 6 weeks postoperatively . Superficial and deep wound infections were defined by the st and ard criteria from the Centers for Disease Control and Prevention . RESULTS The infection rate in the wrap group was 14 % compared with 35 % , for the st and ard group ( p = 0.006 ) . Multivariate analysis showed that wrap technique was the only significant predictor ( negative ) of infection ( odds ratio , 0.19 ; p = 0.001 ) . CONCLUSIONS In saphenous vein harvest wounds , the occlusive wrap dressing technique has the potential to reduce the rate of infection by 50 % . This simple and inexpensive technique is also readily applicable to the radial artery harvest site in the arm and may provide similar benefit STUDY OBJECTIVE To compare three dressing types in terms of their ability to protect against infection and promote healing , patient comfort , and cost-effectiveness . DESIGN Prospect i ve , r and omized controlled trial . SETTING Major metropolitan , academically affiliated , tertiary referral center . PATIENTS Seven hundred thirty-seven patients were r and omized to receive a dry absorbent dressing ( n = 243 ) [ Primapore ; Smith & Nephew ; Sydney , NSW , Australia ] , a hydrocolloid dressing ( n = 267 ) [ Duoderm Thin ConvaTec ; Mulgrave , VIC , Australia ] , or a hydroactive dressing ( n = 227 ) [ Opsite ; Smith & Nephew ] in the operating theater on skin closure . RESULTS There was no difference in the rate of wound infection or wound healing between treatment groups . The Primapore dressing was the most comfortable and cost-effective dressing option for the sternotomy wound . Duoderm Thin dressings were associated with increased wound exu date ( p < 0.001 ) , poor dressing integrity ( p < 0.001 ) , more frequent dressing changes ( p < 0.001 ) , more discomfort with removal ( p < 0.05 ) , and increased cost ( p < 0.001 ) . CONCLUSIONS In the context of no additional benefit for the prevention of wound infection or the rate of wound healing for any of the three dressing products examined , dry absorbent dressings are the most comfortable and cost-effective products for sternotomy wounds following cardiac surgery Objective To determine the effectiveness of a single application of topical chloramphenicol ointment in preventing wound infection after minor dermatological surgery . Design Prospect i ve r and omised placebo controlled double blind multicentre trial . Setting Primary care in a regional centre in Queensl and , Australia . Participants 972 minor surgery patients . Interventions A single topical dose of chloramphenicol ( n=488 ) or paraffin ointment ( n=484 ; placebo ) . Main outcome measure Incidence of infection . Results The incidence of infection in the chloramphenicol group ( 6.6 % ; 95 % confidence interval 4.9 to 8.8 ) was significantly lower than that in the control group ( 11.0 % ; 7.9 to 15.1 ) ( P=0.010 ) . The absolute reduction in infection rate was 4.4 % , the relative reduction was 40 % , and the relative risk of wound infection in the control group was 1.7 ( 95 % confidence interval 1.1 to 2.5 ) times higher than in the intervention group . The number needed to treat was 22.8 . Conclusion Application of a single dose of topical chloramphenicol to high risk sutured wounds after minor surgery produces a moderate absolute reduction in infection rate that is statistically but not clinical ly significant . Trial registration Current Controlled Trials IS RCT N73223053 After elective surgery , 28 patients with 40 wounds were enrolled in a controlled clinical study to assess the effects of two different dressings on incisional healing . Patients served as their own control with one-half of each incision covered with an impregnated gauze ( Xeroform ) and the other half of the incision covered with a thin occlusive hydrocolloid dressing ( DuoDerm Extra Thin CGF ) . All wounds were evaluated 2 to 3 days , 7 to 10 days , 4 weeks , and 7 months postoperatively . None of the incisions segments showed any evidence of infection . At the time of suture removal , the hydrocolloid dressing 's ability to contain exu date , protect the wound , and facilitate mobility and personal hygiene were rated higher compared with the gauze-type dressing ( p < 0.001 , for all variables ) . At the 4-week visit , both the patient and the surgeon rated the scar segments covered with the hydrocolloid dressing better with respect to color , evenness , and suppleness ( p ≤ 0.04 , for all variables ) . These differences were no longer apparent 7 months after surgery BACKGROUND The rising cesarean birth rate has drawn attention to risks associated with repeat cesarean birth . Prevention of adhesions with adhesion barriers has been promoted as a way to decrease operative difficulty . However , robust data demonstrating effectiveness of such interventions are lacking . OBJECTIVE We report data from a multicenter trial design ed to evaluate the short-term safety and effectiveness of a modified sodium hyaluronic acid (HA)-carboxymethylcellulose ( CMC ) absorbable adhesion barrier for reduction of adhesions following cesarean delivery . STUDY DESIGN Patients who underwent primary or repeat cesarean delivery were included in this multicenter , single-blinded ( patient ) , r and omized controlled trial . Patients were r and omized into either HA-CMC ( N = 380 ) or no treatment ( N = 373 ) . No other modifications to their treatment were part of the protocol . Short-term safety data were collected following r and omization . The location and density of adhesions ( primary outcome ) were assessed at their subsequent delivery using a vali date d tool , which can also be used to derive an adhesion score that ranges from 0 - 12 . RESULTS No differences in baseline characteristics , postoperative course , or incidence of complications between the groups following r and omization were noted . Eighty patients from the HA-CMC group and 92 controls returned for subsequent deliveries . Adhesions in any location were reported in 75.6 % of the HA-CMC group and 75.9 % of the controls ( P = .99 ) . There was no significant difference in the median adhesion score ; 2 ( range 0 - 10 ) for the HA-CMC group vs 2 ( range 0 - 8 ) for the control group ( P = .65 ) . One third of the HA-CMC patients met the definition for severe adhesions ( adhesion score > 4 ) compared to 15.5 % in the control group ( P = .052 ) . There were no significant differences in the time from incision to delivery ( P = .56 ) . Uterine dehiscence in the next pregnancy was reported in 2 patients in HA-CMC group vs 1 in the control group ( P = .60 ) . CONCLUSION Although we did not identify any short-term safety concerns , HA-CMC adhesion barrier applied at cesarean delivery did not reduce adhesion formation at the subsequent cesarean delivery INTRODUCTION Recent conflicts have been characterised by the use of improvised explosive devices causing devastating injuries , including heavily contaminated wounds requiring meticulous surgical debridement . After being rendered surgical clean , these wounds are dressed and the patient transferred back to the UK for on-going treatment . A dressing that would prevent wounds from becoming colonised during transit would be desirable . The aim of this study was to establish whether using nanocrystalline silver dressings , as an adjunct to the initial debridement , would positively affect wound microbiology and wound healing compared to st and ard plain gauze dressings . METHODS Patients were prospect ively r and omised to receive either silver dressings , in a nanocrystalline preparation ( Acticoat ™ ) , or st and ard of care dressings ( plain gauze ) following their initial debridement in the field hospital . On repatriation to the UK microbiological swabs were taken from the dressing and the wound , and an odour score recorded . Wounds were followed prospect ively and time to wound healing was recorded . Additionally , patient demographic data were recorded , as well as the mechanism of injury and Injury Severity Score . RESULTS 76 patients were recruited to the trial between February 2010 and February 2012 . 39 received current dressings and 37 received the trial dressings . Eleven patients were not swabbed . There was no difference ( p=0.1384 , Fishers ) in the primary outcome measure of wound colonisation between the treatment arm ( 14/33 ) and the control arm ( 20/32 ) . Similarly time to wound healing was not statistically different ( p=0.5009 , Mann-Whitney ) . Wounds in the control group were scored as being significantly more malodorous ( p=0.002 , Mann-Whitney ) than those in the treatment arm . CONCLUSIONS This is the first r and omised controlled trial to report results from an active theatre of war . Performing research under these conditions poses additional challenges to military clinicians . Meticulous debridement of wounds remains the critical determinant in wound healing and infection and this study did not demonstrate a benefit of nanocrystaline silver dressing in respect to preventing wound colonisation or promoting healing , these dressings do however seem to significantly reduce the unpleasant odour commonly associated with battlefield wounds Two hundred fifty patients undergoing heart surgery were r and omized in a prospect i ve comparative study of a semiocclusive hydroactive wound dressing , an occlusive hydrocolloid dressing , and a conventional absorbent dressing . The wounds were evaluated during the 4 weeks after surgery . Color photographs were used for a blind evaluation of wound healing . The conventional absorbent dressing was more effective in wound heating , compared with the hydroactive dressing . Further , there were fewer skin changes and less redness in the wounds with the conventional dressing than with the hydroactive dressing ; the differences were not significant with the hydrocolloid dressing . The conventional dressing was less painful to remove than the hydroactive and hydrocolloid dressings . More frequent dressing changes , however , were needed when using the conventional dressing . Despite this , it was the least expensive alternative PURPOSE : To compare the safety and efficacy of a hydrogel b and age and a collagen corneal shield in providing wound protection and relief of pain/discomfort in the acute period after uneventful unilateral clear corneal phacoemulsification cataract surgery with foldable intraocular lens ( IOL ) implantation . SETTING : Seventeen investigational sites in the United States . DESIGN : Prospect i ve r and omized single‐masked parallel study . METHODS : The study comprised patients scheduled to have unilateral clear corneal cataract surgery with posterior chamber intraocular lens implantation . The patients were examined preoperatively and frequently for 30 days postoperatively . The design was a noninferiority study of the 2 primary endpoints , device performance and maximum reported postoperative pain . RESULTS : The device performance success was 78.6 % ( 228/290 ) for the hydrogel b and age and 26.5 % ( 26/98 ) for the corneal shield ( P<.0001 for noninferiority ) . Analyses indicated that the hydrogel b and age was superior to the corneal shield in device performance ( P<.001 ; difference = 52.1 % ; 95 % confidence interval , 41.6%‐61.4 % ) . The maximum postoperative pain/discomfort score of the hydrogel b and age ( mean 1.3 ± 1.8 [ SD ] ; scale 0 to 10 ) was noninferior to that of the corneal shield ( 1.1 ± 1.6 ) in the first 4 hours after surgery ( P<.001 ) . Adverse events in the cataract surgeries were reported in 22.2 % ( 70/316 ) and 36.5 % ( 38/104 ) of hydrogel b and age patients and corneal shield patients , respectively ( P = .0045 ) . CONCLUSION : The hydrogel b and age was safe and effective for ocular surface protection and relief of pain/discomfort when applied topically to clear corneal incisions used in cataract or IOL implantation surgery . Financial Disclosure : No author has a financial or proprietary interest in any material or method mentioned . Additional disclosures are found in the footnotes OBJECTIVE To determine whether or not the routine use of postoperative dressings prevents surgical site infection and wound dehiscence . MATERIAL AND METHODS Patients with clean or clean-contaminated ( e.g. hernia , orchidectomy cystolithotomy , ureterolithotomy , appendectomy ) sutured surgical wounds were r and omised into two groups : those who did not receive postoperative dressings ( the study group ) and those who did ( the control group ) . Variables like adequate haemostasis , sterile techniques , obliteration of all wound cavities , and approximation of divided structures were not controlled for . Wounds were assessed after 6 and 24 hours , and on the third and fifth postoperative days for clinical signs of infection and dehiscence . RESULTS A total of 123 patients with 124 clean surgical wounds were recruited into the study . The mean age and ratio of men and women in each group were comparable . There was no significant difference in the rate of wound complications between the two groups : 4.76 % for the study group and 4.92 % for control . CONCLUSION Based on these preliminary data , surgical wounds left open do not have an increased incidence of surgical site infection and wound dehiscence , compared with similar types of wounds dressed postoperatively . In a large teaching hospital , the extrapolated cost savings of dressing material s alone can be significant . Larger studies are needed to confirm these results . CONFLICT OF INTEREST None BACKGROUND The consequences of surgical site infections can be severe and range from short-term delays in discharge from the hospital to life-threatening infections such as mediastinitis . OBJECTIVES To evaluate the effectiveness of silver-impregnated dressings in decreasing surgical site infections in children after cardiac surgery . METHODS A r and omized , controlled trial was used to compare silver-impregnated dressings ( 59 participants ) with st and ard dressings ( 58 participants ) . The study team supervised all dressing changes after a sternotomy and ensured adherence with the hospital 's bundle for reduction of surgical site infections . The ASEPSIS tool was used to evaluate sternal wounds for evidence of infection . RESULTS The 2 groups had comparable Risk Adjustment for Congenital Heart Surgery scores , age , sex , weight , height , operating room characteristics , and number of chest tubes and /or pacemaker wires . No surgical site infections occurred in any study participant . Infections did occur , however , during the same period , in cardiac surgical patients who were not enrolled in the study . CONCLUSIONS The evidence did not support the superiority of silver-impregnated dressings for prevention of surgical site infections in children after cardiac surgery . Adherence to a bundle for prevention of surgical site infections may have decreased the incidence of such infections in the study population during the study period PURPOSE Our goal was to evaluate the local hemostatic effect of n-butyl-2-cyanoacrylate ( Histoacryl ; B. Braun , Melsungen , Germany ) glue in warfarin-treated patients who undergo outpatient oral surgery without a change in their level of anticoagulation . MATERIAL S AND METHODS Thirty consecutive warfarin-treated patients r and omly assigned to study and control groups and 10 patients who had never been on anticoagulant therapy serving as the negative control group were included in this trial . Before multiple teeth extraction s , all patients had a prothrombin time and the international normalized ratio ( INR ) determined . To gain hemostasis and primary closure , gelatin sponge and multiple interrupted resorbable sutures were used in the control and negative control groups , and Histoacryl glue and the minimal number of interrupted resorbable sutures were used in the study group . Postoperatively , patients were to contact the oral surgeon if abnormal bleeding occurred . Patients who did not have postoperative bleeding were seen on the 10th postoperative day . Data were collected , and statistical differences in age and gender distributions , number of teeth extracted , INR levels , and bleeding that required treatment were analyzed with the Mantel-Haenzel test . Statistical significance was defined as a value of P < .05 . RESULTS Local hemostasis was obtained immediately in study patients and only after 10 to 20 minutes in the control and negative control patients . In relation to bleeding complications , there were no cases of postoperative bleeding requiring treatment in both the negative control patients and study patients . In the control patients , 5 cases had postoperative spontaneous bleeding that required treatment . This difference was statistically significant . No patient had wound infection and the healing process appeared to be normal . CONCLUSION Multiple extraction s can be performed in patients taking oral anticoagulant therapy without a change in their level of anticoagulation provided an efficient local hemostatic measure is instituted . And , in this regard , Histoacryl glue , used as a topical adhesive over approximated wound edges , is an effective and easily applicable local hemostatic for oral surgery in such patients Surgical site infection ( SSI ) remains an important complication of cardiac surgery . Prevention is important , as SSI is associated with high mortality and morbidity rates . Incisional care is an important daily issue for surgeons . However , there is still scant scientific evidence on which guidelines can be based . A r and omized clinical trial was performed to compare two options for postoperative incisional care . Patients undergoing sternotomy for cardiothoracic surgery were eligible . To protect an incision from exogenous contamination or direct inoculation by endogenous pathogens , the study group received an adhesive drape , impermeable to water and air . The control group was treated with a water- and air-permeable absorbent dressing . Primary outcome measure was SSI . Between March 2003 and January 2005 , 1,185 patients were included . Both groups were comparable for base-line characteristics . No significant difference was found in the incidence of sternal SSI between groups ( 2.6 vs. 3.3 % ) . In our study , an incisional-care program using a sterile , impermeable adhesive drape did not perform better than an absorbent dressing in reducing SSI after cardiothoracic surgery . In our view , future studies in the field of prevention of SSI should concentrate on other areas of interest INTRODUCTION Cutiplast ( absorbent perforated dressing with adhesive border ; Smith & Nephew ) is commonly used following orthopaedic operation , but complications of its use have been reported . A prospect i ve , r and omised , controlled study was performed to compare the efficacy of Cutiplast versus an Aquacel ( hydrofibre dressing ; ConvaTec ) covered with Tegaderm ( vapour-permeable dressing ; 3 M ) . PATIENTS AND METHODS Two-hundred patients were r and omised to receive one of the two dressings following elective and non-elective surgery of the hip and the knee . We were able to study 183 patients . The condition of the wound and any complications such as skin blistering or signs of infection was noted as was the frequency of dressing changes . RESULTS The Aquacel and Tegaderm dressing was 5.8 times more likely to result in a wound with no complications as compared to a Cutiplast dressing ( odds ratio , 5.8 ; 95 % CI 2.8 - 12.5 ; P < 0.00001 ) . CONCLUSION Aquacel covered by Tegaderm is a superior dressing to Cutiplast following surgery to the hip and knee OBJECTIVE To compare effectiveness and costs of gauze-based vs occlusive , moist-environment dressing principles . DESIGN R and omized clinical trial . SETTING Academic Medical Center , Amsterdam , the Netherl and s. PATIENTS Two hundred eighty-five hospitalized surgical patients with open wounds . INTERVENTION Patients received occlusive ( ie , foams , alginates , hydrogels , hydrocolloids , hydrofibers , or films ) or gauze-based dressings until their wounds were completely healed . MAIN OUTCOME MEASURES Primary end points were complete wound healing , pain during dressing changes , and costs . Secondary end point was length of hospital stay . RESULTS Time to complete wound healing did not differ significantly between occlusive ( median , 66 days ; interquartile range [ IQR ] , 29 - 133 days ) and gauze-based dressing groups ( median , 45 days ; IQR , 26 - 106 days ; log-rank P = .31 ) . Postoperative wounds ( 62 % of the wounds included ) healed significantly ( P = .02 ) quicker using gauze dressings ( median , 45 days ; IQR , 22 - 93 days vs median , 72 days ; IQR , 36 - 132 days ) . Median pain scores were low and similar in the occlusive ( 0.90 ; IQR , 0.29 - 2.34 ) and the gauze ( 0.64 ; IQR , 0.22 - 1.95 ) groups ( P = .32 ) . Daily costs of occlusive material s were significantly higher ( occlusive , euro6.34 [ US $ 9.95 ] vs gauze , euro1.85 [ US $ 2.90 ] ; P < .001 ) , but nursing time costs per day were significantly higher when gauze was used ( occlusive , euro1.28 [ US $ 2.01 ] vs gauze , euro2.41 [ US $ 3.78 ] ; P < .001 ) . Total cost for local wound care per patient per day during hospitalization was euro7.48 ( US $ 11.74 ) in the occlusive group and euro3.98 ( US $ 6.25 ) in the gauze-based group ( P = .002 ) . CONCLUSIONS The occlusive , moist-environment dressing principle in the clinical surgical setting does not lead to quicker wound healing or less pain than gauze dressings . The lower costs of less frequent dressing changes do not balance the higher costs of occlusive material s. Trial Registration trialregister.nl Identifier : 56264738 BACKGROUND Surgical site infections ( SSIs ) are complications of surgery that cause significant postoperative morbidity . SSI has been proposed as a potential indicator of the quality of care in the context of clinical governance and monitoring of the performance of NHS organisations against targets . OBJECTIVES We aim ed to address a number of objectives . Firstly , identify risk factors for SSI , criteria for stratifying surgical procedures and evidence about the importance of postdischarge surveillance ( PDS ) . Secondly , test the importance of risk factors for SSI in surveillance data bases and investigate interactions between risk factors . Thirdly , investigate and vali date different definitions of SSI . Lastly , develop models for making risk-adjusted comparisons between hospitals . DATA SOURCES A single hospital surveillance data base was used to address objectives 2 and 3 and the UK Surgical Site Infection Surveillance Service data base to address objective 4 . STUDY DESIGN There were four elements to the research : ( 1 ) systematic review s of risk factors for SSI ( two review ers assessed titles and abstract s of studies identified by the search strategy and the quality of studies was assessed using the Newcastle Ottawa Scale ) ; ( 2 ) assessment of agreement between four SSI definitions ; ( 3 ) validation of definitions of SSI , quantifying their ability to predict clinical outcomes ; and ( 4 ) development of operation-specific risk models for SSI , with hospitals fitted as r and om effects . RESULTS Review s of SSI risk factors other than established SSI risk indices identified other risk ; some were operation specific , but others applied to multiple operations . The factor most commonly identified was duration of preoperative hospital stay . The review of PDS for SSI confirmed the need for PDS if SSIs are to be compared meaningfully over time within an institution . There was wide variation in SSI rate ( SSI% ) using different definitions . Over twice as many wounds were classified as infected by one definition only as were classified as infected by both . Different SSI definitions also classified different wounds as being infected . The two most established SSI definitions had broadly similar ability to predict the chosen clinical outcomes . This finding is paradoxical given the poor agreement between definitions . Elements of each definition not common to both may be important in predicting clinical outcomes or outcomes may depend on only a subset of elements which are common to both . Risk factors fitted in multivariable models and their effects , including age and gender , varied by surgical procedure . Operative duration was an important risk factor for all operations , except for hip replacement . Wound class was included least often because some wound classes were not applicable to all operations or were combined because of small numbers . The American Association of Anesthesiologists class was a consistent risk factor for most operations . CONCLUSIONS The research literature does not allow surgery-specific or generic risk factors to be defined . SSI definitions varied between surveillance programmes and potentially between hospitals . Different definitions do not have good agreement , but the definitions have similar ability to predict outcomes influenced by SSI . Associations between components of the National Nosocomial Infections Surveillance risk index and odds of SSI varied for different surgical procedures . There was no evidence for effect modification by hospital . Estimates of SSI% should be disseminated within institutions to inform infection control . Estimates of SSI% across institutions or countries should be interpreted cautiously and should not be assumed to reflect quality of medical care . Future research should focus on developing an SSI definition that has satisfactory psychometric properties , that can be applied in everyday clinical setting s , includes PDS and is formulated to detect SSIs that are important to patients or health services . FUNDING The National Institute for Health Research Technology Assessment programme OBJECTIVE Wound complications negatively affect outcomes of lower extremity arterial reconstruction . By way of an investigator initiated clinical trial , we tested the hypothesis that a silver-eluting alginate topical surgical dressing would lower wound complication rates in patients undergoing open arterial procedures in the lower extremity . METHODS The study block-r and omized 500 patients at three institutions to st and ard gauze or silver alginate dressings placed over incisions after leg arterial surgery . This original operating room dressing remained until gross soiling , clinical need to remove , or postoperative day 3 , whichever was first . Subsequent care was at the provider 's discretion . The primary end point was 30-day wound complication incidence generally based on National Surgical Quality Improvement Program guidelines . Demographic , clinical , quality of life , and economic end points were also collected . Wound closure was at the surgeon 's discretion . RESULTS Participants ( 72 % male ) were 84 % white , 45 % were diabetic , 41 % had critical limb ischemia , and 32 % had claudication ( with aneurysm , bypass revision , other ) . The overall 30-day wound complication incidence was 30 % , with superficial surgical site infection as the most common . In intent-to-treat analysis , silver alginate had no effect on wound complications . Multivariable analysis showed that Coumadin ( Bristol-Myers Squibb , Princeton , NJ ; odds ratio [ OR ] , 1.72 ; 95 % confidence interval [ CI ] , 1.03 - 2.87 ; P = .03 ) , higher body mass index ( OR , 1.05 ; 95 % CI , 1.01 - 1.09 ; P = .01 ) , and the use of no conduit/ material ( OR , 0.12 ; 95 % CI , 0.82 - 3.59 ; P < .001 ) were independently associated with wound complications . CONCLUSIONS The incidence of wound complications remains high in contemporary open lower extremity arterial surgery . Under the study conditions , a silver-eluting alginate dressing showed no effect on the incidence of wound complications AIM OF THE STUDY It is important to reduce potential wound complications in total hip and total knee arthroplasty procedures . The purpose of this study was to compare the jubilee dressing method to a st and ard adhesive dressing . METHOD 124 patients ( 62 total hip replacements and 62 total knee replacements ) were r and omly selected to have either a st and ard adhesive dressing or jubilee method dressing . The number of dressing changes , incidence of blistering , leakage , appearance of inflammation , infection rate and the average stay in hospital was recorded for each patient . RESULTS The jubilee dressing significantly reduced the rate of blistering , leakage and number of dressing changes when compare to a traditional adhesive dressing ( p < 0.05 ) . The rate of inflammation and average length of stay in hospital was not significantly different between the two groups . CONCLUSION The authors recommend the use of this dressing for total hip and total knee arthroplasty procedures due to the associated lower complication rate A prospect i ve , r and omised study was conducted to compare the wound closure performance and cosmetic outcome of caesarean section wounds closed with traditional Prolene suture or a new wound closure device ( Leukosan ( ® ) SkinLink ) . Sixty-one patients referred to primary section were allocated to wound closure with either Leukosan ( ® ) SkinLink or Prolene suture . Cosmetic outcome as the primary measure was evaluated by the patient , the surgeon as well as by independent examiners blinded to the method of wound closure . Evaluations were recorded at 3 , 6 and 12 months following wound closure . Both methods of wound closure scored equally high on the visual analogue scale for cosmetic evaluation at the 3- , 6- and 12-month follow-ups as assessed by the patient , surgeon and the blinded observers . The study has shown that innovative methods for wound closure compared with traditional methods such as suture providing excellent cosmetic results represent a valid alternative to physician and patient for surgical incisions Background and purpose Following transtibial amputation , a rigid dressing of plaster of Paris has been reported to have advantages over a soft dressing regarding wound healing and reduction of edema , but use of the former may be limited by difficulties in application and in gaining access to the wound . An easily applicable and removable vacuum‐formed rigid dressing ( ORD ) has recently been introduced . We compared the ORD with a conventional rigid plaster of Paris dressing with regard to wound healing , time to fitting of a prosthesis , and function with the prosthesis . Method Patients undergoing transtibial amputation for peripheral vascular disease were r and omized at surgery to receive ORD ( O ) or conventional rigid dressing ( C ) for 5 to 7 days , followed by compression therapy using silicone liner . The primary outcome measure was time to prosthetic fitting and secondary outcome measures included function with the prosthesis 3 months after amputation , measured with the Locomotor Capability Index ( LCI ) and the Timed “ Up and Go ” ( TUG ) test . All patients received prostheses with a total surface‐bearing socket . Results Of 27 patients r and omized to one or other dressing ( 15 O and 12 C ) , prosthetic fitting was achieved in 23 patients ( mean age 76 ( 43 - 91 ) years ; 13 ( 9 men ) in the O group and 10 ( 5 men ) in the C group ) . Wound healing was similar in both groups . Mean time to prosthetic fitting was 37 ( 26 - 54 ) days in the O group and 34 ( 21 - 47 ) days in the C group ( adjusted mean difference 3 , 95 % CI : -3 - 9 ) . At 3 months , mean LCI was 28 ( 6 - 42 ) in the O group and 25 ( 2 - 41 ) in the C group ( mean difference -0.1 , 95 % CI : -8.5 - 8.2 ) . Mean TUG was 41 ( 10 - 92 ) seconds and 29 ( 10 - 47 ) seconds , respectively ( mean difference 14 , 95 % CI:-2 - 30 ) . Interpretation The vacuum‐formed rigid dressing appears to give results similar to those of the conventional rigid dressing regarding time to prosthetic fitting and patient 's function with prosthesis Although studies in the past have demonstrated the safety of exposure of surgical wounds , it is still common practice to dress them post-operatively , a procedure which involves expense in both material s and nursing time . In experimental studies , the healing wound rapidly develops a coagulum of blood and fibrin within two hours of closure , which is impenetrable to bacteria.1'2 Thus , ifthe wound can be kept free of bacteria until this coagulum has formed , infection is unlikely.3'4 In order to investigate the need for surgical dressings , a prospect i ve r and omized trial was performed , comparing a dry dressing of gauze , a polyurethane film dressing ( Opsite ) , and immediate exposure , in non-contaminated elective surgical wounds OBJECTIVE Surgical site infection ( SSI ) after hip fracture surgery is a well-known complication with serious consequences for both the patient and the medical system . Silver ion treatment is considered an effective antibacterial agent , however , the use of silver dressing ( SD ) in the primary prevention of SSIs is controversial . The aims of this study were to compare SD with regular dressing ( RD ) in the prevention of SSI in elderly patients undergoing surgery for hip fractures , and to compare costs . METHOD A matched group of 55 patients with hip fractures undergoing surgery with dynamic hip screw , cephalomedullary nail or hemiarthroplasty were r and omised to either SD or RD groups . The dressings were applied in the operating theatre , and the patients were followed for one week for clinical signs of infection ( discharge , erythema and fever ) . The RDs were replaced daily . The SDs were not removed for 5 - 7 days and kept moist . Skin swabs were taken from the wound surface on postoperative day 5 - 7 for bacterial skin colonisation . RESULTS The SD ( n=31 ) and RD ( n=24 ) groups were similar in age , sex and comorbidities . Infection signs were seen in two ( 2/31 , 6.4 % ) of the SD patients compared with 2 ( 2/24 , 8.3 % ) RD patients ( p=1.0 ) . Skin colonisation by bacteria at postoperative day 5 - 7 was tested in 27 patients : it was higher in the SD group ( positive skin swab , 12/19 , 63.2 % ) compared to the RD group ( 4/8 , 50 % , p=0.67 ) . The use of SD added ~US$5 ( UK ~£3.19 ) per patient . CONCLUSION The use of SD was associated with higher costs than RD , but not superior in preventing SSIs in elderly patients undergoing hemiarthroplasty or fixation of hip fractures . SD was also not effective in reducing bacterial skin colonisation following hip fracture and surgery |
10,812 | 31,827,646 | Conclusion To our knowledge , this is the first comprehensive systematic review and meta- analysis that examines the prognostic role of circulating miRNAs from blood in head and neck cancer patients .
The combined effect estimates a HR across multiple studies and also supports the previous individual findings that an alteration in miRNA expression is highly associated with poor prognosis . | Background Circulating microRNAs ( miRNAs ) are potential molecular biomarkers for cancer detection ; however , little is known about their prognostic role in head and neck cancer .
This current study is aim ed at evaluating the role of novel miRNAs in the survival of head and neck cancer patients . | 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 Recent findings have reported that human serum microRNAs ( miRNAs ) can be used as prognostic biomarkers in various cancers . We aim ed to explore the prognostic value of serum miRNAs in nasopharyngeal carcinoma ( NPC ) patients . The level of serum miRNA was retrospectively analyzed in 512 NPC patients recruited between January 2001 and December 2006 . In the discovery stage , a microarray followed by reverse transcription‐quantitative polymerase chain reaction was used to identify differentially altered miRNAs in eight patients with shorter survival and eight patients with longer survival who were well matched by age , sex and clinical stage . The identified serum miRNAs were then vali date d in all 512 sample s , which were r and omly divided into a training set and a validation set . Four serum miRNAs ( miR‐22 , miR‐572 , miR‐638 and miR‐1234 ) were found to be differentially altered and were used to construct a miRNA signature . Risk scores were calculated to classify the patients into high‐ or low‐risk groups . Patients with high‐risk scores had poorer overall survival [ hazard ratio ( HR ) , 2.54 ; 95 % confidence interval ( CI ) , 1.57–4.12 ; p < 0.001 ] and distant metastasis‐free survival ( HR , 3.28 ; 95 % CI , 1.82–5.94 ; p < 0.001 ) than those with low‐risk scores in the training set ; these results were confirmed in the validation and combined sets . The miRNA signature and TNM stage were independent prognostic factors . The combination of the miRNA signature and TNM stage had a better prognostic value than the TNM stage or miRNA signature alone . The four‐serum miRNA signature may add prognostic value to the TNM staging system and provide information for personalized therapy in NPC Dysregulation of miRNA expression plays an important role in cancer development , and circulating miRNAs are biomarkers of several cancers . We explored whether the miRNAs in plasma could be useful clinical biomarkers for multiple myeloma . miRNA microarray was conducted to identify elevation of four miRNAs and reduced levels of eight miRNAs in the plasma of nine multiple myeloma patients and seven healthy controls . Increased miR-483 - 5p levels and decreased miR-20a were further vali date d in the plasma of 40 myeloma patients and 20 healthy controls using TaqMan quantitative real-time PCR . Receiver operating characteristic ( ROC ) analysis revealed that miR-483 - 5p and miR-20a had considerable diagnostic accuracy , yielding the areas under the ROC curve of 0.745 ( sensitivity 58 % , specificity 90 % ) and 0.74 ( sensitivity 63 % , specificity 85 % ) , respectively . Plasma levels of miR-483 - 5p were associated with ISS staging . Within 14 months of diagnosis , the median progression-free survival of patients with high levels of plasma miR-483 - 5p was 15 months , in comparison with 21 months for patients with low levels of plasma miR-483 - 5p ( p = 0.025 ) . However , miR-20a levels were not correlated with progression-free survival ( p > 0.05 ) . miR-483 - 5p has the potential to be a predictor of myeloma survival |
10,813 | 28,780,649 | There is not enough evidence to support differences in the effects of the different types of sling with regard to this particular postoperative complication | Introduction and hypothesisDe novo overactive bladder ( OAB ) is a known complication of midurethral sling surgery for the treatment of stress urinary incontinence .
To date , differences in the incidence of de novo OAB following the use of different types of midurethral sling remain relatively unknown .
The purpose of the present systematic review was to evaluate this incidence and summarize current evidence . | AIMS To evaluate the prevalence , associated risk factors and the impact on health related quality of life ( HRQoL ) of overactive bladder ( OAB ) among men and women aged ≥18 years in China , using the 2002 International Continence Society ( ICS ) definition . METHODS The population -based , cross-sectional field survey was conducted between June 2009 and February 2010 in China using question naires regarding demographics , the prevalence and the HRQoL. A stratified r and om sample of men and women aged ≥18 years residing in China who were representative of the general population s was selected for demographic question naires first . The individuals meeting the diagnostic criteria of OAB ( urgency occurring once a week or more ) were further interviewed through King 's health question naire ( KHQ ) to estimate the impact of OAB on HRQoL. Data were stratified by city , age cohort , and gender . RESULTS A total of 21,513 individuals were contacted to participate in the survey , and 14,844 individuals ( 7,614 men , 7,230 women ) with complete data were included in this study . The prevalence of OAB was 6.0 % , OAB(dry ) 4.2 % , and OAB(wet ) 1.8 % . The prevalence varied slightly among six geographical regions of China . Nocturia was the most common OAB symptom besides urgency . Advanced age , higher BMI , lower education level , manual worker , alcohol consumption , and married were associated risk factors for OAB in men . Advanced age , lower education level , manual worker , alcohol consumption , married , menopause , more parities and vaginal delivery were potential risk factors for OAB in women . The symptoms of OAB had a detrimental effect on HRQoL , especially on Coping Measures , Sleep/Energy , General Health Perceptions , and Severity of Urinary Problems . CONCLUSIONS The prevalence of OAB in China is lower than that of most previous reports . Many known risk factors are associated with OAB . The symptoms of OAB have a detrimental effect on HRQoL. Efforts need to be made to improve public and professional education about the problems of OAB and decrease the unnecessary burden of this condition Study Type – Symptom prevalence ( prospect i ve cohort BACKGROUND Inside-out transobturator tape ( tension-free vaginal tape-obturator [ TVT-O ] ) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence ( SUI ) . However , data reporting long-term outcomes are lacking . OBJECTIVE To assess the efficacy and safety of TVT-O 10 yr after implantation for the treatment of female pure SUI . DESIGN , SETTING , AND PARTICIPANTS A multicenter , prospect i ve study was conducted in five tertiary referral centers in three countries . All consecutive women with urodynamically proven pure SUI treated by TVT-O were included . Patients with mixed incontinence and /or anatomic evidence of pelvic organ prolapse were excluded . INTERVENTION TVT-O implantation . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Data regarding subjective outcomes ( International Consultation on Incontinence Question naire-Short Form , Patient Global Impression of Improvement , and patient satisfaction scores ) , objective cure ( stress test ) rates , and adverse events were collected during follow-up . Univariable analysis was performed to investigate outcomes . RESULTS AND LIMITATIONS One hundred sixty-eight women had TVT-O implantation . At 10-yr follow-up , 160 patients ( 95 % ) were available for the evaluation . We did not find any significant change of the surgical outcomes during this time . At 10 yr after surgery , 155 of 160 patients ( 97 % ) declared themselves cured ( p=0.7 ) . Similarly , at 10-yr evaluation , 148 of 160 patients ( 92 % ) were objective ly cured . No significant deterioration of objective cure rates was observed over time ( p=0.4 ) . The history of failure of previous anti-incontinence procedures ( hazard ratio : 5.34 ; 95 % CI , 2.61 - 11.9 ; p=0.009 ) was the only predictor of recurrence of SUI . The onset of de novo overactive bladder was reported by 23 of 160 patients ( 14 % ) at 10-yr follow-up . No other late complications were reported . CONCLUSIONS The 10-yr results of this study showed that TVT-O is a highly effective and safe option for the treatment of SUI . PATIENT SUMMARY At long-term follow up , tension-free vaginal tape-obturator is highly effective and safe for the treatment of stress urinary incontinence BACKGROUND No studies have been published comparing the U- and H-type methods of the TVT SECUR ( TVT-S ) procedure . OBJECTIVE Our aim was to compare the efficacy and safety of the two types of TVT-S for female stress urinary incontinence ( SUI ) . DESIGN , SETTING , AND PARTICIPANTS Women with urodynamic SUI were enrolled in this 12-mo multicenter r and omized study . INTERVENTION Subjects were r and omly allocated to either the U- or H-type method of TVT-S. MEASUREMENTS Pre- and postoperative evaluations included a st and ing stress test , the S and vik question naire , the Incontinence Quality of Life ( I-QOL ) question naire , and the International Consultation on Incontinence Question naire-Female Lower Urinary Tract Symptoms ( ICIQ-FLUTS ) . Patients ' satisfaction and complications were evaluated . Objective and subjective cures were defined as no leakage on the stress test and responses on the S and vik question naire , respectively . We compared the surgical outcomes between the two methods . RESULTS AND LIMITATIONS Of 285 women , 144 had the U-type method and 141 had the H-type method . Objective cure rates were 87.5 % for the U-type method and 80.1 % for the H-type method ( p=0.091 ) . Subjective cure rates were 77.1 % for the U-type method and 75.7 % for the H-type method ( p=0.786 ) . Improvement in I-QOL and domain scores of the ICIQ-FLUTS ( filling and incontinence sum , QOL score ) , and patients ' satisfaction favored the U-type method . There were three cases of intraoperative vaginal wall perforation , one case of increased bleeding , and three cases of temporary postoperative retention . A power calculation was not performed , and some baseline characteristics were not balanced between the two methods . CONCLUSIONS Both methods of TVT-S provided comparable cure rates for female SUI . However , QOL and treatment satisfaction favored the U-type method . TRIAL REGISTRATION The protocol of this study was not registered OBJECTIVE To assess the efficacy and complications associated with use of the TVT SECUR System device with placement of the tape in either a " hammock " or " U " position for management of stress urinary incontinence ( SUI ) . METHODS A prospect i ve study of patients with SUI allocated into one of two groups : " hammock " or " U " tape placement . Preoperative urodynamic results were compared with results at the 6-month and 1-year follow up . Outcome measures were objective cough test assessment and subjective patient responses to a question naire at follow up . RESULTS Of 82 patients included in the study , 43 comprised the " hammock " group and 39 comprised the " U " group . The objective cure rate at 1-year follow up was 62.8 % ( n=27 ) in the " hammock " group and 71.8 % ( n=28 ) in the " U " group . At 1-year follow up , the subjective cure , improvement , and failure rates for the " hammock " group were 60.5 % , 13.9 % , and 25.7 % respectively , and 69.2 % , 12.8 % , and 17.9 % respectively , for the " U " group . CONCLUSION The efficacy of the TVT SECUR System was lower ( < 72 % ) than the cure rates reported for other TVT procedures ; further studies are required Introduction and hypothesisThe aim of this study was to compare the efficacy of the tension-free vaginal tape obturator ( TVT-O ) and single-incision tension-free vaginal tape ( Ajust ™ ) in the treatment of stress urinary incontinence in a r and omized two-arm study with a 1-year follow-up . Methods This single-centre r and omized trial compared the objective and subjective cure rates of TVT-O and Ajust using objective criteria ( cough test ) and subjective criteria ( International Consultation on Incontinence Question naire short form , ICIQ-UI SF ) . The objective cure rate was defined as the number of patients with a negative cough stress test . Subjective cure was defined as no stress leakage of urine after surgery based on the ICIQ-UI SF . The primary outcome was to establish differences in objective and subjective cure rates between the TVT-O and Ajust groups . We also compared postoperative pain profiles using a visual analogue scale ( VAS ) , improvement in quality of life using the ICIQ- UI SF and the Incontinence Quality of Life question naire , and overall satisfaction with the surgical procedure using a VAS and a five-item Likert scale . Inclusion criteria were age over 18 years , signed informed consent , and urodynamic stress urinary incontinence . Following a power calculation , 50 patients were enrolled into each group ( Ajust and TVT-O ) . Results The mean follow-up after surgery was 445 days ( SD 157.6 days ) in the TVT-O group and 451.8 days ( SD 127.6 days ) in the Ajust group ( p = 76.6 % ) . At 1 year , 47 patients were evaluated in the TVT-O group and 49 in the Ajust group . No differences in subjective cure rates or objective cure rates were observed . In the Ajust and TVT-O groups , the rates for no subjective stress leakage were 89.8 % and 91.5 % , respectively ( p = 1.0 , OR 1.22 , 95 % CI 0.24 – 6.58 ) , and the rates for a negative stress test were 89.8 % and 87.2 % , respectively ( p = 0.76 , OR 0.77 , 95 % CI 0.17 – 3.32 ) . In the Ajust group two patients reported de novo pain during sexual intercourse . Conclusions After a 1-year-follow-up , no significant differences were found with regard to subjective and objective outcomes between the single-incision tape Ajust and Background : Food and Drug Administration announcements have highlighted the st and ard rate of mesh-related complications . We aim ed to report the short-term results and complications of tension-free polypropylene mesh ( PROSIMA ™ ) surgical repair of pelvic organ prolapse ( POP ) using the st and ard category ( C ) , timing ( T ) , and site ( S ) classification system . Methods : A prospect i ve cohort study of 48 patients who underwent PROSIMA ™ mesh kit-related surgical repairs were followed for two years at Peking Union Medical College Hospital . Recurrence was defined as symptomatic POP quantification ( POP-Q ) Stage II or higher ( leading edge ≥ −1 cm ) . The Patient Global Impression of Change Question naire , the Chinese version of the Pelvic Floor Impact Question naire short-form-7 and POP/Urinary Incontinence Sexual Question naire short-form-12 were used to evaluate the self-perception and sexual function of each patient . Mesh-related complications conformed to the International Urogynecological Association/International Continence Society joint terminology . The paired- sample t-test , one-way analysis of variance , Fisher 's exact test , Kaplan-Meier survival analysis and log-rank test were used to analyze data . Results : All patients were followed up for ≥12 months ; 30 ( 62.5 % ) patients completed the 24 months study . We observed a 93.8 % ( 45/48 ) positive anatomical outcome rate at 12 months and 90.0 % ( 27/30 ) at 24 months . Recurrence most frequently involved the anterior compartment ( P < 0.05 ) . Pelvic symptoms improved significantly from baseline ( P < 0.05 ) , although the patients ’ impressions of change and sexual function were not satisfying . Vaginal complication was the main complication observed ( 35.4 % , 17/48 ) . The survival analysis did not identify any relationship between vaginal complication and anatomical recurrent prolapse ( POP-Q ≥ Stage II ) ( P = 0.653 ) . Conclusions : Tension-free polypropylene mesh (PROSIMA ™ )-related surgical repair of POP has better short-term anatomical outcomes at the apical and posterior compartments , but a low patient satisfaction rate . The mesh complications were not the definitive cause of recurrence Introduction and hypothesis Data on Altis ® ( Coloplast ) , a new adjustable single-incision sling ( SIS ) procedure for the treatment of female stress urinary incontinence ( SUI ) , are scarce . Our aim was to evaluate the efficacy and complication rates of this procedure . Methods In this prospect i ve observational study , a total of 52 women with SUI were implanted with an Altis ® sling in an ambulatory setting . Before and after intervention ( 3 , 6 , and 12 months ) , women completed the International Consultation on Incontinence Question naire Short Form ( ICIQ-SF ) . In addition , patients underwent a cough stress test at each evaluation and a post-voiding residual urine volume estimation at 3 months . The main outcomes measured were subjective cure ( ICIQ-SF = 0 ) , subjective improvement ( ICIQ-SF > 0 and < preoperative ICIQ-SF ) , and objective cure ( negative cough stress test and no pad usage ) rates . De novo overactive bladder ( OAB ) symptoms , changes in voiding habits and adverse events were also analyzed . Results The subjective cure rate at 12 months was 84.0 % , with an additional improvement rate of 8.0 % . The objective cure rate was 90.2 % . Later postoperative complications included 1 case of vaginal extrusion ( requiring surgical removal of the eroded mesh segment ) , 3 cases of vaginal exposure of the adjustment thread ( managed conservatively ) , de novo urgency in 3 patients , and mild dyspareunia in 2 patients . Conclusions The Altis ® sling is a safe and effective SIS procedure for the treatment of SUI with a short-term follow-up OBJECTIVES To compare the 5-year subjective and objective outcomes of transobturator tension-free vaginal tape alone versus the same procedure with concomitant pelvic floor repair surgery for pelvic organ prolapse in women with urinary stress incontinence . DESIGN Prospect i ve cohort study . SETTING Urogynaecology unit at a university hospital in Hong Kong . PATIENTS Of 218 women , 96 ( 44 % ) received transobturator tension-free vaginal tape alone and 122 ( 56 % ) received transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery from September 2004 to December 2009 . The women were followed up annually for up to 5 years after the operation . MAIN OUTCOME MEASURES The 5-year subjective and objective cure rates were assessed . Subjective cure was defined as no urine loss during physical activity and objective cure was defined as no urine leakage on coughing during urodynamic study . RESULTS Overall , 88 women receiving transobturator tension-free vaginal tape alone and 101 women receiving transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery were followed up for 5 years after operation . The subjective and objective cure rates of the two groups were 70.5 % versus 94.1 % ( P<0.01 ) and 80.3 % versus 85.7 % ( P=0.58 ) , respectively . CONCLUSIONS Transobturator tension-free vaginal tape is an effective treatment for urinary stress incontinence in women who received it alone or with concomitant pelvic floor repair surgery for pelvic organ prolapse , providing high subjective and objective efficacy for up to 5 years after operation . Transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery achieved similar , if not better , long-term outcome compared with transobturator tension-free vaginal tape alone Study design : Retrospective review of prospect ively collected data . Objectives : Stress urinary incontinence ( SUI ) is a cause of significant distress in women with neurogenic bladder dysfunction ( NBD ) due to spinal cord injury ( SCI ) . Transobturator tape ( TOT ) has not previously been studied in this select group for cure of SUI . We aim to determine the long-term safety and efficacy of TOT in SCI patients with NBD and SUI . Setting : London , the United Kingdom . Methods : All patients undergoing TOT between 2005 and 2013 were identified ( 27 patients ) . All patients had pre-operative videocystometrogram ( VCMG ) and all had VCMG-proven SUI . Mean follow-up was 5.2 years . Patient-reported leakage , satisfaction , change in bladder management , complications and de novo overactive bladder ( OAB ) were recorded . Results : Mean age was 56 years ( range 30–82 ) with complete follow-up . Twenty-two patients ( 81.5 % ) reported complete dryness from SUI post surgery . One patient ( 3.7 % ) reported SUI only when her bladder was very full but was satisfied . Twenty-three patients ( 85.2 % ) were happy . Four patients ( 14.8 % ) remained wet . Twenty-five patients ( 92.6 % ) had no change in bladder management . Two out of five patients ( 40 % ) who voided by straining prior to surgery required clean intermittent self-catheterisation ( CISC ) post-operatively . Two patients ( 7.4 % ) developed de novo OAB . No bladder or vaginal injuries , tape erosions or urethral obstruction were seen . Three patients ( 11.1 % ) had transient thigh pain . Conclusion : In women with NBD and SUI , TOT should be considered safe and effective with very good medium/long-term outcomes . There may be an increased risk of CISC in women who void by straining pre-operatively Introduction and hypothesisThe aim of this study was to evaluate the effectiveness of and morbidity associated with the tension-free vaginal tape-secur ( TVT-S ) procedure in women with stress urinary incontinence ( SUI ) . Methods We performed a prospect i ve trial , examining 86 women with primary SUI . Eighty-two patients had a 1-year follow-up ( dropout rate = 4.6 % ) . The preoperative evaluation included urinalysis , urodynamic studies , and vali date d question naires . The 1-year outcome evaluation also included a 1-h pad testing . Results At the 1-year follow-up , 43 ( 52.4 % ) women were objective ly cured , and 14 ( 17.1 % ) women were objective ly improved . Subjectively , 49 ( 59.7 % ) patients did not experience urine loss , and 18 ( 22.2 % ) women improved in this respect . Postoperative de novo urge incontinence symptoms developed in 24.4 % ( n = 20 ) of patients . Vaginal defect healing occurred in 6.1 % ( n = 5 ) of patients , and one ( 1.2 % ) case of urethral erosion was reported . Conclusion Objective and subjective cure rates following TVT-S are inferior to other tape procedures BACKGROUND TVT-Secur has been described as a new minimally invasive sling for women 's stress urinary incontinence ( SUI ) management , showing promising results in short-term studies . OBJECTIVE Our goal was to evaluate the outcome of this procedure after a midterm follow-up . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve evaluation involved 45 consecutive patients presenting SUI associated with urethral hypermobility . Fourteen patients preoperatively reported overactive bladder ( OAB ) symptoms , but none had objective detrusor overactivity . Eight patients had low maximal urethral closure pressure ( MUCP ) . Four patients had pelvic organ prolapse ( POP ) . INTERVENTION Patients with POP were treated under general anesthesia by Prolift and TVT-Secur procedure . The 41 other patients received TVT-Secur under local anesthesia on an outpatient basis . All interventions were made by the same surgeon . MEASUREMENTS Postoperative assessment included pad count , bladder diary , clinical examination with stress test , evaluation of satisfaction with the Patient Global Impression of Improvement ( PGI-I ) scale , and evaluation of side effects . Patients were classified as cured if they used no pads , had no leakage , and had a PGI-I score < or = 2 ; as improved in case of reduction of SUI symptoms > 50 % and PGI-I score < or = 3 ; and as failure otherwise . RESULTS AND LIMITATIONS Mean postoperative follow-up was 30.2 + /- 9.8 mo ( range : 11 - 40 mo ) . Short-term evaluation showed a 93.5 % success rate , but , at last follow-up , only 18 ( 40 % ) patients were cured , while 8 ( 18 % ) were improved , and 19 ( 42 % ) failed . Twelve patients underwent implantation of TVT or transobturator tape during follow-up . Age , MUCP , or OAB were not associated with failure . Side effects were limited to five cases of de novo OAB and three cases of urinary tract infection . This work is limited by the absence of a comparison group . CONCLUSIONS Our experience shows that despite its good short-term efficacy , TVT-Secur is associated with a high recurrence rate of SUI . Therefore , TVT-Secur does not seem appropriate for SUI first-line management in women The objective of this study is to evaluate the efficacy and morbidity of the new minimally invasive TVT-secur procedure . This was a prospect i ve multi-centre trial . All patients with primary urodynamic stress urinary incontinence were prospect ively selected to receive the TVT-secur procedure . The International Consultation on Incontinence — Short Form ( ICIQ-SF ) , Women Irritative Prostate Symptoms Score ( W-IPSS ) , Patient Global Impression of Severity ( PGI-S ) and Patient Global Impression of Improvement ( PGI-I ) question naires were used to evaluate the impact of incontinence and voiding dysfunction on quality of life ( QoL ) and to measure patient ’s perception of incontinence severity and improvement . The SPSS software was used for data analysis . From November 2006 to September 2007 , 95 consecutive patients were enrolled in the study . At 1 year , 91 patients were available for the analysis . The subjective and objective cure rates were 78 % and 81 % , respectively . The ICIQ-SF and W-IPSS symptoms score showed a statistically significant decrease . Post-operative complications included voiding difficulty , recurrent UTI , de novo urgency incontinence and dyspareunia . Our data show that TVT-secur is associated with an 80 % success rate at 1 year Our objective was to evaluate the complications and early follow-up of the tension-free vaginal tape (TVT)-SECUR , a new minimally invasive anti-incontinence operative procedure . A prospect i ve , observational , and consecutive patient series was conducted . Perioperative and 12-month postoperative data were prospect ively collected for the first 50 patients against the next consecutive 50 patients , among which TVT-SECUR specific surgical measurements were adopted ( Canadian Task Force classification 2 ) . In private hospital operative theatres , the TVT-SECUR operation was performed . Patients with urodynamically proved stress urinary incontinence were enrolled in this study after detailed informed consent was given . The TVT-SECUR , in the hammock shape to mimic the TVT-obturator placement , yet with no skin incisions , required neither bladder catheterization nor intraoperative diagnostic cystoscopy . The clinical and surgical data of 100 consecutive patients with TVT-SECUR were collected prospect ively . Two patients had urinary obstructions and needed surgical tape-tension relief . One patient had a 50 mL paravesical self-remitting hematoma . At the first-month postoperative follow-up appointment , the objective therapeutic failure rate for the TVT-SECUR procedure among the 50 patients was 20.0 % ( 10 patients ) . But when the tape was placed close to the urethra with no space allowed in between , the failure rate in the second patient group went down to 8.0 % ( 4 patients ) ; yet no further postoperative bladder outlet obstruction was diagnosed . Four ( 8.0 % ) patients in the first group had vaginal wall penetration with the inserters , requiring withdrawal , reinsertion , and vaginal wall repair . This was avoided with the second patient group by facilitating the inserters ' introduction by widening the submucosal tunnel to 12 mm . Six ( 12.0 % ) other patients in the first group needed postoperative trimming of a vaginally extruded tape segment , performed in the office with satisfactory results . This problem was addressed later by making the submucosal dissection deeper to avoid intimate proximity of the tape with the vaginal mucosa . Consequently the tape protrusion rate was reduced to 8 % ( 4 patients ) . Five ( 10.0 % ) patients in the first group had unintended tape removal at the time of inserter removal , necessitating the use of a second TVT-SECUR . This was addressed by meticulous detachment of the inserter before its withdrawal , after which no further unintended tape displacements were recorded . No clinical signs for bowel , bladder , or urethral injuries ; intraoperative bleeding ; or postoperative infections were evident . Telephone interview at the end of 12 months postoperatively was completed with 44 ( 88.0 % ) of the first patient group and 46 ( 92 % ) of the second patient group . In all , 39 ( 88.6 % ) and 43 ( 93.5 % ) of the telephone-interviewed patients of the first and second groups , respectively , reported objective urinary continence . The TVT-SECUR , a new midurethral sling , was associated with early safety and efficacy problems . These were identified and rectified , to make the TVT-SECUR a safe and effective anti-incontinence procedure . Operative complications associated with the TVT , such as bladder penetration and postoperative outlet obstruction , and TVT-obturator complications , such as postoperative thigh pain and bladder outlet obstruction , may be reduced with the TVT-SECUR . The first 100 operations ' cumulative data analysis yielded some insights , including the necessity of meticulous and proper dissection before placement of the tape and the need for applying minimal extra tension to the tape . However , long-term comparative data collection will be required to draw solid conclusions regarding the appropriate position of this operative technique within the spectrum of anti-incontinence operations OBJECTIVE The purpose of this study was to compare outcomes after anterior colporrhaphy with the use of 3 different surgical techniques . STUDY DESIGN One hundred fourteen women with anterior vaginal prolapse were r and omly assigned to undergo anterior repair by one of 3 techniques : st and ard , st and ard plus polyglactin 910 mesh , or ultralateral anterior colporrhaphy . Before and after operation , patients underwent physical examination staging of prolapse ; the International Continence Society system was used . Symptoms were assessed by question naire and visual analog scales . We defined " cure " as satisfactory ( stage I ) or optimal ( stage 0 ) outcome at points Aa and Ba . RESULTS Of 114 patients who were originally enrolled , 109 patients underwent operation , and 83 patients ( 76 % ) returned for follow-up . Mean age ( + /- SD ) was 64.7 + /- 11.1 years . At entry , 7 patients ( 7 % ) had stage I anterior vaginal prolapse ; 35 patients ( 37 % ) had stage II anterior vaginal prolapse ; 51 patients ( 54 % ) had stage III anterior vaginal prolapse ; and 2 patients ( 2 % ) had stage IV anterior vaginal prolapse . At a median length of follow-up of 23.3 months , 10 of 33 patients ( 30 % ) who were r and omly assigned to the st and ard anterior colporrhaphy group experienced satisfactory or optimal anatomic results , compared with 11 of 26 patients ( 42 % ) with st and ard plus mesh and with 11 of 24 patients ( 46 % ) with ultralateral anterior colporrhaphy . The severity of symptoms that were related to prolapse improved markedly ( preoperative score , 6.9 + /- 2.7 ; postoperative score , 1.1 + /- 0.8 ) . Twenty-three of 24 patients ( 96 % ) no longer required manual pressure to void after operation . CONCLUSION These 3 techniques of anterior colporrhaphy provided similar anatomic cure rates and symptom resolution for anterior vaginal prolapse repair . The addition of polyglactin 910 mesh did not improve the cure rate compared with st and ard anterior colporrhaphy OBJECTIVE To compare the effects of two surgical procedures for the correction of anterior vaginal wall prolapse ( AVWP ) on the lower urinary tract symptoms ( LUTS ) using symptom question naires and quality of life ( QoL ) . MATERIAL S AND METHODS One hundred women with Pelvic Organ Prolapse Quantification stage ( POP-Q ) ≥ 2 were r and omly distributed in two preoperatory groups . The first group ( mesh ) ( n = 45 ) received a polypropylene mesh ( PM ) implant and the control group ( n = 55 ) was su bmi tted to anterior colporraphy with or without synthetic sling . Postoperatory follow-up was done after 12 months . The primary objective was to compare the effect of the surgeries on LUTS using the final scores of the International Consultation on Incontinence Question naire Urinary Incontinence Short Form ( ICIQ-UI SF ) and Overactive Bladder Question naire ( OAB-V8 ) , as well as the analysis of the incapacitating urinary symptoms and ″de novo″ urinary symptoms after 12 months of surgery in both groups . RESULTS Although there was a different number of women in each group , r and omization was adequate , result ed in homogeneous groups that could be compared regarding socio demographic , clinical and gynecological ( POP-Q ) variables . Patients of both groups showed improvements regarding LUTS and QoL , whether using polypropylene mesh or not , based on the final scores of the ICIQ-UI SF and OAB-V8 question naires after 12-month follow-up . There were few incapacitating and ″de novo ″ urinary symptoms , without any significant statistical difference between both groups after 12 months of surgery . CONCLUSION There was a general improvement of LUTS and QoL in both groups after 12-month follow-up . However , there was no significant difference of LUTS , as well as the more incapacitating and ″de novo ″ urinary symptoms between both groups after 12 months of surgery OBJECTIVE To compare the perioperative complications , failure rate , operating time , and length of hospital stay associated with 2 minimally invasive suburethral slings in the management of stress urinary incontinence in women . METHODS Women diagnosed with stress urinary incontinence were treated with tension-free vaginal tape ( TVT ) or transobturator tape ( TOT ) . The participants were followed for the next 2 years , with scheduled evaluations 6 weeks , then 3 , 6 , 12 , and 24 months after surgery . RESULTS Of the 104 participants , 55 were treated with TVT and 49 were treated with TOT . The condition was classified as " cured " in 81.8 % of cases in the TVT group and 83.7 % in the TOT group , and improvement occurred in 10.9 % and 10.2 % of cases , respectively . The mean operating time was shorter for patients treated with TOT than for those treated with TVT . There were no significant differences between the groups in terms of perioperative complications ( abnormal voiding dysfunction , urinary infections , and de novo overactive bladder ) . The temporary and permanent urinary obstruction rates in the TVT group were approximately twice those in the TOT group . CONCLUSION Comparable complications and outcomes were observed with TVT and TOT . Tension-free vaginal implants are effective for the treatment of female stress urinary incontinence OBJECTIVE To prospect ively evaluate the efficacy of a tension-free vaginal mesh ( TVM ) procedure for pelvic organ prolapse ( POP ) . METHODS Between December 2005 and April 2008 , 310 female patients ( mean age 67.2 years , range 42 - 84 ) with POP underwent TVM procedures at our institute . Fifty-six individuals were qualified as stage 2 according to the POP quantification system and 162 and 92 were stage 3 and 4 , respectively . One hundred ninety-one patients underwent anterior TVM , and seven underwent posterior TVM . One hundred twelve cases underwent both anterior and posterior TVM procedures . Each patient was systematic ally assessed at 1 , 3 , 6 and 12 months after surgery . Quality of life ( QOL ) was also assessed by using the Short Form-36 and the prolapse-QOL question naires . RESULTS Perioperative complications were the following : five bladder injuries ( 1.6 % ) , no rectal injuries and three hemorrhages greater than 400 mL ( 1.0 % ) . The anatomical cure rate ( % stage 0 cases ) at 3 , 6 and 12 months after surgery were 94.1 % , 93.5 % , and 92.3 % , respectively . Short Form-36 and prolapse-QOL parameters were significantly improved , and maintained during the follow-up period . Postoperative complications were the following : five pelvic hematomas ( 1.6 % ) , one wound infection ( 0.3 % ) , 10 vaginal mesh extrusions ( 3.2 % ) , and three cases of pelvic pain ( 1.0 % ) . Complications concerning lower urinary tract function were : eight cases of postoperative stress urinary incontinence ( 2.6 % ) , three cases of transient urinary retention ( 1.0 % ) , and two cases of de novo overactive bladder ( 0.6 % ) . CONCLUSIONS The TVM procedure provides a good outcome at 1 year with a low incidence of surgical complications and recurrence . Further evaluation with a longer follow up is needed BACKGROUND Midurethral slings have become the most preferred surgical treatment for female urinary incontinence . OBJECTIVE To compare the efficacy and safety of two midurethral sling procedures with a different technique of sling insertion 5 yr after intervention . DESIGN , SETTING , AND PARTICIPANTS Multicenter r and omized clinical trial conducted in seven public hospitals in Finl and including primary cases of stress urinary incontinence . INTERVENTION Surgical treatment with the retropubic tension-free vaginal tape ( TVT ) procedure or the transobturator tension-free vaginal tape ( TVT-O ) procedure . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Objective treatment success criteria were a negative stress test , a negative 24-h pad test , and no retreatment for stress incontinence . Patient satisfaction was assessed by condition-specific quality -of-life question naires . RESULTS AND LIMITATIONS A total of 95 % of the included women could be assessed according to the protocol 5 yr after surgery . The objective cure rate was 84.7 % in the TVT group and 86.2 % in the TVT-O group , with no statistical difference between the groups . Subjective treatment satisfaction was 94.2 % in the TVT group and 91.7 % in the TVT-O group , with no difference between groups . Complication rates were low , with no difference between groups . CONCLUSIONS Both objective and subjective cure rates were > 80 % in both groups even when women lost to follow-up were included as failures . The complication rates were low , with no difference between the groups . No late-onset adverse effects of the tape material were seen . PATIENT SUMMARY Female urinary stress incontinence can be treated surgically with minimally invasive midurethral sling procedures . Two main approaches of sling placement have been developed : the retropubic and the transobturatory . We compared both approaches and followed the patients for 5 yr . We found no difference in cure rate between the procedures , and patient satisfaction was high . TRIAL REGISTRATION Clinical Trials.gov identifier NCT00379314 OBJECTIVES To analyze the safety and efficacy of the trans-obturator tension-free vaginal tape ( TVT-O ) in elderly versus younger stress-incontinent women . METHODS Ninety-seven consecutive elderly , aged 70 and older , and 256 younger women ( mean age 75 and 55 years , respectively ) who underwent TVT-O for urodynamically confirmed stress urinary incontinence ( SUI ) were prospect ively enrolled . Concomitant pelvic organ prolapse ( POP ) repair was performed in 90 % of the elderly and 70 % of the younger women . The surgical procedures , as well as all pre- and postoperative clinical and urodynamic evaluation , were performed in one university-affiliated medical center . Main outcome measures were operative complications , early and late postoperative morbidity , postoperative urodynamically confirmed SUI ( symptomatic , or asymptomatic ) , persistent , or de novo overactive bladder ( OAB ) and bladder outlet obstruction ( BOO ) . RESULTS Mean follow-up of the patients was 30 ± 17 months ( range 3 - 58 months ) . Early and late postoperative morbidity was similar in both groups , except for significantly more cases of postoperative recurrent UTI 's among elderly women ( 13.7 % vs. 6.2 % ) . The incidence of persistent urodynamically confirmed overt SUI was similar in both age groups ( 5 % ) . However , asymptomatic urodynamic SUI was significantly more common among elderly patients ( 19 % vs. 3.7 % , P<0.05 ) . The incidence of persistent OAB was similar in elderly and younger patients ( 68 % and 62 % , respectively ) , while de novo OAB was significantly more common in elderly patients ( 11.9 % vs. 4.7 % , P<0.05 ) . CONCLUSIONS TVT-O is safe and efficient for both elderly and younger stress-incontinent women . However , elderly patients are in increased risk for postoperative recurrent UTI 's as well as de novo OAB Since the introduction of original tension-free vaginal tape in 1995 , a number of different suburethral slings have been marketed . Much of the published literature on midurethral sling procedures relates to the original TVT . Although there has been a considerable number of publications comparing different routes of tape insertion , there is relatively little published identifying the efficacy of different retropubic slings . This study was design ed to identify the success rate and complications in a case series of Advantage slings . A total of 70 women were assessed 6 months after insertion of an Advantage midurethral sling by question naire . The absence of stress incontinence was reported in 94 % of women . There were no intraoperative complications . Only 3 % had short-term voiding dysfunction ( < 6 weeks ) . De novo overactive bladder symptoms developed in 3 % of women . The Advantage sling has a good success rate , with low complications |
10,814 | 29,498,126 | The results from this systematic review and meta- analysis have shown that lateral ridge augmentation procedures can maintain peri-implant health over time with low mucosal inflammatory changes and a relatively small incidence of peri-implant bone loss | OBJECTIVES This systematic review evaluated the evidence on the effect of the interventions aim ed for lateral ridge augmentation ( both simultaneously with implant placement or as a staged procedure ) on peri-implant health or disease . | AIM The aim of the present prospect i ve study was to evaluate the long-term outcome of implants placed simultaneously with guided bone regeneration ( GBR ) using resorbable and non-resorbable membranes . MATERIAL S AND METHODS The original study population consisted of 72 patients receiving a total of 265 implants . In all GBR-treated sites , demineralized bovine bone mineral ( DBBM ) was used in combination either with a collagen ( CM ) or an Exp and ed polytetrafluoroethylene ( e-PTFE ) membrane . A total of 112 implants was treated with CM , 41 implants were treated with e-PTFE membranes , and 112 served as a control group because implants were entirely surrounded by bone and did not need any GBR procedures . Clinical and radiographic analyses were performed after a period of 12 - 14 years . RESULTS The median follow-up time was 12.5 years ( range 12 - 14 years ) . A total of 58 patients participated in the present investigation , corresponding to 80.5 % of the original study population . The cumulative implant survival rate at the follow-up examination was 93.2 % . For the control group the cumulative survival rate was 94.6 % , for the CM 91.9 % , and for the e-PTFE 92.6 % . Differences among the groups were not statistically significant . The radiographically determined marginal bone level ( MBL ) amounted to : control 2.36 mm ( SD ) , CM 2.4 mm ( SD ) , e-PTFE 2.53 mm ( SD ) . There is no evidence ( P < 0.2 ) that the slope of bone level over time is different for the three treatment groups . CONCLUSION It is concluded that implants placed simultaneously with GBR procedures using resorbable or non-resorbable membranes reveal a high survival rate ranging from 91.9 % to 92.6 % , therefore it is considered to be a safe and predictable therapy . [ Correction added after online publication 30 November 2012 : the marginal bone level of CM , e-PTFE , and control was corrected to ' control 2.36 mm ( SD ) , CM 2.4 mm ( SD ) , e-PTFE 2.53 mm ( SD ) ' in the Results section ] BACKGROUND Two systematic review s have evaluated the quality of research and reporting of observational studies investigating the prevalence of , the incidence of and the risk factors for peri-implant diseases and of experimental clinical studies evaluating the efficacy of preventive and therapeutic interventions . MATERIAL S AND METHODS For the improvement of the quality of reporting for both observational and experimental studies , the STROBE and the Modified CONSORT recommendations were encouraged . RESULTS To improve the quality of research in peri-implant diseases , the following were recommended : the use of unequivocal case definitions ; the expression of outcomes at the subject rather than the implant level ; the implementation of study validation tools ; the reporting of potential sources of bias ; and the use of appropriate statistical methods . CONCLUSIONS In observational studies , case definitions for peri-implantitis were agreed . For risk factor determination , the progressive use of cross-sectional and case-control studies ( univariate analyses ) , to prospect i ve cohorts ( multilevel modelling for confounding ) , and ultimately to intervention studies were recommended . For preventive and interventional studies of peri-implant disease management , parallel arm RCTs of at least 6-months were encouraged . For studies of non-surgical and surgical management of peri-implantitis , the use of a composite therapeutic end point was advocated . The development of st and ard control therapies was deemed essential PURPOSE The aim of the present r and omized controlled clinical study was to test whether small bony dehiscence defects ( ≤5 mm ) left to heal spontaneously result in the same clinical and radiological outcome as defects treated with guided bone regeneration ( GBR ) . MATERIAL S AND METHODS Twenty-two patients who received at least one implant with a small bony dehiscence defect were enrolled in the study . If the defect height was ≤5 mm , the site was r and omly assigned to either the spontaneous healing ( SH ) group or the GBR group . In the SH group , the defect was left without any treatment . In the GBR group , the defects around the implants were grafted with deproteinized bovine bone mineral ( DBBM ) and covered with a native collagen membrane . Clinical and radiographic measurements were performed 6 months after implant placement with a reentry surgery and at the time of crown insertion and the subsequent follow-up appointments at 3 , 6 , 12 and 18 months after loading . For statistical analyses , the mixed linear model was applied for the clinical and radiographic measurements observed around the implants . Simple comparisons of the location of the measurements in the two independent groups are performed with the Mann-Whitney U-test . In addition , the mixed model assumptions were checked . RESULTS The implant and crown survival rate 18 months after loading was 100 % , revealing no serious biologic or prosthetic complication . The mean changes of the buccal vertical bone height between implant placement and reentry surgery after 6 months revealed a small bone loss of -0.17 ± 1.79 mm ( minimum -4 mm and maximum 2.5 mm ) for the SH group and a bone gain of 1.79 ± 2.24 mm ( minimum of -2.5 mm and maximum of 5 mm ) for the GBR group , respectively ( P = 0.017 ) . Radiographic measurements demonstrated a slight bone loss of -0.39 ± 0.49 mm for the SH group and a stable bone level of 0.02 ± 0.48 mm for GBR group after 18 months . All peri-implant soft tissue parameters revealed healthy tissues with no difference between the two groups . CONCLUSION Small bony dehiscence defects left for spontaneous healing demonstrated high implant survival rates with healthy and stable soft tissues . However , they revealed more vertical bone loss at the buccal aspect 6 months after implant insertion and also more marginal bone loss between crown insertion and 18 months after loading compared to sites treated with GBR OBJECTIVES The aim of this r and omized controlled trial was to assess the 10-year effects of three different augmentation techniques ( augmentation with chin bone , augmentation with chin bone plus a membrane and augmentation with a bone substitute plus a membrane ) for implant-supported restorations in the maxillary aesthetic region regarding clinical and radiographic parameters , and patient-centred outcomes . MATERIAL S AND METHODS Ninety-three patients requesting single tooth replacement and presenting with a horizontal bone deficiency were included . After augmentation , 93 implants were placed . Clinical variables , st and ardized radiographs and photographs and patient question naires were analysed to assess the impact of the various augmentation techniques 1 month ( T1 ) , 12 months ( T12 ) and 120 months ( T120 ) after final crown placement . RESULTS 10-years implant survival was 95.7 % and did not differ between the groups neither were significant differences observed in the other treatment outcomes assessed . Peri-implant bone loss was low , viz . 0.48 ± 1.19 mm ( mesial ) and 0.30 ± 1.24 mm ( distal ) at T120 . Loss of midbuccal marginal gingival level at T120 was 0.32 ± 0.83 mm . Mean overall satisfaction at T120 was 8.6 with 98.6 % of the patients satisfied . CONCLUSIONS Clinical , radiographic , aesthetic and patient centred outcomes were very favourable after 10 years and did not differ between the groups with different bone augmentation techniques OBJECTIVE The aim of this r and omized-controlled clinical trial was to evaluate the long-term outcome of implants placed in bone augmented with a xenogenic bone substitute material and a collagen membrane with or without the addition of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) . MATERIAL AND METHODS Eleven patients received a total of 34 implants placed into sites exhibiting lateral bone defects . In a split mouth design , the defects were r and omly treated with the graft material and the collagen membrane either with ( test ) or without ( control ) rhBMP-2 . The patients were examined 3 and 5 years after insertion of the prosthetic restoration . Student 's paired t-test was performed to detect differences between the two groups . RESULTS The survival rate at 3 and 5 years was 100 % for both groups . The peri-implant soft tissues were stable and healthy without any difference between the two groups . The prosthetic reevaluation demonstrated four loose prosthetic screws during the first 3 years and seven ceramic chippings after 3 and 5 years . The mean distance between the first bone to implant contact to implant abutment junction at 3 years was 1.37 mm ( test ) , 1.22 mm ( control ) , and 1.38 mm ( test ) , and 1.23 mm ( control ) at 5 years . The difference of < 0.2 mm between test and control implants was not statistically significant . The mean change of the marginal bone level between baseline and 5 years ranged from -0.07 mm ( mesial , test ) , -0.11 mm ( distal , test ) , -0.03 mm ( mesial , control ) , to + 0.13 mm ( distal , control ) . No statistically significant differences were observed between test and control sites . CONCLUSION Implants placed in bone augmented with and without rhBMP-2 revealed excellent clinical and radiological outcomes after 3 and 5 years OBJECTIVES To assess the clinical outcomes of simultaneous guided bone regeneration using native ( CM ) and cross-linked ( VN ) collagen membranes at 8 years . MATERIAL S AND METHODS A total of n = 19 patients ( 19 implants ) were available for the analysis . Each subject had received a simultaneous grafting of dehiscence-type defects using a natural bone mineral ( NBM ) and a r and om allocation to either CM and VN membranes ( submerged healing of 4 months ) . Clinical parameters ( e.g. , bleeding on probing - BOP , probing pocket depth - PD , mucosal recession - MR , clinical attachment level - CAL ) were recorded at 8 years after prosthesis installation . RESULTS At 8 years , CM and VN groups revealed comparable median BOP , PD , MR and CAL values at both vestibular and oral aspects . From 4 to 8 years ( n = 14 patients ) , median CAL at the vestibular aspect improved in both groups ; however , these changes were significantly higher at CM-treated sites ( CM : 0.7 mm vs. VN : 0.5 mm ) . CONCLUSION The clinical long-term outcomes at 8 years were comparable in both VN and CM groups PURPOSE The aim of this r and omized clinical trial was to compare the potential of deproteinized bovine bone added to autologous bone or corticocancellous allograft block with or without the addition of recombinant human platelet-derived growth factor-BB ( rhPDGF-BB ) to regenerate m and ibular atrophic ridges . MATERIAL S AND METHODS TRIAL DESIGN parallel , allocation ratio of 1:1 using a split-mouth model . Eligibility criteria for patients : adult patients ; bilateral atrophic edentulous areas in the posterior area of the m and ible ; a preoperatory cone beam computed tomography scan ; and absence of systemic diseases affecting the bone metabolism . Bone graft intervention for control group consisted of bone chips collected with a scraper mixed with deproteinized bovine bone covered with a resorbable membrane . Bone graft intervention for test group consisted of a corticocancellous allograft block , shaped before surgery , and protected with a collagen membrane . In addition , both groups received rhPDGF-BB or a saline solution as control . As primary outcome quantity , bone variation after a 1-year healing period was considered . A p-value of.05 was considered statistically significant . RESULTS Sixteen patients were enrolled in this trial . A total of 50 implants and 32 bone grafts were placed . All patients concluded the study ( no dropouts ) . Change at 1 year in bone volume was not significantly different between the two groups ( p-value = .25 ) . Effect of treatment in terms of change in bone volume at 1 year was not significant ( p-value = .89 ) when saline solution was used while was at limit of significance when rhPDGF-BB was used ( p-value = .052 ) . After 1 year , all the implants were successfully integrated . CONCLUSIONS The block allograft and the st and ard regenerative procedure showed similar results in terms of regenerated bone volume after 1 year of functional loading . The rhPDGF-BB positively influenced soft-tissue healing OBJECTIVES To investigate the impact of residual defect height ( RDH ) following guided bone regeneration ( GBR ) in dehiscence-type defects on the long-term stability of peri-implant health after a period of 4 years . MATERIAL AND METHODS The RDH values in dehiscence-type defects at titanium implants were clinical ly assessed after 4 months of submerged healing following augmentation using a natural bone mineral ( NBM ) and a r and omized application of either a cross-linked- ( VN ) or a native collagen membrane ( BG ) ( n=12 patients each ) . The RDH values were classified as absent ( 0 mm , control ; n=8 ) , minimal ( 1 mm , test 1 ; n=8 ) , or advanced ( > 1 mm , test 2 ; n=8 ) . Clinical parameters ( i.e. bleeding on probing [ BOP ] , probing pocket depth [ PD ] , mucosal recession [ MR ] ) were recorded ( mesio- , mid- , and disto-buccal aspects ) at 4 years after prosthesis installation . RESULTS The mean PD ( 2.9±0.7 , 2.8±0.7 , 2.7±0.8 mm ) values at 4 years were comparable in all the groups investigated . The mean MR values tended to be increased in both the test groups ( 0.5±0.7 , 0.4±0.6 mm , respectively ) , when compared with the control group ( 0.2±0.3 mm ) ( P>0.05 , respectively ) . The mean BOP values were also increased in both the test groups ( 45.8±30.5 % , 54.1±24.8 % , respectively ) , even reaching statistical significance when comparing test 2 and control ( 29.1±21.3 % ) groups ( P=0.02 ) . CONCLUSION The present study indicated that ( i ) implants exhibiting RDH values > 1 mm are at a higher risk of developing peri-implant disease and ( ii ) positive RDH values may be associated with an increase in MR and may therefore compromise the overall esthetic outcome of implant therapy BACKGROUND While information on the prevalence of peri-implantitis is available , data describing onset and progression of the disease are limited . MATERIAL & METHODS A 9-year follow-up examination of 596 r and omly selected implant-carrying individuals identified 62 patients with moderate/severe peri-implantitis . Longitudinal assessment s of peri-implant marginal bone levels were used to construct a statistical model with bone loss as the dependent variable . A multilevel growth model estimated the pattern of bone loss for each implant/patient . Onset of peri-implantitis was determined by evaluating the cumulative percentage of implants/ patients presenting with estimated bone loss at each year following prosthesis delivery . RESULTS The analysis showed a non-linear , accelerating pattern of bone loss at the 105 affected implants . The onset of peri-implantitis occurred early , and 52 % and 66 % of implants presented with bone loss of > 0.5 mm at years 2 and 3 respectively . A total of 70 % and 81 % of subjects presented with ≥1 implants with bone loss of > 0.5 mm at years 2 and 3 respectively . CONCLUSIONS It is suggested that peri-implantitis progresses in a non-linear , accelerating pattern and that , for the majority of cases , the onset occurs within 3 years of function OBJECTIVES To assess the bleeding on probing ( BOP ) tendency and periodontal probe penetration when applying various probing forces at implant sites in patients with a high st and ard of oral hygiene with well-maintained peri-implant tissues . MATERIAL AND METHODS Seventeen healthy patients with excellent oral hygiene in a maintenance program after having been treated for periodontitis or gingivitis were recruited . Missing teeth had been replaced using oral implants . The BOP and probing depth ( PPD ) were assessed at the mid-buccal , mid-oral , mesial and distal aspects of the buccal surfaces of each implant . Moreover , contralateral teeth were design ated and assessed for BOP and PPD in the same locations and at the same observation visits . At each visit , implants and contralateral teeth were r and omly assigned to one of the st and ardized probing forces ( 0.15 or 0.25 N ) . The second probing force was applied at the repetition of the examination 7 days later . RESULTS Increasing the probing pressure by 0.1 N from 0.15 N result ed in an increase of BOP percentage by 13.7 % and 6.6 % for implants and contralateral teeth , respectively . There appeared to be a significant difference of the mean BOP percentage at implant and tooth sites when a probing pressure of 0.25 N was applied . A significantly deeper mean PPD at implant sites compared with tooth sites was found irrespective of the probing pressure applied . CONCLUSIONS The results of the present study demonstrated that 0.15 N might represent the threshold pressure to be applied to avoid false positive BOP readings around oral implants . Hence , probing around implants demonstrated a higher sensitivity compared with probing around teeth AIMS The objective of this working group was to assess and make specific recommendations to improve the quality of reporting of clinical research in implant dentistry and discuss ways to reach a consensus on choice of outcomes . MATERIAL AND METHODS Discussion s were informed by three systematic review s on quality of reporting of observational studies ( case series , case-control and cohort ) and experimental research ( r and omized clinical trials ) . An additional systematic review provided information on choice of outcomes and analytical methods . In addition , an open survey among all workshop participants was utilized to capture a consensus view on the limits of currently used survival and success-based outcomes as well as to identify domains that need to be captured by future outcome systems . RESULTS The Workshop attempted to clarify the characteristics and the value in dental implant research of different study design s. In most areas , measurable quality improvements over time were identified . The Workshop recognized important aspects that require continued attention by clinical research ers , funding agencies and peer review ers to decrease potential bias . With regard to choice of outcomes , the limitations of currently used systems were recognized . Three broad outcome domains that need to be captured by future research were identified : ( i ) patient reported outcome measures , ( ii ) peri-implant tissue health and ( iii ) performance of implant supported restorations . Peri-implant tissue health can be measured by marginal bone level changes and soft tissue inflammation and can be incorporated in time to event analyses . CONCLUSIONS The Workshop recommended that collaboration between clinicians and epidemiologists/ clinical trials specialists should be encouraged . Aspects of design aim ed at limitation of potential bias should receive attention by clinical research ers , funding agencies and journal editors . Adherence to appropriate reporting guidelines such as STROBE and CONSORT are necessary st and ards . Research on outcome measure domains is an area of top priority and should urgently inform a proper process leading to a consensus on outcome measures in dental implant research OBJECTIVES To investigate the impact of a cross-linked- ( VN ) collagen membrane on the long-term stability of peri-implant health over 6 years . MATERIAL AND METHODS Vestibular dehiscence-type defects at titanium implants ( 19 patients , 19 implants ) were augmented using a natural bone mineral and r and omly allocated to either VN or a native collagen membrane ( CM ) and left to heal in a submerged position for 4 months . Clinical parameters ( i.e. Bleeding on Probing-BOP , probing pocket depth-PD , mucosal recession-MR ) were recorded at 4 and 6 years after prosthesis installation . RESULTS At 4 and 6 years , both VN and CM revealed comparable mean BOP , PD and MR values at both vestibular and oral aspects . Changes in these parameters from 4 to 6 years were minimal ( vestibular aspect-VN : -3.3 ± 48.2 % , -0.1 ± 0.5 mm , -0.1 ± 0.3 mm ; CM : -1.8 ± 33.7 % , 0.0 ± 0.4 mm , -0.1 ± 0.7 mm ) and not significantly different between groups . At 6 years , the incidence of mucositis and peri-implantitis was comparable in both groups ( VN : 60.0 % and 20.0 % ; CM : 33.3 % and 33.3 % ) . CONCLUSION In conclusion , the present follow-up observation failed to identify any beneficial impact of VN over CM on peri-implant health at 4 and 6 years PURPOSE The aim of this controlled clinical study was to compare a polyethylene glycol membrane ( PEG ) used for bone regeneration of peri-implant defects to a collagen membrane with respect to implant survival rate , dimensions of buccal peri-implant bone and mucosa . MATERIAL S AND METHODS Thirty-seven patients who received single tooth implants with simultaneous guided bone regeneration ( GBR ) in the posterior maxilla or m and ible were enrolled in the study . Intra-operative heights of bone defects were assessed prior to bone augmentation . The defects were augmented with xenogenic bone mineral and r and omly covered either with a porcine collagen membrane ( control ) or with a PEG membrane ( test ) . Five years after implant placement , clinical evaluation and cone beam computed tomography ( CBCT ) scans were performed . Remaining height of bone defect , horizontal bone thickness , level of mucosal margin , and mucosal thickness were assessed in CBCT images . The difference of height of bone defect at implant placement and at 5-year follow-up was calculated . The differences between the two groups were analyzed using two-sided t-test and Mann-Whitney U-test . RESULTS After 5 years , 32 patients could be included and exhibited an implant survival rate of 100 % for both groups . The buccal vertical bone gain between implant placement and 5-year follow-up amounted at 4.3 ± 1.5 ( SD ) mm and 4.8 ± 2.6 ( SD ) mm for the control and the test group , respectively ( P = 0.493 ) . Neither the bone height nor the thickness reached statistical significant differences between the two groups . The distance between mucosal margin and implant shoulder result ed in 0.8 ± 0.7 ( SD ) mm in the control and 0.5 ± 0.8 ( SD ) mm in the test group ( P = 0.198 ) . The mucosal thickness reached 1.4 ± 0.5 ( SD ) mm in the control and 1.3 ± 0.3 ( SD ) mm in the test group ( P = 0.715 ) . There were no significant correlations between height of bone defect at baseline and at follow-up examination and between different 5-year parameters . CONCLUSION A polyethylene glycol membrane used for bone regeneration of peri-implant defects performed as successfully as a collagen membrane with respect to implant survival rate and dimensions of the buccal peri-implant bone and mucosa after 5 years AIM This in vivo split-mouth r and omized controlled trial compared a synthetic bone substitute with a bovine bone mineral to cover bone dehiscences after implant insertion . MATERIAL S AND METHODS Fourteen patients received four to six implants to support an overdenture . Two comparable dehiscences within the same patient were first covered with a layer of autogenous bone , followed by a layer of either Bio-Oss ® ( group 1 ; Geistlich Pharma AG , Wolhusen , Switzerl and ) or Straumann BoneCeramic ® ( group 2 ; Institut Straumann AG , Basel , Switzerl and ) and sealed by a resorbable membrane . The change in vertical dimension of the defect was measured at implant placement and at abutment connection ( 6.5 months ) . Clinical and radiological parameters were evaluated up to 1 year of loading . RESULTS The vertical size of the defect at surgery was 6.4 ± 1.6 mm for group 1 and 6.4 ± 2.2 mm for group 2 sites , measured from the implant shoulder . After 6.5 months , the depth of the defect was reduced to 1.5 ± 1.2 mm and 1.9 ± 1.2 mm for group 1 and group 2 sites , respectively ( p > 0.05 ) . No implants failed during follow-up . Mean marginal bone loss over the SLActive surface was 0.94 mm ( group 1 ) , 0.81 mm ( group 2 ) , and 0.93 mm ( group 3 , no dehiscence ) after 1 year of loading . CONCLUSION Both bone substitutes behaved equally effectively OBJECTIVES To assess in a r and omized- clinical trial the influence of three augmentation techniques ( chinbone with or without a Bio-Gide membrane and Bio-Oss with a Bio-Gide membrane ) on the clinical and radiographic characteristics of hard and soft tissues around implants and adjacent teeth in the reconstructed maxillary anterior region , up to 1 year after functional loading . MATERIAL S AND METHODS Ninety-three patients requesting single-tooth replacement and presenting with a horizontal ( bucco-palatinal ) bone deficiency were included . After augmentation , 93 ITI-Esthetic(Plus ) implants were placed . Clinical variables , st and ardized photographs and radiographs were analysed to assess the impact on the levels of the marginal gingiva ( MGL ) and marginal bone ( MBL ) around implants and adjacent teeth , viz at pre-augmentation , pre-implantation ( TPI ) and 1 ( T(1 ) ) and 12 ( T(12 ) ) months after final crown placement . RESULTS Implant survival was 97.8 % . No significant differences were observed in the treatment outcomes of the three augmentation modalities . Combining the three modalities , a slight but significant increase in the implants approximal pocket depth was found between T(1 ) and T(12 ) . Approximal bone loss at the implant between T(1 ) and T(12 ) was 0.14 + /- 0.76 mm ( mesial ) and 0.14 + /- 0.47 mm ( distal ) ; the approximal MGL slightly increased ( mesial : 0.24 + /- 0.46 mm , distal : 0.25 + /- 0.66 mm ) , and the buccal MGL decreased ( 0.11 + /- 0.61 mm ) . Bone loss at the adjacent teeth , although minor , was significant between TPI and T(1 ) . No correlations were observed in changes of MBL and MGL . CONCLUSIONS None of the three applied augmentation technique procedures influenced the characteristics of the MGL and MBL or the implant survival of single-tooth replacements . Peri-implant hard and soft tissues were very stable in the first year after loading AIM The aim of the present study was to evaluate if the use of deprotenized bovine bone mineral ( DBBM ) and collagen barrier membranes ( CM ) in combination with m and ibular bone block grafts could reduce bone block graft resorption during healing . METHODS A prospect i ve r and omized controlled study has been design ed . Twenty-two ridges presenting horizontal alveolar deficiency ( crest width < 4 mm ) and at least two adjacent missing teeth were included in the study . In the control group , one or multiple m and ibular blocks were used to gain horizontal augmentation of the ridge . In the test group , DBBM granules were added at the periphery and over the graft . The reconstructions were covered by two layers of CM . Implants were placed 4 months after grafting . Direct measurements of crest width were performed before and immediately after bone augmentation , and immediately before implant placement . RESULTS Statistical analysis showed no significant differences in crest width between test and control groups at baseline and immediately after grafting . Mean augmentation at first surgery in the test group was 4.18 vs. 4.57 mm in the control group . Final gain obtained at the time of implant placement was 3.93 mm in the test and 3.67 mm in the control groups . The difference in mean graft resorption between test and control sites was statistically significant ( 0.25 mm in the test group vs. 0.89 mm in the control group , P=0.03 ) . Complications seem to occur more often in the test group ( complications recorded in three cases in the test group vs. one complication recorded in the control group ) . In all cases , implants could be placed in the planned sites and a total of 55 implants were placed ( 28 in the test group and 27 in the control group ) . All implants could be considered successfully integrated at the 24-month follow-up visit . CONCLUSION The results from this study showed that the addition of bovine bone mineral and a CM around and over a m and ibular bone block graft could minimize graft resorption during healing . On the other h and , the use of bone substitutes and barrier membranes in combination with block grafts increased the frequency of complications and the difficulty of their management |
10,815 | 28,075,166 | Ki-67 could predict pCR in those who received anthracyclines plus taxanes , and anthracyclines only , and those from Asia and Europe .
High Ki-67 before NAC was a predictor for pCR in neoadjuvant setting for breast cancer patients | AIM To review the predictive values of Ki-67 before neoadjuvant chemotherapy ( NAC ) for breast cancer patients . | BACKGROUND The proliferation marker Ki67 has been suggested as a promising cancer biomarker . As Ki67 needs an exact quantification , this marker is a prototype of a new generation of tissue-based biomarkers . In this study , we have systematic ally evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort . PATIENTS AND METHODS We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial . We used the st and ardized cutoff-finder algorithm for three end points [ response to neoadjuvant chemotherapy ( pCR ) , disease-free ( DFS ) and overall-survival ( OS ) ] . The analyses were stratified for hormone receptor ( HR ) and HER2 status by molecular subtype radar diagrams ( MSRDs ) . RESULTS A wide range of Ki67 cut points between 3%-94 % ( for pCR ) , 6%-46 % ( for DFS ) and 4%-58 % ( for OS ) were significant . The three groups of Ki67 ≤ 15 % versus 15.1%-35 % versus > 35 % had pCR-rates of 4.2 % , 12.8 % , and 29.0 % ( P < 0.0005 ) , this effect was also present in six of eight molecular subtypes . In MSRD , Ki67 was significantly linked to prognosis in uni- and multivariate analysis in the complete cohort and in HR-positive , but not triple-negative tumors . CONCLUSIONS Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data -derived cut point optimization might not be possible . Ki67 could be used as a continuous marker ; in addition , the scientific community could define st and ardized cut points for Ki67 . Our analysis explains the variability observed for Ki67 cut points in previous studies ; however , this should not be seen as weakness , but as strength of this marker . MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer . The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers Background Recent studies have indicated that response to chemotherapy and the prognostic impact of a pathologic complete response ( pCR ) after neoadjuvant chemotherapy differ among breast cancer subtypes . Methods Women with Stage I to III breast cancer treated with anthracycline and taxane-based neoadjuvant chemotherapy ( four cycles of docetaxel every 3 weeks followed by four cycles of FEC every 3 weeks ) between 2006 and 2011 were retrospectively analyzed . Trastuzumab was concurrently added to docetaxel for HER2-positive breast cancer . Expression of estrogen receptor ( ER ) , progesterone receptor ( PgR ) , HER2 , and Ki67 was examined by immunohistochemistry in pre- and post-treatment specimens . Predictive factors for neoadjuvant chemotherapy and prognosis were analyzed by breast cancer subtype . Results Of 64 patients , 30 ( 47 % ) were ER-positive ( ER+ ) HER2-negative ( HER2− ) , including eight as luminal A ( Ki67 labeling index ( LI ) < 14 % ) and 22 as luminal B ( Ki67 LI ≥ 14 % ) subtypes , 11 ( 17 % ) were ER+ HER2-positive ( HER2 + ) , 12 ( 19 % ) were ER-negative ( ER− ) HER2 + , and 11 ( 17 % ) were ER− HER2−. The clinical response rates were significantly higher in luminal B , ER+ HER2 + , and ER− HER2 + subtypes compared with luminal A subtype . Patients whose tumors contained high Ki67 expression effectively responded to neoadjuvant chemotherapy . Ki67 LI was a predictive marker for pCR , and all patients whose tumors achieved pCR are currently disease-free . Furthermore , high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free and overall survival regardless of subtype . Conclusions It is necessary to establish additional strategies to improve survival for patients whose residual tumors show high Ki67 expression after neoadjuvant chemotherapy PURPOSE This is one of the first reports of weekly docetaxel ( Taxotere ) in the neoadjuvant treatment of stage II and III breast cancer . We evaluated docetaxel 's efficacy and safety and analyzed correlations between response and the expression of c-erbB2 , ER status , and Ki-67 labeling index . EXPERIMENTAL DESIGN Patients with previously untreated , stage II and III breast cancer were entered into the study . Docetaxel ( 40 mg/m(2 ) ) was given i.v . once weekly for the first 6 weeks of an 8-week cycle for 2 cycles . RESULTS A total of 56 patients were evaluated by intention-to-treat analysis for efficacy and safety . The overall clinical response rate was 68 % ( complete and partial response , 29 and 39 % , respectively ) . Nine patients ( 16 % ) achieved a pathological complete response . There was no correlation between response to docetaxel and the expression of molecular markers , however , the majority of the pathological complete responses were observed in patients with c-erbB2-negative tumors . Nonhematological toxicity was more common than hematological toxicity , with alopecia and asthenia the most frequently reported adverse events ( 89 and 77 % of patients , respectively ) . Severe hematological toxicity was rare . CONCLUSIONS Weekly docetaxel appears to be very effective in the neoadjuvant setting . A high pathological response rate was achieved with tolerable toxicity Abstract This r and omized , multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide ( FEC ) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker . Patients were r and omized to 4 cycles of docetaxel/capecitabine ( docetaxel : 75 mg/m2 on day 1 ; capecitabine : 1,650 mg/m2 on days 1–14 every 3 weeks ) or docetaxel alone ( 75 mg/m2 on day 1 every 3 weeks ) after completion of 4 cycles of FEC ( 5-fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks ) . The primary endpoint was the pathological complete response ( pCR ) rate . Predictive factor analysis was conducted using clinicopathological markers , including hormone receptors and Ki67 labeling index ( Ki67LI ) . A total of 477 patients were r and omized ; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 % , respectively . There were no significant differences in the pCR rate ( docetaxel/capecitabine : 23 % ; docetaxel : 24 % ; p = 0.748 ) , disease-free survival , or overall survival . However , patients with mid-range Ki67LI ( 10–20 % ) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone . Furthermore , multivariate logistic regression analysis showed pre-treatment Ki67LI ( odds ratio 1.031 ; 95 % CI 1.014–1.048 ; p = 0.0004 ) to be a significant predictor of pCR in this neoadjuvant treatment setting . Docetaxel/capecitabine ( after 4 cycles of FEC ) did not generate significant improvement in pCR compared to docetaxel alone . However , exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer BACKGROUND Combinations of anthracyclines , taxanes and gemcitabine have shown high activity in breast cancer . This trial was design ed to evaluate a modified combination regimen as primary chemotherapy . Non-pegylated liposomal doxorubicin ( NPLD ) was used instead of conventional doxorubicin to improve cardiac safety . Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites . PATIENTS AND METHODS Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD ( 60 mg/m(2 ) ) and docetaxel ( 75 mg/m(2 ) ) on day 1 and gemcitabine as 4-h infusion ( 350 mg/m(2 ) ) on day 4 . Treatment was repeated every 3 weeks for a maximum of six cycles . All patients received prophylactically recombinant granulocyte colony-stimulating factor . Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide , methotrexate and fluorouracil . RESULTS The clinical response rate was 80 % , and complete remissions of the primary tumor occurred in 10 patients ( 25 % ) . Breast conservation surgery was performed in 19 out of 20 patients ( 95 % ) with an initial tumor size of less than 3 cm and in 14 patients ( 70 % ) with a tumor size < or=3 cm . Seven patients had histologically confirmed complete responses accounting for a pCR rate of 17.5 % . Expression of Ki--67 was the most important predictive parameter for response with high 38.9 % breast pCR rate in patients with elevated Ki--67 expression . Although the predominant toxicity was myelosuppression with grade 3/4 neutropenia in 61 % of patients few neutropenic complications result ed . Non-hematological toxicity was generally moderate with grade 3 or 4 toxicity in 10.0 % of cycles . Most common non-hematologic toxicities were nausea , vomiting , alopecia , mucositis , asthenia and elevation of liver enzymes . CONCLUSION The evaluated schedule provides a safe and highly effective combination treatment for patients with early breast cancer , which is suitable for phase III studies PURPOSE OF THE STUDY Trastuzumab combined with sequential chemotherapy with taxanes and anthracyclines as primary systemic therapy achieved high rates of pathologic complete response ( pCR ) . Non-pegylated liposome-encapsulated doxorubicin ( NPLD ) has shown equal efficacy but minor cardiotoxicity compared to doxorubicin . This phase II study aim ed to evaluate the activity and safety of trastuzumab with sequential chemotherapy for early or locally advanced HER2 positive BC . METHODS Preoperative treatment included NPLD ( 60 mg/mq iv ) plus cyclophosphamide ( 600 mg/mq iv ) every 3 weeks for 4 cycles followed by docetaxel ( 35 mg/mq iv ) plus trastuzumab ( 4 mg/mq loading dose iv , then 2 mg/mq iv ) weekly for 16 weeks . Primary endpoint was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes . Clinical staging was exploratory evaluated by CT-PET . RESULTS 43 pts were treated from december 2005 to September 2011 , 39 of them were evaluable for the purpose of study . Median age was 53 years ( range : 31 - 78 ) , the majority of pts had tumour stage cT2 ( 63 % ) , tumour grade 3 ( 86 % ) , clinical nodes involvement N+ ( 77 % ) , ER positive ( 56 % ) and Ki-67 ≥20 % ( 77 % ) . pCR was reported in 19 ( 49 % ) of 39 pts . There was an association between Ki-67 ≥20 % at baseline and pCR ( p = 0.018 ) . No cardiac toxicity or discontinuation of trastuzumab was reported . CT-PET modified the clinical stage for 10 patients showing new loco-regional lymph nodes . CONCLUSIONS This study confirms that integrating anti-HER2 therapy in primary treatment for HER2 positive breast cancer is active . NPLD is a safe option to minimize cardiotoxicity Oestrogen receptor ( ER ) negative breast cancers are more likely to achieve a pathological complete response ( pCR ) to neoadjuvant chemotherapy compared to those with ER positive tumours . ER positive tumours exhibit low proliferation and ER negative cancers high proliferation . The aim of this study was to determine to what extent the better response of ER negative cancers correlates with proliferation rate . A retrospective analysis of a prospect ively maintained data base identified 175 neoadjuvant chemotherapy patients with tissue available for Ki67 analysis . On univariate analysis , pre-therapy Ki67 ( P = 0.04 ) , ER status ( P = 0.002 ) , HER2 status ( P = 0.004 ) and grade ( P = 0.0009 ) were associated with a pCR . In a multivariate model , HER2 was the only significant predictor of pCR . No significant relationship between pre-therapy Ki67 and relapse-free and overall survival was demonstrated . Ki67 is not an independent predictor of clinical CR or pCR . Aspects of ER status beyond its inverse relationship with proliferation may contribute to its predictive value for pCR BACKGROUND To assess the molecular subtypes determined by hormonal receptors ( HR ) and human epidermal growth factor receptor 2 ( HER2 ) status and the role of proliferation measured by the Ki-67 marker as predictive and prognostic factors in breast cancer patients treated with neoadjuvant chemotherapy . METHODS A total of 127 breast cancer patients were treated with neoadjuvant chemotherapy every 2 weeks as part of 2 studies . Study A consisted of the administration of Adriamycin ( 40 mg/m(2 ) ) on day 1 plus paclitaxel ( 150 mg/m(2 ) ) and gemcitabine 2000 mg/m(2 ) ) on day 2 for 6 cycles ( n = 54 ) . Study B consisted of the administration of epirubicin ( 90 mg/m(2 ) ) , cyclophosphamide ( 600 mg/m(2 ) ) on day 1 for 3 cycles , followed by the administration of paclitaxel ( 150 mg/m(2 ) ) and gemcitabine 2500 ( mg/m(2 ) ) on day 1 with or without trastuzumab according to HER2 status ( n = 73 ) . In study A , patients did not receive trastuzumab regardless of HER2 status . The molecular subtypes of the patients with breast cancer were classified as 49 % HR(+)/HER2(- ) , 17.5 % HR(+)/HER2(+ ) , 13.5 % HR(-)/HER2(+ ) , and 20 % HR(-)/HER2(- ) . RESULTS Pathologic complete response ( pCR ) , defined as the absence of invasive cells in the breast and the lymph nodes , was achieved in 35 ( 28 % ) patients . The pCR rate was significantly different between the molecular subtypes of breast cancer , with 9 % in HR(+)/HER2(- ) , 23 % in HR(+)/HER2(+ ) , 50 % in HR(-)/HER2(+ ) , and 56 % in HR(-)/HER2(- ) tumors ( P < .001 ) . The pCR rate was significantly higher in tumors that had high Ki-67 ( ≥20 % ) expression and were HR(- ) . HER2(+ ) was associated with a higher trend of pCR but did not reach statistical significance . The median follow-up was 81 months ( r = 15 - 150 months ) . Patients who achieved a pCR had a significantly lower recurrence ( P = .01 ) and higher overall survival ( P = .02 ) compared with those who did not achieve pCR . A multivariate analysis revealed that pCR ( hazard ratio 0.24 [ 95 % CI , 0.07 - 0.7 ] ; P = .019 ) , the molecular subtype ( hazard ratio 0.3 [ 95 % CI , 0.1 - 0.8 ] ; P = .02 ) , and the Ki-67 index ( hazard ratio 3.2 [ 95 % CI , 1.4 - 7.1 ] ; P = .004 ) were significant independent predictors of disease-free survival . Similar results were obtained for overall survival , in which the pCR rate ( hazard ratio 0.119 [ 95 % CI , 0.028 - 0.5 ] ; P = .004 ) , the molecular subtype ( hazard ratio 0.17 [ 95 % CI , 0.03 - 0.86 ] ; P = .02 ) , and the Ki-67 index ( hazard ratio 3.6 [ 95 % CI , 1.3 - 9.7 ] ; P = .01 ) also displayed a significant influence on survival . CONCLUSIONS Molecular subtypes and Ki-67 index were independent prognostic factors for disease-free survival and overall survival in breast cancer patients treated with neoadjuvant chemotherapy . A high rate of Ki-67 and HR(- ) expression were predictors of pCR The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response ( pCR ) to neoadjuvant chemotherapy ( NCT ) in patients with locally advanced triple-negative breast cancers ( TNBCs ) . Forty-one patients ( 18.6 % ) among 220 breast cancer patients were identified as TNBCs from March 2006 to 2009 were included in this prospect i ve study . The pre-NCT treatment expression levels of Ki-67 proliferation index , estrogen receptor ( ER ) , progesterone receptor ( PgR ) , epidermal growth factor receptor 2 ( HER-2 ) , CK5/6 , epidermal growth factor receptor ( EGFR ) , cyclin D1 , and nm23-H1 were detected by immunohistochemistry ( IHC ) . A total of 180 cycles were administered with the median number of four cycles per patient ( range , 4–6 ) . The pCR rate was 34.1 % ( 95 % CI , 19.6–48.6 % ) . In univariate analysis , early T stage , clinical response after 2 cycles , negative basal-like , negative EGFR , high Ki-67 proliferation index , and positive nm23-H1 were found to be significantly predictive of a pCR ( P = 0.010 , 0.040 , 0.007 , 0.001 , 0.019 , and 0.010 , respectively ) . Basal-like status and nm23-H1 status were significant for pCR on multivariate analysis ( P = 0.004 and 0.031 , respectively ) . Basal-like status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with TNBCs Background The aim of the study was to identify reliable predictive biological markers for treatment outcome following neoadjuvant adriamycin/docetaxel ( AT ) chemotherapy in locally advanced breast cancer patients . Material s and methods This study was a phase II study on AT neoadjuvant chemotherapy in locally advanced breast cancer patients . Patients received 50 mg/m2 of doxorubicin intravenously ( IV ) over 15 min followed by docetaxel 75 mg/m2 infused over 1 h , repeated every 3 weeks for three cycles . Surgery was performed within 3–4 weeks following the last cycle of chemotherapy . We analyzed the pre-treatment and post-treatment expression levels of ER , PgR , HER-2 , Ki-67 proliferation index , and p53 and examined the correlation between the markers and clinical parameters with treatment response , overall survival and relapse-free survival following neoadjuvant treatment . Results From July 2001 to September 2004 , 61 patients were enrolled . The meaningful parameters adversely influencing survival were post-treatment ER(− ) status ( P = 0.013 ) and post-treatment Ki-67 index above 1.0 % ( P = 0.013 ) . At the multivariate level , the post-treatment Ki-67 proliferation index ≤ 1.0 was the only meaningful prognostic factor for better survival ( P = 0.033 ) . Notably , tumors with Ki-67 index ≤ 1.0 were more likely to express ER with statistical significance ( P = 0.002 ) . Tumors with ER(+ ) and Ki-67 index ≤ 1.0 showed the highest survival rate , followed by ER(+ ) and Ki-67 index > 1.0 % , ER(− ) and Ki-67 ≤ 1.0 % , and ER(− ) and Ki-67 > 1.0 % with the worst survival ( P = 0.033 ) . Conclusion Collectively , post-treatment ER status and Ki-67 proliferation index were prognostic of overall survival following neoadjuvant AT chemotherapy The current study exp and s upon previous work using a data base of 710 patients treated with neoadjuvant chemotherapy . First , we studied phenotypic characteristics of tumors before and after chemotherapy using the following factors : the mitotic index of the Scarff-Bloom-Richardson grade , Ki-67 , cyclin D1 , and cyclo-oxygenase-2 . Second , the predictive value of these factors on response was assessed . Third , we measured the prognostic impact of these markers post-therapy in comparison with clinical and pathological responses according to the Chevallier and Sataloff classifications . Patients were treated using different neoadjuvant chemotherapy combinations , mainly in successive prospect i ve phase II trials . They received a median number of six cycles ( range , 1 - 9 ) . After neoadjuvant chemotherapy , patients underwent surgery and radiotherapy . In cases of important residual disease , some received additional courses of chemotherapy . In addition , menopausal patients with hormone receptor-positive tumors received tamoxifen for 5 years . According to our analysis , we found significant variations before and after neoadjuvant chemotherapy only for cyclin D1 and the mitotic index . Concerning the predictive value of biomarkers for response , Ki-67 and the mitotic index were predictive on univariate analysis , both for objective clinical and pathological complete responses . Because these two factors were correlated , no multivariate analyses were conducted . We then assessed the prognostic impact of the biopathological factors . When the factors were measured before chemotherapy , all were prognostic . When evaluated after chemotherapy , the mitotic index , objective clinical response , and pathological complete response were prognostic . Because these factors were correlated , no multivariate model was done . The main clinical fact is that there were significant correlations between clinical and pathological responses and variations in the biological factors studied OBJECTIVE To identify the predictive markers associated with chemotherapy sensitivity , especially those producing pathological complete response ( pCR ) following neoadjuvant chemotherapy ( NACT ) in patients with locally advanced breast cancer . METHODS Core needle biopsy of 50 locally advanced breast cancer patients was analysed for histopathology , grade , oestrogen receptor , progesterone receptor , HER2 , Ki-67 , p53 , Bcl-2 , and BAX before starting NACT . This was correlated with response to NACT using Response Evaluation Criteria in Solid Tumours criteria . RESULTS The mean tumour reduction rate per chemotherapy cycle was significantly higher in BAX-positive ( p = 0.01 ) and Bcl-2-negative ( p = 0.04 ) tumours . BAX expression significantly ( p = 0.043 ) correlated with a response of an at least 30 % reduction in tumour size post-NACT on multivariate analysis . A significant relationship was seen between loss of Bcl-2 expression and pCR on univariate ( p = 0.048 ) analysis . Overall , all of the above 12 parameters had 30.4 % and 28.5 % success in predicting clinical complete response and pCR , respectively , by the Cox and Snell formula . CONCLUSION Of all parameters examined , only the apoptosis-related genes ( Bcl-2 and BAX ) seemed to exert some influence on the response to NACT , and neither by itself was sufficient to predict pCR ; however , 50 patients is not sufficient to simultaneously analyse several predictive markers |
10,816 | 24,996,963 | The most promising strategies for improving the FV environment for children are through local school food service policies .
Similarly family interventions had no or small impact on home accessibility , with smaller impact on consumption . | Background Low fruit and vegetable ( FV ) consumption is one of the top 10 global risk factors for mortality , and is related to increased risk for cancer , cardiovascular disease and diabetes .
Many environmental , sociodemographic and personal factors affect FV consumption .
The purpose of this review is to examine the effects of interventions delivered in the home , school and other nutritional environments design ed to increase FV availability for five to 18-year olds . | Aims : To estimate the impact of school fruit tuck shops on children ’s consumption of fruit and sweet and savoury snacks . Design : Cluster r and omised effectiveness trial with school as the unit of r and omisation . Setting : 43 primary schools in deprived areas in south Wales and south-west Engl and with a range of school food policies . Intervention : Schools operated fruit tuck shops throughout one academic year . Control schools did not do so . Measures : Repeated cross-sections of children aged 9–11 years completed a computerised 24-hour recall question naire at baseline ( n = 1902 ) and at 1-year follow-up ( n = 1924 ) , when a brief question naire was also completed ( n = 1976 ) . Results : Approximately 70 000 fruits were sold in the 23 intervention schools over the year , equivalent to 0.06 fruits per student per day . Children in intervention schools were more likely to report eating fruit as a snack at school ‘ often ’ ( OR 1.49 , 95 % CI 1.15 to 1.95 ) . There were no significant differences in children ’s intake of fruit or other snacks . There was a significant interaction ( p<0.02 ) between the intervention group and school food policy : where students were only allowed to bring fruit to school , fruit consumption was 0.37 portions per day ( 0.11 to 0.64 ) higher in intervention schools , compared to 0.14 portions ( −0.30 to 0.58 ) where no food was allowed and −0.13 portions ( −0.33 to 0.07 ) where there were no restrictions . Conclusions : In isolation , fruit tuck shops were not effective in changing children ’s snacking behaviour in schools . However , the results suggest that fruit tuck shops had a greater impact when reinforced by school policies restricting the types of foods students were allowed to bring to school BACKGROUND Boy Scouts are an important channel to complement school-based programs to enable boys to eat more fruit , 100 % juice , and vegetables ( FJV ) for chronic disease prevention . The " 5 a Day Achievement Badge " program was presented on a pilot study basis to African-American Boy Scout troops in Houston . METHODS Troops were the unit of recruitment and r and om assignment to treatment and control groups . The badge program was presented in Fall 1997 by trained dietitians and included activities to increase availability and accessibility of fruit and vegetables at scouts ' homes , increase preferences for vegetables , and train in the preparation of FaSST ( fast , simple , safe , and tasty ) recipes . Weekly comic books demonstrated and reinforced what scouts were expected to do at home . A weekly newsletter with recipes was sent to parents . The program was revised and presented to the control group in Winter 1998 . Two 24-h recalls were the primary assessment tools . Telephone interviews were conducted with parents . RESULTS The intervention result ed in a 0.8 FJV serving difference ( post values of treatment versus control groups with pre value covaried ) . CONCLUSIONS The changes obtained suggest that the intervention was effective in promoting dietary change PURPOSE OBJECTIVES The purpose of this study is to report the impact of the three-year middle school-based HEALTHY study on intervention school vending machine offerings . There were two goals for the vending machines : serve only dessert/snack foods with 200 kilocalories or less per single serving package , and eliminate 100 % fruit juice and beverages with added sugar . METHODS Six schools in each of seven cities ( Houston , TX , San Antonio , TX , Irvine , CA , Portl and , OR , Pittsburg , PA , Philadelphia , PA , and Chapel Hill , NC ) were r and omized into intervention ( n=21 schools ) or control ( n=21 schools ) groups , with three intervention and three control schools per city . All items in vending machine slots were tallied twice in the fall of 2006 for baseline data and twice at the end of the study , in 2009 . The percentage of total slots for each food/beverage category was calculated and compared between intervention and control schools at the end of study , using the Pearson chi-square test statistic . RESULTS At baseline , 15 intervention and 15 control schools had beverage and /or snack vending machines , compared with 11 intervention and 11 control schools at the end of the study . At the end of study , all of the intervention schools with beverage vending machines , but only one out of the nine control schools , met the beverage goal . The snack goal was met by all of the intervention schools and only one of the four control schools with snack vending machines . APPLICATIONS TO CHILD NUTRITION PROFESSIONALS The HEALTHY study 's vending machine beverage and snack goals were successfully achieved in intervention schools , reducing access to less healthy food items outside the school meals program . Although the effect of these changes on student diet , energy balance and growth is unknown , these results suggest that healthier options for snacks can successfully be offered in school vending machines OBJECTIVE To assess lunchtime provision of food and drink in English primary schools and to assess both choices and consumption of food and drink by pupils having school lunches . These findings were compared with similar data collected in 2005 . DESIGN Cross-sectional data collected between February and April 2009 . In each school , food and drink provision , including portion weights and number of portions of each item served at lunchtime , were recorded over five consecutive days . Caterers provided school lunchtime menus and recipes . SETTING Engl and . SUBJECTS A r and om selection of 6696 pupils having school lunches in a nationally representative sample of 136 primary schools in Engl and . RESULTS Compared with 2005 , schools in 2009 provided significantly more fruit , fruit-based desserts , vegetables and salad , water and fruit juice , and less ketchup , sauces and gravy , starchy foods cooked in fat , snacks and confectionery ( P < 0·01 ) . Pupils were also making healthier choices , choosing an average of 2·2 portions of fruit and vegetables from their ' five a day ' , but about one-third to two-fifths of these were wasted . CONCLUSIONS Lunchtime food provision and consumption in primary schools have improved substantially since 2005 , following the introduction of new st and ards for school food in 2008 . However , improvements still need to be made to increase the Fe and Zn content and to decrease the Na content of recipes , and in encouraging pupils to eat more of the fruits and vegetables taken at lunchtime OBJECTIVES The effects of a Boy Scout Five-A-Day Badge program on fruit juice ( FJ ) and low-fat vegetable ( LV ) consumption were evaluated using a two-condition ( treatment , active-attention-placebo-control ) group r and omized trial , with three data collection periods ( baseline , immediate post , 6-month post ) . METHODS Forty-two Boy Scout troops ( n=473 , 10- to 14-year-old Scouts ) in Houston , TX , were r and omly assigned to condition . The 9-week program included approximately 30 min of weekly troop time , plus approximately 25 min of weekly Internet programming . The intervention was delivered in two waves ( Spring and Fall ) . Data were collected in 2003 - 2004 , and analyses were completed in 2008 . Main outcomes were FJ and LV consumption ( vali date d food frequency question naire ) . FV self-efficacy , preferences , and home availability were also measured . RESULTS Significant increases in FJ consumption ( p=.003 ) , FJ home availability ( p=.009 ) , and LV self-efficacy ( p=.004 ) were observed among the intervention group immediately following the intervention but were not maintained 6 months later . CONCLUSION A Boy Scout troop-plus-Internet intervention promoting FJ and LV consumption result ed in short-term changes in FJ consumption among U.S. Boy Scouts . Future research should investigate ways to extend these results to LV and maintain the increases over time To increase opportunities for healthy eating and physical activity , US school districts participating in the National School Lunch Program were required to create a Local Wellness Policy ( LWP ) by June 2006 . The What 's Working project described the initial influence of this m and ate on nutrition environments and policies . In 2005 and 2007 ( before and after the m and ate went into effect ) , a survey about school features related to nutrition and physical activity was sent to a r and om sample of 45 low-income , rural elementary foodservice managers and principals . Schools averaged 204 students , 27 % Hispanic . Districts ' LWPs were coded for strength and comprehensiveness . In addition , key informant interviews were conducted with foodservice managers almost 2 years after the LWP went into effect . Three improvements were observed : increases in the percent of schools with policies stipulating predominantly healthy items be offered in classroom parties ( 21.4 % in 2005 vs 48.7 % in 2007 ) , daily fresh fruit offerings in the lunchroom ( 0.80 choices in 2005 vs 1.15 choices in 2007 ) , and the percent of schools using skinless poultry ( 27 % in 2005 vs 59 % in 2007 ) . LWPs were weakly worded and rarely addressed energy content . Nutrition guideline elements most commonly addressed included vending machines , school stores , and à la carte food offerings . Seveny-three percent of foodservice managers were familiar with their district 's LWP but did not perceive it changed lunchroom practice s. Although LWPs offer a framework to support opportunities for healthy eating , few evidence -based practice s were implemented as a direct result of the m and ate . Schools need more information about evidence -based practice s , as well as technical and financial assistance for implementation OBJECTIVE Previous studies on the relationship of dietary intake to the neighbourhood food environment have focused on access to supermarkets , quantified by geographic distance or store concentration measures . However , in-store food availability may also be an important determinant , particularly for urban neighbourhoods with a greater concentration of small food stores . This study synthesis es both types of information - store access and in-store availability - to determine their potential relationship to fruit and vegetable consumption . DESIGN Residents in four census tracts were surveyed in 2001 about their fruit and vegetable intake . Household distances to food stores in these and surrounding tracts were obtained using geographical information system mapping techniques . In-store fruit and vegetable availability was measured by linear shelf space . Multivariate linear regression models were used to measure the association of these neighbourhood availability measures with consumption . SETTING Four contiguous census tracts in central -city New Orleans . SUBJECTS A r and om sample of 102 households . RESULTS Greater fresh vegetable availability within 100 m of a residence was a positive predictor of vegetable intake ; each additional metre of shelf space was associated with 0.35 servings per day of increased intake . Fresh fruit availability was not associated with intake , although having a small food store within this same distance was a marginal predictor of fruit consumption . CONCLUSIONS The findings suggest the possible importance of small neighbourhood food stores and their fresh produce availability in affecting fruit and vegetable intake The Nutrition , Prevention and Health for Children and Teenagers in Aquitaine program is a regional implementation of the French National Program of Nutrition and Health ( PNNS ) . The first of two surveys of a representative sample of Aquitaine preschools was conducted in 2004 - 2005 . This survey showed that more than 2/3 of teachers offered a morning snack to their pupils at around 10 o'clock in the morning , mainly composed of sweet cakes , cookies , or c and ies . Following this initial survey , actions were implemented starting in September 2005 , aim ing to stop systematic morning snacks or improve their composition . The same survey was repeated during 2007 - 2008 in order to analyze the changes in morning snack practice s in preschools between 2004 - 2005 and 2007 - 2008 . Data were collected from teachers of Aquitaine 's preschools who filled out question naires . Schools were r and omly chosen according to their size and whether or not they belonged to a priority education zone ( ZEP ) . The results show that 57.9 % of teachers organized a morning snack in 2007 - 2008 , versus 68.7 % in 2004 - 2005 . In 2004 - 2005 , 22 % of teachers considered the morning snack as " unjustified " compared to 44 % in 2007 - 2008 . The composition of morning snacks improved : 17.7 % of teachers offered fruit and /or milk in 2007 - 2008 versus 8.5 % in 2004 - 2005 . Morning snacks composed of other foods ( such as sweets , chocolate pieces , cookies , pastries , bread , fruit juice ) decreased from 60.2 % in 2004 - 2005 to 40.2 % in 2007 - 2008 . In 2007 - 2008 , 19 % of the teachers reported that children had snacks in their schoolbag versus 34 % in 2004 - 2005 . The proportion of teachers reporting children having snacks in their schoolbag decreased from 34 % in 2004 - 2005 to 19 % in 2007 - 2008 . Comparison between these two surveys is encouraging as it shows an improvement of the perception and practice s of teachers regarding morning snacks . These results encourage the partners of this program to continue the fieldwork actions |
10,817 | 12,726,975 | On current evidence , washing h and s with soap can reduce the risk of diarrhoeal diseases by 42 - 47 % and interventions to promote h and washing might save a million lives . | null | null |
10,818 | 23,852,992 | Although generally well-tolerated with no significant adverse effects , there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments .
Oral thiol derivatives were generally well-tolerated with no significant adverse effects , however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments .
We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis . | BACKGROUND Cystic fibrosis is an inherited condition result ing in thickened , sticky respiratory secretions .
Respiratory failure , due to recurrent pulmonary infection and inflammation , is the most common cause of mortality .
Muco-active therapies ( e.g. dornase alfa and nebulized hypertonic saline ) may decrease sputum viscosity , increase airway clearance of sputum , reduce infection and inflammation and improve lung function .
Thiol derivatives , either oral or nebulized , have shown benefit in other respiratory diseases .
Their mode of action is likely to differ according to the route of administration .
There are several thiol derivatives , and it is unclear which of these may be beneficial in cystic fibrosis .
OBJECTIVES To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis . | Objective We conducted a single-centre , r and omised , double-blinded , placebo-controlled phase II clinical study to test safety and efficacy of a 12-week therapy with low-dose ( 700 mg/daily ) or high-dose ( 2800 mg/daily ) of NAC . Methods Twenty-one patients ( ΔF508 homo/heterozygous , FEV1 > 40 % pred . ) were included in the study . After a 3-weeks placebo run-in phase , 11 patients received low-dose NAC , and 10 patients received high-dose NAC . Outcomes included safety and clinical parameters , inflammatory ( total leukocyte numbers , cell differentials , TNF-α , IL-8 ) measures in induced sputum , and concentrations of extracellular glutathione in induced sputum and blood . Results High-dose NAC was a well-tolerated and safe medication . High-dose NAC did not alter clinical or inflammatory parameters . However , extracellular glutathione in induced sputum tended to increase on high-dose NAC . Conclusions High-dose NAC is a well-tolerated and safe medication for a prolonged therapy of patients with CF with a potential to increase extracellular glutathione in CF airways BACKGROUND Inhaled hypertonic saline acutely increases mucociliary clearance and , in short-term trials , improves lung function in people with cystic fibrosis . We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial . METHODS In this double-blind , parallel-group trial , 164 patients with stable cystic fibrosis who were at least six years old were r and omly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent ( control ) saline twice daily for 48 weeks , with quinine sulfate ( 0.25 mg per milliliter ) added to each solution to mask the taste . A bronchodilator was given before each dose , and other st and ard therapies were continued during the trial . RESULTS The primary outcome measure , the rate of change ( slope ) in lung function ( reflected by the forced vital capacity [ FVC ] , forced expiratory volume in one second [ FEV1 ] , and forced expiratory flow at 25 to 75 percent of FVC [ FEF25 - 75 ] ) during the 48 weeks of treatment , did not differ significantly between groups ( P=0.79 ) . However , the absolute difference in lung function between groups was significant ( P=0.03 ) when averaged across all post-r and omization visits in the 48-week treatment period . As compared with the control group , the hypertonic-saline group had significantly higher FVC ( by 82 ml ; 95 percent confidence interval , 12 to 153 ) and FEV1 ( by 68 ml ; 95 percent confidence interval , 3 to 132 ) values , but similar FEF25 - 75 values . The hypertonic-saline group also had significantly fewer pulmonary exacerbations ( relative reduction , 56 percent ; P=0.02 ) and a significantly higher percentage of patients without exacerbations ( 76 percent , as compared with 62 percent in the control group ; P=0.03 ) . Hypertonic saline was not associated with worsening bacterial infection or inflammation . CONCLUSIONS Hypertonic saline preceded by a bronchodilator is an inexpensive , safe , and effective additional therapy for patients with cystic fibrosis . ( Clinical Trials.gov number , NCT00271310 . Neutrophilic airway inflammation is a hallmark of cystic fibrosis ( CF ) . As high oxidant producers , airway neutrophils contribute largely to the systemic redox imbalance seen in CF . In turn , this chronic and profound imbalance can impact circulating neutrophils before their migration into airways . Indeed , in 18 CF patients with stable disease , blood neutrophils were readily deficient in the pivotal antioxidant glutathione ( P = 0.003 , compared with 9 healthy controls ) . In a phase 1 study , this deficiency was improved ( P = 0.025 ) by the glutathione prodrug N-acetylcysteine , given orally in high doses ( 0.6 to 1.0 g three times daily , for 4 weeks ) . This treatment was safe and markedly decreased sputum elastase activity ( P = 0.006 ) , the strongest predictor of CF pulmonary function . Consistently , neutrophil burden in CF airways was decreased upon treatment ( P = 0.003 ) , as was the number of airway neutrophils actively releasing elastase-rich granules ( P = 0.005 ) , as measured by flow cytometry . Pulmonary function measures were not improved , as expected with short-term treatment . After excluding data from subjects without baseline airway inflammation , positive treatment effects were more pronounced and included decreased sputum IL-8 levels ( P = 0.032 ) . Thus , high-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF S-nitrosoglutathione ( GSNO ) , a naturally occurring constituent of airway lining fluid , enhances ciliary motility , relaxes airway smooth muscle , inhibits airway epithelial amiloride-sensitive sodium transport , and prevents pathogen replication . Remarkably , airway levels of GSNO are low in patients with cystic fibrosis ( CF ) . We hypothesized that replacement of airway GSNO would improve gas exchange in CF . In a double-blind , placebo controlled study , we administered 0.05 ml/kg of 10 mM GSNO or phosphate buffered saline by aerosol to patients with CF and followed oxygen saturation , spirometry , respiratory rate , blood pressure , heart rate , and expired nitric oxide ( NO ) . Nine patients received GSNO and 11 placebo . GSNO inhalation was associated with a modest but sustained increase in oxygen saturation at all time points . Expired NO increased in the low ppb range with GSNO treatment , peaking at 5 minutes but remaining above baseline at 30 minutes . There were no adverse effects . We conclude that GSNO is well tolerated in patients with CF and improves oxygenation through a mechanism that may be independent of free NO . Further , GSNO breakdown increases expired NO . We suggest that therapy aim ed at restoring endogenous GSNO levels in the CF airway may merit study The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug , Nacystelyn ( NAL ) , for the treatment of cystic fibrosis ( CF ) lung disease . In study 1 , involving 10 CF patients , the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo , in order to establish an optimal dose for further testing . On five consecutive scheduled treatment days , patients inhaled either from two ( 4 mg ) to eight puffs ( 16 mg ) of a single dose of NAL from the range , administered in an open-label fashion , or 12 puffs of active NAL ( 24 mg ) versus 12 puffs of placebo , administered in a r and omized double-blind fashion . Pulmonary function data were unaffected and clinical ly-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug . Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity , accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations . In study 2 , involving 12 CF patients , the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days , 7 days apart , patients inhaled a single dose of 12 puffs of active NAL ( 24 mg ) or 12 puffs of placebo drug in a r and omized , double-blind sequence , with sputum sample s taken at intervals before and after inhalation . Mucus rigidity decreased following NAL inhalation , with the maximum effect observed at 4 h ; the 1- , 2- and 4-h NAL rheology results were significantly different from placebo . No adverse effects were observed . The drug was well tolerated in both studies . Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms Twenty-seven patients with cystic fibrosis completed a controlled trial comparing the effects of an inhaled mucolytic drug , sodium-2-mercaptoethane sulphonate ( Mistabron , UCB Pharmaceutical Division , Brussels , Belgium ) , with inhaled iso-osmolar hypertonic saline . As a group the 22 patients with chronic sputum production showed small but statistically significant improvement in pulmonary function tests after Mistabron therapy , both when compared with a control period , and with iso-osmolar saline results . Subjective measurements by diary card failed to show any changes . No significant changes were found in five patients with no measurable sputum production . The inhalations were given after physiotherapy and were well tolerated . There were no significant side effects . The results suggest that Mistabron has a beneficial therapeutic effect unrelated to its high osmolality , and the intermittent inhalation of Mistabron may have a role in the treatment of selected patients with cystic fibrosis The effect of peroral N-acetylcysteine ( NAC ) in patients with cystic fibrosis ( CF ) and primary ciliary dyskinesia ( PCD ) was investigated . 41 CF patients and 13 PCD patients completed the study which was a double-blind , placebo-controlled , cross-over trial . The patients received either NAC or placebo for two periods of three months followed by a three month follow-up period . Active treatment consisted of NAC , either 200 mg x 3 daily ( patients weighing less than 30 kg ) or 400 mg x 2 daily ( greater than 30 kg ) . The effect was evaluated in terms of a subjective clinical score , weight , sputum bacteriology , blood leucocyte count , sedimentation rate , titres of specific antimicrobial antibodies , lung function parameters and measurement of the ciliary function . No effect was seen in PCD patients , but in CF patients an improved lung function was seen in the period when the patients suffer most from lower airway infections Examined in this study are the immediate effects of bronchial drainage preceded by the inhalation of aerosol solutions of a mucolytic agent , a bronchodilator , and their combination upon four measures of pulmonary function in 20 patients with cystic fibrosis . On three separate occasions , pulmonary function was tested preceding and following treatments consisting of one of the above three aerosol solutions followed by bronchial drainage . The order of solutions used was r and om and each subject received one treatment with each solution . The greatest overall improvement in function was seen with the bronchodilator and bronchial drainage . The combination of the bronchodilator/mucolytic agents and bronchial drainage was the next most effective technique . The mucolytic agent , when used alone with bronchial drainage , decreased function . Comparison of the pulmonary function scores indicated a significant difference among the three treatments The therapeutic efficacy of oral N-acetylcysteine ( NAC ) and ambroxol as compared with the effect of placebos was studied in 36 cystic fibrosis ( CF ) patients with mild to moderate pulmonary disease . The patients were r and omly assigned to one of three regimens , matched on the basis of age and Chrispin-Norman scores . The trial was conducted over a period of 12 weeks . Patients were assessed clinical ly and by extensive pulmonary function techniques ( body-plethysmography , maximal expiratory flow-volume curves , trapped air determination ) . Although no clinical differences could be observed between the three groups , significant impairment in the placebo group was found for trapped air and FEV1 when compared to the active groups , suggesting a therapeutic effect of ambroxol and NAC in CF BACKGROUND Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick , purulent secretions , which results in recurrent , symptomatic exacerbations . The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I ( rhDNase ) , a bioengineered copy of the human enzyme . METHODS We performed a r and omized , double-blind , placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function . A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as out patients . RESULTS One or more exacerbations occurred in 27 percent of the patients given placebo , 22 percent of those treated with rhDNase once daily , and 19 percent of those treated with rhDNase twice daily . As compared with placebo , the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent ( P = 0.04 ) and 37 percent ( P < 0.01 ) , respectively . The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean ( + /- SD ) of 5.8 + /- 0.7 and 5.6 + /- 0.7 percent , respectively . None of the patients had anaphylaxis . Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset . CONCLUSIONS In patients with cystic fibrosis , the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms , result ed in slight improvement in pulmonary function , and was well tolerated The effect of peroral N-acetylcysteine ( NAC ) in patients with cystic fibrosis ( CF ) and chronic pulmonary Pseudomonas aeruginosa infection was studied in 52 patients in a double-blind , placebo-controlled , cross-over trial of two , 3 month duration s. Active treatment consisted of NAC , 200 mg x 3 daily ( patients weighing less than 30 kg ) or 400 mg x 2 daily ( greater than 30 kg ) . The effect was evaluated by a subjective clinical score , weight , sputum bacteriology , blood leucocyte count , sedimentation rate , titres of specific antimicrobial antibodies , lung function parameters and measurement of nasal ciliary function in vitro . 31 patients completed the study . No significant differences in lung function or subjective clinical scores were seen between NAC and placebo for the study group as a whole . Patients with peak expiratory flow rate ( PEFR ) below 70 % of predicted normal values showed a satisfactory significant increase in PEFR , forced vital capacity ( FVC ) and forced expiratory volume in one second ( FEV1 ) during NAC treatment . No effect of NAC on ciliary activity was observed STUDY OBJECTIVES To assess the impact of inhaled , buffered reduced glutathione ( GSH ) on clinical indicators of cystic fibrosis ( CF ) pathophysiology . DESIGN AND PATIENTS A r and omized , double-blind , placebo-controlled pilot study was conducted over an 8-week period . Nineteen subjects , age 6 to 19 years , with CF status documented by positive sweat chloride test results ( > 60 mEq/L ) were recruited for the trial . After matching on age and sex , 10 patients were r and omly assigned to the treatment group and 9 patients to the placebo group . Primary outcomes were FEV1 , FVC , forced expiratory flow at 25 to 75 % of vital capacity , and peak flow ; secondary outcomes were body mass index , 6-min walk distance , and self-reported cough frequency , mucus production/viscosity/color , wellness , improvement , and stamina . INTERVENTIONS AND ANALYSIS : Treatment was buffered GSH , and placebo was sodium chloride with a hint of quinine . The total daily dose of buffered GSH was approximately 66 mg/kg of body weight , and the total daily dose of placebo was approximately 15 mg/kg of body weight ( quinine , 25 to 30 microg/kg ) . Doses were distributed across four inhalation sessions per day and spaced 3- to 4-h apart . General linear mixed models were used to analyze the data . The final sample size was nine subjects in the treatment group and seven subjects in the placebo group . RESULTS Mean change for peak flow was -6.5 L/min for the placebo group and + 33.7 L/min for the GSH group ( p = 0.04 ) , and self-reported average improvement on a scale from 1 to 5 ( 1 being much worse and 5 being much better ) was 2.8 for placebo and 4.7 for GSH ( p = 0.004 ) . Of the 13 primary and secondary outcomes examined , 11 outcomes favored the treatment group over the placebo group ( p = 0.002 ) , indicating a general tendency of improvement in the GSH group . No adverse events in the treatment group were noted . CONCLUSION This pilot study indicates the promise of nebulized buffered GSH to ameliorate CF disease , and longer , larger , and improved studies of inhaled GSH are warranted The effectiveness of carbocysteine lysine salt monohydrate ( SCMC-Lys ) and ambroxol hydrochloride ( ABX ) in the management of respiratory impairment was compared in a single-blind , r and omized study of 26 cystic fibrosis patients with similar baseline characteristics . Adults received either SCMC-Lys 900 mg or ABX 33 mg three times a day and children under 14 years of age either SCMC-Lys 270 mg three times a day or ABX 10 mg four times a day . All treatments were given orally for 80 days and at the end of this control period both groups showed significant improvement in chest sound score but improvement in cough score was observed only in those receiving SCMC-Lys . Expectorate viscosity and elasticity decreased significantly in both groups . In SCMC-Lys-treated patients paCO2 decreased and paO2 and Hb O2 saturation increased while only paO2 increased significantly in those treated with ABX . An increase in tidal volume , peak expiratory flow values and forced expiratory volume were evident in those receiving SCMC-Lys while significant increases in forced expiratory flow were recorded in those receiving ABX . SCMC-Lys patients ' Shwachmann index improved significantly and conversely to the ABX patients . No adverse events were recorded in either treatment group . The study concluded that SCMC-Lys is at least as effective as ABX in improving respiratory function in patients with cystic fibrosis The relative benefits and hazards of bronchial lavage with 10 % acetylcysteine ( Mucomyst ) compared to sodium chloride solution was studied in 14 patients with cystic fibrosis who were treated on 16 occasions . Lavage with acetylcysteine produced a significant increase in arterial carbon dioxide tension ( Paco 2 ) and a decrease in arterial oxygen tension ( Pao 2 ) immediately after lavage . Lavage with sodium chloride solution produced a decrease in Paco and an increase in ` Pao 2 . Regardless of lavage agent , pulmonary function was impaired for 48 to 72 hours after lavage , and three patients developed pneumonia within three days after lavage . When bronchial lavage was used as one part of a complete therapeutic program , some improvement in pulmonary function could be demonstrated two to six weeks after therapy Chronic neutrophilic inflammation leads to oxidative damage , which may play an important role in the pathogenesis of cystic fibrosis lung disease . Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in patients with cystic fibrosis . Here we evaluated the effects of glutathione aerosol on lower airway glutathione levels , lung function , and oxidative status . Pulmonary deposition of a radiolabeled monodisperse aerosol generated with a Pari LC Star nebulizer ( Allergy Asthma Technology , Morton Grove , IL ) connected to an AKITA inhalation device ( Inamed , Gauting , Germany ) was determined in six patients . In 17 additional patients bronchoalveolar lavage fluid was assessed before and after 14 days of inhalation with thrice-daily doses of 300 or 450 mg of glutathione . Intrathoracic deposition was 86.3 + /- 1.4 % of the emitted dose . Glutathione concentration in lavage 1 hour postinhalation was increased three- to fourfold and was still almost doubled 12 hours postinhalation . FEV(1 ) transiently dropped after inhalation but increased compared with pretreatment values after 14 days ( p < 0.001 ) . This improvement was not related to the lavage content of oxidized proteins and lipids , which did not change with treatment . These results show that , using a new inhalation device with high efficacy , glutathione treatment of the lower airways is feasible . Reversion of markers of oxidative injury may need longer treatment , higher doses , or different types of antioxidants RATIONALE Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis ( CF ) . OBJECTIVES We aim ed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease . METHODS This r and omized , double-blind , placebo-controlled trial evaluated inhaled glutathione in subjects with CF 8 years of age and older and FEV1 of 40 - 90 % of predicted . Subjects were r and omized to receive 646 mg glutathione in 4 ml ( n = 73 ) or placebo ( n = 80 ) via an investigational eFlow nebulizer every 12 hours for 6 months . MEASUREMENTS AND MAIN RESULTS FEV1 ( absolute values ) , both as pre-post differences ( P = 0.180 ) and as area under the curves ( P = 0.205 ) , were the primary efficacy endpoints , and were not different between the glutathione group and the placebo group over the 6-month treatment period . Exploratory analysis showed an increase of FEV1 from baseline over placebo of 100 ml or 2.2 % predicted ; this was significant at 3 months , but not later . Subjects receiving glutathione had neither fewer pulmonary exacerbations , nor better scores for quality of life . Whereas increased glutathione and metabolites in sputum demonstrated significant delivery to the lungs , there was no indication of diminished oxidative stress to proteins or lipids , and no evidence for anti-inflammatory or antiproteolytic actions of glutathione supplemented to the airways . The adverse event incidence was similar between glutathione and placebo . CONCLUSIONS Inhaled glutathione in the dose administered did not demonstrate clinical ly relevant improvements in lung function , pulmonary exacerbation frequency , or patient-reported outcomes . Glutathione delivery to the airways was not associated with changes in markers of oxidation , proteolysis , or inflammation . Clinical trial registered with www . clinical trials.gov ( NCT00506688 ) and https://eudract.ema.europa.eu/index.html ( EudraCT 2005 - 003870 - 88 ) . To assess the efficacy of oral N-acetylcysteine ( NAC ) 200 mg given thrice daily in cystic fibrosis ( CF ) we conducted a double blind placebo controlled cross over trial on 20 patients with mild to moderate pulmonary disease . No significant difference between the 3 month treatment periods with NAC and placebo were detected on daily peak expiratory flow rates ( PEFR ) , subjective sputum viscosity , and cough frequency scores . Neither was there any statistically significant difference in weight gain , antibiotic usage or chest radiograph ( CXR ) scores |
10,819 | 17,509,828 | In general , statistically significant positive but modest and varying therapy effects are found . | Medical as well as paramedical treatments should be evaluated by scientific methods .
This systematic review focuses on the effects of voice therapy , excluding pharmacological or surgical treatments . | Manual circumlaryngeal therapy ( manual laryngeal musculoskeletal tension reduction ) was used to treat 25 consecutive functional dysphonia patients . Pre- and post-treatment audio recordings of connected speech and sustained vowel sample s were su bmi tted to auditory-perceptual and acoustical analysis to assess the immediate and long-term effects of a single treatment session . To complement audio recordings , subjects were interviewed in follow-up regarding the stability of treatment effects . Pre- and post-treatment comparisons demonstrated significant voice improvements . No significant differences were observed between post-treatment measures , suggesting that vocal gains were maintained . Interviews revealed 68 % of subjects reported occasional partial recurrences , typically less than 4 days in duration , which resolved spontaneously . These results replicate and extend previous research suggesting the utility of manual circumlaryngeal therapy for functional voice disorders A prospect i ve study was carried out to examine the degree to which a st and ard voice assessment could discriminate between the potential benefits of two different voice therapy programmes for individual patients . The study encompassed 200 dysphonia subjects who were referred for voice therapy and had completed treatment within a prescribed two-year period . A st and ard assessment procedure was carried out on first attendance for each patient and guidelines were used to assign patients to different treatment programmes on the basis of the assessment results . The assessment discriminated well between patients requiring voice therapy to change physiological parameters of voice usage and patients able to self adjust voice usage , and provided an objective means of measuring outcomes Although the terms " breathy " and " rough " are frequently applied to pathological voices , widely accepted definitions are not available and the relationship between these qualities is not understood . To investigate these matters , expert listeners judged the dissimilarity of pathological voices with respect to breathiness and roughness . A second group of listeners rated the voices on unidimensional scales for the same qualities . Multidimensional scaling analyses suggested that breathiness and roughness are related , multidimensional constructs . Unidimensional ratings of both breathiness and roughness were necessary to describe patterns of similarity with respect to either quality . Listeners differed in the relative importance given to different aspects of voice quality , particularly when judging roughness . The presence of roughness in a voice did not appear to influence raters ' judgments of breathiness ; however , judgments of roughness were heavily influenced by the degree of breathiness , the particular nature of the influence varying from listener to listener . Differences in how listeners focus their attention on the different aspects of multidimensional perceptual qualities apparently are a significant source of interrater unreliability ( noise ) in voice quality ratings After treatment for early glottic carcinoma , a considerable number of patients end up with voice problems that interfere with daily life activities . The objective of this r and omized and controlled study was to assess the efficacy of voice therapy in these patients Abstract Objectives : To assess the overall efficacy of voice therapy for dysphonia . Design : Single blind r and omised controlled trial . Setting : Outpatient clinic in a teaching hospital . Participants : 204 out patients aged 17 - 87 with a primary symptom of persistent hoarseness for at least two months . Interventions : After baseline assessment s , patients were r and omised to six weeks of either voice therapy or no treatment . Assessment s were repeated at six weeks on the 145 ( 71 % ) patients who continued to this stage and at 12 - 14 weeks on the 133 ( 65 % ) patients who completed the study . The assessment s at the three time points for the 70 patients who completed treatment and the 63 patients in the group given no treatment were compared . Main outcome measures : Ratings of laryngeal features , Buffalo voice profile , amplitude and pitch perturbation , voice profile question naire , hospital anxiety and depression scale , clinical interview schedule , SF-36 . Results : Voice therapy improved voice quality as assessed by rating by patients ( P=0.001 ) and rating by observer ( P<0.001 ) . The treatment effects for these two outcomes were 4.1 ( 95 % confidence interval 1.7 to 6.6 ) points and 0.82 ( 0.50 to 1.13 ) points . Amplitude perturbation showed improvement at six weeks ( P=0.005 ) but not on completion of the study . Patients with dysphonia had appreciable psychological distress and lower quality of life than controls , but voice therapy had no significant impact on either of these variables . Conclusion : Voice therapy is effective in improving voice quality as assessed by self rated and observer rated methods . What is already known on this topic Many patients with dysphonia are treated by voice therapy The effectiveness of voice therapy in a diverse group of patients is unknown What this study adds Voice therapy is an effective treatment for dysphonia in terms of report by patients and perceptual ratings by an expert Psychological distress and reduction in general health status are common in patients with dysphonia but are not significantly affected by a course of voice For many years all patients with dysphonia referred to in the literature as result ing from non-organic ( functional ) voice disorders were sent to speech therapy . Medical diagnoses were not taken into account . In our earlier Cochrane review on vocal cord nodules we discovered that evidence -based research in the area of benign voice disorders with dysphonia , and with or without slight benign swellings including nodules on the vocal cords , was lacking at that time . Therefore , a prospect i ve r and omised pilot study based on our Cochrane review has been made on dysphonic patients with non-organic ( function provoked ? ) voice disorders as the basis for further evidence -based studies .Medical treatment was based on the scientific approach that once a micro-organic disorder caused by reflux , infection , allergy or environmental irritatants ( e.g. , dust or noise in the workplace ) was discovered by very careful anamnesis and systematic objective routine analyses and was treated effectively , with documentation , the non-organic voice disorder disappeared , as , e.g. , in the case of a diagnosis and treatment of helicobakter pylori . The reason is that the mucosal swelling/dysfunction of the vocal cords is secondary .In order to try to underst and why the recommendation to all these patients for many years was only voice therapy , which the speech therapists “ felt to be effective ” , up date d voice-hygiene advice ( for posture , accents of the diaphragm , intonation pattern and resonance ) was given by experienced laryngologists , r and omised with the up date d medical diagnosis/therapy in order to eluci date what effect the training might have . No evidence -based studies in the literature document any effect . The crucial point seemed to be that doctors mostly did not examine any other diagnoses other than the “ dysphonia ” and did not dig down to any of the medical reasons when the vocal fold diagnosis of “ non- organic disorders ” was made . This should be changed in the future . This pilot study was based on a comparison of ten dysphonic patients with stroboscopic non- organic ( functional ) voice disorders , where a micro-organic diagnosis was search ed for and treated systematic ally in a medical regime ( for infections , allergies , gastrooesophageal reflux and environmental irritants such as dust , noise , etc . ) versus ten dysphonic patients with stroboscopically confirmed non-organic ( functional ) voice disorders , having only the traditional but optimal voice advice , which we can call medical voice-hygiene advice , including the use of the Accent method . A retrospective group of ten patients treated medically was included , too . A dem and can not be made that the functional group being treated by r and omisation with voice advice should also be medically treated at once , the medical approach being the new one . On the other h and , it is strange that no evidence -based research was made before . All patients were measured two times with stored videostroboscopy , a quality -of-life question naire and phonetograms with 1-month intervals . All patient groups improved . There was no statistical improvement in favour of the medical group with the voice-related quality -of-life score , also not for the group who received voice-hygiene advice . The geometrical mean values of the phonetogram areas in decibels times semitones were better in all groups , but a statistical difference was not found between the medically treated group and the voice-hygiene advice group . The pilot study showed that both medical treatment and medical voice-hygiene advice had a positive effect on dysphonia in non-organic ( functional ) voice disorders . There is need of an extensive prospect i ve r and omised trial on dysphonia including vocal cord nodules to find out which treatment should be used for this group of patients . It is suggested that an eventual r and omisation for microsurgical treatment or regular voice therapy should be made after a period of systematic medical diagnosis and treatment including medical voice-hygiene advice Previous studies of students study ing to be teachers have indicated that these students commonly have voice disorders . Ideally , voice disorders should be treated before students start their work as teachers , but the re sources for this treatment are often limited . This study examines whether group voice therapy is effective for teacher students . Accordingly , 20 teacher students with mild voice disorders received group voice therapy ( in three small groups ) , whereas 20 students with similar voice disorders served as a control group and consequently did not receive voice therapy . Two out of three outcome measures ( perceptual evaluation of voice quality and a question naire on the occurrence of vocal symptoms ) indicated significant changes in the treatment group compared with the control group . No differences between groups were noted in the laryngeal status . The results suggest that group voice therapy seems to be an effective method to treat students with mild voice disorders The aim of this study was to assess the effects on vocal function of voice therapy for vocal nodules . Perceptual and physiological progressive changes were examined during a strictly structured , behaviorally based voice therapy protocol in which 11 women with vocal nodules participated . R and omized audio recordings from pretherapy and from each of the therapy approaches ( vocal hygiene , respiration , direct facilitation , carryover ) were used for perceptual evaluations . Six speech- language pathologists rated ten voice quality parameters . Two evaluation procedures were performed and compared . Interlistener reliability was sufficiently high in both tests . Significant effects of therapy were found for decreased overall dysphonia , press , instability , gratings , roughness , vocal fry , and " scrape . " Nonsignificant group effects were found for breathiness , aphonic instances , and lack of sonority . No significant parameter changes occurred between baseline assessment and the completion of the initial ( vocal hygiene ) phase of therapy . Significant changes were found following the direct facilitation and respiration phases of therapy . Videostroboscopic evaluations made by two laryngologists showed that in no case were the nodules completely resolved . However , the nodules had decreased in size and edema was reduced after therapy for all clients , but one . Combined results suggest : ( 1 ) Alterations in vocal function were reflected in perceptual parameters , and ( 2 ) the voice therapy had a positive effect on voice quality , vocal status , and vocal function for the majority of the vocal nodule clients Traditional clinical review articles , also known as up date s , differ from systematic review s and meta-analyses . Up date s selectively review the medical literature while discussing a topic broadly . Non-quantitative systematic review s comprehensively examine the medical literature , seeking to identify and synthesize all relevant information to formulate the best approach to diagnosis or treatment . Meta-analyses ( quantitative systematic review s ) seek to answer a focused clinical question , using rigorous statistical analysis of pooled research studies . This article presents guidelines for writing an evidence -based clinical review article for American Family Physician . First , the topic should be of common interest and relevance to family practice . Include a table of the continuing medical education objectives of the review . State how the literature search was done and include several sources of evidence -based review s , such as the Cochrane Collaboration , BMJ 's Clinical Evidence , or the InfoRetriever Web site . Where possible , use evidence based on clinical outcomes relating to morbidity , mortality , or quality of life , and studies of primary care population s. In articles su bmi tted to American Family Physician , rate the level of evidence for key recommendations according to the following scale : level A ( r and omized controlled trial [ RCT ] , meta- analysis ) ; level B ( other evidence ) ; level C ( consensus/expert opinion ) . Finally , provide a table of key summary points BACKGROUND The use of outcome measures to monitor improved quality of care has been advocated for 20 years but has only achieved prominence with the increasing re source pressures and related changed in health service provision in the past 6 years . OBJECTIVE This paper describes the development of an approach to outcome measurement suitable for all patients receiving speech and language therapy . The measure , which is based on rating the dimensions of impairment , disability , h and icap and well-being , is tested to assess whether it can usefully be used to compare the services of different providers . METHOD Five trusts volunteered for the study . Service descriptions suggest that these services are typical for the purpose s of providing speech and language therapy . Twenty-five therapists were trained to use the Therapy Outcome Measure ( TOM ) ; their reliability was assessed and they provided prospect i ve data on clients with speech and language impairments related to dysphasia , stammering and dysphonia . RESULTS The study provides evidence indicating the differences in the types of patients being referred to different providers of speech and language therapy . Different services have different impacts on the number and type of domains and that services discharge patients at different points in their recovery . DISCUSSION Different outcomes by different providers may be associated with different referral policies , base population s , skills and work policies of therapists . Differences in outcomes associated with certain therapy services can initiate the task of analysing attributions and progress endeavours to provide equitable quality of care which is the philosophy underpinning the move towards benchmarking in health service delivery Transnasal flexible laryngoscopy ( TFL ) is an examination of laryngeal anatomy and physiology using continuous light . TFL is being used increasingly by voice pathologists in treatment but with little scientific evidence to support it . The purpose of this study was to evaluate the effectiveness and efficiency of TFL as a therapeutic tool . The study used a prospect i ve r and omized controlled trial . Fifty dysphonic subjects were recruited and r and omly assigned to either a traditional treatment group or a TFL-assisted treatment group . The effectiveness of voice therapy in both treatment groups was measured with a package of voice outcome measures . Subjects in both treatment groups demonstrated statistically significant improvements after voice therapy ( perceptual auditory rating of voice quality measurement p < 0.01 ; instrumental electroglottographic measurement p < 0.01 ; patient question naire measurement p < 0.01 ) . The time taken to complete treatment in both groups was recorded . The average ( median ) time taken to complete voice therapy in the TFL-assisted treatment group was 2 hours less than in the traditional treatment group ( p < 0.01 ) . Voice therapy with TFL as a therapy tool was effective and more efficient than traditional voice therapy Voice problems are common among schoolteachers . This prospect i ve , r and omized clinical trial used patient-based treatment outcomes measures combined with acoustic analysis to evaluate the effectiveness of two treatment programs . Forty-four voice-disordered teachers were r and omly assigned to one of three groups : voice amplification using the ChatterVox portable amplifier ( VA , n = 15 ) , vocal hygiene ( VH , n = 15 ) , and a nontreatment control group ( n = 14 ) . Before and after a 6-week treatment phase , all teachers completed : ( a ) the Voice H and icap Index ( VHI ) , an instrument design ed to appraise the self-perceived psychosocial consequences of voice disorders ; ( b ) a voice severity self-rating scale ; and ( c ) an audiorecording for later acoustic analysis . Based on pre- and posttreatment comparisons , only the amplification group experienced significant reductions on mean VHI scores ( p = .045 ) , voice severity self-ratings ( p = .012 ) , and the acoustic measures of percent jitter ( p = .031 ) and shimmer ( p = .008 ) . The nontreatment control group reported a significant increase in level of vocal h and icap as assessed by the VHI ( p = .012 ) . Although most pre- to posttreatment changes were in the desired direction , no significant improvements were observed within the VH group on any of the dependent measures . Between-group comparisons involving the three possible pairings of the groups revealed a pattern of results to suggest that : ( a ) compared to the control group , both treatment groups ( i.e. , VA and VH ) experienced significantly more improvement on specific outcomes measures and ( b ) there were no significant differences between the VA and VH groups to indicate superiority of one treatment over another . Results , however , from a posttreatment question naire regarding the perceived benefits of treatment revealed that , compared to the VH group , the VA group reported more clarity of their speaking and singing voice ( p = .061 ) , greater ease of voice production ( p = .001 ) , and greater compliance with the treatment program ( p = .045 ) . These findings clearly support the clinical utility of voice amplification as an alternative for the treatment of voice problems in teachers Forty-five patients diagnosed as having non-organic dysphonia were assigned in rotation to one of three groups . Patients in one group received no treatment and acted as a control group . Patients in the other two groups received a programme of either ' indirect ' therapy or ' direct with indirect ' therapy , respectively . A self-report question naire of vocal performance , observed ratings of voice quality , and computer-derived acoustic measurements ( signal-to-noise ratio , pitch perturbation and amplitude perturbation ) were carried out on all patients before and after treatment to evaluate the changes in voice quality over time . There was a significant difference between the three groups on the self-report question naire , voice quality ratings and pitch perturbation measurements ( P = < 0.05 ) . Thirteen out of 15 control patients showed no significant change on any of the measures . Seven patients who received indirect treatment showed significant improvement in voice quality following treatment . Fourteen out of 15 patients who received direct treatment showed significant improvement in voice quality A breathing technique , or effective breath method is important for both singers and speakers for effective vocalization , and also useful for helping people with a voice problem . Here a diaphragm support breath pattern was used in voice therapy for patients with vocal nodules , recurrent laryngeal nerve paralysis , and incomplete glottal closure . Singing teachers use a technique , called the diaphragm breath support . This is called the yawning breath pattern ( YBP ) in our voice clinic and is used in teaching the patients with some kinds of voice disorder . In order to correct patients ' breath pattern , an equipment system was design ed to check their breath patterns conveniently in voice therapy practice . A respiratory kinematic sensor which connected to a TV monitor was attached to the patients ' rib cage near the diaphragm , and by bio-feedback , patients could observe and adjust their breath pattern to the desired pattern during vocalization . In each of the 10 outpatient sessions , the patients performed for 20 to 30 min , and were instructed to practice at home for 3 or more times daily . The YBP method was applied to 91 patients , 17 males and 74 females , with ages ranging from 17 to 79 years . Of the 91 patients 41 had vocal nodules , 20 had recurrent laryngeal nerve paralysis and 30 had incomplete glottal closure associated with chronic laryngitis and sulcus vocalis . Most of the patients could master the YBP technique successfully . The higher the patients ' ability to master the YBP was the better the results of both voice tests and subjective evaluation . The scientific background of the YBP method and its clinical effects in voice therapy was review ed There is an increasing need for studies of efficacy of behavior readjustment therapy procedures in human communicative disorders . Legal , social , scientific and professional considerations point up the need for more careful documentation of the effects of treatment techniques used by phoniatricians and speech- language pathologists . This study is conducted in order to evaluate the efficacy of the accent method of voice therapy ( AM ) . The AM is one of the holistic approaches for behavior readjustment voice therapy . It tackles collectively and simultaneously the various parameters of voice such as pitch , loudness and timbre . The results of intervention utilizing the AM in this clinical trial are assessed in a relatively controlled setup . Patients with voice problems result ing from various etiologic vocal pathologies are distributed r and omly into two groups . Group 1 ( G1 ) is given the full aspect of the AM , that is , voice hygiene advice plus the accent exercises to correct the faulty vocal technique ( habit ) . Group 2 ( G2 ) receives only voice hygiene advice . The AM is administered in individual sessions 20 min each , twice a week , while the voice hygiene advice counseling is given once a week . The assessment of the vocal pathology is done following a diagnostic protocol utilizing subjective as well as quasi- objective measures of evaluation . The initial assessment presents the baseline ( pretest ) data for both groups . The follow-up evaluations are done at mid intervention ( mid-test ) , that is , 10 sessions for G1 and 5 sessions for G2 , and at the termination of intervention/therapy ( post-test ) . The difference in improvement between G1 and G2 at the end of the observation was generally significant in favor of G1 . There were significant improvements in G1 in certain items specific for the various etiologic categories . The improvement from pretest to mid-test to post-test values followed a linear tendency . The significance of the results is discussed and the conclusions are outlined and criticized |
10,820 | 27,507,832 | Studies of inhaled tobramycin have revealed conflicting results regarding quality of life ( QoL ) , exacerbations and admissions , but may result in sputum cultures negative for Pseudomonas aeruginosa , whereas studies investigating the effect of inhaled gentamycin have shown positive effects on sputum bacterial density , decrease in sputum cultures positive for P. aeruginosa , QoL and exacerbation rate , but no improvement in forced expiratory volume in first second ( FEV1 ) .
Oral azithromycin can reduce exacerbations , together with minor improvements in QoL and FEV1 .
Furthermore , oral erythromycin reduces exacerbations , but has no effect on lung function , symptoms or QoL. Inhaled ciprofloxacin may reduce P. aeruginosa in sputum cultures , but without changes in lung function , exacerbations or QoL. Although with limited evidence , inhaled colistin may have effects on P. aeruginosa density , exacerbations and QoL , whereas studies on aztreonam revealed no significant clinical improvements in the outcomes of interest , including exacerbation rate .
Adverse events , including bronchospasm , have been reported in association with tobramycin and aztreonam .
Several antibiotic treatment regimens have been shown to improve QoL and exacerbation rate , whereas findings regarding sputum production , lung function and admissions have been conflicting . | To provide an up date on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis ( CF ) bronchiectasis ( BE ) . | The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa , after st and ard endovenous and oral therapy for long-term control of the infection had failed . After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status , 17 patients were r and omly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin ( group A ) or a symptomatic treatment ( group B ) . One patient from group A ab and oned inhaled treatment because of bronchospasm and another from group B died before the end of the study . The remaining 15 patients , seven from group A and eight from group B , completed the study . Both groups had similar previous characteristics . The number of admissions and days of admission ( mean + /- SEM ) of group A [ 0.6 ( 1.5 ) and 13.1 ( 34.8 ) ] were lower than those of group B [ 2.5 ( 2.1 ) and 57.9 ( 41.8 ) ] ( P < 0.05 ) . Forced vital capacity ( FVC ) , forced expiratory volume in 1 sec ( FEV1 ) , PAO2 and PACO2 were similar in the two groups at the end of follow-up , showing a comparable decline in these parameters . There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups . Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains . None of the patients presented impaired renal or auditory function at the end of the study . This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes 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 ) 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 ) Rationale : Previous studies have demonstrated that long-term low-dose macrolides are efficacious in cystic fibrosis ( CF ) and diffuse panbronchiolitis , two chronic neutrophilic airway diseases . Aims : The aims of this study were to evaluate the efficacy and safety of low-dose neomacrolides as add-on therapy in patients with severe asthma and /or bronchiectasis and to identify predictors for therapeutic response . Methods : In a retrospective observational cohort study , we examined 131 adult , non-CF patients with severe asthma and /or bronchiectasis , receiving low-dose neomacrolides as add-on treatment . Pulmonary function tests and symptom scores were assessed at baseline and after 3 to 8 weeks of therapy . Results : After 3–8 weeks of treatment with low-dose neomacrolides , 108 patients were available for evaluation . In asthma patients ( n = 47 ) , pulmonary function tests and symptom scores improved significantly . Responders ( ≥7 % forced expiratory volume in one second predicted [ FEV1 % ] improvement ) were older ( 55 vs. 47 years ; p = 0.042 ) and had a longer duration of asthma ( 29 vs. 9 years ; p = 0.052 ) . In patients with bronchiectasis only ( n = 61 ) , symptom scores improved significantly . Responders ( ≥60 % symptom score improvement ) were older ( 61 vs. 53 years ; p = 0.004 ) , more frequently male ( 53 % vs. 27 % ; p = 0.043 ) , and there was a nonsignificant trend towards higher high-resolution CT ( H RCT ) score for bronchiectasis in responders ( 6.4 vs. 4.6 ; p = 0.053 ) . In multivariate logistic regression analysis , age and male gender were independent predictors for improvement in this group . Conclusion : The results of this retrospective study suggest that neomacrolides may be useful as an add-on therapy in patients with severe asthma and /or bronchiectasis . Older age may predict good response in patients with severe asthma , whereas older age , male gender and a higher H RCT score for bronchiectasis may predict therapeutic response in patients with bronchiectasis only . Prospect i ve controlled trials of neomacrolides in patients with severe asthma are needed to confirm these observations 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 Background The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis ( CF ) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis . Dual release ciprofloxacin for inhalation ( DRCFI ) contains liposomal ciprofloxacin , formulated to optimise airway antibiotic delivery . Methods Phase II , 24-week Australian/New Zeal and multicentre , r and omised , double-blind , placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening . Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off . The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 ( day 28 ) , analysed by modified intention to treat ( mITT ) . Key secondary outcomes included safety and time to first pulmonary exacerbation — after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study . Results DRCFI result ed in a mean ( SD ) 4.2 ( 3.7 ) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 ( vs −0.08 ( 3.8 ) with placebo , p=0.002 ) . DRCFI treatment delayed time to first pulmonary exacerbation ( median 134 vs 58 days , p=0.057 mITT , p=0.046 per protocol ) . DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group , but fewer pulmonary adverse events . Conclusions Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa . In this modest-sized phase II study , DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population 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 We conducted a placebo-controlled , double-blind , r and omized study to evaluate the microbiological efficacy and safety of inhaled tobramycin for treatment of patients with bronchiectasis and Pseudomonas aeruginosa . Patients were r and omly assigned to receive either tobramycin solution for inhalation ( TSI ) ( n = 37 ) or placebo ( n = 37 ) , which was self-administered twice daily for 4 wk and followed by 2-wk off-drug . At Week 4 , the TSI group had a mean decrease in P. aeruginosa density of 4.54 log(10 ) colony-forming units (cfu)/g sputum compared with no change in the placebo group ( p < 0.01 ) . At Week 6 , P. aeruginosa was eradicated in 35 % of TSI patients but was detected in all placebo patients . Investigators indicated that 62 % of TSI patients showed an improved medical condition compared with 38 % of placebo patients ( odds ratio = 2.7 , 95 % confidence interval [ CI ] 1.1 to 6.9 ) . Tobramycin-resistant P. aeruginosa strains developed in 11 % of TSI patients and 3 % of placebo patients ( p = 0.36 ) . The mean percent change in FEV(1 ) percent predicted from Week 0 to Week 4 was similar for the TSI and placebo groups ( p = 0.41 ) . More TSI-treated patients than placebo patients reported increased cough , dyspnea , wheezing , and noncardiac chest pain , but the symptoms did not limit therapy . Additional study is warranted to further evaluate TSI in bronchiectasis patients 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 Patients with bronchiectasis suffer from sputum production , recurrent exacerbations , and progressive airway destruction . Erythromycin is effective in diffuse panbronchiolitis , another suppurative airway disorder , although its efficacy is unknown in idiopathic bronchiectasis . A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin ( 500 mg b.i.d . ) in steady-state idiopathic bronchiectasis . Patients in the erythromycin group ( n=11 , 8 female , mean age 50+/-15 yrs ) , but not the placebo group ( n=10 , 8 female , mean age 59+/-16 yrs ) had significantly improved forced expiratory volume in one second , forced vital capacity and 24-h sputum volume after 8 weeks ( p<0.05 ) . There was no parallel improvement in sputum pathogens , leukocytes , interleukin (IL)-1alpha and IL-8 , tumour necrosis factor-alpha , or leukotriene B4 . The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis . Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a r and omized , double-blinded , crossover trial . Exacerbations were defined in terms of increased dyspnea , sputum production , and sputum purulence . Exacerbations were followed at 3-day intervals by home visits , and those that resolved in 21 days were design ated treatment successes . Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary , and those in which the patient 's condition deteriorated so that intervention was necessary . Over 3.5 years in 173 patients , 362 exacerbations were treated , 180 with placebo and 182 with antibiotic . The success rate with placebo was 55 % and with antibiotic 68 % . The rate of failure with deterioration was 19 % with placebo and 10 % with antibiotic . There was a significant benefit associated with antibiotic . Peak flow recovered more rapidly with antibiotic treatment than with placebo . Side effects were uncommon and did not differ between antibiotic and placebo To investigate whether aerosolized gentamicin ( GM ) prevents myeloperoxidase (MPO)-mediated airway injury and mucus hypersecretion , a short course of aerosol therapy ( 3 d ) with GM 40 mg or 0.45 % saline ( saline ) twice per day was conducted . Twenty-eight patients with bronchiectasis and mucus hypersecretion after adequate chest care and hydration were enrolled in a r and omized , double-blind fashion . MPO levels in sputum collected on arising were determined by fluorometric assay at 655 nm before and after treatment . The sputum MPO level significantly decreased in patients receiving aerosolized GM , from 0.22 + /- 0.04 to 0.14 + /- 0.04 U/g ( n = 15 ) , but not in patients with saline inhalation ( 0.23 + /- 0.03 to 0.17 + /- 0.02 U/g ; n = 11 ) . The daily sputum amount significantly decreased from 94.6 + /- 21.6 to 58.1 + /- 17.8 ml ( n = 13 , p < 0.01 ) in the GM group , whereas it increased from 78.6 + /- 25.4 ml to 120.5 + /- 33.9 ml ( n = 11 , p < 0.05 ) in the saline group . The change in the amount of daily sputum was related to that in the sputum MPO level in the GM group ( r = 0.61 ; p < 0.01 ) . Inhalation of GM , but not saline , significantly ( p < 0.05 ) increased the value of peak expiratory flow ( PEF ) from 186.4 + /- 25.1 to 216.4 + /- 26.4 L/min and decreased the variability of PEF from 24.6 + /- 5.1 to 6.1 + /- 2.3 % . The nocturnal desaturation and the 6-min walking distances were also significantly improved in the GM group ( 11.2 + /- 3.8 to 0.6 + /- 0.5 min/h ; 324.9 + /- 43.1 to 408.1 + /- 25.9 m ; p < 0.05 ; respectively ) , but not in the saline group . Subjective improvements in the Borg scale and self-sputum assessment were found in the GM group only . In conclusion , aerosolized GM is effective in improving airway hypersecretion and inflammation in patients with bronchiectasis Introduction Bronchiectasis is a chronic pulmonary process characterized by recurrent respiratory infections leading to destruction of airways secondary to inflammation . We investigated whether the addition of 6-months ’ twice-weekly azithromycin to the existing treatment regimen in patients with pulmonary bronchiectasis decreased the number of exacerbations and improved pulmonary function compared with a similar period of time without concurrent azithromycin . Methods Thirty patients with high-resolution computed tomography scan-confirmed bronchiectasis were to be recruited . In r and om order , patients received usual medications for 6 months , and usual medications plus oral azithromycin 500 mg twice weekly for 6 months . Patients receiving azithromycin first had a 1-month washout period prior to entering the second phase . Patients recorded weekly peak flow ( PF ) measurements . Pulmonary function tests ( PFTs ) , 24-hour sputum volume , and needs for intervention with medication or ancillary support were collected at baseline and every 3 months . Exacerbation incidence and sputum volume measurements were compared from baseline to the end of each study phase . Results Twelve patients were enrolled ; 11 were included in the analysis . Owing to r and omization , most patients received the azithromycin first , which was fairly well tolerated . PFTs did not change significantly during either study phase and PFs appeared to remain stable during azithromycin therapy and throughout the subsequent control phase . Azithromycin significantly decreased the incidence of exacerbations compared with usual medications ( 5 vs 16 ; p = 0.019 ) . Mean 24-hour sputum volume significantly decreased ( 15 % [ p = 0.005 ] ) during the active treatment phase , and remained decreased during the control phase ( p = 0.028 ) . Subjectively , patients reported increased energy and quality of life while receiving treatment with azithromycin . Conclusions The addition of twice-weekly azithromycin significantly decreased the incidence of exacerbation and 24-hour sputum volume and may have stabilized the PFTs and PFs in this 11-patient pilot study . The results of this study justify further investigation of adding azithromycin to the treatment regimens of patients with bronchiectasis for its disease-modifying effects There is minimal published longitudinal data about pathogenic microorganisms in adults with bronchiectasis . Therefore a study was undertaken to assess the microbiologic profile over time in bronchiectasis . A prospect i ve study of clinical and microbiologic outcomes was performed . Subjects were assessed by a respiratory physician and sputum sample were collected for analysis . Subjects were followed up and had repeat assessment performed . Eighty-nine subjects were followed up for a period of 5.7+/-3.6 years . On initial assessment the two most common pathogens isolated were Haemophilus influenzae ( 47 % ) and Pseudomonas aeruginosa ( 12 % ) whilst 21 % had no pathogens isolated . On follow-up review results were similar ( 40 % H. influenzae , 18 % P. aeruginosa and 26 % no pathogens ) . The prevalence of antibiotic resistance of isolates increased from 13 % to 30 % . Analysis of a series of H. influenzae isolates showed they were nearly all nontypeable and all were different subtypes . Subjects with no pathogens isolated from their sputum had the mildest disease , while subjects with P. aeruginosa had the most severe bronchiectasis . Many subjects with bronchiectasis are colonized with the same bacterium over an average follow-up of 5 years . Different pathogens are associated with different patterns of clinical disease BACKGROUND Macrolide antibiotics are increasingly prescribed for subjects with non-cystic fibrosis ( CF ) bronchiectasis , an empiric extension of their proven efficacy in CF . Widespread , injudicious use of long-acting macrolides , particularly azithromycin , risks significantly increasing population antimicrobial resistance . METHODS In an attempt to power a definitive r and omised-controlled trial ( RCT ) , an uncontrolled evaluation of the impact of long-term , low-dose oral erythromycin therapy upon pulmonary exacerbation frequency in non-CF bronchiectasis subjects was performed . Adult bronchiectasis subjects with at least 2 infective exacerbations in the preceding 12 months were followed for 12 months following commencement of prophylactic oral erythromycin 250 mgs daily . The co- primary outcome measures , comparing the 12 month erythromycin and pre-erythomycin periods , were numbers of infective exacerbations and days of antibiotic therapy for infective exacerbations . RESULTS In the 24 evaluable subjects completing a minimum of 12 months of therapy , erythromycin was associated with halving of both the median ( range ) annual number of infective exacerbations ( 2 ( 0 - 8 ) vs. 4 ( 2 - 11 ) , 95 % CI 1.5 to 3.5 , p < 0.0001 ) and annual days of antibiotic use ( 21 ( 0 - 78 ) vs. 44 ( 15 - 138 ) , 95 % CI 18 to 40 , p < 0.0001 ) compared with the preceding 12 month period . CONCLUSIONS Low-dose erythromycin may have a robust effect upon exacerbation frequency in non-CF bronchiectasis subjects with frequent exacerbations and this warrants proceeding to a definitive intervention study . These data have enabled powering of an RCT of long-term , low-dose erythromycin , which is now underway and also incorporates bronchoscopic evaluation for pathophysiologic data BACKGROUND AND OBJECTIVE To explore the effect of long-term therapy with azithromycin in regards to airway oxidative stress markers in exhaled breath condensate ( EBC ) of adult patients with stable non-cystic fibrosis ( CF ) bronchiectasis . METHODS Open-label prospect i ve study of 30 patients r and omized to azithromycin 250 mg three times per week during 3 months ( 16 patients ) or control ( 14 patients ) . Primary outcome were changes in nitric oxide , 8-isoprostane , pH , nitrites and nitrates in EBC . Secondary outcomes were changes in exacerbation rates , dyspnoea ( Borg scale ) , sputum volume ( cc ) , sputum colour ( 15-point scale ) , bacterial infection , health-related quality of life ( St George 's Respiratory Question naire ) , lung function and radiological extension . RESULTS Azithromycin produced a significant decrease in sputum volume ( 8.9 ( 1.8 ) mL vs 2.1 ( 3.4 ) mL ) and number of exacerbations ( 0.1 ( 0.6 ) vs 1.2 ( 0.9 ) ) . Dyspnoea ( 0.4 ( 0.1 ) vs 0.1 ( 0.2 ) ) and health-related quality of life also improved after therapy . However , oxidative stress markers in EBC , systemic inflammatory markers as well as functional respiratory tests did not differ from the control group after therapy . A post-hoc analysis comparing patients infected or not with Pseudomonas aeruginosa revealed that these effects were more pronounced in infected patients . In this subgroup , treatment was followed by a significant reduction in sputum volume , number of exacerbations , dyspnoea and St George 's Respiratory Question naire total score . Of all airway oxidative stress markers , only nitrates in EBC were reduced after therapy . CONCLUSIONS Long-term azythromicin treatment has some clinical benefits in patients with non-CF stable bronchiectasis , but it does not affect airway oxidative stress markers 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 The efficacy and safety of long-term ciprofloxacin therapy in the management of severe bronchiectasis were retrospectively assessed in patients who had taken oral ciprofloxacin continuously for at least 90 days . The drug was well tolerated , with only one reported side effect . Treatment result ed in a symptomatic improvement in seven of the ten patients and significant improvements in peak expiratory flow rate and residual volume . There was a decrease in the number of infective exacerbations from 6.2 + /- 2.9 during 365 days to 0.5 + /- 0.53 during 412 days . Resistance to ciprofloxacin developed in 2 patients with Pseudomonas aeruginosa infection and this was associated with clinical deterioration , but in a further two patients with P. aeruginosa the pathogen was eradicated . Two patients had persistent Streptococcus pneumoniae cultured from sputum but this was not associated with clinical deterioration . The study suggests that ciprofloxacin is effective and safe in the long-term treatment of chronic bronchial sepsis due to bronchiectasis , but emergence of P. aeruginosa resistance is of some concern BACKGROUND : Non — cystic fibrosis ( CF ) patients with bronchiectasis usually develop chronic bronchial infection with Pseudomonas aeruginosa ( PA ) that is related to worsening lung function and increased morbidity and mortality . OBJECTIVE : To determine whether direct aerosol delivery of tobramycin to the lower airways may control infection and produce only low systemic toxicity . METHODS : A double-blind , placebo-controlled crossover trial involving 30 patients was conducted to determine the clinical effectiveness and safety of 6-month tobramycin inhalation therapy . Patients received 300 mg of aerosolized tobramycin or placebo twice daily in 2 cycles , each for 6 months , with a one-month washout period . The number of exacerbations , number of hospital admissions , number of hospital admission days , antibiotic use , pulmonary function , quality of life , tobramycin toxicity , density of PA in sputum , emergence of bacterial resistance , and emergence of other opportunistic bacteria were recorded . RESULTS : The number of admissions and days of admission ( mean ± SD ) during the tobramycin period ( 0.15 ± 0.37 and 2.05 ± 5.03 ) were lower than those during the placebo period ( 0.75 ± 1.16 and 12.65 ± 21.8 ) ( p < 0.047 ) . A decrease in PA density in sputum was associated with tobramycin administration in the analysis of the first 6-month cycle ( p = 0.038 ) . No significant differences were observed in the number of exacerbations , antibiotic use , pulmonary function , and quality of life . The emergence of bacterial resistance and other bacteria did not differ between the 2 periods of study . Inhaled tobramycin was associated with bronchospasm in 3 patients , but not with detectable ototoxicity or nephrotoxicity . CONCLUSIONS : Aerosol administration of high-dose tobramycin in non-CF bronchiectatic patients for endobronchial infection with PA appears to be safe and decreases the risk of hospitalization and PA density in sputum . Nevertheless , pulmonary function and quality of life are not improved , and the risk of bronchospasm is appreciable 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 A r and omized , placebo-controlled , multicenter trial evaluated the safety and efficacy of 300 mg aerosolized tobramycin solution for inhalation ( TSI ) administered twice daily for 4 weeks in 74 bronchiectasis patients colonized with Pseudomonas aeruginosa ( PA ) . Patients were evenly divided between TSI therapy and placebo . After 2 weeks of treatment , patients treated with TSI had a mean reduction in sputum PA density of 4.8 log(10 . ) This reduction was maintained for the duration of treatment . The placebo group showed no change in PA density during the study . Two weeks after the end of therapy , PA had been eradicated in 13 TSI-treated patients . PA was not eradicated in any placebo patients . Among those colonized with Staphylococcus aureus at baseline , 6 of 9 patients in the TSI group and 2 of 9 patients in the placebo group were culture negative for this organism 2 weeks posttreatment . Sixty-two percent of TSI-treated patients were judged by a physician as having an improved general health status , compared with 38 % of placebo-treated patients . Dyspnea , wheezing , and chest tightness were reported more frequently in the TSI-treated patient group than in the placebo-treated patient group STUDY OBJECTIVE To evaluate the efficacy and safety of tobramycin solution for inhalation ( TSI ) in patients with severe bronchiectasis . DESIGN Open-label clinical trial consisting of three treatment cycles ( 14 days of drug therapy , and 14 days off drug ) and an additional 40-week follow-up by chart review . SETTING Nine clinical sites throughout the United States . SUBJECTS Forty-one adult patients ( > /= 18 years old ) with diffuse bronchiectasis affecting two or more lung segments and a history of Pseudomonas aeruginosa infection . INTERVENTIONS TSI , 300 mg tobramycin per dose bid . MEASUREMENTS AND RESULTS During the 12-week treatment period , significant improvements ( reduction of 1.5 U [ p = 0.006 ] ) occurred in mean pulmonary total symptom severity score , a composite score that assesses the severity of cough , shortness of breath , sputum production , fatigue , and wheezing . Significant improvements ( reduction of 9.8 U [ p < 0.001 ] ) were also observed in St. George Respiratory Question naire scores , which measure health-related quality of life . Eradication or presumed eradication of P aeruginosa occurred in 6 of 27 evaluable subjects ( 22.2 % ) . Tobramycin-resistant P aeruginosa developed in two subjects ( minimal inhibitory concentration > /= 16 microg/mL ) . Ten subjects withdrew from the study due to adverse events ; in nine of these subjects , adverse events were considered probably or possibly related to treatment . The most common adverse events were cough , wheezing , and dyspnea . CONCLUSIONS TSI therapy result ed in significant improvements in respiratory symptoms and health-related quality of life in subjects with severe bronchiectasis , but some subjects did not tolerate TSI therapy . Bronchiectasis patients receiving this therapy should be monitored for signs of intolerance |
10,821 | 30,294,938 | The meta- analysis found that , overall , nutrition interventions had a significant effect on pain reduction with studies testing an altered overall diet or just one nutrient having the greatest effect .
This review highlights the importance and effectiveness of nutrition interventions for people who experience chronic pain | BACKGROUND This systematic review aim ed to evaluate the impact of nutrition interventions on participant reported pain severity and intensity in population s with chronic pain . | OBJECTIVES A r and omized , placebo-controlled , double-blind trial of the relative effectiveness of glucosamine sulphate and placebo in managing pain in osteoarthritis ( OA ) of the knee . METHODS Eighty patients with OA of the knee were recruited from a rheumatology out-patient clinic and received either glucosamine sulphate 1500 mg daily for 6 months or dummy placebo . The primary outcome measure was patients ' global assessment of pain in the affected knee . RESULTS Area under the curve analysis for the primary outcome measure showed no difference between placebo and glucosamine [ mean difference 0.15 mm , 95 % confidence interval ( CI ) -8.78 to 9.07 ] . The placebo response was 33 % . There was a statistically significant difference between groups in knee flexion ( mean difference 13 degrees , 95 % CI -23.13 to -1.97 ) , but this difference was small and could have been due to measurement error . CONCLUSIONS As a symptom modifier in OA patients with a wide range of pain severities , glucosamine sulphate was no more effective than placebo Objective : To investigate the efficacy of a Mediterranean diet ( MD ) versus an ordinary Western diet for suppression of disease activity in patients with rheumatoid arthritis ( RA ) . Methods : Patients with well controlled , although active RA of at least two years ’ duration , who were receiving stable pharmacological treatment , were invited to participate . All patients were r and omly allocated to the MD or the control diet ( CD ) . To achieve good compliance with prescribed diets all patients were for the first three weeks served the MD or the CD , respectively , for lunch and dinner at the outpatient clinic ’s canteen . Clinical examinations were performed at baseline , and again in the 3rd , 6th , and 12th week . A composite disease activity index ( DAS28 ) , a physical function index ( Health Assessment Question naire ( HAQ ) ) , a health survey of quality of life ( Short Form-36 ( SF-36 ) ) , and the daily consumption of non-steroidal anti-inflammatory drugs were used as primary efficacy variables . Results : From baseline to the end of the study the patients in the MD group ( n=26 ) showed a decrease in DAS28 of 0.56 ( p<0.001 ) , in HAQ of 0.15 ( p=0.020 ) , and in two dimensions of the SF-36 Health Survey : an increase in “ vitality ” of 11.3 ( p=0.018 ) and a decrease in “ compared with one year earlier ” of 0.6 ( p=0.016 ) . For the control patients ( n=25 ) no significant change was seen at the end of the study . This difference between the two treatment groups was notable only in the second half of the trial . Conclusion : The results indicate that patients with RA , by adjusting to a Mediterranean diet , did obtain a reduction in inflammatory activity , an increase in physical function , and improved vitality Background The purpose of the present study was to examine the effectiveness of an anti-inflammatory intervention as a treatment for neuropathic pain following spinal cord injury ( SCI ) . Methods This r and omized , parallel-group , controlled clinical trial ( NCT02099890 ) examined 20 participants with varying levels and severities of SCI , r and omized ( 3:2 ) to either a 12-week anti-inflammatory diet , or control group . Outcome measures consisted of self-determined indices of pain as assessed using the neuropathic pain question naire ( NPQ ) and markers of inflammation as assessed by various pro- and anti-inflammatory cytokines , as well as the eicosanoids PGE2 and LTB4 . Results A significant group × time interaction was found for sensory pain scores ( p < 0.01 ) . A Mann-Whitney test revealed that the change scores ( 3-month baseline ) were significantly different between groups for IFN-y ( U = 13.0 , p = 0.01 ) , IL-1β ( U = 14.0 , p = 0.01 ) , and IL-2 ( U = 12.0 , p = 0.01 ) . A Friedman test revealed the treatment group had a significant reduction in IFN-y ( x2 = 8.67 , p = 0.01 ) , IL-1β ( x2 = 17.78 , p < 0.01 ) , IL-6 ( x2 = 6.17 , p < 0.05 ) , while the control group showed no significant change in any inflammatory mediator . A stepwise backward elimination multiple regression analysis showed that the change in sensory neuropathic pain was a function of the change in the proinflammatory cytokines IL-2 and IFN-y , as well as the eicosanoid PGE2 ( R = 0.689 , R2 = 0.474 ) . Conclusions Overall , the results of the study demonstrate the efficacy of targeting inflammation as a means of treating neuropathic pain in SCI , with a potential mechanism relating to the reduction in proinflammatory cytokines and PGE2.Trial registration Clinical Trials.gov , Objective . To evaluate the effectiveness of a whole-foods , plant-based diet ( WFPB ) to reduce symptoms of osteoarthritis . Methods . Six-week , prospect i ve r and omized open-label study of patients aged 19–70 with osteoarthritis . Participants were r and omized to a WFPB ( intervention ) or continuing current diet ( control ) . Outcomes were assessed by mixed models analysis of participant self-assessed weekly SF-36v2 domain t scores , weekly Patient Global Impression of Change ( PGIC ) scales , and mean weekly Visual Analog Scale ( VAS ) pain assessment . Mixed models analysis also evaluated pre-post change from baseline level for st and ard clinical measures : weight , BMI , body temperature , pulse , and blood pressure . Results . Forty participants were r and omized . Thirty-seven of them , 18 control and 19 intervention , completed the study . The intervention group reported a significantly greater improvement than the control group in SF-36v2 energy/vitality , physical functioning , role physical , and the physical component summary scale . The differences between the intervention and control PGIC scales were statistically significant over time . Intervention group improvement in VAS weekly mean was also significantly greater than that of the control group from week 2 onward . Conclusion . Study results suggest that a whole-foods , plant-based diet significantly improves self-assessed measures of functional status among osteoarthritis patients Background Osteoarthritis ( OA ) is a slowly destructive process that may be influenced by a nutritional mineral balance in the body . Methods This small , double blind , placebo controlled pilot study investigated the impact of treatment with a natural multi-mineral supplement from seaweed ( Aquamin ) on 6 minute walking distance ( 6 MWD ) , range of motion ( ROM ) , and pain and joint mobility measured by the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index in subjects with moderate to severe OA of the knee during gradual withdrawal of non-steroidal anti-inflammatory drugs ( NSAIDs ) that were being used daily for pain management . Subjects ( n = 29 ) with moderate to severe OA of the knee were r and omised to receive either Aquamin ( 2400 mg/d ) or Placebo for up to 12 weeks . Results Of the 29 subjects initially r and omized , only 22 subjects proceeded to treatment due to 7 subjects not meeting study selection criteria at baseline . Fourteen subjects completed the study and an ITT analysis ( n = 22 ) of the data showed no significant differences in WOMAC scores however , the data did reveal significant improvements in passive and active extension ROM ( 0.83 ° ± 1.54 vs. -1.54 ° ± 2.43 ; difference , 5.2 ° ± 2.2 , p = 0.028 ) and 6 MWD ( 150 ± 48 ft vs. 12.5 ± 31.5 ft ; difference , 136 ± 57 ft , p = 0.03 ) in the Aquamin group compared to the placebo group ; respectively , following a 50 % reduction in NSAID use . The treatments were well tolerated and the adverse event profiles were not significantly different between the groups . Conclusion This small preliminary study suggests Aquamin may increase range of motion and walking distances in subjects with OA of the knee and may allow partial withdrawal of NSAIDs over 12 weeks of treatment . Additional research is needed to confirm these preliminary observations . Trial registration Background and Aims : Patients with fibromyalgia frequently present with symptoms similar to those experienced by patients with gluten-related disorders , raising the possibility that a subgroup of these patients could be experiencing underlying gluten sensitivity . This study aim ed to evaluate the effects of a gluten-free diet ( GFD ) compared with a hypocaloric diet ( HCD ) among patients with fibromyalgia . Methods : Adult patients diagnosed with fibromyalgia were r and omly allocated to receive a GFD or a HCD over a 24-week period . The primary outcome measure was the change in the number of gluten sensitivity symptoms . The following secondary outcomes were evaluated : body mass index , Revised Fibromyalgia Impact Question naire , Pittsburgh Sleep Quality Index , Brief Pain Inventory , Beck Depression Inventory-II , State-Trait Anxiety Inventory , Short-Form Health Survey , Patient Global Impression Scale of Severity , Patient Global Impression Scale of Improvement , and adverse events . Results : Seventy-five subjects were r and omly allocated to receive either a GFD ( n=35 ) or an HCD ( n=40 ) . The least squares mean change in the total number of gluten sensitivity symptoms from baseline did not differ significantly between the GFD and HCD groups ( −2.44±0.40 for the GFD ; −2.10±0.37 for the HCD ; P=0.343 ) . Similarly , the 2 dietary interventions did not differ in any of the remaining measured secondary outcomes . Both dietary interventions were well tolerated . Conclusions : Both dietary interventions were associated with similar beneficial outcomes in reducing gluten sensitivity symptoms and other secondary outcomes . However , despite its specificity , GFD was not superior to HCD in reducing the number of gluten sensitivity symptoms or secondary outcomes Plants are rich natural sources of antioxidants in addition to other nutrients . Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food ( LF ) have been carried out . We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns . LF is an uncooked vegan diet and consists of berries , fruits , vegetables and roots , nuts , germinated seeds and sprouts , i.e. rich sources of carotenoids , vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes , lycopen and lutein in their sera . Also the increases of vitamin C and vitamin E ( adjusted to cholesterol ) were statistically significant . As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin , myricetin and kaempherol was much higher than in the omnivorous controls . The LF diet is rich in fibre , substrate of lignan production , and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF . The shift of fibromyalgic subjects to LF result ed in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health . The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding . The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms . In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants , lactobacilli and fibre , and this was also seen in objective measures Objective : Pain is a common complaint among postmenopausal women . It has been postulated that vascular dysfunction caused by estrogen decline at menopause plays a key role in the initiation and progression of degradative joint disease , namely age-related osteoarthritis . We evaluated whether supplementation with resveratrol , a phytoestrogen , could improve aspects of well-being such as chronic pain that is commonly experienced by postmenopausal women . Methods : A 14-week r and omized , double-blind , placebo-controlled intervention with trans-resveratrol ( 75 mg , twice daily ) was conducted in 80 healthy postmenopausal women . Aspects of well-being , including pain , menopausal symptoms , sleep quality , depressive symptoms , mood states , and quality of life were assessed by Short form-36 at baseline and at the end of treatment . Rating scales were averaged to provide a composite score representing overall well-being . Cerebral vasodilator responsiveness to hypercapnia was also assessed as a surrogate marker for cerebrovascular function . Results : Compared with placebo treatment , there was a significant reduction in pain and an improvement in total well-being after resveratrol supplementation . Both benefits , including measures of quality of life , correlated with improvements in cerebrovascular function . Conclusions : Our preliminary findings indicate potential for resveratrol treatment to reduce chronic pain in age-related osteoarthritis . Resveratrol consumption may also boost perceptions of well-being in postmenopausal women . Further investigation to eluci date underlying mechanisms is warranted Background Non-medical , non-pharmacological and pharmacological treatments are recommended for the prevention of migraine . The purpose of this r and omized double-blind placebo controlled , multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium , riboflavin and Q10 as prophylactic treatment for migraine . Methods 130 adult migraineurs ( age 18 – 65 years ) with ≥ three migraine attacks per month were r and omized into two treatment groups : dietary supplementation or placebo in a double-blind fashion . The treatment period was 3 months following a 4 week baseline period without prophylactic treatment . Patients were assessed before r and omization and at the end of the 3-month-treatment-phase for days with migraine , migraine pain , burden of disease ( HIT-6 ) and subjective evaluation of efficacy . Results Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group ( p = 0.23 compared to placebo ) . The intensity of migraine pain was significantly reduced in the supplement group compared to placebo ( p = 0.03 ) . The sum score of the HIT-6 question naire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group ( p = 0.01 ) . The evaluation of efficacy by the patient was better in the supplementation group compared to placebo ( p = 0.01 ) . Conclusions Treatment with a proprietary supplement containing magnesium , riboflavin and Q10 ( Migravent ® in Germany , Dolovent ® in USA ) had an impact on migraine frequency which showed a trend towards statistical significance . Migraine symptoms and burden of disease , however , were statistically significantly reduced compared to placebo in patients with migraine attacks Fibromyalgia poses a challenge for therapy . Recent guidelines suggest that fibromyalgia should be treated within a multidisciplinary therapy approach . No data are available that evaluated multimodal treatment strategies of Integrative Medicine ( IM ) . We conducted a controlled , nonr and omized pilot study that compared two inpatient treatment strategies , an IM approach that included fasting therapy and a conventional rheumatology ( CM ) approach . IM used fasting cure and Mind-Body-Medicine as specific methods . Of 48 included consecutive patients , 28 were treated with IM , 20 with CM . Primary outcome was change in the Fibromyalgia Impact Question naire ( FIQ ) score after the 2-week hospital stay . Secondary outcomes included scores of pain , depression , anxiety , and well being . Assessment s were repeated after 12 weeks . At 2 weeks , there were significant improvements in the FIQ ( P < 0.014 ) and for most of secondary outcomes for the IM group compared to the CM group . The beneficial effects for the IM approach were reduced after 12 weeks and no longer statistically significant with the exception of anxiety . Findings indicate that a multimodal IM treatment with fasting therapy might be superior to CM in the short term and not inferior in the mid term . Longer-term studies are warranted to assess the clinical impact of integrative multimodal treatment in fibromyalgia OBJECTIVE Evaluation of the efficacy and safety of a food supplement made of collagen hydrolysate 1200 mg/day versus placebo during 6 months , in subjects with joint pain at the lower or upper limbs or at the lumbar spine . DESIGN Comparative double-blind r and omized multicenter study in parallel groups . SETTING 200 patients of both genders of at least 50 years old with joint pain assessed as ≥30 mm on a visual analogical scale ( VAS ) . INTERVENTION Collagen hydrolysate 1200 mg/day or placebo during 6 months . MAIN OUTCOME MEASURE Comparison of the percentage of clinical responder between the active collagen hydrolysate group and the placebo group after 6 months of study . A responder subject was defined as a subject experiencing a clinical ly significant improvement ( i.e. by 20 % or more ) in the most painful joint using the VAS score . All analyses were performed using an intent-to-treat procedure . RESULTS At 6 months , the proportion of clinical responders to the treatment , according to VAS scores , was significantly higher in the collagen hydrolysate ( CH ) group 51.6 % , compared to the placebo group 36.5 % ( p<0.05 ) . However , there was no significant difference between groups at 3 months ( 44.1 % vs. 39.6 % , p=0.53 ) . No significant difference in terms of security and tolerability was observed between the two groups . CONCLUSIONS This study suggests that collagen hydrolysate 1200 mg/day could increase the number of clinical responders ( i.e. improvement of at least 20 % on the VAS ) compared to placebo . More studies are needed to confirm the clinical interest of this food supplement Background Fibromyalgia engulfs patients in a downward , reinforcing cycle of unrestorative sleep , chronic pain , fatigue , inactivity , and depression . In this study we tested whether a mostly raw vegetarian diet would significantly improve fibromyalgia symptoms . Methods Thirty people participated in a dietary intervention using a mostly raw , pure vegetarian diet . The diet consisted of raw fruits , salads , carrot juice , tubers , grain products , nuts , seeds , and a dehydrated barley grass juice product . Outcomes measured were dietary intake , the fibromyalgia impact question naire ( FIQ ) , SF-36 health survey , a quality of life survey ( QOLS ) , and physical performance measurements . Results Twenty-six subjects returned dietary surveys at 2 months ; 20 subjects returned surveys at the beginning , end , and at either 2 or 4 months of intervention ; 3 subjects were lost to follow-up . The mean FIQ score ( n = 20 ) was reduced 46 % from 51 to 28 . Seven of the 8 SF-36 subscales , bodily pain being the exception , showed significant improvement ( n = 20 , all P for trend < 0.01 ) . The QOLS , scaled from 0 to 7 , rose from 3.9 initially to 4.9 at 7 months ( n = 20 , P for trend 0.000001 ) . Significant improvements ( n = 18 , P < 0.03 , paired t-test ) were seen in shoulder pain at rest and after motion , abduction range of motion of shoulder , flexibility , chair test , and 6-minute walk . 19 of 30 subjects were classified as responders , with significant improvement on all measured outcomes , compared to no improvement among non-responders . At 7 months responders ' SF-36 scores for all scales except bodily pain were no longer statistically different from norms for women ages 45–54 . Conclusion This dietary intervention shows that many fibromyalgia subjects can be helped by a mostly raw vegetarian diet OBJECTIVES The objective of this double-blind r and omised , placebo-controlled study was to examine the efficacy and safety intramuscular vitamin B12 ( Tricortin 1000 ) in the treatment of low back pain in patients with mechanical or irritative lumbago . METHODS 60 patients aged between 18 and 65 years with lumbago or sciatic neuritis of mechanical origin without need for surgical procedures were enrolled . Patients had to present with a proven medical history for back pain ( lasting from 6 months to 5 years ) and a pain intensity [ as evaluated with a Visual Analogic Scale ( VAS ) ] equal or greater than 60 mm . Efficacy primary end-point was evaluated by means of a visual analogic scale ( VAS ) and a Disability Question naire ( DQ ) . Consumption of paracetamol during the study period was the secondary efficacy end-point . RESULTS Both treatment groups experienced a sharp decrease in pain and disability . However , comparison between groups at the end of the treatment period showed a statistically significant difference in favour of the active treatment both for VAS and DQ ( p < 0.0001 and p < 0.0002 , respectively ) . Consumption of paracetamol proved significantly higher in the placebo group than in the active treatment ( p < 0.0001 ) . CONCLUSIONS The efficacy and safety of parenteral Vitamin B12 in alleviating low back pain and related disability and in decreasing the consumption of paracetamol was confirmed in patients with no signs of nutritional deficiency BACKGROUND Oral glucosamine and chondroitin sulfate , alone and in combination , have been used worldwide for the treatment of osteoarthritis ( OA ) , but their efficacy is controversial . This clinical study was aim ed at investigating the potential of a dietary supplement containing glucosamine and chondroitin sulfate in combination with derivatives of quercetin , a naturally occurring flavonoid , ( GCQ supplement ) for knee OA care . RESULTS A r and omized , double-blind , placebo-controlled study was conducted in 40 Japanese subjects with symptomatic knee OA . Subjects were r and omly assigned to GCQ supplement ( 1200 mg glucosamine hydrochloride , 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day ) or placebo and the treatment and follow-up were continued for 16 weeks . The results of symptomatic efficacy assessment based on Japanese Orthopaedic Association criteria showed that scores for two of the four symptom/function subscales , as well as the aggregate scores , were significantly improved at week 16 or earlier in the GCQ group compared to the placebo group . Moreover , analyses of cartilage metabolism biomarkers showed a trend of improvement in type II collagen synthesis /degradation balance in the GCQ group during follow-up . CONCLUSION GCQ supplement was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms Objective To investigate how changes in the gastrointestinal tract ( GIT ) microbiota profile may influence nutraceutical efficacy in osteoarthritis ( OA ) and allow the formulation of a hypothesis that explains in part the inconsistent and contentious findings from OA clinical studies with green-lipped mussel ( GLM ) and glucosamine . Methods A non-blinded r and omised clinical trial was conducted with 38 subjects diagnosed with knee OA . Each participant received either 3,000 mg/day of a whole GLM extract or 3,000 mg/day of glucosamine sulphate ( GS ) , p.o . for 12 weeks . Faecal microbial analyses were carried out after collecting stools at T0 and T12 weeks . Additional pharmacometric measures were obtained from changes in arthritic scores in the Western Ontario McMaster Universities Arthritis Index ( WOMAC ) and the Lequesne algofunctional indices and the Gastrointestinal Symptom Rating Scale ( GSRS ) . An intention-to-treat analysis was employed and participant data collected at T0 , T6 and T12 weeks . Results There were no statistically significant changes in bacterial growth patterns determined by the Wilcoxon test . In both groups there was a trend towards a decrease in Clostridium and Staphylococcus species and increase in Lactobacillus , Streptococcus and Eubacterium species . In the GLM group Bifidobacterium tended to increase and Enterococcus and yeast species to decrease . The GS-treated group demonstrated a trend towards a decrease in Bacteroides and an increase in yeasts and Coliforms species , most notably Escherichia coli . We further confirm significant improvement ( p < 0.05 ) in all OA outcome measures from T0 to T12 weeks for both the GLM and GS groups . The GSRS scores indicated that GIT function significantly improved over the 12 weeks duration with GLM and GS supplementation . Conclusion Both GLM and GS reduced OA symptoms and non-significantly altered the gut microbiota profile from baseline . Changes in the microbiota profiles occurred in both treatment groups ; the most notable being a reduction in the Clostridia sp. This study suggests that nutritional supplements such as GLM and GS may regulate some of the metabolic and immunological activities of the GIT microbiota . The decrease in Clostridia , a potent modulator of colonic Th17 and CD4 + regulatory T cells , was consistent with a decrease in inflammation ; improved GSRS scores and OA symptoms for these OA participants . The GIT microbiota may be important factor in the first-pass metabolism of these nutraceuticals Background : Diabetic neuropathy is a common and often debilitating condition for which available treatments are limited . Because a low-fat plant-based diet has been shown to improve glycemic control in individuals with type 2 diabetes , we hypothesized that such a diet would reduce painful symptoms of diabetic neuropathy . Methods : In this 20-week pilot study , individuals with type 2 diabetes and painful diabetic neuropathy were r and omly assigned to two groups . The intervention group was asked to follow a low-fat , plant-based diet , with weekly classes for support in following the prescribed diet , and to take a vitamin B12 supplement . The control group was asked to take the same vitamin B12 supplement , but received no other intervention . At baseline , midpoint and 20 weeks , clinical , laboratory and question naire data were collected . Question naires included an analog ‘ worst pain ’ scale , Michigan Neuropathy Screening Instrument , global impression scale , Short Form McGill Pain Question naire , Neuropathy Total Symptom Score , a weekly pain diary and Norfolk Quality of Life Question naire . Results : After 20 weeks , body weight change with the intervention was −6.4 kg ( 95 % confidence interval ( CI ) −9.4 to −3.4 , P<0.001 ) in an effect size analysis . Electrochemical skin conductance in the foot improved by an average of 12.4 microseimens ( 95 % CI 1.2–23.6 , P=0.03 ) with the intervention in an effect size analysis . The between-group difference in change in pain , as measured by the McGill pain question naire , was −8.2 points ( 95 % CI −16.1 to −0.3 , P=0.04 ) . Michigan Neuropathy Screening Instrument question naire score change was −1.6 points ( 95 % CI −3.0 to −0.2 , P=0.03 ) . Conclusions : Improvements were seen in some clinical and pain measures . This pilot study suggests the potential value of a plant-based diet intervention , including weekly support classes , for treating painful diabetic neuropathy & NA ; Little is known about the relationship between chronic pain status and overall use of healthcare . We examined whether disabling chronic pain was associated with more frequent use of healthcare in three setting s : primary care , emergency departments , and hospital admissions . We used data from Computer‐Assisted Telephone Interviews ( CATI ) of 17,543 residents in New South Wales , Australia aged 16 and over who were r and omly sample d using a population ‐based two‐stage stratified sample and r and om digit dialling methods . The overall response rate was 70.8 % . Compared to chronic pain respondents with no or limited pain‐related disability , those with most pain‐related disability reported more : primary care visits in the last 2 weeks and last 12 months ( adjusted mean number of visits 0.59 vs 0.40 and 10.72 vs 4.81 , both P<0.005 ) ; hospital admissions ( 0.46 vs 0.18 , P<0.005 ) ; and emergency department visits ( 0.85 vs 0.17 , P>0.005 ) . In modelling , having chronic pain per se , or having chronic pain with any level of activity interference predicted health care use after adjusting for age , gender , self‐rated health , psychological distress , comorbidity and access to care . Higher levels of pain‐related disability predicted health care use more than other pain status variables . There was a strong association between pain‐related disability and greater use of services . Further work is needed to underst and the nature of this association . Given the fluctuating course of chronic pain over time , there is a significant segment of the population that may be at risk of developing higher levels of disability associated with increased use of services In rheumatoid arthritis ( RA ) benefit from non-steroidal anti-inflammatory drugs ( NSAIDs ) is mediated through inhibition of the cyclo-oxygenase enzyme , thereby decreasing production of the 2 series prostagl and ins ( PGs ) . The lipoxygenase enzyme is intact , however , allowing leucotriene ( LT ) production , e.g. , LTB4 ( an inflammatory mediator ) . Treatment with evening primrose oil ( EPO ) which contains gamma-linolenic acid ( GLA ) leads to production of the 1 series PGs , e.g. , PGE1 , which has less inflammatory effects . Also LT production is inhibited . Eicosapentaenoic acid ( EPA , fish oil ) treatment provides a substrate for PGs and LTs , which are also less inflammatory . In this study 16 patients with RA were given 540 mg GLA/day ( EPO ) , 15 patients 240 mg EPA and 450 mg GLA/day ( EPO/fish oil ) , and 18 patients an inert oil ( placebo ) . The aim of this study was to determine if EPO or EPO/fish oil could replace NSAID treatment in RA . The initial 12 month treatment period was followed by three months of placebo for all groups . Results at 12 months showed a significant subjective improvement for EPO and EPO/fish oil compared with placebo . In addition , by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs . After 3 months of placebo those receiving active treatment had relapsed . Despite the decrease in NSAIDs , measures of disease activity did not worsen . It is suggested that EPO and EPO/fish oil produce a subjective improvement and allow some patients to reduce or stop treatment with NSAIDs . There is , however , no evidence that they act as disease modifying agents To study the safety and efficacy of a new medical food ( Theramine ) in the treatment of low back pain , we performed a 28-day double-blind r and omized controlled trial in 129 patients . Back pain was present for at least 6 weeks and was not mild . Patients were r and omly assigned to receive medical food alone ( n = 43 ) , naproxen alone ( 250 mg/d , n = 42 ) , or both medical food and naproxen ( n = 44 ) . All patients were assessed by using Rol and –Morris Disability Question naire , Oswestry Low Back Pain Scale , Visual Analog Scale Evaluation and laboratory analysis performed at baseline and at 28 days for assessing the safety and impact on inflammatory markers , which included complete blood counts , C-Reactive protein ( CRP ) , and liver function ( alkaline phosphatase , aspartate transaminase , and alanine transaminase ) . At baseline , there were no statistically significant differences in low back pain when assessed by Rol and –Morris function or Oswestry assessment s nor were there differences in the blood indices of inflammation . At day 28 , both the medical food group and combined therapy group ( medical food with naproxen ) were statistically significantly superior to the naproxen-alone group ( P < 0.05 ) . The medical food and naproxen group showed functional improvement when compared to the naproxen-alone group . The naproxen-alone group showed significant elevations in CRP , alanine transaminase , and aspartate transaminase when compared with the other groups . Medical food alone or with naproxen showed no significant change in liver function tests or CRP , with medical food potentially mitigating the effects seen with naproxen alone . The medical food ( Theramine ) appeared to be effective in relieving back pain without causing any significant side effects and may provide a safe alternative to presently available therapies Fibromyalgia syndrome is a common , chronic musculoskeletal disorder of unknown aetiology . While available therapy is often disappointing , most patients can be helped with a combination of medication , exercise and maintenance of a regular sleep schedule . The objective of the present study was to determine if adding nutritional supplements derived from the unicellular green alga , Chlorella pyrenoidosa , produced any improvements in the clinical and functional status in patients with moderately severe symptoms of fibromyalgia syndrome . Eligible patients had 2 + palpable tenderness at 11 or more of 18 defined tender points and had a tender point index ( TPI ) of at least 22 . Each day for 2 months , participants consumed two commercially available Chlorella-based products , 10 g of ' Sun Chlorella ' tablets and 100 mL of liquid ' Wakasa Gold ' . Any amelioration of symptoms was vali date d and quantified using semi- objective and subjective outcome measures systematic ally administered at clinic visits on days 0 , 30 and 60 of the diet therapy . Eighteen of the 20 patients enrolled completed the 2 month trial . The average TPI for the group which at onset was 32 , decreased to a mean of 25 after 2 months . This decrease was statistically significant ( p = 0.01 ) , representing a 22 % decrease in pain intensity . Blood sample s taken on each occasion indicated no significant alterations in serum chemistries , formed elements , and circulating lymphocyte subsets . Compilations of the results of patient interviews and self- assessment question naires revealed that seven patients felt that the dietary supplement had improved their fibromyalgia symptoms , while six thought they had experienced no change , and five believed the symptoms had worsened over the time of the trial . The results of this pilot study suggest that dietary Chlorella supplementation may help relieve the symptoms of fibromyalgia in some patients and that a larger , more comprehensive double-blind , placebo-controlled clinical trial in these patients is warranted Background The possible therapeutic impact of dietary changes on existing mental illness is largely unknown . Using a r and omised controlled trial design , we aim ed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes . Methods ‘ SMILES ’ was a 12-week , parallel-group , single blind , r and omised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression . The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician . The control condition comprised a social support protocol to the same visit schedule and length . Depression symptomatology was the primary endpoint , assessed using the Montgomery – Åsberg Depression Rating Scale ( MADRS ) at 12 weeks . Secondary outcomes included remission and change of symptoms , mood and anxiety . Analyses utilised a likelihood-based mixed-effects model repeated measures ( MMRM ) approach . The robustness of estimates was investigated through sensitivity analyses . Results We assessed 166 individuals for eligibility , of whom 67 were enrolled ( diet intervention , n = 33 ; control , n = 34 ) . Of these , 55 were utilising some form of therapy : 21 were using psychotherapy and pharmacotherapy combined ; 9 were using exclusively psychotherapy ; and 25 were using only pharmacotherapy . There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks . The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group , t(60.7 ) = 4.38 , p < 0.001 , Cohen ’s d = –1.16 . Remission , defined as a MADRS score < 10 , was achieved for 32.3 % ( n = 10 ) and 8.0 % ( n = 2 ) of the intervention and control groups , respectively ( χ2 ( 1 ) = 4.84 , p = 0.028 ) ; number needed to treat ( NNT ) based on remission scores was 4.1 ( 95 % CI of NNT 2.3–27.8 ) . A sensitivity analysis , testing departures from the missing at r and om ( MAR ) assumption for dropouts , indicated that the impact of the intervention was robust to violations of MAR assumptions . Conclusions These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder , the benefits of which could extend to the management of common co-morbidities . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : ACTRN12612000251820 . Registered on 29 February 2012 OBJECTIVE To assess the efficacy of tart cherry juice in treating pain and other features of knee osteoarthritis ( OA ) . METHODS 58 non-diabetic patients with Kellgren grade 2 - 3 OA were r and omized to begin treatment with cherry juice or placebo . Two 8 oz bottles of tart cherry juice or placebo were consumed daily for 6 weeks with a 1 week washout period before switching treatments ( crossover design ) . Western Ontario McMaster Osteoarthritis Index ( WOMAC ) scores and walking times were recorded prior to and after each treatment period . Additionally , plasma urate , creatinine and high sensitivity C-reactive protein ( hsCRP ) were recorded at baseline , after the first treatment period and after the second treatment period . Acetaminophen was allowed as a rescue drug and self reported after each treatment period . Treatment effect was examined with repeated measures analysis of variance ( ANOVA ) using an intention-to-treat ( ITT ) analysis . RESULTS There were five withdrawals during the cherry juice treatment ( four adverse events ( AEs ) ) and seven withdrawals during the placebo treatment ( three AEs ) . WOMAC scores decreased significantly ( P < 0.01 ) after the cherry juice treatment but not after the placebo treatment ( P = 0.46 ) ; differences between treatments were not significant ( P = 0.16 ) . hsCRP declined during the cherry juice treatment vs placebo ( P < 0.01 ) . The decline in hsCRP was associated with WOMAC improvement ( P < 0.01 ) . Walking time , acetaminophen use , plasma urate and creatinine were unaffected by treatments . CONCLUSIONS Tart cherry juice provided symptom relief for patients with mild to moderate knee OA , but this effect was not significantly greater than placebo . Tart cherry juice lowered hsCRP levels and this effect was associated with improved WOMAC scores Therapeutic effects of fish oil ( 10 g/day ) in rheumatoid arthritis were investigated in a r and omized , controlled , double-blind study . Forty-three patients completing the study were evaluated at 0 , 3 and 6 months . The nutrient intake in the fish oil group and in the control group was essentially similar . In the fish oil group , the percentage of n-3 fatty acids in serum phosphatidylcholine increased by 9.6 ( range 2.6 - 16.1 ) . Patients in the fish oil group reported a significantly decreased consumption of NSAID at 3 and 6 months , and the status of global arthritic activity improved at 3 months in physician 's assessment . Control patients reported an increased global arthritic activity at 6 months . No change was found in patient assessment of pain , duration of morning stiffness or functional capacity . Essentially no change occurred in biochemical markers of inflammation . We conclude that fish oil has small anti-inflammatory effects with at most a NSAID-saving potential . The value of prolonged supplementation remains to be evaluated Background Undenatured type II collagen ( UC-II ) is a nutritional supplement derived from chicken sternum cartilage . The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis ( OA ) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate ( GC ) . Methods One hundred ninety one volunteers were r and omized into three groups receiving a daily dose of UC-II ( 40 mg ) , GC ( 1500 mg G & 1200 mg C ) , or placebo for a 180-day period . The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) from baseline through day 180 for the UC-II group versus placebo and GC . Secondary endpoints included the Lequesne Functional Index ( LFI ) , the Visual Analog Scale ( VAS ) for pain and the WOMAC subscales . Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures , while incremental area under the curve was calculated by the intent-to-treat method . Results At day 180 , the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo ( p = 0.002 ) and GC ( p = 0.04 ) . Supplementation with UC-II also result ed in significant changes for all three WOMAC subscales : pain ( p = 0.0003 vs. placebo ; p = 0.016 vs. GC ) ; stiffness ( p = 0.004 vs. placebo ; p = 0.044 vs. GC ) ; physical function ( p = 0.007 vs. placebo ) . Safety outcomes did not differ among the groups . Conclusion UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated . Additional studies that eluci date the mechanism for this supplement ’s actions are warranted . Trial registration CTRI/2013/05/003663 ; CTRI/2013/02/003348 Twelve female fibromyalgia syndrome ( FMS ) patients were given 500 mg per day of a blend containing 100 mg ascorbigen and 400 mg broccoli powder in a preliminary , one-month , open-label trial . This group of patients showed a mean 20.1 percent ( p=0.044 ) decrease in their physical impairment score and a mean 17.8 percent ( p=0.016 ) decrease in their total fibromyalgia impact scores as measured by the Fibromyalgia Impact Question naire . The mean physical impairment score two weeks post-treatment showed a significant return to near pre-treatment level ( p=0.028 ) . Analysis of ten of the patients ' mean threshold pain levels at the 18 possible tender points obtained before and at the end of treatment showed a strong trend toward an increase in the mean threshold pain level ( p=0.059 ) . The reduced sensitivity to pain and improvement in quality of life measured in this study appear to be clinical ly relevant and a larger , double-blind study is warranted Background : Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects . Purpose : This present study tested a Maritech ® extract formulation , containing a blend of extracts from three different species of brown algae , plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee . Patients and methods : Participants ( n = 12 , five females [ mean age , 62 ± 11.06 years ] and seven males [ mean age , 57.14 ± 9.20 years ] ) with a confirmed diagnosis of osteoarthritis of the knee were r and omized to either 100 mg ( n = 5 ) or 1000 mg ( n = 7 ) of a Maritech ® extract formulation per day . The formulation contained Maritech ® seaweed extract containing Fucus vesiculosis ( 85 % w/w ) , Macrocystis pyrifera ( 10 % w/w ) and Laminaria japonica ( 5 % w/w ) plus vitamin B6 , zinc and manganese . Primary outcome was the average comprehensive arthritis test ( COAT ) score which is comprised of four sub-scales : pain , stiffness , difficulty with physical activity and overall symptom severity measured weekly . Safety measures included full blood count , serum lipids , liver function tests , urea , creatinine and electrolytes determined at baseline and week 12 . All adverse events were recorded . Results : Eleven participants completed 12 weeks and one completed 10 weeks of the study . Using a multilevel linear model , the average COAT score was reduced by 18 % for the 100 mg treatment and 52 % for the 1000 mg dose at the end of the study . There was a clear dose response effect seen between the two treatments ( P ≤ 0.0005 ) on the average COAT score and each of the four COAT subscales ( pain , stiffness , difficulty with physical activity and overall symptom severity ) ( P ≤ 0.05 ) . The preparation was well tolerated and the few adverse events were unlikely to be related to the study medication . There were no changes in blood parameters measured over the course of the study with the exception of an increase in serum albumin which was not clinical ly significant . Conclusion : The seaweed extract nutrient complex when taken orally over twelve weeks decreased the symptoms of osteoarthritis in a dose-dependent manner . It was demonstrated to be safe to use over the study period at the doses tested . The efficacy of the preparation now needs to be demonstrated in a phase III r and omized controlled trial ( RCT ) . Australian and New Zeal and Clinical Trials Register : ACTRN12607000229471 The effects of an orally administered combination of a glucosamine-chondroitin-quercetin glucoside ( GCQG ) supplement on the synovial fluid properties of patients with osteoarthritis ( OA ) and rheumatoid arthritis ( RA ) were investigated from the clinical nutrition view point . In this study , forty-six OA and twenty-two RA patients were administered with the GCQG supplement orally for 3 months . Several parameters of the knee joints were monitored before and after supplementation . The OA patients showed a significant improvement in pain symptoms , daily activities ( walking and climbing up and down stairs ) , and visual analogue scale , and changes in the synovial fluid properties with respect to the protein concentration , molecular size of hyaluronic acid , and chondroitin 6-sulphate concentration were also observed . However , no such effects were observed in the RA patients . These results suggest that the GCQG supplement exerted a special effect on improving the synovial fluid properties in OA patients Abstract This study evaluated the effects of consumption of hydrolyzed water-soluble egg membrane ( WSEM ) on joint function in an otherwise healthy population experiencing chronic pain . A r and omized , double-blind , placebo-controlled crossover study included two 4-week periods of placebo and WSEM consumption , separated by a 4-week washout period . Twenty-five study participants were r and omized to either the “ placebo-first ” or “ WSEM first ” sequence in the crossover trial , and 22 participants completed the study requirements . Range of motion ( ROM ) was assessed using digital inclinometry for joints associated with vertical weight bearing from neck to knees and for shoulders . Pain at rest and when physically active was scored for the same anatomical areas using visual analog scales ( VAS ) . Physical functioning was tracked using question naires with VAS . Consumption of WSEM was associated with improved ROM for neck , spine , hips , and knees , with ROM for the neck and right knee being significantly improved during WSEM consumption compared to placebo ( P < .05 ) . ROM improvement for the dominant shoulder was highly significant during WSEM consumption ( P < .01 ) . Physical activity levels were significantly higher after WSEM than after placebo consumption ( P < .05 ) . Many aspects of physical functioning as part of daily living improved . Subgroup analysis showed rapid improvement of lower back pain after 5 days of WSEM consumption compared to placebo consumption ( P < .05 ) in subjects who participated in the study during the winter season . Daily consumption of 450 mg WSEM was associated with improved joint function , comfort during daily activities , and increased physical activity 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 OBJECTIVES The aim of this study was to test the efficacy of an antioxidant/anti-inflammatory supplement containing st and ardized lemon verbena ( Aloysia triphylla , Lippia citriodora ) extract and fish oil omega-3 fatty acid in a human pilot trial as an alternative treatment for joint management . METHODS AND DESIGN First , antioxidant activity of the supplement was determined through an oxygen radical absorbance capacity ( ORAC ) assay . In a r and omized , double-blinded placebo-controlled trial , 45 subjects with pain discomfort received the nutritional supplement or placebo for 9 weeks . Western Ontario MacMaster ( WOMAC ) and Lequesne 's question naires , which are disease-specific measurements vali date d to measure joint dysfunction and pain , were administered and evaluated once per week in the placebo and intervention groups . OUTCOME MEASURES Pain and stiffness symptoms , and joint function were determined once per week through recording their respective WOMAC and Lequesne 's scores in the placebo and intervention groups . Statistically significant differences were determined at every measurement point between the two groups . RESULTS Lemon verbena extract showed strong antioxidant properties as measured by the ORAC assay . The nutritional supplement containing st and ardized lemon verbena extract ( 14 % verbascoside , w/w ) and fish oil omega-3 fatty acid reduced symptoms of pain and stiffness significantly , and improved physical function as shown by WOMAC and Lequesne 's scores after 9 weeks of treatment . WOMAC and Lequesne 's total scores decreased 53 % and 78 % , respectively , at the end of the study compared to initial conditions . Onset of the effect was observed at the third and fourth weeks , when statistically significant differences were detected , compared to placebo . CONCLUSIONS This pilot study reveals that supplementation with lemon verbena combined with omega-3 fatty acids may be considered for further investigation as a complementary and alternative treatment for improving joint status in subjects with joint discomfort Our aim was to assess the effect of dietary elimination of monosodium glutamate ( MSG ) and aspartame on perceived pain in fibromyalgia . A total of 72 female patients with fibromyalgia were r and omized to discontinuation of dietary MSG and aspartame ( n = 36 ) or waiting list ( n = 36 ) . Patients were requested to rate their pain using a seven-point scale . Comparisons between both groups showed no significant differences on pain referred during the baseline or after the elimination of dietary MSG and aspartame . The discontinuation of dietary MSG and aspartame did not improve the symptoms of fibromyalgia Brain tryptophan is low in fibromyalgia . Intake of protein rich in large neutral amino acids is reported to lower brain tryptophan . This study was undertaken to assess whether any reduction of such proteins by exclusion of animal protein from the diet reduced pain and morbidity in fibromyalgia patients . It was an open , r and omized controlled trial . 37 subjects with fibromyalgia were enrolled in the vegetarian diet and 41 in the amitriptyline groups . The outcome was assessed with the help of frequencies of fatigue , insomnia & non-restorative sleep , pain score on a 10-point VAS and tender point count . Fatigue , insomnia and non-restorative sleep were present in 41 , 26 and 32 subjects before and in 3 , 0 and 0 subjects respectively at six weeks of treatment in the amitriptyline group . The pain score and tender point count were 6.2 + /- 1.9 & 16.1 + /- 2.3 before and 2.3 + /- 1.3 & 6.4 + /- 3.0 after treatment . All these differences were significant ( P < 0.001 ) . In the vegetarian diet group , fatigue , insomnia and non-restorative sleep were present in 36 , 24 and 27 subjects before and in 34 , 29 and 29 subjects at six weeks of treatment . The pain score and tender point count were 5.7 + /- 1.8 and 15.7 + /- 2.4 before and 5.0 + /- 1.8 & 14.7 + /- 3.6 after treatment . All these differences were insignificant except that in the pain score . The decrease in the pain score , though significant , was much smaller than that in the amitriptyline group . So , it may be concluded that vegetarian diet is a poor option in the treatment of fibromyalgia Introduction Current options to promote joint comfort are limited to medicines that can reduce pain but can also have adverse effects . Collagen , a major component of joint cartilage , is found in the diet , particularly in meat . Its hydrolysed form , collagen hydrolysate ( CH ) , is well absorbed . CH may stimulate the joint matrix cells to synthesize collagen , so helping to maintain the structure of the joint and potentially to aid joint comfort . Methods In a r and omized , double-blind , controlled multicentre trial , 250 subjects with primary osteoarthritis of the knee were given 10 g CH daily for 6 months . Results There was a significant improvement in knee joint comfort as assessed by visual analogue scales to assess pain and the Womac pain subscale . Subjects with the greatest joint deterioration , and with least intake of meat protein in their habitual diets , benefited most . Conclusion CH is safe and effective and warrants further consideration as a food ingredient OBJECTIVES To examine the effects of a challenge with monosodium glutamate ( MSG ) as compared to placebo on the symptoms of fibromyalgia ( FM ) , in participants who initially experienced > 30 % remission of symptoms on an excitotoxin elimination diet . METHODS Fifty-seven FM patients who also had irritable bowel syndrome ( IBS ) were placed on a 4-week diet that excluded dietary additive excitotoxins including MSG and aspartame . Thirty-seven people completed the diet and 84 % of those reported that > 30 % of their symptoms resolved , thus making them eligible to proceed to challenges . Subjects who improved on the diet were then r and omised to a 2-week double-blind placebo-controlled crossover challenge with MSG or placebo for 3 consecutive days each week . The primary outcome measure was total symptom score . Secondary outcome measures included visual analogue pain scales ( VAS for FM and IBS ) , an IBS Quality of Life Question naire ( IBS QOL ) and the Fibromyalgia Impact Question naire-Revised ( FIQR ) . Repeated measures ANOVA was used to analyse crossover challenge results . RESULTS The MSG challenge , as compared to placebo , result ed in a significant return of symptoms ( total symptom score , p<0.02 ) ; a worsening of fibromyalgia severity as determined by the FIQR ( p<0.03 ) ; decreased quality of life in regards to IBS symptoms ( IBS QOL , p<0.05 ) ; and a non-significant trend toward worsening FM pain based on visual analogue scale ( VAS , p<0.07 ) . CONCLUSIONS These findings suggest that dietary glutamate may be contributing to FM symptoms in some patients . Future research on the role of dietary excitotoxins in FM is warranted Dehydration is commonly believed to result in headache , but the effectiveness of increasing the water intake in patients who frequently suffer from headaches has not been studied thus far . In a pilot study , we examined the possible effects and feasibility of increased water intake in headache patients . Eighteen headache patients ( all had migraine , two also had tension-type headache ) were r and omly allocated to placebo medication , or the advice to additionally drink 1.5 l of water per day , for a period of 12 weeks . Effect measurements consisted of a 2 weeks headache diary and the Migraine Specific Quality of Life ( MSQOL ) question naire . The advice to increase the daily fluid intake by 1.5 l increased the fluid intake in the intervention group by approximately 1 l. This reduced the total hours of headache in 2 weeks by 21 h ( 95 % CI : -48 to 5 ) . Mean headache intensity decreased by 13 mm ( 95 % CI : -32 to 5 ) on a visual analogue scale ( VAS ) . The effects on MSQOL , number of headache episodes , and medication seemed to be small . The data of the present study suggest a reduction in the total number of hours and intensity of headache episodes after increased water intake . Our results seem to justify larger scaled research on the effectiveness of increased water intake in headache patients BACKGROUND AND AIM There is uncertainty regarding the prevention of migraine crises by changing the lifestyle of patients . The aim of this r and omized , crossover intervention trial was to evaluate the effects of a low lipid intake on the incidence and severity of migraine crises , in comparison to a diet with moderate lipid intake . METHODS AND RESULTS After a 2-month run-in when patients received preventive medication but were left on their habitual diet , a low-lipid or a normal-lipid diet was r and omly prescribed for 3 months and thereafter diets were crossed over for the following 3 months . Headache was diagnosed based on the International Classification of Headache Disorders ( IHCD ) III criteria . The number and severity of attacks were assessed using a self-reported calendar . Adherence to the diet was assessed by a food frequency question naire . An analysis was performed on the 83 episodic or chronic migraineurs ( 63 female and 20 male ) , in the age range of 18 - 57 years , who completed both intervention periods . Obese subjects had a significantly higher number of attacks than those overweight or with normal body weight ( 24.7 ± 8 , 16.3 ± 12 , and 15.6 ± 11 , respectively , p < 0.03 ) with a significant relationship between the body mass index ( BMI ) and the number of monthly attacks ( r = 0.238 , p < 0.03 ) . The number ( 2.9 ± 3.7 vs. 6.8 ± 7.5 , p < 0.001 ) and severity ( 1.2 + 0.9 vs. 1.7 ± 0.9 , p < 0.01 ) of attacks significantly decreased during both intervention periods , with a significant difference in favour of the low-lipid diet . CONCLUSIONS In this group of patients , the low-lipid diet significantly affected the number and severity of migraine attacks in comparison to a normal-lipid diet . Clinical Trials.gov Identifier : NCT 01917474 OBJECTIVES A 6 wk , double-blind , placebo-controlled study investigated the effects of a nutritional supplement beverage containing milk-based micronutrients and fortified with vitamins and minerals on pain symptoms and activity in adults with osteoarthritis . METHODS Thirty-one subjects with osteoarthritis of both knees were r and omized into two groups and given 12 oz daily of the micronutrient-containing beverage or a placebo for 6 wk . Subjects were instructed not to change their normal activities and diets . Body weights , vital signs , blood chemistries , and adverse events were monitored to assess safety . The principal outcome measurement for efficacy was the Western Ontario MacMaster Universities Osteoarthritis Index ( WOMAC ) derived from the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) question naire administered weekly . RESULTS Safety indicators remained unchanged in the test and placebo groups . All KOOS scores improved significantly ( P < 0.03 ) over time in the micronutrient group , whereas scores only for sport function and knee-related quality of life improved in the placebo group . The overall treatment effect ( based on changes in the WOMAC composite score ) was significant ( P = 0.016 ) . The effect size was moderate at 0.555 . CONCLUSIONS Thus , daily consumption of the nutritional beverage containing milk-based micronutrients , vitamins , and minerals was beneficial in alleviating symptoms and dysfunction in subjects with osteoarthritis The clinical response to therapeutic doses of two vitamins were determined in diabetic patients with symptomatic peripheral neuropathy . Of 200 consecutive patients , 100 were r and omly allocated to treatment with both thiamine ( 25 mg/day ) and pyridoxine ( 50 mg/day ) group A and the rest group B to treatment with an identical tablet containing 1 mg/day each of thiamine and pyridoxine . Pain , numbness , paraesthesia and impairment of sensation and ankle in the legs were grade d into none , mild , moderate or severe . Blood thiamine levels were measured using HPLC fluorimetry . Four weeks after starting treatment the grade was less than on the first visit in 88.9 % , 82.5 % and 89.7 % of those whose worst symptoms were pain , numbness and paraesthesia respectively for group A compared with 11.1 % , 40.5 % and 39.4 % respectively for group B. The severity of signs of peripheral neuropathy decreased in 48.9 % of patients in group A compared with 11.4 % in group B. The mean ( s.e . ) pre-treatment whole blood thiamine levels decreased with increasing severity of symptoms : 64.2 ( 2.81 ) , 57.7 ( 3.25 ) and 52.2 ( 2.14 ) micrograms/l for those with mild , moderate and severe symptoms respectively ( analysis of variance , p = 0.03 ) . Diabetic peripheral neuropathy in Dar es Salaam is associated with thiamine deficiency . Dietary guidelines for diabetic patients should emphasize a balanced diet This study deals with the nutritional status of Danish RA patients and address the question of whether or not RA can be directly influenced by dietary manipulation . In a prospect i ve , single-blinded study of 6 months duration , 109 patients with active RA were r and omly assigned to either treatment with or without a specialized diet . The energy consumption was adjusted to normal st and ards of body weights and the intake of fish meals and antioxidants were increased . A daily food diary was completed by the patients , and the total intake of 47 different food-elements was calculated . Nutritional status together with disease activity parameters were recorded . At baseline , the Danish RA- patients had neglected food habits with a significant reduction in intake of total energy , of D-vitamin and of E-vitamin . A very low intake of n-3 fatty acids was also found . During the study , 28 of the 109 patients dropped out , introducing a confounding effect on the overall result . In the remaining 81 , those following the diet demonstrated a significant improvement in the duration of morning stiffness , number of swollen joints , pain status , and reduced cost of medicine , while doctors global assessment , laboratory data , X-ray , and daily activities were unaltered . In conclusion , dietary analysis and appropriate , corrective advice should be offered to Danish RA patients OBJECTIVE We investigated the effects of dietary fiber on symptoms of irritable bowel syndrome . METHODS A single-blind r and omized clinical trial was design ed . Fifty-six subjects with irritable bowel syndrome were prospect ively and r and omly assigned to one of two groups : group 1 received a diet containing 10.4 g/d of fiber and group 2 received a diet containing 30.5 g/d of fiber . Patients ' body weights , nutritional intakes as assessed with 3-d written food records , and symptom scores were assessed at baseline and at 3 mo . RESULTS There were no dropouts during the study . Total energy intake and the distribution of macronutrients were not significantly different between groups . Total dietary fiber intake did not reach recommended levels in either group but was higher in group 2 than in group 1 ( 25.95 + /- 2.12 g/d versus 6.06 + /- 2.7 g/d , P < 0.05 ) . Initial fiber intake did not differ significantly between groups . Pain scores , bowel scores , and general scores improved in both groups ( from baseline to 3 mo ) , and no significant differences were detected between groups . CONCLUSIONS A modest fiber intake in patients with irritable bowel syndrome relieved symptoms , but this therapeutic benefit of fiber may have been due to a placebo effect because the results were similar in the low-fiber group Fasting is an effective treatment for rheumatoid arthritis , but most patients relapse on re introduction of food . The effect of fasting followed by one year of a vegetarian diet was assessed in a r and omised , single-blind controlled trial . 27 patients were allocated to a four-week stay at a health farm . After an initial 7 - 10 day subtotal fast , they were put on an individually adjusted gluten-free vegan diet for 3.5 months . The food was then gradually changed to a lactovegetarian diet for the remainder of the study . A control group of 26 patients stayed for four weeks at a convalescent home , but ate an ordinary diet throughout the whole study period . After four weeks at the health farm the diet group showed a significant improvement in number of tender joints , Ritchie 's articular index , number of swollen joints , pain score , duration of morning stiffness , grip strength , erythrocyte sedimentation rate , C-reactive protein , white blood cell count , and a health assessment question naire score . In the control group , only pain score improved score . In the control group , only pain score improved significantly . The benefits in the diet group were still present after one year , and evaluation of the whole course showed significant advantages for the diet group in all measured indices . This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis Objective : Excess generation of reactive oxygen species in damaged joints accelerates inflammatory responses in RA ( rheumatoid arthritis ) patients . The complementary effects of dietary antioxidant supplementation on the blood level of inflammatory mediators and the severity of the disease in RA patients were evaluated . Study Design and Setting s : The study was conducted as a r and omized , placebo-controlled , double-blind , three-treatment cross-over design trial . The participants visited the hospital as out patients . Subjects : Twenty patients meeting the 1987 criteria for the classification of rheumatoid arthritis completed the study . Interventions : The subjects were r and omized in three groups to receive one of following supplementation ; quercetin+vitamin C ( 166mg+133mg/capsule ) , α-lipoic acid ( 300mg/capsule ) or placebo for 4 weeks ( 3 capsules/day ) . Each treatment period consisted of 4 weeks with 2 weeks of wash-out period before the subject starts next supplementation . Outcome Parameters : Serum levels of tumor necrosis factor-α(TNF-α ) , interleukin-1β(IL-1β ) , interleukin -6(IL-6 ) , and C-reactive protein ( CRP ) were measured . The severity of disease was evaluated using Korean Health Assessment Question naire(KHAQ ) and Visual Analogue Scale(VAS ) . Nutrient intake was measured at baseline and at the end of each intervention period . Results : The mean energy and nutrient intakes remained constant during study period . No significant differences were found in the serum concentrations of pro-inflammatory cytokines and CRP between treatments . The scores of disease severity measurements were not significantly different between treatments , although quercetin supplementation had a tendency to reduce VAS . Conclusions : Dietary supplementation of antioxidants at 900 mg/day for 4 weeks did not change the blood biomarkers of inflammation and disease severity of RA patients under conventional medical treatments . Further considerations for dose-response relationships , duration of supplementation , and susceptible biomarkers are required Objective : To investigate in a double-blind placebo-controlled , parallel group study , the effects of a nutrient supplement , containing , among other ingredients , the omega-3 fatty acids eicosapentaenoic acid ( 1.4 g EPA ) , docosahexaenoic acid ( 0.211 g DHA ) , omega-6 fatty acid gamma-linolenic acid ( 0.5 g GLA ) and micronutrients in patients with active rheumatoid arthritis ( RA ) . Design , subjects and intervention : RA patients were r and omized to receive either daily liquid nutrient supplementation or placebo for 4 months . The primary end point was the change in tender joint count at 2 and 4 months . Other clinical variables included swollen joint count , visual analogue scales for pain and disease activity , grip strength , functionality score and morning stiffness . Biochemical parameters included plasma concentrations of PUFA and vitamins C and E. Setting : Outpatient university clinic . Results : In all , 66 patients enrolled , 55 completed the study . No significant change from baseline in tender joint count or any of the other clinical parameters was detected in either group . Patients receiving nutrient supplementation , but not those receiving placebo , had significant increases in plasma concentrations of vitamin E ( P=0.015 ) , and EPA , DHA and docosapentaenoic acid concomitant with decreases of arachidonic acid ( P=0.01 ) . Intergroup differences for PUFA and vitamin E were significantly different ( P=0.01 and 0.03 , respectively ) . Conclusions : This double-blind , placebo-controlled study in RA patients did not show superior clinical benefit of daily nutrient supplementation with EPA , GLA and micronutrients at the doses tested as compared to placebo . The study adds information regarding doses of omega-3 fatty acids , below which anti-inflammatory effects in RA are not seen Alternative and complementary therapeutic approaches , such as the use of a wide array of herbal , nutritional , and physical manipulations , are becoming popular for relieving symptoms of osteoarthritis ( OA ) . The present study evaluated the efficacy of soy protein ( SP ) supplementation in relieving the pain and discomfort associated with OA . One hundred and thirty-five free-living individuals ( 64 men and 71 women ) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind , placebo-controlled , parallel design study . Study participants were assigned r and omly to consume 40 g of either supplemental SP or milk-based protein ( MP ) daily for 3 months . Pain , knee range of motion , and overall physical activity were evaluated prior to the start of treatment and monthly thereafter . Serum levels of glycoprotein 39 ( YKL-40 ) , a marker of cartilage degradation , and insulin-like growth factor-I ( IGF-I ) , a growth factor associated with cartilage synthesis , were assessed at baseline and at the end of the study . Overall , SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP . However , these beneficial effects were mainly due to the effect of SP in men rather than women . Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP . This study is the first to provide evidence of possible beneficial effects of SP in the management of OA . Examining and verifying the long-term effects of SP on improving symptoms of OA , particularly in men , is warranted OBJECTIVE To evaluate anti-inflammatory properties of a nutraceutical blend containing L-ergothioneine in concert with other anti-inflammatory and analgesic ingredients , combined with nutritional cartilage support . METHODOLOGY Twelve human subjects were tested over a 6-week period of product consumption followed by a 6-week wash-out period , conducted at NIS Labs during late fall/early winter 2010 . Range of motion ( ROM ) assessment of joint motility was performed using JTECH dual digital inclinometry and included flexion , extension , and rotation through the vertical weight-bearing column ( neck , thorax , lumbar , hip , knees ) and shoulders . Pain evaluation included question naires and Visual Analogues Scales regarding primary and secondary pain complaints at rest and at use . RESULTS ROM improvements were seen after 1 week , and further improved at 6 weeks ( primary pain area P<0.2 , secondary pain area P<0.03 ) . Pain in primary and secondary areas at use was significantly reduced already at 1 week , compared to baseline ( P<0.05 ) . Pain reduction for both primary and secondary pain areas during use reached a high level of statistical significance at 6 weeks ( P<0.004 ) , and remained highly significant after the 6-week wash-out period . CONCLUSION Pain reduction and improved ROM were observed during the 6-week consumption . Residual effects were seen 6 weeks after stopping consumption of the ergothioneine supplement STUDY OBJECTIVE To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids ( n-3 PUFA ) on disease variables in patients with rheumatoid arthritis . DESIGN Multicenter , r and omized , placebo controlled , double blind . SETTING Three Danish hospital Departments of Rheumatology . PATIENTS Fifty-one patients with active rheumatoid arthritis . INTERVENTION R and om allocation to 12 weeks of treatment with either six n-3 PUFA capsules ( 3.6 g ) or six capsules with fat composition as the average Danish diet . MAIN RESULTS Significant improvement of morning stiffness and joint tenderness . No significant effect on the four other assessed clinical parameters . No serious side effects . CONCLUSIONS Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters . Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis 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 Objectives To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis ( OA ) . Methods A r and omised , double-blind , multicentre trial enrolled 202 patients with knee OA and regular knee pain . They were r and omised 1:1 to high-dose fish oil ( 4.5 g omega-3 fatty acids ) 15 mL/day or ( 2 ) low-dose fish oil ( blend of fish oil and sunola oil ; ratio of 1:9 , 0.45 g omega-3 fatty acids ) 15 mL/day . The primary endpoints were Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain score at 3 , 6 , 12 and 24 months , and change in cartilage volume at 24 months . Secondary outcomes included WOMAC function , quality of life , analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score . Results Although there was improvement in both groups , the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group , whereas between-group differences at 1 year did not reach statistical significance . There was no difference between the two groups in cartilage volume loss at 2 years . For other secondary endpoints , there was no difference between the two groups at 2 years . Conclusions In people with symptomatic knee OA , there was no additional benefit of a high-dose fish oil compared with low-dose fish oil . The combination comparator oil appeared to have better efficacy in reducing pain at 2 years , suggesting that this requires further investigation . Trial registration number Australian New Zeal and Clinical Trials Registry ( ACTRN 12607000415404 ) We tested the effects of an uncooked vegan diet , rich in lactobacilli , in rheumatoid patients r and omized into diet and control groups . The intervention group experienced subjective relief of rheumatic symptoms during intervention . A return to an omnivorous diet aggravated symptoms . Half of the patients experienced adverse effects ( nausea , diarrhoea ) during the diet and stopped the experiment prematurely . Indicators of rheumatic disease activity did not differ statistically between groups . The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity ( Health Assessment Question naire , duration of morning stiffness , pain at rest and pain on movement ) . However , a composite index showed a higher number of patients with 3 - 5 improved disease activity measures in the intervention group . Stepwise regression analysis associated a decrease in the disease activity ( measured as change in the Disease Activity Score , DAS ) with lactobacilli-rich and chlorophyll-rich drinks , increase in fibre intake , and no need for gold , methotrexate or steroid medication ( R2=0.48 , P=0.02 ) . The results showed that an uncooked vegan diet , rich in lactobacilli , decreased subjective symptoms of rheumatoid arthritis . Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis Background : Therapeutic dietary interventions are effective treatments for rheumatoid arthritis ( RA ) . The mechanisms to affect inflammation and clinical outcome in rheumatoid arthritis are only partly understood . Alterations in intestinal microflora are believed to be associated with disease activity in RA . Aim : To evaluate changes in short-chain fatty acid ( SCFA ) profiles and clinical outcome in RA during medical fasting or mediterranean diet . Methods : Fifty consecutive in- patients from an Integrative Medicine Department were included in a prospect i ve observational , non-r and omised , clinical trial . Patients underwent a 7-day fasting ( MF ) therapy or a Mediterranean diet ( MD ) as part of a multimodal therapeutic treatment approach . Results : The mean Disease Activity Score ( DAS-28 ) significantly decreased in both groups ( p < 0.001 ) from 5.7 ± 0.9 to 4.1 ± 1.3 in the MF and from 5.4 ± 1.4 to 4.5 ± 1.3 in the MG group , with no significant difference between the groups ( p = 0.115 ) . VAS showed a consecutive decrease of pain in both study groups which was significantly higher in the fasting group on day 7 ( p = 0.049 ) . No significant differences between the study groups were found in the profile of total-fatty acids ( p = 0.069 ) , butyrate ( p = 0.611 ) and propionate ( p = 0.419 ) . Measurement of acetate , however , showed significant differences ( p = 0.044 ) with an increase from 17,4 ± 9.8 µmol/g to 21,4 ± 16.4 µmol/g in MF compared to a decrease from 15,2 ± 10.4 µmol/g to 13,8 ± 9.3 µmol/g in MD . There was no significant correlation between dietary induced changes of SCFA and changes of disease activity . Conclusion : Alterations in SCFA were found in terms of significant changes to increased acetate levels in the fasting group . A correlation between changes of SCFA from intestinal microflora and disease activity in RA could not be revealed . Further studies are needed in the field of dietary inducible changes of the intestinal microflora in patients with RA The primary objective of this study was to determine whether it is the fish oil itself or the alpha-tocopherol that is added to the fish oil preparations ( to prevent peroxidation ) that is responsible for the beneficial effects of dietary supplementation with fish oil in patients with rheumatoid arthritis ( RA ) . One group of RA patients took fish oil supplements and another group took alpha-tocopherol-enriched coconut oil supplements ( placebo controls ) , both for 3 months . Clinical and laboratory indices of RA activity in relation to cellular and plasma vitamin E levels were assessed at the beginning and the end of the trial . The results of the study provide evidence that the beneficial effects of fish oil supplementation can not be ascribed to the antioxidizing properties of the alpha-tocopherol per se In a double blind noncrossover study , dietary supplementation with fish oil ( 18 g/day ) , was compared with an olive oil supplement over a 12-week period in patients with rheumatoid arthritis receiving established conventional therapies . An improvement in tender joint score and grip strength was seen at 12 weeks in the fish oil treated group but not in the olive oil treated group . The more subjective measures of mean duration of morning stiffness and analogue pain score improved to a similar extent in both groups , although statistical significance was only achieved in paired analyses in the olive oil treated group . Production of leukotriene B4 by isolated neutrophils stimulated in vitro was reduced by 30 % in the fish oil treated group and unchanged in the olive oil treated group Study Design . A r and omized controlled trial . Objective . The aim of this study was to evaluate whether a tailored and manualized cognitive behavior therapy ( CBT ) or nutritional supplements of seal oil and soy oil had any additional benefits over a brief cognitive intervention ( BI ) on return to work ( RTW ) . Summary of Background Data . Brief intervention programs are clinical ly beneficial and cost-effective for patients with low back pain ( LBP ) . CBT is recommended for LBP , but evidence on RTW is lacking . Seal oil has previously been shown to have a possible effect on muscle pain , but no r and omized controlled trials have so far been carried out in LBP patients . Methods . Four hundred thirteen adults aged 18 to 60 years were included . Participants were sick-listed 2 to 10 months due to LBP . Main outcome was objective ly ascertained work participation at 12-month follow-up . Participants were r and omly assigned to BI ( n = 100 ) , BI and CBT ( n = 103 ) , BI and seal oil ( n = 105 ) , or BI and soy oil ( n = 105 ) . BI is a two-session cognitive , clinical examination program followed by two booster sessions , while the CBT program is a tailored , individual , seven-session manual-based treatment . Results . At 12-month follow-up , 60 % of the participants in the BI group , 50 % in the BI and CBT group , 51 % in the BI and seal oil group , and 53 % in the BI and soy oil group showed reduced sick leave from baseline , and had either partly or fully RTW . The differences between the groups were not statistically significant ( & khgr;2 = 2.54 , P = 0.47 ) . There were no significant differences between the treatment groups at any of the other follow-up assessment s either , except for a significantly lower sick leave rate in the BI group than the other groups during the first 3 months of follow-up ( & khgr;2 = 9.50 , P = 0.02 ) . Conclusion . CBT and seal oil had no additional benefits over a brief cognitive intervention on sick leave . The brief cognitive intervention alone was superior in facilitating a fast RTW . Level of Evidence : 16 patients with classical rheumatoid arthritis ( RA ) selected at r and om underwent fasting for 7 - -10 days , followed by a 9-week period on a lactovegetarian diet . 10 RA patients acted as controls , taking normal diet . Pain , stiffness , medication , and clinical and biochemical findings were recorded before fasting , on the first day after the conclusion of the fasting period , and at the end of the lactovegetarian period . After fasting , 5 of 15 patients showed objective signs of improvement , compared with only one of the controls . The fasting patients showed reduced pain , stiffness , consumption of analgetics , several clinical variables , and serum concentration of orosomucoid . At the conclusion of the lactovegetarian diet period only one Diet patient showed objective improvement . No differences were found between the Diet patients and the controls concerning symptoms , drug consumption , or clinical and biochemical variables . We conclude that fasting may produce subjective and objective improvements in RA , though of short duration , but the findings of this investigation do not indicate that lactovegetarian diet has any beneficial effects Elemental diets provide food in its simplest formulation and have been used in the treatment of rheumatoid arthritis ( RA ) and other chronic inflammatory diseases . Such a diet is supposed to be less antigenic to the human immune system than normal food . The aim of this study was to evaluate the clinical effect of an artificial peptide diet as a temporary supplement to conventional treatment . Patients with active RA were single-blindly r and omized either to a liquid elemental peptide-diet for four weeks or to continuation of the usual food ( control group ) . In the diet group all normal foods were renounced . Thirty patients were included and followed for six months . The outcome measurements were pain intensity , morning stiffness , HAQ-score , number of swollen joints , joint tenderness , erythrocyte sedimentation rate , and patient 's global assessment of health . Two of the fifteen patients assigned to the diet dropped out . The diet result ed in a transient but statistically significant improvement in the average level of pain ( P = 0.02 ) , in HAQ-score ( P=0.03 ) , and a significant reduction in Body Mass Index ( P=0.001 ) . Only one patient in the diet group had a clear remission . Side-effects were frequent but compliance good . The study showed that the peptide diet can improve some subjective and objective disease parameters . Due to the low remission ratio the peptide diet is not a treatment of choice in unselected RA- patients . but the peptide diet might be beneficial to a subset of RA- patients , e.g. patients where foods aggravate disease activity STUDY OBJECTIVE to determine the efficacy of fish-oil dietary supplements in active rheumatoid arthritis and their effect on neutrophil leukotriene levels . DESIGN nonr and omized , double-blinded , placebo-controlled , crossover trial with 14-week treatment periods and 4-week washout periods . SETTING academic medical center , referral-based rheumatology clinic . PATIENTS forty volunteers with active , definite , or classical rheumatoid arthritis . Five patients dropped out , and two were removed for noncompliance . INTERVENTIONS treatment with nonsteroidal anti-inflammatory drugs , slow-acting antirheumatic drugs , and prednisone was continued . Twenty-one patients began with a daily dosage of 2.7 g of eicosapaentanic acid and 1.8 g of docosahexenoic acid given in 15 MAX-EPA capsules ( R.P. Scherer , Clearwater , Florida ) , and 19 began with identical-appearing placebos . The background diet was unchanged . MEASUREMENTS AND MAIN RESULTS the following results favored fish oil placebo after 14 weeks : mean time to onset of fatigue improved by 156 minutes ( 95 % confidence interval , 1.2 to 311.0 minutes ) , and number of tender joints decreased by 3.5 ( 95 % Cl , -6.0 to -1.0 ) . Other clinical measures favored fish oil as well but did reach statistical significance . Neutrophil leukotriene B4 production was correlated with the decrease in number of tender joints ( Spearman rank correlation r=0.53 ; p less than 0.05 ) . There were no statistically significant differences in hemoglobin level , sedimentation rate , or presence of rheumatoid factor or in patient-reported adverse effects . An effect from the fish oil persisted beyond the 4-week washout period . CONCLUSIONS fish-oil ingestion results in subjective alleviation of active rheumatoid arthritis and reduction in neutrophil leukotriene B4 production . Further studies are needed to eluci date mechanisms of action and optimal dose and duration of fish-oil supplementation |
10,822 | 31,041,601 | Bone area and cortical thickness at the tibia were identified as altered both in women with menstrual disturbances and in women with stress fractures ; however , there was inconsistency in the results observed for all bone parameters .
The majority of skeletal parameters of the lower extremities were not significantly different between exercising women with and without stress fractures and between those with and without menstrual disturbances .
The lack of observed differences in skeletal parameters suggests that risk factors other than bone geometry and structure may be the primary causes of stress fracture in these women | Background Stress fractures can lead to short- and long-term consequences , impacting participation in sport and general health .
Recognizing which skeletal characteristics render bones susceptible to stress fracture may aid stress-fracture prevention .
Menstrual disturbances among exercising women are a known risk factor for stress fracture ; therefore , assessing skeletal commonalities between women with stress fractures and women with menstrual disturbances may increase our underst and ing of why menstrual disturbances put athletes at greater risk for stress fracture .
Three-dimensional ( 3D ) bone imaging tools provide detailed information about volumetric bone mineral density ( vBMD ) and bone structure that can not be obtained using traditional two-dimensional ( 2D ) techniques .
Objectives This systematic review serves to : ( 1 ) evaluate the current literature available on vBMD , bone geometry , and bone structure in exercising women with menstrual disturbances and exercising women with stress fractures , and ( 2 ) assess the common skeletal characteristics between both conditions .
Our aim is to reveal bone properties beyond 2D areal BMD that may indicate increased susceptibility to stress fracture among exercising women with menstrual disturbances . | PURPOSE The purpose of this prospect i ve study was to examine rates and risk factors for overuse injuries among 824 women during Marine Corps Recruit Depot basic training at Parris Isl and , SC , in 1999 . METHODS Data collected included training day exposures ( TDE ) , baseline performance on a st and ardized 1.5-mile timed run , and a pretraining question naire highlighting exercise and health habits . The women were followed during training for occurrence of stress fracture and other lower-extremity overuse injury . RESULTS There were 868 lower-extremity overuse injuries for an overall injury rate of 12.6/1000 TDE . Rates for initial and subsequent injury were 8.7/1000 and 20.7/1000 TDE , respectively . There were 66 confirmed lower-extremity stress fractures among 56 ( 6.8 % ) women ( 1.0/1000 TDE ) . Logistic regression modeling indicated that low aerobic fitness ( a slower time on the timed run ( > 14.4 min ) ) , no menses in six or more consecutive months during the past year , and less than 7 months of lower-extremity weight training were significantly associated with stress fracture incidence . Self-rated fair-poor fitness at baseline was the only variable significantly associated with other non-stress fracture overuse injury during basic training . CONCLUSIONS Among this sample of women , the risk of lower-extremity overuse injury was high , with a twofold risk of subsequent injury . The results suggest that stress fracture injury might be decreased if women entered training with high aerobic fitness and participated frequently in lower-extremity strength training . Furthermore , women reporting a history of menstrual irregularity at their initial medical exam may require closer observation during basic training Strenuously exercising young women with hypothalamic amenorrhea are hypoleptinemic and have low bone mineral density ( BMD ) and content ( BMC ) , which predispose them to increased fracture risk . Short-term leptin replacement in these women corrects many neuroendocrine abnormalities and increases circulating levels of bone formation markers . Whether treatment with recombinant methionyl human leptin ( metreleptin ) for a long period improves BMD and BMC remains unknown . We studied 20 strenuously exercising young women with hypoleptinemia ( leptin concentration < 5 ng/mL ) and hypothalamic amenorrhea of at least 6 months ' duration . Eleven were r and omized to metreleptin ( initial dose , 0.08 mg/[kg·d ] for 3 months ; altered thereafter to 0.12 mg/kg for lack of efficacy or 0.04 mg/[kg d ] for more than 5 % weight loss ) and 9 were r and omized to placebo for 9 months . After a 3-month washout period , subjects were reexamined at the 1-year time point . Six subjects elected to continue on open-label metreleptin treatment for another 12 months . Two subjects dropped out after 18 months , and 4 completed the entire 2-year study . The BMD and BMC of the total body , lumbar spine ( L1-L4 ) , hip , and radius were assessed by using dual-energy x-ray absorptiometry at baseline and at 3 , 6 , 9 , 12 , 18 , and 24 months of treatment . Metabolic and hormonal parameters and bone markers were measured in blood and urine . Metreleptin significantly increased BMC ( P = .034 ) and tended to increase BMD ( P = .069 ) at the lumbar spine at 9 months in the entire study group ( intention-to-treat analysis ) . In subjects who completed the entire 2-year study ( n = 4 ) , metreleptin significantly increased BMD ( P = .024 ) and BMC ( P = .049 ) at the lumbar spine by 4 % to 6 % . Changes were not significant at the whole body , hip , and radius . Changes in hormonal and metabolic parameters and bone markers were moderate during the first year of treatment , but metreleptin further increased insulin-like growth factor 1 and decreased cortisol and cross-linked C-terminal telopeptide of type 1 collagen concentrations in serum during the second year of treatment ( P < .05 ) . The incremental area under the estradiol concentration curve over the 2-year course of the study correlated positively with the corresponding increase in lumbar spine BMD ( ρ = 0.42 , P = .039 ) . Long-term metreleptin administration in strenuously exercising young women with hypothalamic amenorrhea and hypoleptinemia increases lumbar spine BMD and BMC and alters bone remodeling milieu to favor bone accretion . Results from this pilot study should be confirmed by future , larger clinical trials and need to be extended by study ing bone microarchitecture and fracture risk PURPOSE To identify risk factors for stress fracture among young female distance runners . METHODS Participants were 127 competitive female distance runners , aged 18 - 26 , who provided at least some follow-up data in a r and omized trial among 150 runners of the effects of oral contraceptives on bone health . After completing a baseline question naire and undergoing bone densitometry , they were followed an average of 1.85 yr . RESULTS Eighteen participants had at least one stress fracture during follow-up . Baseline characteristics associated ( P<0.10 ) in multivariate analysis with stress fracture occurrence were one or more previous stress fractures ( rate ratio [ RR ] [ 95 % confidence interval]=6.42 ( 1.80 - 22.87 ) , lower whole-body bone mineral content ( RR=2.70 [ 1.26 - 5.88 ] per 1-SD [ 293.2 g ] decrease ) , younger chronologic age ( RR=1.42 [ 1.05 - 1.92 ] per 1-yr decrease ) , lower dietary calcium intake ( RR=1.11 [ 0.98 - 1.25 ] per 100-mg decrease ) , and younger age at menarche ( RR=1.92 [ 1.15 - 3.23 ] per 1-yr decrease ) . Although not statistically significant , a history of irregular menstrual periods was also associated with increased risk ( RR=3.41 [ 0.69 - 16.91 ] ) . Training-related factors did not affect risk . CONCLUSION The results of this and other studies indicate that risk factors for stress fracture among young female runners include previous stress fractures , lower bone mass , and , although not statistically significant in this study , menstrual irregularity . More study is needed of the associations between stress fracture and age , calcium intake , and age at menarche . Given the importance of stress fractures to runners , identifying preventive measures is of high priority CONTEXT Stress fractures are common in endurance athletes . Whereas studies have described distal tibia bone structure in athletes , there are few data regarding hip geometric parameters . Hip structural analysis ( HSA ) using dual-energy x-ray absorptiometry is a vali date d technique to assess hip bone structure . OBJECTIVES The purpose of this study was to compare hip geometry in young oligoamenorrheic athletes ( AAs ) , eumenorrheic athletes ( EAs ) , and nonathletes using HSA . We hypothesized that AAs would have impaired bone structure compared with that of EAs . DESIGN This was a cross-sectional study . SETTING The setting was a clinical research center . SUBJECTS We enrolled 55 AAs , 24 EAs , and 23 nonathletes of normal weight who were 14 to 22 years old . Athletes ran ≥20 miles/wk or were engaged in weight-bearing sports for ≥4 hours/wk . MAIN OUTCOME MEASURES Dual-energy x-ray absorptiometry was used for HSA and hip areal bone mineral density ( aBMD ) . RESULTS Hip aBMD Z-scores were lower in AAs and in nonathletes than in EAs ( P = .002 ) . A larger proportion of AAs than EAs and nonathletes had hip Z-scores < -1 ( 30.9 , 4.2 , 17.4 % , P = .01 ) . At the narrow neck , trochanteric region , and femoral shaft , subperiosteal width , cross-sectional moment of inertia , and section modulus were higher in EAs than in nonathletes ; values in AAs did not differ from those of nonathletes . Cross-sectional area was lower in AAs and in nonathletes than in EAs . Groups did not differ for cortical thickness or buckling ratio . Group differences were lost after adjustment for lean mass but not aBMD . CONCLUSIONS In an eugonadal state , athletic activity confers benefits for hip structure independent of aBMD . This advantage is lost in AAs , who do not differ from nonathletes for most parameters and fare worse than EAs for cross-sectional area Studies of stress fracture ( SF ) incidence are limited in number and geographical location ; this study determined the incidence of SF injury in female endurance athletes based in the United Kingdom . A total of 70 athletes aged between 18 and 45 years were recruited and prospect ively monitored for 12 months . Question naires at baseline and 12 months assessed SF , menstrual and training history , eating psychopathology , and compulsive exercise . Peak lower leg muscle strength was assessed in both legs using an isometric muscle rig . Bone mineral density ( BMD ) of total body , spine , hip , and radius was assessed using dual X-ray absorptiometry . Among the 61 athletes who completed the 12-month monitoring , two sustained a SF diagnosed by magnetic resonance imaging , giving an incidence rate ( 95 % confidence intervals ) of 3.3 ( 0.8 , 13.1 ) % of the study population sustaining a SF over 12 months . The SF cases were 800 m runners aged 19 and 22 years , training on average 14.2 h a week , eumenorrheic with no history of menstrual dysfunction . Case 1 had a higher than average energy intake and low eating psychopathology and compulsive exercise scores , while the reverse was true in case 2 . BMD in both cases was similar to mean values in the non-SF group . The incidence of SF in our female endurance athlete population based in the United Kingdom was 3.3 % , which is lower than previously reported . Further work is needed to confirm the current incidence of SF and evaluate the associated risk factors Introduction Osteoporosis is associated with increased risk for fracture . However , most postmenopausal women have bone mineral density ( BMD ) within the normal or osteopenic range . The aim of this study was to determine the proportion of the population burden of fragility fractures arising from women at modest risk for fracture . Methods We measured baseline BMD in a population -based r and om sample of 616 postmenopausal women aged 60–94 years and followed these individuals for a median of 5.6 years ( IQR 3.9–6.5 ) to determine the incidence of fractures according to age , BMD and the presence of a prior fracture . Results Based on WHO criteria , 37.6 % of the women had normal total hip BMD , 48.0 % had osteopenia and 14.5 % had osteoporosis . The incidence of fracture during follow-up was highest in women with osteoporosis , but only 26.9 % of all fractures arose from this group ; 73.1 % occurred in women without osteoporosis ( 56.5 % in women with osteopenia , 16.6 % in women with normal BMD ) . Decreasing BMD , increasing age and prior fracture contributed independently to increased fracture risk ; in a multivariate model , the relative risk for fracture increased 65 % for each SD decrease in BMD ( RR=1.65 , 95%CI 1.32–2.05 ) , increased 3 % for every year of age ( RR=1.03 , 95%CI 1.01–1.06 ) and doubled with prevalent fracture ( RR=2.01 , 95 % CI 1.40–2.88 ) . A prevalent fracture increased the risk for fractures such that women with osteopenia and prevalent fracture had the same , if not greater , risk as women with osteoporosis alone . Conclusions Reducing the population burden of fractures requires attention to women with osteopenia , as well as osteoporosis , because over half of the fragility fractures in the population arise in these individuals , and women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis A prospect i ve study of 295 infantry recruits has shown that the mediolateral width of the tibia measured radiographically at each of three different levels in the bone had a statistically significant correlation with the total incidence of stress fractures as well as with those in the tibia alone or the femur alone . A narrow tibial width was shown to be a risk factor , but cortical thickness was not found to be significant UNLABELLED The cumulative effect of the female athlete triad ( Triad ) risk factors on the likelihood of low bone mineral density ( BMD ) in exercising women is unclear . PURPOSE This study aim ed to determine the risk of low BMD in exercising women with multiple Triad risk factors . METHODS We retrospectively examined cross-sectional data from 437 exercising women ( mean ± SD age of 18.0 ± 3.5 yr , weighed 57.5 ± 7.1 kg with 24.5 % ± 6.1 % body fat ) obtained at baseline from 4 prospect i ve cohort studies examining Triad risk factors . Question naires were completed to obtain information on demographic characteristics , self-reported eating attitudes/behaviors , menstrual function , sport/activity participation , and medication use . Height and body weight were measured . BMD was measured using dual energy x-ray absorptiometry . Low BMD was defined as z-scores of < -1 and ≤-2 . Chi-square tests were performed to determine the percentage of women with low BMD who met the criteria for individual ( current oligo/amenorrhea , late menarche , low body mass index ( BMI ) , elevated dietary restraint , lean sport/activity participation ) or multiple ( 2 , 3 , 4 , or 5 ) Triad risk factors . RESULTS Late menarche and low BMI were associated with the highest percentage of low BMD ( z-score < -1 ) , 55 % and 54 % , respectively , and low BMD ( z-score ≤-2 ) , 14 % and 16 % , respectively . The percentage of participants with low BMD ( z-score < -1 and ≤-2 ) increased from 10 % to 62 % and from 2 % to 18 % , respectively , as women met the criteria for an increasing number of Triad risk factors . CONCLUSIONS A cumulative number of Triad risk factors were associated with an increased risk of low BMD , suggesting a dose-response association between the number of Triad risk factors and BMD in exercising women . Further research should be conducted to develop a user-friendly algorithm integrating these indicators of risk for low BMD in exercising women ( particularly factors associated with low BMI /body weight , menstrual dysfunction , lean sport/activity participation , and elevated dietary restraint ) INTRODUCTION Physical activity is known to enhance the mechanical competence of bone . However , information about the optimal type of exercise is limited . The aim of this study was to evaluate the contribution of jumping exercise to changes in bone geometry . METHODS We carried out a 12-month population -based trial with 120 women ( aged 35 - 40 years ) , r and omly assigned to an exercise group or to a control group . The exercise regimen consisted of supervised , progressive high-impact exercises three times per week and an additional home program . The intensity of impact loading was assessed as the magnitude of acceleration peaks using an accelerometer-based body movement monitor . The activity was analyzed as the daily number of impacts within five acceleration ranges ( 0.3 - 1.0 g , 1.1 - 2.4 g , 2.5 - 3.8 g , 3.9 - 5.3 g and 5.4 - 9.2 g ; g = acceleration of gravity , 9.81 m/s(2 ) ) . Bone geometry was assessed with spiral quantitative computed tomography ( QCT ) scanner at mid-femur , proximal tibia and distal tibia . RESULTS Thirty-nine women ( 65 % ) in the exercise group and 41 women ( 68 % ) in the control group completed the study . QCT and physical activity data were available from 65 subjects . The exercise group showed a significant 0.2 % ( p=0.033 ) higher gain in bone circumference compared to the control group at mid-femur . Subgroup analyses revealed geometric changes indicating up to a 2.5 % increment in bone strength in favor of the most active exercisers ( > 66 exercise sessions during the 12 months ) compared to the least active exercisers ( < 19 sessions ) . In pooled groups , the changes in cortical attenuation and cross-sectional moment of inertia correlated positively ( p<0.05-p<0.01 ) with the number of impacts exceeding 1.1 g , while changes in cortical thickness ( p<0.05 ) and bone circumference ( p<0.05-p<0.01 ) were positively associated with impacts 3.9 g , or more . The number and intensity of impacts during the 12 months were the most significant predictors of changes in bone geometry explaining up to 36 % of changes . CONCLUSIONS Bone geometry adapts to impact exercise and the adaptation is most marked at the mid-femur . The changes in bone geometry are associated with the number and intensity of daily impacts while the redistribution of bone mineral appears to be the main mechanism in the skeletal adaptation to varying intensities of exercise STUDY OBJECTIVE To compare the bone mineral density ( BMD ) of the axial and appendicular skeleton between regularly exercising collegiate dancers and age matched non-exercising young females between the age of 17 and 19 to assess the impact of weight-bearing exercises and menstrual status on BMD . DESIGN Prospect i ve observational cohort . SETTING Sports clinic in a collegiate school of dance and a hospital-based adolescent clinic . PARTICIPANTS The adolescent dancers consisted of full-time collegiate dance students from a tertiary Performing Arts Institute ( n = 35 ) . The non-exercising controls consisted of eumenorrhoeic patients of the same age presenting to the Adolescent Clinic ( n = 35 ) . INTERVENTIONS All subjects had a full hormonal profile , bio-impedance estimation of body fat , and dual energy X-ray absorptiometry and quantitative peripheral CT scans ( pQCT ) to determine bone density . MAIN OUTCOME MEASURES Comparison of the mean bone mineral density in the axial and appendicular skeleton between the two groups . RESULTS The incidence of oligo/amenorrhoea in the dancers was 20 % . The lumbar spine BMD ( 1.006 g/cm(2 ) vs. 0.938 , P = 0.048 ) and hip BMD ( neck of femur 0.978 g/cm(2 ) vs. 0.838 , P < 0.001 ; Ward 's triangle 0.816 g/cm(2 ) vs. 0.720 , P = 0.003 ; trochanter 0.777 g/cm(2 ) vs. 0.682 ; P < 0.001 ) were significantly higher in the eumenorrhoeic dancers as compared to controls . The radial BMD as measured by pQCT did not differ between the two groups , but the core trabecular tibial BMD was also higher in the dancers ( 321 mg/cm(3 ) vs. 286 , P = 0.006 ) . When only oligo/amenorrhoeic dancers ( n = 7 ) were compared with the controls , the same differences in BMD values were no longer observed . CONCLUSION Young women undergoing regular intensive weight-bearing exercises as in the collegiate dancers here studied have higher BMD in the axial and appendicular skeleton as compared to non-exercising females of the same age if they remain eumenorrhoeic during their training . This advantage was apparently lost when they developed oligo/amenorrhoea UNLABELLED To help refine nutritional guidelines for military servicewomen , we assessed bone turnover after manipulating the energy availability of 29 young women . Bone formation was impaired by less severe restrictions than that which increased bone resorption . Military servicewomen and others may need to improve their nutrition to avoid these effects . INTRODUCTION We determined the dose-response relationship between energy availability ( defined as dietary energy intake minus exercise energy expenditure ) and selected markers of bone turnover in 29 regularly menstruating , habitually sedentary , young women of normal body composition . MATERIAL S AND METHODS For 5 days in the early follicular phase of two menstrual cycles separated by at least 2 months , subjects expended 15 kcal/kgLBM/day in supervised exercise at 70 % of aerobic capacity and consumed controlled amounts of a clinical dietary product in balanced ( 45 kcal/kgLBM/day ) and one of three restricted ( either 10 , 20 , or 30 kcal/kgLBM/day ) energy availability treatments in r and om order . Blood was sample d at 10-minute intervals , and urine was collected for 24 h. Sample s were assayed for plasma osteocalcin ( OC ) , serum type I procollagen carboxy-terminal propeptide ( PICP ) , and urinary N-telopeptide ( NTX ) . RESULTS NTX concentrations ( p < 0.01 ) and indices of bone resorption/formation uncoupling ( Z(NTX-OC ) and Z(NTX-PICP ) ; both p < 10(-4 ) ) were increased by the 10 kcal/kgLBM/day treatment . OC and PICP concentrations were suppressed by all restricted energy availability treatments ( all p < 0.05 ) . PICP declined linearly ( p < 10(-6 ) ) with energy availability , whereas most of the suppression of OC occurred abruptly between 20 and 30 kcal/kgLBM/day ( p < 0.05 ) . CONCLUSIONS These dose-response relationships closely resembled those of particular reproductive and metabolic hormones found in the same experiment and reported previously : similar relationships were observed for NTX and estradiol ; for PICP and insulin ; and for OC , triiodothyronine ( T3 ) , and insulin-like growth factor (IGF)-I. The uncoupling of bone resorption and formation by severely restricted energy availability , if left to continue , may lead to irreversible reductions in BMD , and the suppression of bone formation by less severe restrictions may prevent young women from achieving their genetic potential for peak bone mass . More prolonged experiments are needed to determine the dose-response relationships between chronic restrictions of energy availability and bone turnover Background : Bone stress injuries are common in track and field athletes . Knowledge of risk factors and correlation of these to magnetic resonance imaging ( MRI ) grading could be helpful in determining recovery time . Purpose : To examine the relationships between MRI grading of bone stress injuries with clinical risk factors and time to return to sport in collegiate track and field athletes . Study Design : Cohort study ( prognosis ) ; Level of evidence , 2 . Methods : A total of 211 male and female collegiate track and field and cross-country athletes were followed prospect ively through their competitive seasons . All athletes had preparticipation history , physical examination , and anthropometric measurements obtained annually . An additional question naire was completed regarding nutritional behaviors , menstrual patterns , and prior injuries , as well as a 3-day diet record . Dual-energy X-ray absorptiometry was performed at baseline and each year of participation in the study . Athletes with clinical evidence of bone stress injuries had plain radiographs . If radiograph findings were negative , MRI was performed . Bone stress injuries were evaluated by 2 independent radiologists utilizing an MRI grading system . The MRI grading and risk factors were evaluated to identify predictors of time to return to sport . Results : Thirty-four of the athletes ( 12 men , 22 women ) sustained 61 bone stress injuries during the 5-year study period . The mean prospect i ve assessment for participants was 2.7 years . In the multiple regression model , MRI grade and total-body bone mineral density ( BMD ) emerged as significant and independent predictors of time to return to sport . Specifically , the higher the MRI grade ( P = .004 ) and lower the BMD ( P = .030 ) , the longer the recovery time . Location of the bone injury at predominantly trabecular sites of the femoral neck , pubic bone , and sacrum was also associated with a prolonged time to return to sport . Female athletes with oligomenorrhea and amenorrhea had bone stress injuries of higher MRI grade s compared with eumenorrheic athletes ( P = .009 ) . Conclusion : Higher MRI grade , lower BMD , and skeletal sites of predominant trabecular bone structures were associated with a delayed recovery of bone stress injuries in track and field athletes . Knowledge of these risk factors , as well as nutritional and menstrual factors , can be clinical ly useful in determining injury severity and time to return to sport To investigate the influence of exercise on thyroid metabolism , 46 healthy young regularly menstruating sedentary women were r and omly assigned to a 3 x 2 experimental design of aerobic exercise and energy availability treatments . Energy availability was defined as dietary energy intake minus energy expenditure during exercise . After 4 days of treatments , low energy availability ( 8 vs. 30 kcal.kg body wt-1.day-1 ) had reduced 3,5,3'-triiodothyronine ( T3 ) by 15 % and free T3 ( fT3 ) by 18 % and had increased thyroxine ( T4 ) by 7 % and reverse T3 ( rT3 ) by 24 % ( all P < 0.01 ) , whereas free T4 ( fT4 ) was unchanged ( P = 0.08 ) . Exercise quantity ( 0 vs. 1,300 kcal/day ) and intensity ( 40 vs. 70 % of aerobic capacity ) did not affect any thyroid hormone ( all P > 0.10 ) . That is , low-T3 syndrome was induced by the energy cost of exercise and was prevented in exercising women by increasing dietary energy intake . Selective observation of low-T3 syndrome in amenorrheic and not in regularly menstruating athletes suggests that exercise may compromise the availability of energy for reproductive function in humans . If so , athletic amenorrhea might be prevented or reversed through dietary reform without reducing exercise quantity or intensity Background : Identifying the risk factors associated with a bone stress injury ( BSI ) , including stress reactions and stress fractures , may aid in targeting those at increased risk and in formulating prevention guidelines for exercising girls and women . Purpose : To evaluate the effect of single or combined risk factors as defined by the female athlete triad — a syndrome involving 3 interrelated spectrums consisting of energy availability , menstrual function , and bone mass — with the incidence of BSIs in a multicenter prospect i ve sample of 4 cohorts of physically active girls and women . Study Design : Cohort study ; Level of evidence , 3 . Methods : At baseline , participants ’ ( N = 259 ; mean age , 18.1 ± 0.3 years ) anthropometric characteristics , eating attitudes and behaviors , menstrual function , sports participation or exercise activity , and pathological weight control behaviors were assessed . Dual-energy x-ray absorptiometry ( DXA ) measured the bone mass of the whole body , total hip , femoral neck , lumbar spine , and body composition . Participants were followed prospect ively for the occurrence of injuries ; those injuries confirmed by a physician were recorded . Results : Twenty-eight participants ( 10.8 % ) incurred a BSI . Forty-six percent of those who had ≥12 h/wk of purpose ful exercise , a bone mineral density ( BMD ) Z score < –1.0 , and who exhibited 3 to 4 of the following : BMI < 21.0 kg/m2 , oligo- or amenorrhea , elevated dietary restraint , and /or participation in a leanness sport exercise/activity at baseline , incurred a BSI during the prospect i ve study period . Single factors significantly ( P < .05 ) associated with the development of a BSI included ≥12 h/wk of purpose ful exercise ( 14.7 % ) , BMI < 21.0 kg/m2 ( 15.3 % ) , and low bone mass ( BMD Z score < –1.0 ; 21.0 % ) . The strongest 2- and 3-variable combined risk factors were low BMD ( Z score < –1.0 ) + ≥12 h/wk of exercise , with 29.7 % incurring a BSI ( odds ratio [ OR ] , 5.1 ; 95 % CI , 2.2 - 12.1 ) , and ≥12 h/wk of exercise + leanness sport/activity + dietary restraint , with 46.2 % incurring a BSI ( OR , 8.7 ; 95 % CI , 2.7 - 28.3 ) . Conclusion : In the sample , which included female adolescents and young adults participating in competitive or recreational exercise activities , the risk of BSIs increased from approximately 15 % to 20 % for significant single risk factors to 30 % to 50 % for significant combined female athlete triad – related risk factor variables . These data support the notion that the cumulative risk for BSIs increases as the number of Triad-related risk factors accumulates |
10,823 | 29,605,144 | This study provides the precise effects of metformin monotherapy regarding the decreases in fasting plasma glucose and glycosated hemoglobin that physician can expected in drug-naive patients with type 2 diabetes mellitus .
No evidence was found for the effects on weight | AIM OF THE STUDY Metformin is recommended as the first-line treatment of type 2 diabetes mellitus .
Despite its common use , few studies have been conducted to precisely measure the efficacy of metformin versus placebo as a first-line treatment .
This study aims to assess the precise effects of metformin monotherapy on glycemic control and weight in drug-naive patients with type 2 diabetes mellitus . | The effects of metformin therapy on whole body and splanchnic amino acid turnover are not known . Therefore , we have studied fasting and postpr and ial phenylalanine kinetics in type 2 diabetic subjects ( non-insulin-dependent diabetes mellitus ) , previously treated with diet only , both before and after 4 weeks of either metformin ( 850 mg twice a day ) ( n = 11 ) or placebo administration ( n = 6 ) . Phenylalanine kinetic was evaluated by means of a multiple isotope technique : tritiated phenylalanine was infused i.v . , whereas carbon-labeled phenylalanine was incorporated into a chemically-defined meal . Compared with placebo , metformin administration decreased both fasting ( from 162 + /- 17 to 141 + /- 20 mg/dl ) and postpr and ial ( from 217 + /- 20 to 164 + /- 20 mg/dl ) glucose concentrations ( P < 0.05-P < 0.01 ) . Fasting insulin concentrations were unaffected , but postmeal insulin tended to be lower ( P < 0.06 ) after metformin . Compared with the pretreatment period , metformin administration did not change total phenylalanine rate of appearance ( fasted state , 0.74 + /- 0.10 vs. 0.71 + /- 0.08 mumol/kg.min ; fed state , 0.77 + /- 0.10 vs. 0.75 + /- 0.08 mumol/kg.min , respectively ) , dietary and endogenous phenylalanine rate of appearance , dietary phenylalanine oxidation , and splanchnic uptake , similar to what was observed in the placebo group . Our data indicate that , at least after a 4-week treatment , metformin does not affect fasting and postpr and ial protein turnover , as indicated by phenylalanine data , in subjects with mild non-insulin-dependent diabetes mellitus Rosiglitazone , a thiazolidinedione , enhances peripheral insulin sensitivity in patients with type 2 diabetes . Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance , the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes . Therefore , 45 patients with newly diagnosed or diet-treated type 2 diabetes were r and omized for treatment with rosiglitazone ( 4 mg b.i.d . ) , metformin ( 1 g b.i.d . ) , or placebo in a 26-week double-blind trial . Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography ( PET ) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period . Rosiglitazone ( P < 0.05 ) and metformin ( P < 0.0001 ) treatment lowered the mean glycosylated hemoglobin . The skeletal muscle glucose uptake was increased by 38 % ( P < 0.01 ) and whole-body glucose uptake by 44 % in the rosiglitazone group . Furthermore , the exercise-induced increment during insulin stimulation was enhanced by 99 % ( P < 0.0001 ) . No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group . In conclusion , rosiglitazone but not metformin 1 ) improves insulin responsiveness in resting skeletal muscle and 2 ) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes . Our results suggest that rosiglitazone improves synergic action of insulin and exercise Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES This study was design ed to assess the effect of metformin on impaired endothelial function in type 2 diabetes mellitus . BACKGROUND Abnormalities in vascular endothelial function are well recognized among patients with type 2 ( insulin-resistant ) diabetes mellitus . Insulin resistance itself may be central to the pathogenesis of endothelial dysfunction . The effects of metformin , an antidiabetic agent that improves insulin sensitivity , on endothelial function have not been reported . METHODS Subjects with diet-treated type 2 diabetes but without the confounding collection of cardiovascular risk factors seen in the metabolic syndrome were treated with metformin 500 mg twice daily ( n = 29 ) or placebo ( n = 15 ) for 12 weeks . Before and after treatment , blood flow responses to intraarterial administration of endothelium-dependent ( acetylcholine ) , endothelium-independent ( sodium nitroprusside ) and nitrate-independent ( verapamil ) vasodilators were measured using forearm plethysmography . Whole-body insulin resistance was assessed on both occasions using the homeostasis model ( HOMA-IR ) . RESULTS Subjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo ( p = 0.0027 by 2-way analysis of variance ) , whereas no significant effect was seen on nitroprusside-stimulated ( p = 0.27 ) or verapamil-stimulated ( p = 0.40 ) flows . There was a significant improvement in insulin resistance with metformin ( 32.5 % reduction in HOMA-IR , p = 0.01 ) , and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment ( r = -0.659 , p = 0.0012 ) . CONCLUSIONS Metformin treatment improved both insulin resistance and endothelial function , with a strong statistical link between these variables . This supports the concept of the central role of insulin resistance in the pathogenesis of endothelial dysfunction in type 2 diabetes mellitus . This has important implication s for the investigation and treatment of vascular disease in patients with type 2 diabetes mellitus BACKGROUND Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus ( NIDDM ) in the United States . Recently , however , metformin has been approved for the treatment of NIDDM . METHODS We performed two large , r and omized , parallel-group , double-blind , controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet ( protocol 1 : metformin vs. placebo ; 289 patients ) , or diet plus glyburide ( protocol 2 : metformin and glyburide vs. metformin vs. glyburide ; 632 patients ) . To determine efficacy we measured plasma glucose ( while the patients were fasting and after the oral administration of glucose ) , lactate , lipids , insulin , and glycosylated hemoglobin before , during , and at the end of the study . RESULTS In protocol 1 , at the end of the study the 143 patients in the metformin group , as compared with the 146 patients in the placebo group , had lower mean ( + /- SE ) fasting plasma glucose concentrations ( 189 + /- 5 vs. 244 + /- 6 mg per deciliter [ 10.6 + /- 0.3 vs. 13.7 + /- 0.3 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.6 + /- 0.2 percent , P < 0.001 ) . In protocol 2 , the 213 patients given metformin and glyburide , as compared with the 210 patients treated with glyburide alone , had lower mean fasting plasma glucose concentrations ( 187 + /- 4 vs. 261 + /- 4 mg per deciliter [ 10.5 + /- 0.2 vs. 14.6 + /- 0.2 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.7 + /- 0.1 percent , P < 0.001 ) . The effect of metformin alone was similar to that of glyburide alone . Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia , as compared with 3 percent in the glyburide group and 2 percent in the metformin group . In both protocol s the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations , whereas the values in the respective control groups did not change . There were no significant changes in fasting plasma lactate concentrations in any of the groups . CONCLUSIONS Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone OBJECTIVE To determine the effect of metformin on the acute metabolic response to submaximal exercise , the effect of exercise on plasma metformin concentrations , and the interaction between metformin and exercise on the subsequent response to a st and ardized meal . RESEARCH DESIGN AND METHODS Ten participants with type 2 diabetes were recruited for this r and omized crossover study . Metformin or placebo was given for 28 days , followed by the alternate condition for 28 days . On the last 2 days of each condition , participants were assessed during a nonexercise and a subsequent exercise day . Exercise took place in the morning and involved a total of 35 min performed at three different submaximal intensities . RESULTS Metformin increased heart rate and plasma lactate during exercise ( both P ≤ 0.01 ) but lowered respiratory exchange ratio ( P = 0.03 ) without affecting total energy expenditure , which suggests increased fat oxidation . Metformin plasma concentrations were greater at several , but not all , time points on the exercise day compared with the nonexercise day . The glycemic response to a st and ardized meal was reduced by metformin , but the reduction was attenuated when exercise was added ( metformin × exercise interaction , P = 0.05 ) . Glucagon levels were highest in the combined exercise and metformin condition . CONCLUSIONS This study reveals several ways by which metformin and exercise therapies can affect each other . By increasing heart rate , metformin could lead to the prescription of lower exercise workloads . Furthermore , under the tested conditions , exercise interfered with the glucose-lowering effect of metformin BACKGROUND In patients with type 2 diabetes , intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks . This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage . METHODS Of 4075 patients recruited to UKPDS in 15 centres , 1704 overweight ( > 120 % ideal bodyweight ) patients with newly diagnosed type 2 diabetes , mean age 53 years , had raised fasting plasma glucose ( FPG ; 6.1 - 15.0 mmol/L ) without hyperglycaemic symptoms after 3 months ' initial diet . 753 were included in a r and omised controlled trial , median duration 10.7 years , of conventional policy , primarily with diet alone ( n=411 ) versus intensive blood-glucose control policy with metformin , aim ing for FPG below 6 mmol/L ( n=342 ) . A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated intensive blood-glucose control with chlorpropamide ( n=265 ) , glibenclamide ( n=277 ) , or insulin ( n=409 ) . The primary outcome measures were aggregates of any diabetes-related clinical endpoint , diabetes-related death , and all-cause mortality . In a supplementary r and omised controlled trial , 537 non-overweight and overweight patients , mean age 59 years , who were already on maximum sulphonylurea therapy but had raised FPG ( 6.1 - 15.0 mmol/L ) were allocated continuing sulphonylurea therapy alone ( n=269 ) or addition of metformin ( n=268 ) . FINDINGS Median glycated haemoglobin ( HbA1c ) was 7.4 % in the metformin group compared with 8.0 % in the conventional group . Patients allocated metformin , compared with the conventional group , had risk reductions of 32 % ( 95 % CI 13 - 47 , p=0.002 ) for any diabetes-related endpoint , 42 % for diabetes-related death ( 9 - 63 , p=0.017 ) , and 36 % for all-cause mortality ( 9 - 55 , p=0.011 ) . Among patients allocated intensive blood-glucose control , metformin showed a greater effect than chlorpropamide , glibenclamide , or insulin for any diabetes-related endpoint ( p=0.0034 ) , all-cause mortality ( p=0.021 ) , and stroke ( p=0.032 ) . Early addition of metformin in sulphonylurea-treated patients was associated with an increased risk of diabetes-related death ( 96 % increased risk [ 95 % CI 2 - 275 ] , p=0.039 ) compared with continued sulphonylurea alone . A combined analysis of the main and supplementary studies showed fewer metformin-allocated patients having diabetes-related endpoints ( risk reduction 19 % [ 2 - 33 ] , p=0.033 ) . Epidemiological assessment of the possible association of death from diabetes-related causes with the concurrent therapy of diabetes in 4416 patients did not show an increased risk in diabetes-related death in patients treated with a combination of sulphonylurea and metformin ( risk reduction 5 % [ -33 to 32 ] , p=0.78 ) . INTERPRETATION Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients , and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas , it may be the first-line pharmacological therapy of choice in these patients AIMS To evaluate the efficacy and safety of initial combination therapy with linagliptin plus metformin versus linagliptin or metformin monotherapy in patients with type 2 diabetes . METHODS In this 24-week , double-blind , placebo-controlled , Phase III trial , 791 patients were r and omized to one of six treatment arms . Two free combination therapy arms received linagliptin 2.5 mg twice daily ( bid ) + either low ( 500 mg ) or high ( 1000 mg ) dose metformin bid . Four monotherapy arms received linagliptin 5 mg once daily , metformin 500 mg or 1000 mg bid or placebo . Patients with haemoglobin A1c ( HbA1c ) ≥11.0 % were not eligible for r and omization and received open-label linagliptin + high-dose metformin . RESULTS The placebo-corrected mean ( 95 % confidence interval ) change in HbA1c from baseline ( 8.7 % ) to week 24 was -1.7 % ( -2.0 , -1.4 ) for linagliptin + high-dose metformin , -1.3 % ( -1.6 , -1.1 ) for linagliptin + low-dose metformin , -1.2 % ( -1.5 , -0.9 ) for high-dose metformin , -0.8 % ( -1.0 , -0.5 ) for low-dose metformin and -0.6 ( -0.9 , -0.3 ) for linagliptin ( all p < 0.0001 ) . In the open-label arm , the mean change in HbA1c from baseline ( 11.8 % ) was -3.7 % . Hypoglycaemia occurred at a similar low rate with linagliptin + metformin ( 1.7 % ) as with metformin alone ( 2.4 % ) . Adverse event rates were comparable across treatment arms . No clinical ly significant changes in body weight were noted . CONCLUSIONS Initial combination therapy with linagliptin plus metformin was superior to metformin monotherapy in improving glycaemic control , with a similar safety and tolerability profile , no weight gain and a low risk of hypoglycaemia Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus ( NIDDM ) . The mechanism may be attributed to decreased food intake . This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss . Twelve diet-treated NIDDM women with obesity were r and omly given two dose levels ( 850 mg or 1700 mg ) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3x3 Latin square design . The number of s and wich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake , and the level of subjective hunger was rated just before the s and wich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast . The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment . The 1700-mg metformin dose had the most marked appetite suppressant action . Similarly , hunger ratings were significantly lowered after metformin , and the effect was most pronounced after the administration of 1700 mg of metformin . To assess the efficacy of metformin in reducing bodyweight , 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA ( American Diabetes Association ) diet before being r and omized to receive either metformin ( 850 mg ) or placebo twice daily in a double-blind fashion for 24 weeks . A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period . Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment ; their mean maximum weight loss was 8 kg greater than that of the placebo group , with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period . These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity OBJECTIVE To study the dose response to metformin in type II diabetic patients . RESEARCH DESIGN AND METHODS Type II diabetic patients with a BMI > 25 were treated with 3,000 mg/day ( n = 27 ) , 1,500 mg/day ( n = 25 ) , or placebo ( n = 23 ) for 6 months . Venous blood sample s were taken at each visit for plasma glucose and insulin , HbA1c , triglyceride and cholesterol , plasminogen activator inhibitor-1 ( PAI-1 ) antigen and activity , tissue plasminogen activator ( TPA ) , and euglobulin clot lysis time ( ECLT ) . Blood pressure was recorded at each visit . RESULTS There were no changes in BMI or blood pressure . Blood glucose fell ( mean ) by 3.6 mmol/l in the high-dose and 0.5 mmol/l in the low-dose group over the 6-month study ( P < 0.001 and NS compared with placebo ) . HbA1c and plasma insulin fell in both treatment groups ( HbA1c , P < 0.001 ; insulin , P < 0.003 and 0.03 ) . There was a fall in triglyceride ( P < 0.05 ) and cholesterol ( P < 0.008 ) with high-dose metformin . PAI-1 antigen and activity fell by ∼ 20 % of baseline in both treatment groups ( PAI-1 antigen high dose , P < 0.01 ; PAI-1 antigen low dose , P < 0.002 : PAI-1 activity high and low dose , P < 0.003 ) . There were significant falls in total tPA in both groups ( P < 0.004 ) , but the overall effect was a fall in ECLT ( P < 0.03 ) . CONCLUSIONS The results indicate that metformin has favorable effects on cardiovascular risk factors associated with type II diabetes . The effects on glycemic control and lipids are dose-dependent , while the enhanced fibrinolytic response is independent of the doses used The effect of metformin therapy on glucose metabolism was examined in eight overweight newly presenting untreated type II diabetic patients ( five males , three females ) . Patients were treated for 12 weeks with either metformin ( 850 mg x 3 ) or matching placebo using a double-blind crossover study design ; patients were studied at presentation and at the end of each treatment period . Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase ( GS ) before and during a 4-hour hyperinsulinemic euglycemic clamp ( 100 mU.kg-1 x h-1 ) . Metformin therapy was associated with a significant decrease in fasting blood glucose ( 6.8 + /- 0.6 v 8.3 + /- 0.9 mmol . L-1 , P < .01 ) and glycosylated hemoglobin ( [ HbA1 ] 7.7 % + /- 0.4 % v 8.5 % + /- 0.5 % , P < .01 ) levels . Fasting hepatic glucose production ( HGP ) was also significantly decreased following metformin therapy ( 1.98 + /- 0.13 v 2.41 + /- 0.20 mg.kg-1 x min-1 , P < .02 ) , whereas fasting insulin and C-peptide concentrations remained unaltered . The decrease in basal HGP correlated closely with the decrease in fasting blood glucose concentration ( r = .92 , P < .001 ) . Insulin-stimulated glucose uptake was assessed using the hyperinsulinemic euglycemic clamp technique and was increased post-metformin ( 3.8 + /- 0.6 v 3.1 + /- 0.7 mg.kg-1 x min-1 , P < .05 ) . This was primarily the result of increased nonoxidative glucose metabolism ( 1.1 + /- 0.6 v 0.4 + /- 0.6 mg.kg-1 x min-1 , P < .05 ) ; oxidative glucose metabolism did not change . Metformin had no measurable effect on insulin activation of skeletal muscle GS , the rate-limiting enzyme controlling muscle glucose storage . ( ABSTRACT TRUNCATED AT 250 WORDS SUMMARY Objective : To assess the efficacy and tolerability of the combination of nateglinide ( 120 mg , ac ) and metformin ( 500 mg , tid ) as initial treatment in drug-naïve patients with type 2 diabetes mellitus ( T2DM ) . Research design and methods : This study reports data from the treatment-naïve ( TN ) subgroup of patients in a previously published , r and omized , multicenter , placebo-controlled , 24-week trial that compared nateglinide , metformin , and the combination therapy ( CT ) in 701 patients with T2DM with baseline HbA1c between 6.8 % and 11.0 % . Of the 401 TN patients , 104 , 104 , 89 , and 104 patients received nateglinide ( 120 mg , ac ) , metformin ( 500 mg , tid ) , CT , and placebo , respectively . The baseline characteristics of each group were similar , with mean age , BMI , duration of diabetes , HbA1c , and fasting plasma glucose ( FPG ) levels of approximately 58 years , 30 kg/m2 , 4 years , 8.2 % , and 10.2 mmol/L , respectively . Results : In patients receiving initial CT , HbA1c decreased substantially ( ▵ = –1.6 ± 0.1 % , p < 0.0001 vs. baseline or placebo ) from a mean baseline of 8.2 ± 0.1 % , an effect significantly greater than the 0.8 % reduction observed with both monotherapies ( p < 0.001 ) ; whereas , in placebo-treated patients , HbA1c increased modestly ( ▵ = + 0.3 ± 0.1 % , p < 0.05 ) from an identical baseline value . Seventy percent of CT-treated patients achieved a target HbA1c of < 7.0 % . Both fasting plasma glucose ( FPG ) and the 2-hour postpr and ial glucose excursion ( PPGE ) after a liquid meal challenge decreased by 2.3 mmol/L in patients receiving CT , while the changes from baseline values in FPG and PPGE were + 0.2 ± 0.3 mmol/L and –0.5 ± 0.2 mmol/L , respectively , in placebo-treated patients . The incremental 30-minute post-load insulin levels increased by 88 ± 32 pmol/L ( p = 0.006 ) in patients receiving CT and did not change significantly in placebo-treated patients . Gastrointestinal side effects occurred in 27 % of patients receiving CT ( vs. 27.9 % in the metformin monotherapy , and 14.4 % in the placebo groups ) . Confirmed hypoglycemia ( glucose ≤ 2.8 mmol/L ) occurred in 3.4 % of patients receiving CT . Conclusions : Initial CT with the rapid-acting insulinotropic agent , nateglinide , and metformin , an agent with insulin-sensitizing effects in the liver and periphery , is a safe and effective means of achieving glycemic targets in TN patients with T2DM PURPOSE To compare the therapeutic potential of acarbose , metformin , or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . PATIENTS AND METHODS Ninety-six patients with NIDDM ( 35 - 70 years of age , body mass index ( BMI ) < or = 35 kg/m2 , insufficiently treated with diet alone , glycated hemoglobin ( HbA1c ; 7 % to 11 % ) were r and omized into 3 groups and treated for 24 weeks with acarbose , 3 x 100 mg/day , or metformin , 2 x 850 mg/day , or placebo . Efficacy , based on HbA1c ( primary efficacy criterion ) , fasting blood glucose ( BG ) and insulin , 1 hour postpr and ial BG and insulin ( after st and ard meal test ) , postpr and ial insulin increase , plasma lipid profile , and tolerability , based on subjective symptoms and laboratory values were determined every 6 weeks . Analysis of covariance was performed for endvalues with adjustment on baseline values . Ninety-four patients were valid for efficacy evaluation . RESULTS Both active drugs showed the same improvement of efficacy criteria compared with placebo . Baseline adjusted means at endpoint were as follows : BG , fasting and 1 hour postpr and ial , 9.2 mM and 10.9 mM with placebo , 7.6 mM and 8.7 mM with acarbose , and 7.8 mM and 9.0 mM with metformin ; HbA1c was 9.8 % with placebo , 8.5 % with acarbose , and 8.7 % with metformin . Comparisons : acarbose versus placebo and metformin versus placebo were statistically significant , but not acarbose versus metformin . No effect on fasting insulin could be observed . Relative postpr and ial insulin increase was 1.90 with placebo , 1.09 with acarbose , and 1.03 with metformin . Comparisons : acarbose versus placebo and metformin versus placebo were statistically significant , but not acarbose versus metformin . With respect to lipid profile , acarbose was superior to metformin . Low-density lipoprotein (LDL)/high-density lipoprotein ( HDL ) cholesterol ratio increased by 14.4 % with placebo , was unchanged with metformin , but decreased by 26.7 % with acarbose . Comparisons : acarbose versus placebo and acarbose versus metformin were statistically significant , but not metformin versus placebo . Slight body weight changes were observed with acarbose ( -0.8 kg ) and metformin ( -0.5 kg ) , but not with placebo . Acarbose led to mild or moderate intestinal symptoms in 50 % of the patients within the first 4 weeks , but in only 13.8 % of the patients within the last 4 weeks . CONCLUSIONS Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM . With respect to plasma lipid profile , especially HDL cholesterol , LDL cholesterol and LDL/HDL cholesterol ratio acarbose may be superior to metformin 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 Nineteen obese patients with Type 2 diabetes mellitus were treated for periods of 3 months with placebo , guar gum ( 5 g three times daily ) and metformin ( 500 mg three times daily ) in a r and omized double-blind , double-placebo , cross-over study . Both active agents decreased fasting blood glucose from 11.4 + /- 3.7 mmol l-1 ( mean + /- SD ) to 8.6 + /- 2.8 mmol l-1 on metformin ( p less than 0.001 ) and to 9.5 + /- 3.9 mmol l-1 on guar gum ( p less than 0.01 ) . Metformin significantly reduced the very low density lipoprotein ( VLDL ) cholesterol concentration from 0.62 ( + 0.73 , -0.34 ) mmol l-1 ( geometric mean ( + SD , -SD ) ) to 0.43 ( + 0.58 , -0.25 ) mmol l-1 , ( p less than 0.02 ) , but unless hyperlipidaemia was present there were no changes in other serum lipid or lipoprotein levels . In patients with serum cholesterol greater than 6.5 mmol l-1 decreases in serum triglycerides from 3.29 ( + 3.27 , -1.64 ) to 2.46 ( + 2.55 , -1.25 ) mmol l-1 ( p less than 0.02 ) occurred with metformin . In these patients guar gum produced a reduction in serum cholesterol ( from 7.70 + /- 0.90 to 6.41 + /- 1.11 mmol l-1 , p less than 0.01 ) due to an effect on low density lipoproteins . These differential effects may be important in planning therapy when hyperlipidaemia accompanies Type 2 diabetes OBJECTIVE To assess the reversibility of the defect in glycogen synthase ( GS ) activity in skeletal muscle from obese patients with NIDDM treated with a hypocaloric diet and metformin . RESEARCH DESIGN AND METHODS Eighteen obese patients newly diagnosed with NIDDM were included in a r and omized placebo-controlled double-blind parallel group trial and followed for 3 months . Euglycemic-hyperinsulinemic clamp including indirect calorimetry and biopsy of m. vastus lateralis was performed before and after treatment with a hypocaloric diet plus metformin or placebo . The patients were studied at basal , low , and high insulin concentrations . RESULTS The impaired GS activity in muscle biopsies was not reversed either by acute normalization of glycemia ( for 8 h ) or by chronic reduction of hyperglycemia by diet plus metformin . In both treatment groups , comparable effects on glycemic control and weight loss were found together with marked insulin suppression of nonesterified fatty acids and increased glucose oxidation . Total glucose disposal at euglycemic-hyperinsulinemic clamp increased significantly in the metformin group by 25 % at high insulin level ( 259 ± 31 vs. 207 ± 21 mg · m−2 · min−1 , P < 0.05 ) . An insignificant increase by 13 % was found in the placebo group . There were no significant changes in nonoxidative glucose metabolism . GS activity and glucose utilization showed no significant differences between the two treatment groups when regression coefficients , expressed as incremental changes by increments of insulin , were compared . CONCLUSIONS Defective GS activity in obese NIDDM patients is not secondary to hyperglycemia . Metformin and diet had no significant influence on GS activity . The added effect of metformin to that of a hypocaloric diet in improving insulin-stimulated glucose utilization is marginal when blood glucose reduction is obtained by weight loss OBJECTIVE Dapagliflozin , a novel inhibitor of renal sodium-glucose cotransporter 2 , allows an insulin-independent approach to improve type 2 diabetes hyperglycemia . In this multiple-dose study we evaluated the safety and efficacy of dapagliflozin in type 2 diabetic patients . RESEARCH DESIGN AND METHODS Type 2 diabetic patients were r and omly assigned to one of five dapagliflozin doses , metformin XR , or placebo for 12 weeks . The primary objective was to compare mean change from baseline in A1C . Other objectives included comparison of changes in fasting plasma glucose ( FPG ) , weight , adverse events , and laboratory measurements . RESULTS After 12 weeks , dapagliflozin induced moderate glucosuria ( 52–85 g urinary glucose/day ) and demonstrated significant glycemic improvements versus placebo ( ΔA1C −0.55 to −0.90 % and ΔFPG −16 to −31 mg/dl ) . Weight loss change versus placebo was −1.3 to −2.0 kg . There was no change in renal function . Serum uric acid decreased , serum magnesium increased , serum phosphate increased at higher doses , and dose-related 24-h urine volume and hematocrit increased , all of small magnitude . Treatment-emergent adverse events were similar across all groups . CONCLUSIONS Dapagliflozin improved hyperglycemia and facilitates weight loss in type 2 diabetic patients by inducing controlled glucosuria with urinary loss of ∼200–300 kcal/day . Dapagliflozin treatment demonstrated no persistent , clinical ly significant osmolarity , volume , or renal status changes |
10,824 | 26,071,496 | Conclusion Imaging differences between 0.5 M and 1.0 M GBCAs were essentially observed under non-equimolar delivery rates .
However , they did not result into greater diagnostic efficacy when performed under equimolar conditions | Background To date there is no agreement as to what is the optimal concentration for gadolinium-based contrast agents ( GBCAs ) .
Purpose To assess whether diagnostic performance differences exist between 0.5 M and 1.0 M GBCAs used for magnetic resonance imaging ( MRI ) . | PURPOSE To evaluate the diagnostic efficacy of macrocyclic paramagnetic gadolinium ( Gd ) chelates gadoterate ( 0.5 mmol/mL ) and gadobutrol ( 1.0 mmol/mL ) for the diagnosis of clinical ly significant abdominal/lower limb arterial diseases at 3.0 T . MATERIAL S AND METHODS This study was conducted as a prospect i ve , single-center , r and omized , double-blind , intraindividual study comparing single dose ( 0.1 mmol/kg ) gadoterate enhanced-MRA ( magnetic resonance angiography ) with gadobutrol enhanced-MRA at 3.0 T for their diagnostic potential in patients with peripheral artery disease . A total of 20 patients were included in this trial . RESULTS Fourteen patients were eligible for the final efficacy analysis . The overall image quality ( excellent/more than adequate ) was better rated with gadoterate than with gadobutrol ( 100 % vs. 78.6 % , 100 % vs. 92.9 % , 100 % vs. 85.7 % , 100 % vs. 85.7 % for readers 1 , 2 , 3 , 4 , respectively ) . Diagnostic confidence was rated high/excellent in 100 % ( readers 1 , 2 , and 3 ) and 92.9 % ( reader 4 ) with gadoterate compared to 92.9 % ( readers 1 and 2 ) and 85.7 % ( readers 3 and 4 ) with gadobutrol . Higher signal-to-noise ratio ( SNR ) and contrast-to-noise ratio ( CNR ) values were obtained for gadobutrol compared to gadoterate ( 26.1/23.4 , P = 0.01 , and 22.7/20.2 , P = 0.01 ) . For the secondary criteria , no differences between groups were reported . No adverse events were reported . CONCLUSION Gadobutrol yielded significantly higher SNR/CNR while gadoterate was better rated in terms of overall image quality and diagnostic confidence ( P > 0.05 ) Objective : To evaluate the diagnostic efficacy ( accuracy , sensitivity , specificity ) of 1.0 M gadobutrol versus 0.5 M gadopentetate for the classification of lesions as either benign or malignant in patients with known or suspected liver lesions . Methods and Material s : A multicenter , phase-III , r and omized , interindividually controlled comparison study with blinded reader evaluation was performed to investigate the diagnostic efficacy of a bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentetate at a dose of 0.1 mmol Gd/kg BW . The imaging protocol included a dynamic 3D-evaluation , static conventional , and fat saturated T1-weighted sequences . MR data sets were evaluated by 3 independent radiologists . The st and ard of reference was defined by an independent truth panel ( radiologist or hepatologist ) . The safety evaluation included adverse events , vital signs , and physical examination . Results : A total of 497 of 572 patients were eligible for the final efficacy analysis . Noninferiority of gadobutrol-enhanced magnetic resonance imaging ( MRI ) for the classification of liver lesions was demonstrated on the basis of diagnostic accuracy determined by the on-site investigators ( −0.098 , 0.021 ) as well as for the average reader of the blinded evaluation ( −0.096 , 0.014 ) ( 95 % confidence interval ) , compared with the predefined st and ard of reference . Very similar increases in sensitivity ( ranging from ∼10 % to ∼55 % ) and specificity ( ranging from ∼1%–∼18 % ) compared with precontrast MRI were also observed for the 2 contrast agent groups , with maximum differences of 4%.Very similar , low rates of adverse events were recorded for each of the 2 groups . No clinical ly relevant changes in vital signs or the results of the physical examination were observed in any patient . Conclusion : This study documents evidence for the noninferiority of a single i.v . bolus injection of 1.0 M gadobutrol ( 0.1 mmol/kg body weight ) to 0.5 M gadopentetate ( 0.1 mmol/kg body weight ) in the diagnostic assessment of liver lesions with contrast-enhanced MRI . The known excellent safety profile of gadobutrol was confirmed in this clinical trial and is similar to that of gadopentetate PURPOSE To prospect ively compare 0.5-M gadopentetate dimeglumine ( Gd-DTPA ) with 1.0-M gadobutrol for contrast-enhanced magnetic resonance angiography ( CE-MRA ) of the blood supplying arteries of the spinal cord in patients referred for open surgical repair of a thoracoabdominal aortic aneurysm ( TAAA ) . MATERIAL S AND METHODS A total of 11 patients with a TAAA underwent two three-dimensional CE-MRA exams of the aorta , segmental arteries ( SAs ) , artery of Adamkiewicz ( AKA ) , and anterior spinal artery ( ASA ) . Imaging was performed on two separate occasions using Gd-DTPA and gadobutrol as contrast agents at 0.3 mmol/kg . Images were evaluated by measuring signal-to-noise ( SNR ) and contrast-to-noise ( CNR ) ratios and were judged for different image quality criteria by two blinded observers . RESULTS In all patients both CE-MRA exams were of sufficient image quality to detect the AKA and ASA . No significant differences in SNR and CNR were observed between the two contrast agents . According to the observers , no significant differences in subjective image quality were found . CONCLUSIONS Using both contrast agents it was possible to visualize the ultrasmall spinal cord arteries in all cases . The use of the 1.0-M contrast agent did not improve image quality of CE-MRA images of the blood supplying arteries of the spinal cord compared to the 0.5-M contrast agent The purpose of this phase III clinical trial was to compare two different extracellular contrast agents , 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine , for magnetic resonance imaging ( MRI ) in patients with known or suspected focal renal lesions . Using a multicenter , single-blind , interindividual , r and omized study design , both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy , sensitivity , and specificity to correctly classify focal lesions of the kidney . To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading . The average diagnostic accuracy across the three blinded readers ( ‘ average reader ’ ) was 83.7 % for gadobutrol and 87.3 % for gadopentate dimeglumine . The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0 % for gadobutrol and 6.9 % for gadopentate dimeglumine . Sensitivity of the average reader was 85.2 % for gadobutrol and 88.7 % for gadopentate dimeglumine . Specificity of the average reader was 82.1 % for gadobutrol and 86.1 % for gadopentate dimeglumine . In conclusion , this study documents evidence for the noninferiority of a single i.v . bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI PURPOSE To perform a quantitative and qualitative comparison of gadobutrol and gadoterate in three-station contrast enhanced magnetic resonance angiography ( CE-MRA ) of the lower limbs . MATERIAL S AND METHODS In this prospect i ve r and omized controlled trial , 52 patients with leg ischemia were r and omly assigned to one of two groups receiving either gadobutrol ( 1.0 mmol Gd/mL , 15 mL ) or gadoterate ( 0.5 mmol Gd/mL , 30 mL ) . Three-station 3D CE-MRAs from the pelvis to the ankles were performed with moving-table technique on a 1.5 T MR scanner . Injection time was identical in both groups . Signal-to-noise ( SNR ) and contrast-to-noise ratios ( CNR ) were calculated for 816 arteries . Contrast quality in 1196 vessel segments was evaluated separately by two blinded readers on a three-point scale . RESULTS Mean SNR ( 61.8 + /- 7.8 for gadobutrol vs. 61.9 + /- 9.1 for gadoterate , P = 0.257 ) , CNR ( 52.8 + /- 9.1 vs. 52.8 + /- 10.7 , P = 0.154 ) , and qualitative ranking ( 1.41 vs. 1.44 , P = 0.21 ) for all vessels did not differ significantly between the two patient groups . The overall quality was good in 90.4 % with gadoterate and 94.2 % with gadobutrol ( P = 0.462 ) . CONCLUSION High-concentration gadobutrol allows neither a higher CNR nor any qualitative advantage over the ordinary unspecific Gd agent gadoterate when the same Gd load and injection times are used in multistation CE-MRA of the peripheral arteries OBJECTIVE The purpose of this study was to compare a macrocyclic 1.0 M contrast agent with a linear ionic 0.5 M contrast agent at equimolar dosage in regard to image quality and number of vessel segments visualized at abdominal dynamic contrast-enhanced 3D MR angiography . SUBJECTS AND METHODS In an intraindividual comparative study , 15 patients ( six women , nine men ; mean age , 53 + /- 12.1 years ; range , 25 - 72 years ) underwent 32 1.5-T whole-body contrast-enhanced 3D MR angiographic examinations performed with parallel imaging technique . At r and om and in separate sessions , each patient was examined after IV injection of 0.1 mmol/kg body weight 1.0 M macrocyclic gadobutrol and 0.5 M linear ionic gadopentetate dimeglumine . Three-dimensional data sets were acquired in the arterial , portal venous , and venous phases with identical imaging protocol s. Quantitative analysis included contrast measurements of vessels compared with adjacent background tissue ( Student 's t test ) . Qualitative analysis was performed independently by two radiologists with regard to visualization of arterial and venous vessel segments and overall image quality ( Wilcoxon 's test ) . RESULTS Visualization of individual vessel segments was rated significantly better after administration of 1.0 M macrocyclic gadobutrol compared with 0.5 M linear ionic gadopentetate dimeglumine ( p < 0.001 ) . Overall image quality was superior with 1.0 M macrocyclic gadobutrol , but the difference was not significant . Vessel-to- background contrast after injection of 1.0 M macrocyclic gadobutrol was significantly higher ( arterial phase , 0.90 , p = 0.02 ; portal venous phase , 0.78 , p = 0.0002 ; venous phase , 0.74 , p = 0.0002 ) compared with 0.5 M linear ionic gadopentetate dimeglumine ( arterial phase , 0.89 ; portal venous phase , 0.73 ; venous phase , 0.67 ) . CONCLUSION At abdominal contrast-enhanced 3D MR angiography , depiction of small abdominal vessels was significantly better and vessel-to-tissue contrast significantly higher with 1.0 M macrocyclic gadobutrol than with an equimolar dose of 0.5 M linear ionic gadopentetate dimeglumine OBJECTIVE Two macrocyclic extracellular contrast agents , one-molar neutral gadobutrol and ionic gadoterate meglumine , were compared to determine the overall preference for one or the other in a clinical setting . MATERIAL S AND METHODS Multicenter , r and omized , single-blind , intra-individually controlled , comparison study with a corresponding blinded read . Efficacy analysis was based on 136 patients who underwent identical MRI examinations : group A first received 1.0 M gadobutrol followed by 0.5 M gadoterate meglumine 48 h to 7 days later ; group B had a reversed administration order . Three independent blinded readers assessed off-site their overall diagnostic preference ( primary efficacy parameter ) based on a matched pairs approach . RESULTS Superiority of gadobutrol over gadoterate meglumine was demonstrated for the qualitative assessment of overall preference across all readers by a statistically significant difference between both contrast agents for this primary endpoint . Preferences in lesion enhancement ( secondary endpoint ) were also found significantly in favor of gadobutrol . For preference in lesion delineation from surrounding tissue/edema and for internal structure only a trend towards a higher proportion for gadobutrol was found ( except for internal structure reported by one reader , which showed a result of statistical significance ) . Lesion contrast and relative lesion enhancement ( quantitative parameters ) were statistically significantly higher for gadobutrol compared to gadoterate meglumine . CONCLUSION Contrast-enhanced MRI of neoplastic brain lesions at a dose of 0.1 mmol Gd/kg body weight , assessed in a st and ardized off-site blinded reading , results in a significantly higher qualitative and quantitative preference for gadobutrol compared to gadoterate meglumine |
10,825 | 22,433,932 | concentration of exhaled nitric oxide was significantly greater in children receiving placebo than in those receiving L. rhamnosus strain GG , suggesting the possibility of more underdiagnosed or sub clinical cases of respiratory allergic diseases in the placebo group .
2 years , challenge-proven patients with mild-to-moderate eczema ) improved the eczema score significantly [ 7 ] .
Studies in infants with eczema supplemented with LGG have also shown benefit in decreasing gastrointestinal symptoms [ 8 ] .
To conclude , the available evidence neither supports nor refutes the role of probiotics in the prevention of allergic diseases .
In their informative review , the authors describe that there is no evidence that any probiotics prevent other allergic conditions apart from the eczema-reducing effect of Lactobacillus rhamnosus . | Several published studies report that oral administration of Bifidobacterium or Lactobacillus strains could alleviate the manifestation of food allergy or food hypersensitivity [ 6 ] .
But , this is not totally true , as some trials have found beneficial effects of probiotics in the prevention of allergic diseases . | BACKGROUND The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier . We have previously shown that a human intestinal floral strain , Lactobacillus GG ( ATCC 53103 ) , promotes local antigen-specific immune responses ( particularly in the IgA class ) , prevents permeability defects , and confers controlled antigen absorption . OBJECTIVE The aim of this study was to evaluate the clinical and immunologic effects of cow 's milk elimination without ( n = 14 ) and with ( n = 13 ) the addition of Lactobacillus GG ( 5 x 10(8 ) colony-forming units/gm formula ) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow 's milk allergy . The second part of the study involved 10 breast-fed infants who had atopic eczema and cow 's milk allergy . In this group Lactobacillus GG was given to nursing mothers . METHODS The severity of atopic eczema was assessed by clinical scoring . The concentrations of fecal alpha 1- antitrypsin , tumor necrosis factor-alpha , and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention . RESULTS The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG . The concentration of alpha 1-antitrypsin decreased significantly in this group ( p = 0.03 ) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68 ) . In parallel , the median ( lower quartile to upper quartile ) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group , from 709 pg/gm ( 91 to 1131 pg/gm ) to 34 pg/gm ( 19 to 103 pg/gm ) ( p = 0.003 ) , but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38 ) . The concentration of fecal eosinophil cationic protein remained unaltered during therapy . CONCLUSION These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy , and by alleviating intestinal inflammation , may act as a useful tool in the treatment of food allergy Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG ( ATCC 53103 ) , reduces incidence of atopic eczema in at-risk children during the first 2 years of life ( infancy ) . We have therefore assessed persistence of the potential to prevent atopic eczema at 4 years . Atopic disease was diagnosed on the basis of a question naire and a clinical examination . 14 of 53 children receiving lactobacillus had developed atopic eczema , compared with 25 of 54 receiving placebo ( relative risk 0.57 , 95 % CI 0.33 - 0.97 ) . Skin prick test reactivity was the same in both groups : ten of 50 children previously given lactobacillus compared with nine of 50 given placebo tested positive . Our results suggest that the preventive effect of lactobacillus GG on atopic eczema extends beyond infancy Over the last two decades the incidence of allergic diseases has increased in industrialized countries , and consequently new approaches have to be explored Objectives : To examine the immunological and clinical influence of 4 months ' feeding with either yoghurt or partially skimmed milk or nothing , on 20 volunteers . Subjects : Thirteen subjects had a demonstrated allergic rhinopathy and seven were healthy subjects and participated as controls . Research design : Either a group of seven or a group of six rhinopathic patients were fed either 450 g yoghurt or 450 g partially skimmed milk , respectively , for 4 months between March and October 1999 . All subjects maintained their usual diet throughout the study .Peripheral blood mononuclear cells ( P BMC ) were isolated before and after the experimental period and cultured for periods of 40 and 64 h. Proliferation index assay and release of IFNγ and IL-4 without and with PHA stimulation were assessed . Allergic rhinopathy was evaluated before and after the 4 months period by performing the nasal functionality tests ( Active Anterior Rhinomanometry , Acoustic Rhinometry ) , the prick test , the nasal specific provocation test ( NPT ) , the dosage of specific IgE blood levels , the evaluation of the symptomatological score and the nasal mucociliary transport test . Results : No significant change of the proliferation index was noted among the three groups . Cultured P BMC of the group fed with yoghurt released more IFNγ and less IL-4 . Cytokine plasma levels were at and remained at basal levels . Prick test , specific serum IgEs and NPT remained immodified . Muco-ciliary transport time ( MCTt ) and symptomatological score showed a definitive improvement after yoghurt feeding . Conclusion : Yoghurt feeding appears to improve or prevent allergic recurrences in rhinopatic patients .Sponsorship : This study was funded , in part , by a grant from Parmalat , Parma , Italy Background : Lactobacillus casei strain Shirota ( LcS ) has been found to exert antiallergic effects in animal experiments , but there is little information about its clinical effects in human patients with allergy . Methods : We performed a r and omized double-blind , placebo-controlled study to investigate the effects of LcS in patients with allergic rhinitis triggered by Japanese cedar pollen ( JCP ) . Participants were asked to drink fermented milk containing LcS ( LcS group ) or placebo ( control group ) for 8 weeks . Clinical symptoms and immunological parameters were compared between the two groups . Results : Symptom-medication scores ( SMS ) worsened in accordance with the increase in the amount of scattered JCP . In terms of the nasal and ocular SMS , there was no significant difference between the LcS group and the placebo group during the ingestion period . In the subgroup of patients with moderate-to-severe nasal symptom scores before starting the ingestion of test sample s , supplementation with LcS tended to reduce nasal SMS . Conclusion : These results indicate that fermented milk containing LcS does not prevent allergic symptoms in patients sensitive to JCP , but may delay the occurrence of allergic symptoms in patients with moderate-to-severe nasal symptom scores |
10,826 | 31,820,360 | There was also no significant reduction in cardiovascular mortality and all-cause mortality .
Our review indicated that aspirin use in CKD patients had no prevention effect on cardiovascular events and no statistically significant reduction in risk of cardiovascular or all-cause mortality , with a significant increased risk of minor bleeding and renal events | To perform a systematic review and meta- analysis to evaluate the cardiovascular prevention effect of aspirin among patients with chronic kidney disease ( CKD ) . | BACKGROUND Chronic kidney disease is an important cause of global mortality and morbidity . Data for epidemiological features of chronic kidney disease and its risk factors are limited for low-income and middle-income countries . The International Society of Nephrology 's Kidney Disease Data Center ( ISN-KDDC ) aim ed to assess the prevalence and awareness of chronic kidney disease and its risk factors , and to investigate the risk of cardiovascular disease , in countries of low and middle income . METHODS We did a cross-sectional study in 12 countries from six world regions : Bangladesh , Bolivia , Bosnia and Herzegovina , China , Egypt , Georgia , India , Iran , Moldova , Mongolia , Nepal , and Nigeria . We analysed data from screening programmes in these countries , matching eight general and four high-risk population cohorts collected in the ISN-KDDC data base . High-risk cohorts were individuals at risk of or with a diagnosis of either chronic kidney disease , hypertension , diabetes , or cardiovascular disease . Participants completed a self-report question naire , had their blood pressure measured , and blood and urine sample s taken . We defined chronic kidney disease according to modified KDIGO ( Kidney Disease : Improving Global Outcomes ) criteria ; risk of cardiovascular disease development was estimated with the Framingham risk score . FINDINGS 75,058 individuals were included in the study . The prevalence of chronic kidney disease was 14·3 % ( 95 % CI 14·0 - 14·5 ) in general population s and 36·1 % ( 34·7 - 37·6 ) in high-risk population s. Overall awareness of chronic kidney disease was low , with 409 ( 6 % ) of 6631 individuals in general population s and 150 ( 10 % ) of 1524 participants from high-risk population s aware they had chronic kidney disease . Moreover , in the general population , 5600 ( 44 % ) of 12,751 individuals with hypertension did not know they had the disorder , and 973 ( 31 % ) of 3130 people with diabetes were unaware they had that disease . The number of participants at high risk of cardiovascular disease , according to the Framingham risk score , was underestimated compared with KDIGO guidelines . For example , all individuals with chronic kidney disease should be considered at high risk of cardiovascular disease , but the Framingham risk score detects only 23 % in the general population , and only 38 % in high-risk cohorts . INTERPRETATION Prevalence of chronic kidney disease was high in general and high-risk population s from countries of low and middle income . Moreover , awareness of chronic kidney disease and other non-communicable diseases was low , and a substantial number of individuals who knew they were ill did not receive treatment . Prospect i ve programmes with repeat testing are needed to confirm the diagnosis of chronic kidney disease and its risk factors . Furthermore , in general , health-care workforces in countries of low and middle income need strengthening . FUNDING International Society of Nephrology BACKGROUND We investigated aspirin-prescribing patterns and potential benefits on cardiovascular morbidity and mortality in hemodialysis patients . STUDY DESIGN Cohort study . SETTING & PARTICIPANTS Data included 28,320 r and omly selected hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study I and II . PREDICTOR Aspirin prescription at study baseline . OUTCOMES & MEASUREMENTS Prescription was investigated by means of logistic regression . All-cause mortality , all-cause hospitalization , cardiac event , myocardial infa rct ion , cerebrovascular ( CVA ) , gastrointestinal bleed , transient ischemic attack , and subdural hematoma were examined . Cox regression examined the risk of mortality and hospitalization . All models accounted for facility clustering and demographics and comorbid conditions . RESULTS Wide variation was found in aspirin prescription , from 8 % in Japan to 41 % in Australia and New Zeal and . Characteristics significantly associated with increased odds of prescription included coronary artery disease , cerebrovascular disease , diabetes , male sex , nonblack race , peripheral vascular disease , age , hypertension , and absence of gastrointestinal bleeding . Aspirin was associated with decreased risk of stroke in all patients ( relative risk [ RR ] , 0.82 ; P < 0.01 ) and increased risk of myocardial infa rct ion ( RR , 1.21 ; P = 0.01 ) and cardiac event ( RR , 1.08 ; P < 0.01 ) in all patients , with similar results for patients with coronary artery disease . There was no increase in gastrointestinal bleeding . LIMITATIONS Observational studies are not protected from biases , despite adjustments . There is potential for aspirin use to be underreported because of its availability without prescription . CONCLUSIONS The hypothesis that prescribing aspirin to hemodialysis patients decreases cardiovascular disease risk is not supported . Aspirin might decrease CVA and appears not to increase hemorrhagic risk . This should be an incentive for r and omized controlled trials BACKGROUND Patients with chronic kidney disease are at increased risk for cardiovascular disease , but the efficacy and safety of simvastatin and aspirin are unknown in this patient group . METHODS Patients were r and omly assigned in a 2 x 2 factorial design to the administration of : ( 1 ) 20 mg of simvastatin daily versus matching placebo , and ( 2 ) 100 mg of modified-release aspirin daily versus matching placebo . RESULTS Overall , 448 patients with chronic kidney disease were r and omly assigned ( 242 predialysis patients with a creatinine level > or = 1.7 mg/dL [ > or = 150 micromol/L ] , 73 patients on dialysis therapy , and 133 patients with a functioning transplant ) . Compliance with study treatments was 80 % at 12 months . Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds ( aspirin , 4 of 225 patients [ 2 % ] versus placebo , 6 of 223 patients [ 3 % ] ; P = not significant [ NS ] ) , although there was a 3-fold excess of minor bleeds ( 34 of 225 [ 15 % ] versus 12 of 223 patients [ 5 % ] ; P = 0.001 ) . Among those with predialysis renal failure or a functioning transplant at baseline , aspirin did not increase the number of patients who progressed to dialysis therapy ( 7 of 187 [ 4 % ] versus 6 of 188 patients [ 3 % ] ; P = NS ) or experienced a greater than 20 % increase in creatinine level ( 63 of 187 patients [ 34 % ] versus 56 of 188 patients [ 30 % ] ; P = NS ) . After 12 months of follow-up , allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18 % ( simvastatin , 163 mg/dL [ 4.22 mmol/L ] versus placebo , 196 mg/dL [ 5.08 mmol/L ] ; P < 0.0001 ) , directly measured low-density lipoprotein cholesterol levels by 24 % ( 89 mg/dL [ 2.31 mmol/L ] versus 114 mg/dL [ 2.96 mmol/L ] ; P < 0.0001 ) , and triglyceride levels by 13 % ( 166 mg/dL [ 1.87 mmol/L ] versus 186 mg/dL [ 2.10 mmol/L ] ; P < 0.01 ) , but there was no significant effect on high-density lipoprotein cholesterol levels ( 2 % increase ; P = NS ) . Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels . CONCLUSION During a 1-year treatment period , simvastatin , 20 mg/d , produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels , with no evidence of toxicity , and aspirin , 100 mg/d , did not substantially increase the risk for a major bleeding episode . Much larger trials are now needed to assess whether these treatments can prevent vascular events OBJECTIVES The purpose of this study was to determine the benefit and risk associated with antiplatelet therapy in the chronic kidney disease ( CKD ) population . BACKGROUND Cardiovascular and possibly bleeding risks are elevated in patients with CKD . The balance of benefit and harm associated with antiplatelet therapy remains uncertain . METHODS The HOT ( Hypertension Optimal Treatment ) study r and omly assigned participants with diastolic hypertension to aspirin ( 75 mg ) or placebo . Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate ( eGFR ) with trends tested by adding interaction terms . End points included major cardiovascular events , total mortality , and major bleeding . RESULTS The study included 18,597 participants treated for 3.8 years . Baseline eGFR was < 60 ml/min/1.73 m(2 ) in 3,619 participants . Major cardiovascular events were reduced by 9 % ( 95 % confidence interval [ CI ] : -9 % to 24 % ) , 15 % ( 95 % CI : -17 % to 39 % ) , and 66 % ( 95 % CI : 33 % to 83 % ) for patients with baseline eGFR of ≥ 60 , 45 to 59 , and < 45 ml/min/1.73 m(2 ) , respectively ( p trend = 0.03 ) . Total mortality was reduced by 0 % ( 95 % CI : -20 % to 17 % ) , 11 % ( 95 % CI : -31 % to 40 % ) , and 49 % ( 95 % CI : 6 % to 73 % ) , respectively ( p trend = 0.04 ) . Major bleeding events were nonsignificantly greater with lower eGFR ( hazard ratio [ HR ] : 1.52 [ 95 % CI : 1.11 to 2.08 ] , HR : 1.70 [ 95 % CI : 0.74 to 3.88 ] , and HR : 2.81 [ 95 % CI : 0.92 to 8.84 ] , respectively ; p trend = 0.30 ) . Among every 1,000 persons with eGFR < 45 ml/min/1.73 m(2 ) treated for 3.8 years , 76 major cardiovascular events and 54 all-cause deaths will be prevented while 27 excess major bleeds will occur . CONCLUSIONS Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with CKD than with normal kidney function . An increased risk of major bleeding appears to be outweighed by the substantial benefits A six year r and omised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke , myocardial infa rct ion , or other vascular conditions . Though total mortality was 10 % lower in the treated than control group , this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infa rct ion . Likewise , there was no significant difference in the incidence of non-fatal myocardial infa rct ion or stroke — indeed , disabling strokes were somewhat commoner among those allocated aspirin . The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infa rct ion , however , was a substantial 25 % reduction . Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group , but as the control group was not given a placebo the relevance of these findings was difficult to assess . There was no apparent reduction in the incidence of cataract in the treated group . The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease Background Patients with chronic kidney disease ( CKD ) are at high risk for developing cardiovascular events . However , limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression . Study Design Prospect i ve , multicenter , open-label r and omized controlled trial . Setting and Participants One hundred eleven patients with estimated glomerular filtration rate ( eGFR ) 15–60 ml/min/1.73 m2 without previous cardiovascular events . InterventionAspirin treatment ( 100 mg/day ) ( n = 50 ) or usual therapy ( n = 61 ) . Mean follow-up time was 64.8 ± 16.4 months . Outcomes The primary endpoint was composed of cardiovascular death , acute coronary syndrome ( nonfatal MI , coronary revascularization , or unstable angina pectoris ) , cerebrovascular disease , heart failure , or nonfatal peripheral arterial disease . Secondary endpoints were fatal and nonfatal coronary events , renal events ( defined as doubling of serum creatinine , ≥ 50 % decrease in eGFR , or renal replacement therapy ) , and bleeding episodes . Results During follow-up , 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups , respectively . Aspirin did not significantly reduce primary composite endpoint ( HR , 0.396 ( 0.146–1.076 ) , p = 0.069 . Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group . Aspirin significantly reduced the risk of coronary events ( log-rank , 5.997 ; p = 0.014 ) . Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group . Aspirin treatment decreased renal disease progression in a model adjusted for age , baseline kidney function , and diabetes mellitus ( HR , 0.272 ; 95 % CI , 0.077–0.955 ; p = 0.043 ) but did not when adjusted for albuminuria . No differences were found in minor bleeding episodes between groups and no major bleeding was registered . Limitations Small sample size and open-label trial . Conclusions Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint ; however , there were reductions in secondary endpoints with fewer coronary events and renal outcomes . Clinical Trials.gov Identifier : NCT01709994 |
10,827 | 32,305,104 | The application of a topical benzoyl peroxide antibiotic in the days leading up to surgery in combination with preoperative antibiotic prophylaxis significantly reduces the prevalence of C acnes in shoulder arthroscopy patients | BACKGROUND Cutibacterium acnes is a gram-positive anaerobe that can lead to postoperative shoulder infections .
The purpose of this study was to determine the incidence of C acnes infections following shoulder arthroscopy and evaluate the efficacy of perioperative antibiotic prophylaxis in the prevention of these infections . | BACKGROUND Propionibacterium acnes is a gram-positive anaerobe that can lead to devastating postoperative shoulder infections . The objective of this study was to investigate whether a benzoyl peroxide and clindamycin preoperative skin preparation reduces the incidence of P. acnes colonization during shoulder arthroscopy . METHODS Sixty-five shoulder arthroscopy patients were prospect ively enrolled . A skin culture specimen was taken at the preoperative visit from st and ard arthroscopic portal sites . Topical benzoyl peroxide 5 % and clindamycin 1.2 % ( BPO/C ) gel was applied to the shoulder every night before surgery . Skin culture was repeated in the operating room before preparation with chlorhexidine gluconate . Shoulder arthroscopy proceeded , with final culture specimens obtained from within the shoulder . RESULTS P. acnes skin colonization remained similar to prior studies at 47.7 % ( 31 of 65 patients . ) With > 1 application , BPO/C was 78.9 % ( 15 of 19 patients ) effective in eliminating P. acnes superficial colonization . With 1 application , it was 66.7 % ( 8 of 12 patients ) effective in eliminating superficial colonization . Deep colonization was reduced to 3.1 % ( 2 of 65 patients ) compared with previous studies of 15 % to 20 % ( P = .006 ) . BPO/C was 100 % effective at decreasing deep colonization with > 1 application . CONCLUSIONS P. acnes skin colonization is high at arthroscopic shoulder portals , especially in men . Despite st and ard skin preparation and prophylactic antibiotics , the rate of joint inoculation is much higher than the rate of infection reported in the literature . BPO/C effectively reduces P. acnes colonization in shoulder arthroscopy . It should be considered for use before shoulder procedures with a time-related trend of > 1 application PURPOSE To examine the contamination rate of the anchor-suture and to determine the efficacy of 2 different surgical skin preparation solutions with or without a plastic adhesive drape from suture contamination in arthroscopic rotator cuff repair . METHODS A prospect i ve r and omized study was undertaken to evaluate 126 consecutive patients undergoing arthroscopic rotator cuff repair . Each shoulder was prepared with one of 2 r and omly selected solutions according to an assigned envelope that indicated the procedure to be used : chlorhexidine-alcohol ( 1 % chlorhexidine gluconate and 70 % isopropyl alcohol ) or povidone-iodine . Then , each group was further divided according to the usage of a plastic drape . The first cut-tails of the anchor-suture after cuff fixation were su bmi tted to aerobic and anaerobic cultures . RESULTS The overall rate of Propionibacterium acnes-positive cultures was 47 % ( 14 of 31 cases ) in the povidone-iodine group , 33 % ( 11 of 33 cases ) in the povidone-iodine with a drape group , 33 % ( 10 of 30 cases ) in the chlorhexidine-alcohol group , and 9.3 % ( 3 of 32 cases ) in the chlorhexidine-alcohol with a drape group . The positive culture rate in the chlorhexidine-alcohol with a drape group was lower than that in the povidone-iodine group ( relative risk , 0.2 ; 95 % confidence interval : 0.064 - 0.63 ; number needed to treat , 2.7 ; P < .0001 ) . Coagulase-negative staphylococci were isolated in the povidone-iodine with a drape ( 1 case ) and chlorhexidine-alcohol with a drape group ( 2 cases ) . No other bacteria were isolated , and no infections occurred in any of the patients treated in this study during the minimum 12-month follow-up period . CONCLUSIONS Chlorhexidine-alcohol solution with an adhesive plastic drape was more effective than chlorhexidine-alcohol without a plastic drape and povidone-iodine with/without a plastic drape in eliminating P acnes suture contamination . However , the usage of a plastic drape slightly increased the risk of coagulase-negative Staphylococcus proliferation . LEVEL OF EVIDENCE Level I , therapeutic , prospect i ve , r and omized trial HYPOTHESIS Deep infection after shoulder surgery is a rare but devastating problem . This study tested the hypothesis that the home application of a 2 % chlorhexidine gluconate cloth before shoulder surgery would be more efficacious than a st and ard shower of soap and water at decreasing the preoperative cutaneous levels of pathogenic bacteria on the shoulder . MATERIAL S AND METHODS This r and omized , prospect i ve study evaluated 100 consecutive patients undergoing shoulder surgery . Patients were r and omly assigned to use 2 % chlorhexidine gluconate-impregnated cloths ( treatment group ) or to shower with soap and water before surgery ( control group ) . Cutaneous cultures were taken from the patients ' shoulders in the preoperative holding area . Patients were monitored for 2 months postoperatively for clinical signs of infection . RESULTS In the treatment group vs the control group , the overall positive culture rate was 66 % vs 94 % ( P = .0008 ) , and the positive culture rate for coagulase-negative Staphylococcus was 30 % vs 70 % ( P = .0001 ) . The positive culture rate for Propionibacterium acnes was 46 % in the treatment group vs 58 % in the control group ( P = .32 ) . No infections occurred in any patients at a minimum of 2-months after surgery . DISCUSSION The use of the 2 % chlorhexidine cloth was effective at decreasing overall bacterial culture rates before shoulder surgery and was particularly effective at decreasing the quantity of coagulase-negative Staphylococcus , a known causative agent of postoperative shoulder infections . CONCLUSION Use of chlorhexidine impregnated cloths prior to shoulder surgery may be a useful adjunct to presently used infection prevention strategies BACKGROUND : Benzoyl peroxide and clindamycin are the two most widely prescribed topical antimicrobials in the treatment of acne . AIM : To compare the antimicrobial efficacy , in vivo , of benzoyl peroxide and clindamycin against Propionibacterium acnes . METHODS : Two groups of 10 subjects each , with comparable mean P. acnes baseline counts of log 5.75 to 5.85 , underwent twice daily application of benzoyl peroxide or clindamycin for 14 days . RESULTS : The results of quantitatively sampling P. acnes after 3 , 7 and 14 days of treatment showed that TriazA 6 % benzoyl peroxide special gel produced faster and significantly greater reductions in P. acnes than did the 1 % clindamycin phosphate in Cleocin-TA lotion ( p < 0.01 ) . These results were paralleled by the greater reductions produced by Triaz versus Cleocin ( p < 0.05 ) in P. acnes fluorescence . CONCLUSION : Benzoyl peroxide formulations suppress the follicular population of P. acnes more rapidly and to a greater degree than topical antibiotics such as clindamycin BACKGROUND Propionibacterium acnes has arisen as the most common microorganism identified at the time of revision shoulder arthroplasty . There is limited evidence to suggest how frequently false-positive cultures occur . The purpose of this prospect i ve controlled study was to evaluate culture growth from specimens obtained during open shoulder surgery . METHODS Patients undergoing an open deltopectoral approach to the shoulder were prospect ively enrolled . Patients with a history of shoulder surgery or any concern for active or previous shoulder infection were excluded . Three pericapsular soft-tissue sample s were taken from the shoulder for bacterial culture and were incubated for fourteen days . A sterile sponge was also analyzed in parallel with the tissue cultures . In addition , similar cultures were obtained from patients who had undergone previous shoulder surgery . RESULTS Overall , 20.5 % of surgeries ( twenty-four of 117 ) yielded at least one specimen removed for culture that was positive for bacterial growth , and 13.0 % of sterile control specimens ( seven of fifty-four ) had positive culture growth ( p = 0.234 ) . P. acnes represented 83.0 % of all positive cultures ( thirty-nine of forty-seven ) at a median incubation time of fourteen days . Among the subjects who had not undergone previous surgery , 17.1 % ( fourteen of eighty-two ) had at least one positive P. acnes culture . Male sex was univariably associated with a greater likelihood of bacterial growth ( p < 0.01 ) , and patients who had not undergone previous surgery and had received two or more preoperative corticosteroid injections had a higher likelihood of bacterial growth ( p = 0.047 ) . CONCLUSIONS The clinical importance of positive P. acnes cultures from specimens obtained from open shoulder surgery remains uncertain . Male sex and preoperative corticosteroid injections were associated with a higher likelihood of bacterial growth on culture and are risk factors that merit further investigation . Previously reported incidences of positive P. acnes culture results from specimens from primary and revision shoulder arthroplasty may be overestimated because of a substantial level of culture contamination . CLINICAL RELEVANCE P. acnes is isolated via culture at a substantial rate from shoulders undergoing a deltopectoral approach . The clinical importance of culture growth by this low-virulence organism still remains uncertain . Further study is necessary to more specifically characterize culture growth by P. acnes as an infection , commensal presence , or contaminant PURPOSE To document the skin colonization and deep tissue inoculation rates associated with arthroscopic shoulder surgery and how these rates differ with procedural and demographic factors . METHODS We prospect ively recruited outpatient shoulder arthroscopy patients who agreed to participate and met the inclusion criteria from February 2013 to May 2014 . All patients received routine antibiotic prophylaxis intravenously . Initial cultures were obtained before the skin preparation by swabbing the skin at the 3 st and ard portal sites : posterior , anterosuperior , and anterolateral . The skin preparation used 4 % chlorhexidine scrub and 2 % chlorhexidine gluconate/70 % isopropyl alcohol paint applied to the entire shoulder . After completion of the arthroscopic procedure , a second culture was obtained through a cannula at the surgical site . All cultures were plated for 21 days using Brucella medium . RESULTS We enrolled 51 patients over a 15-month period . Cultures showed a 72.5 % Propionibacterium acnes superficial colonization rate : 46.1 % of female and 81.6 % of male patients ( P = .027 ) . We identified a deep culture-positive inoculation rate of 19.6 % , all with positive P acnes skin colonization . No correlation could be made concerning diagnosis , procedure , suture anchor use , age , or sex . CONCLUSIONS The rate of skin colonization with P acnes is high at arthroscopic portals , especially in men . Despite st and ard skin preparation and prophylactic antibiotics , the rate of deep tissue inoculation with P acnes in shoulder arthroscopy is much higher than the rate of infection reported in the literature . CLINICAL RELEVANCE Shoulder arthroscopy introduces a significant amount of P acnes into the deep tissues BACKGROUND To examine the rates and predictors of deep periprosthetic infections after shoulder hemiarthroplasty . METHODS We used prospect ively collected institutional registry data on all primary shoulder hemiarthroplasty patients from 1976 - 2008 . We estimated survival free of deep periprosthetic infections using Kaplan-Meier survival curves . Using univariate Cox regression analyses , we examined the association of patient-related factors ( age , sex , body mass index ) , comorbidity ( Deyo-Charlson index ) , American Society of Anesthesiologists grade , underlying diagnosis , and implant fixation with the risk of infection . RESULTS A total of 1,349 patients , with a mean age of 63 years ( SD , 16 years ) , 63 % of whom were women , underwent 1,431 primary shoulder hemiarthroplasties . Mean follow-up was 8 years ( SD , 7 years ) . Fourteen deep periprosthetic infections occurred during the follow-up , confirmed by medical record review . The most common organisms were Staphylococcus aureus , coagulase-negative Staphylococcus , and Propionibacterium acnes , each accounting for 3 cases ( 21 % each ) . The 5- , 10- , and 20-year prosthetic infection-free rates were 98.9 % ( 95 % confidence interval [ CI ] , 98.3%-99.5 % ) , 98.7 % ( 95 % CI , 98.1%-99.4 % ) , and 98.7 % ( 95 % CI , 98.1%-99.4 % ) , respectively . None of the factors evaluated were significantly associated with risk of prosthetic infection after primary shoulder hemiarthroplasty , except that an underlying diagnosis of trauma was associated with a significantly higher hazard ratio of 3.18 ( 95 % CI , 1.06 - 9.56 ) for infection compared with all other diagnoses ( P = .04 ) . A higher body mass index showed a non-statistically significant trend toward an association with higher hazard ( P = .13 ) . CONCLUSION The periprosthetic infection rate after shoulder hemiarthroplasty was low , estimated at 1.3 % at 20-year follow-up . An underlying diagnosis of trauma was associated with a higher risk of periprosthetic infection . These patients should be observed closely for development of infection PURPOSE To evaluate the prevalence of Cutibacterium acnes in the shoulder region and to analyze changes in C acnes contamination during shoulder arthroscopy , as well as to investigate the influence of sex and type of arthroscopic surgery on those parameters . METHODS Forty-eight consecutive patients undergoing reconstructive or non-reconstructive shoulder arthroscopy , after hair removal with a medical clipper , routine antibiotic prophylaxis , and skin preparation with an alcohol-based skin disinfectant , were prospect ively enrolled in this study . The shoulder was divided into 4 regions of interest ( anterior , medial , posterior , and axilla ) . Skin swabs were taken from each region at 3 time points ( preoperatively before and after skin preparation , and at the conclusion of surgery ) , cultured for 21 days , and analyzed for the prevalence of C acnes . RESULTS The rate of C acnes-positive skin cultures was significantly increased at the end of surgery compared with preoperatively before ( 44.3 % vs 27.6 % , P < .001 ) and after ( 44.3 % vs 31.3 % , P = .001 ) skin preparation . No reduction in C acnes was observed with preoperative skin preparation ( 27.6 % vs 31.3 % , P = .401 ) . At the end of shoulder arthroscopy , 64.6 % of patients showed at least 1 culture positive for C acnes . The C acnes prevalence was significantly higher in male patients ( 48.3 % ) than female patients ( 20.1 % , P < .001 ) , at all time points ( P < .016 ) , and in all regions of interest ( P < .001 ) except the axilla . No differences in the prevalence of C acnes were found between non-reconstructive and reconstructive procedures . CONCLUSIONS Skin contamination with C acnes around the shoulder increased significantly from before and after skin preparation to the conclusion of surgery in patients undergoing shoulder arthroscopy despite perioperative preventive measures . LEVEL OF EVIDENCE Level IV , therapeutic case series BACKGROUND The purpose of this study was to determine whether preoperative skin preparation with hydrogen peroxide reduces intraoperative culture positivity for Cutibacterium acnes in shoulder arthroplasty . METHODS This was a prospect i ve , controlled , parallel/noncrossover , nonr and omized , single-blinded trial registered at clinical trials.gov . We included a consecutive series of patients scheduled to undergo primary anatomic or reverse total shoulder arthroplasty . The first group of patients underwent a st and ard skin preparation and the second group underwent the same preparation with the addition of hydrogen peroxide . We then took skin , dermis , glenohumeral joint , and air ( negative control ) aerobic and anaerobic culture swabs . We blinded the laboratory analyzing the sample s. An a priori power analysis determined that 56 patients would be needed to see a 50 % reduction in culture positivity rates . We also conducted a post hoc gender-stratified analysis . RESULTS Between January 2017 and October 2018 , the authors performed 124 primary shoulder arthroplasties , of which we included 65 and collected sample s on 61 . There were no demographic differences . There were fewer patients within the peroxide group with triple-positive cultures ( skin , dermis , and joint ) ( 0 % vs. 19 % , P = .024 ) and positive cultures from the joint ( 10 % vs. 35 % , P = .031 ) . In our subgroup analysis , these differences were only significant in males . The vast majority of positive cultures were with C. acnes . CONCLUSION Although larger , r and omized studies are needed , adding hydrogen peroxide to the preoperative skin preparation may be a low-cost , low-risk method to reduce deep tissue contamination with C. acnes , particularly within males BACKGROUND Recent studies have identified Propionibacterium acnes as the causal organism in an increasing number of postoperative shoulder infections . Most reports have found a high rate of P acnes infection after open surgery , particularly shoulder arthroplasty . However , there are limited data regarding P acnes infections after shoulder arthroscopy . MATERIAL S AND METHODS We prospect ively collected data on all shoulder arthroscopies performed by the senior author from January 1 , 2009 , until April 1 , 2013 . Cultures were taken in all revision shoulder arthroscopy cases performed for pain , stiffness , or weakness . In addition , 2 cultures were taken from each of a cohort of 32 primary shoulder arthroscopy cases without concern for infection to determine the false-positive rate . RESULTS A total of 1,591 shoulder arthroscopies were performed during this period , 68 ( 4.3 % ) of which were revision procedures performed for pain , stiffness , or weakness . A total of 20 revision arthroscopies ( 29.4 % ) had positive culture findings , and 16 ( 23.5 % ) were positive for P acnes . In the control group , 1 patient ( 3.2 % ) had P acnes growth . CONCLUSIONS The rate of P acnes infection in patients undergoing revision shoulder arthroscopy is higher than previously published and should be considered in cases characterized by refractory postoperative pain and stiffness Background Frozen shoulder has not previously been shown to be associated with infection . The present study set out to confirm the null hypothesis that there is no relationship between infection and frozen shoulder using two modern scientific methods , extended culture and polymerase chain reaction ( PCR ) for bacterial nucleic acids . Methods A prospect i ve cohort of 10 patients undergoing arthroscopic release for stage II idiopathic frozen shoulder had two biopsies of tissue taken from the affected shoulder joint capsule at the time of surgery , along with control biopsies of subdermal fat . The biopsies and controls were examined with extended culture and PCR for microbial nucleic acid . Results Eight of the 10 patients had positive findings on extended culture in their shoulder capsule and , in six of these , Propionibacterium acnes was present . Conclusions The findings mean that we must reject the null hypothesis that there is no relationship between infection and frozen shoulder . More studies are urgently needed to confirm or refute these findings . If they are confirmed , this could potentially lead to new and effective treatments for this common , painful and disabling condition . Could P. acnes be the Helicobacter of frozen shoulder BACKGROUND Deep infection following shoulder surgery is a rare but devastating problem . The use of an effective skin-preparation solution may be an important step in preventing infection . The purpose s of the present study were to examine the native bacteria around the shoulder and to determine the efficacy of three different surgical skin-preparation solutions on the eradication of bacteria from the shoulder . METHODS A prospect i ve study was undertaken to evaluate 150 consecutive patients undergoing shoulder surgery at one institution . Each shoulder was prepared with one of three r and omly selected solutions : ChloraPrep ( 2 % chlorhexidine gluconate and 70 % isopropyl alcohol ) , DuraPrep ( 0.7 % iodophor and 74 % isopropyl alcohol ) , or povidone-iodine scrub and paint ( 0.75 % iodine scrub and 1.0 % iodine paint ) . Aerobic and anaerobic cultures were obtained prior to skin preparation for the first twenty patients , to determine the native bacteria around the shoulder , and following skin preparation for all patients . RESULTS Coagulase-negative Staphylococcus and Propionibacterium acnes were the most commonly isolated organisms prior to skin preparation . The overall rate of positive cultures was 31 % in the povidone-iodine group , 19 % in the DuraPrep group , and 7 % in the ChloraPrep group . The positive culture rate for the ChloraPrep group was lower than that for the povidone-iodine group ( p < 0.0001 ) and the DuraPrep group ( p = 0.01 ) . ChloraPrep and DuraPrep were more effective than povidone-iodine in eliminating coagulase-negative Staphylococcus from the shoulder region ( p < 0.001 for both ) . No significant difference was detected among the agents in their ability to eliminate Propionibacterium acnes from the shoulder region . No infections occurred in any of the patients treated in this study at a minimum of ten months of follow-up . CONCLUSIONS ChloraPrep is more effective than DuraPrep and povidone-iodine at eliminating overall bacteria from the shoulder region . Both ChloraPrep and DuraPrep are more effective than povidone-iodine at eliminating coagulase-negative Staphylococcus from the shoulder |
10,828 | 26,633,769 | Exp and ing home and mobile testing , self-testing and outreach to key population s with facilitated linkage can increase the proportion of men , young adults and high-risk individuals linked to HIV treatment and prevention , and decrease HIV burden . | HIV testing and counselling is the first crucial step for linkage to HIV treatment and prevention .
However , despite high HIV burden in sub-Saharan Africa , testing coverage is low , particularly among young adults and men .
Community-based HIV testing and counselling ( testing outside of health facilities ) has the potential to reduce coverage gaps , but the relative impact of different modalities is not well assessed . | Objective : To investigate HIV incidence during a trial of two voluntary counselling and testing ( VCT ) strategies . Counselling may promote beneficial behavioural change , although knowledge of negative status does not appear to contribute further benefit . Design : The parent cluster-r and omized trial demonstrated much greater uptake of VCT when counselling and rapid testing were available on-site ( intensive VCT ) than through pre-paid vouchers to an external provider ( st and ard VCT ) . Anonymous HIV tests had been requested from all employees at enrolment and after 2 years intervention . Methods : The study setting was 22 businesses in Harare , Zimbabwe . Participants were 3146 HIV-negative individuals remaining in employment at the end of intervention , of whom 2966 ( 94.3 % ) consented to repeat testing . VCT linked to basic HIV care was provided and the main outcome measures were HIV incidence under each study arm , as a retrospective secondary analysis . Results : Mean VCT uptake in this cohort was 70.7 and 5.2 % , respectively , in the intensive and st and ard arms . Crude HIV incidence was 1.21 per 100 person-years , with non-significantly higher rates in the intensive VCT arm [ mean site incidence 1.37 and 0.95 per 100 person-years , respectively ; adjusted rate ratio 1.49 ( 95 % confidence interval 0.79–2.80 ) . Conclusions : Highly acceptable VCT did not reduce HIV incidence in this predominantly male cohort . HIV incidence was highest in the high uptake VCT arm , lending support to a US trial in which rapid testing appeared to have adverse behavioural consequences in some HIV-negative clients . Careful comparison of outcomes under different counselling and testing strategies is needed to maximize HIV prevention from global scale-up of VCT OBJECTIVE To assess the possible impact of HIV infection on the management of general surgical patients at the Ga-Rankuwa Hospital . DESIGN A prospect i ve study . SETTING Ga-Rankuwa Hospital/Medical University of Southern Africa ( MEDUNSA ) Academic Complex , Pretoria , South Africa . SUBJECTS Nine hundred and forty one patients admitted to general surgical wards . MAIN OUTCOME MEASURES HIV infection and CD4 counts . RESULTS Nine hundred and forty one patients admitted to general surgical wards from January 1966 to December 1997 were tested for HIV infection . Twelve per cent tested positive . HIV positive patients were significantly younger [ 33 + /- 10 versus 41 + /- 7 ( men + /- SD ) years , Chi-square = 51 , p < 0.0001 ] . There was no correlation of HIV positivity to the patient 's sex ( p = 0.7 ) . In forty three HIV positive patients treated surgically , mortality was attributed to HIV/AIDS in only one patient with a CD4 count of 47/ul who died following laparotomy for peritonitis . CD4 counts done during follow up in thirty one HIV positive patients revealed a count of < 500/ul in eleven patients . CONCLUSION It is predicted that an increasing number of patients with HIV/AIDS will be admitted to general surgery wards of the Ga-Rankuwa Hospital . Surgeons are advised to take universal pre caution s to prevent HIV infection Background HIV counselling and testing is a key component of both HIV care and HIV prevention , but uptake is currently low . We investigated the impact of rapid HIV testing at the workplace on uptake of voluntary counselling and testing ( VCT ) . Methods and Findings The study was a cluster-r and omised trial of two VCT strategies , with business occupational health clinics as the unit of r and omisation . VCT was directly offered to all employees , followed by 2 y of open access to VCT and basic HIV care . Businesses were r and omised to either on-site rapid HIV testing at their occupational clinic ( 11 businesses ) or to vouchers for off-site VCT at a chain of free-st and ing centres also using rapid tests ( 11 businesses ) . Baseline anonymised HIV serology was requested from all employees . HIV prevalence was 19.8 % and 18.4 % , respectively , at businesses r and omised to on-site and off-site VCT . In total , 1,957 of 3,950 employees at clinics r and omised to on-site testing had VCT ( mean uptake by site 51.1 % ) compared to 586 of 3,532 employees taking vouchers at clinics r and omised to off-site testing ( mean uptake by site 19.2 % ) . The risk ratio for on-site VCT compared to voucher uptake was 2.8 ( 95 % confidence interval 1.8 to 3.8 ) after adjustment for potential confounders . Only 125 employees ( mean uptake by site 4.3 % ) reported using their voucher , so that the true adjusted risk ratio for on-site compared to off-site VCT may have been as high as 12.5 ( 95 % confidence interval 8.2 to 16.8 ) . Conclusions High-impact VCT strategies are urgently needed to maximise HIV prevention and access to care in Africa . VCT at the workplace offers the potential for high uptake when offered on-site and linked to basic HIV care . Convenience and accessibility appear to have critical roles in the acceptability of community-based VCT Background Voluntary HIV counselling and testing ( VCT ) is one of the key strategies in the prevention and control of HIV/AIDS in Ug and a. However , the utilization of VCT services particularly among men is low in Kasese district . We therefore conducted a study to determine the prevalence and factors associated with VCT use among men in Bukonzo West health sub-district , Kasese district . Methods A population -based cross-sectional study employing both quantitative and qualitative techniques of data collection was conducted between January and April 2005 . Using cluster sampling , 780 men aged 18 years and above , residing in Bukonzo West health sub-district , were sample d from 38 r and omly selected clusters . Data was collected on VCT use and independent variables . Focus group discussion s ( 4 ) and key informant interviews ( 10 ) were also conducted . Binary logistic regression was performed to determine the predictors of VCT use among men . Results Overall VCT use among men was 23.3 % ( 95 % CI 17.2–29.4 ) . Forty six percent ( 95 % CI 40.8–51.2 ) had pre-test counselling and 25.9 % ( 95%CI 19.9–31.9 ) had HIV testing . Of those who tested , 96 % returned for post-test counselling and received HIV results . VCT use was higher among men aged 35 years and below ( OR = 2.69 , 95%CI 1.77–4.07 ) , the non-subsistence farmers ( OR = 2.37 , 95%CI 2.37 ) , the couple testing ( OR = 2.37 , 95%CI 1.02–8.83 ) and men with intention to disclose HIV test results to sexual partners ( OR = 1.64 , 95%CI 1.04–2.60 ) . The major barriers to VCT use among men were poor utilization of VCT services due to poor access , stigma and confidentiality of services . Conclusion VCT use among men in Bukonzo West , Kasese district was low . In order to increase VCT use among men , the VCT programme needs to address HIV stigma and improve access and confidentiality of VCT services . Among the more promising interventions are the use of routine counselling and testing for HIV of patients seeking health care in health units , home based VCT programmes , and mainstreaming of HIV counselling and testing services in community development programmes Objectives : To assess self‐ selection in a population ‐based voluntary HIV testing and counseling ( VTC ) program by comparing the HIV risk characteristics of users and nonusers of VTC in rural Ug and a. Design : A 1994 to 1995 community‐r and omized trial in the Rakai District of Ug and a enrolled adults aged 15 to 59 years and ascertained their HIV status , sociodemographic characteristics , risk behaviors , and AIDS‐associated symptoms . All subjects were offered confidential individual VTC at no cost . Methods : We compared users and nonusers of VTC among 10,950 participants ( 4764 male and 6186 female ) enrolled at baseline using multivariate logistic regression . Results : Women were significantly less likely to receive VTC than men ( 31.5 % vs. 34.8 % , p < .001 ) . In multivariate analysis , younger age , HIV‐positive status , and having no sexual partners in the past 5 years ( and , significant for women only , having 2 or more sexual partners ) were associated with lower VTC participation for both men and women . Among women , higher VTC participation was associated with symptoms suggestive of AIDS and other illnesses and shopkeeper occupations . Conclusions : During the initial phase of a population ‐based free VTC program in rural Ug and a , certain high‐risk groups were underrepresented among VTC recipients . There is a need to target VTC to ensure participation by high‐risk individuals most in need of services Introduction According to the 2011–2012 HIV and Malaria Indicator Survey , the prevalence of HIV infection in Tanzania is 5.1 % , with limited information on its magnitude among older people , as the community believes that the elderly are not at risk . Consequently , little attention is given to the fight against HIV and AIDS in this group . The present study investigated the magnitude of HIV and AIDS infection among older people in rural and urban areas of the Tanzania mainl and . Subjects and methods The study was conducted in Mufindi and Babati districts of Iringa and Manyara regions , respectively , through multistage sampling procedures . Dried blood spot cards were used to collect blood sample s for HIV testing among consenting participants . HIV testing was done and retested using different enzyme-linked immunosorbent assay kits . Results A total of 720 individuals , 340 ( 47.2 % ) males and 380 ( 52.8 % ) females , were r and omly selected , of whom 714 ( 99.2 % ) consented to HIV testing while six ( 0.8 % ) refused to donate blood . The age ranged from 50 to 98 years , with a mean age of 64.2 years . Overall , a total of 56 ( 7.8 % ) participants were HIV-positive . Females had a higher prevalence ( 8.3 % ) than males ( 7.4 % ) , with Mufindi district recording the higher rate ( 11.3 % ) compared to the 3.7 % of Babati district . The prevalence was higher in the rural population ( 9.4 % ) compared to 6.4 % of their urban counterparts . Conclusion Although HIV/AIDS is considered a disease of individuals aged 15–49 years , the overall prevalence among the older people aged 50 years and above for Mufindi and Babati districts was higher than the national prevalence in the general population . These findings point to the need to consider strengthening interventions targeting older population s against HIV/AIDS in these districts while establishing evidence countrywide to inform policy decisions BACKGROUND Access to HIV-1 voluntary counselling and testing ( VCT ) is severely limited in less-developed countries . We undertook a multisite trial of HIV-1 VCT to assess its impact , cost , and cost-effectiveness in less-developed country setting s. METHODS The cost-effectiveness of HIV-1 VCT was estimated for a hypothetical cohort of 10000 people seeking VCT in urban east Africa . Outcomes were modelled based on results from a r and omised controlled trial of HIV-1 VCT in Tanzania and Kenya . Our main outcome measures included programme cost , number of HIV-1 infections averted , cost per HIV-1 infection averted , and cost per disability-adjusted life-year ( DALY ) saved . We also modelled the impact of targeting VCT by HIV-1 prevalence of the client population , and the proportion of clients who receive VCT as a couple compared with as individuals . Sensitivity analysis was done on all model parameters . FINDINGS HIV-1 VCT was estimated to avert 1104 HIV-1 infections in Kenya and 895 in Tanzania during the subsequent year . The cost per HIV-1 infection averted was US$ 249 and $ 346 , respectively , and the cost per DALY saved was $ 12.77 and $ 17.78 . The intervention was most cost-effective for HIV-1-infected people and those who received VCT as a couple . The cost-effectiveness of VCT was robust , with a range for the average cost per DALY saved of $ 5.16 - 27.36 in Kenya , and $ 6.58 - 45.03 in Tanzania . Analysis of targeting showed that increasing the proportion of couples to 70 % reduces the cost per DALY saved to $ 10.71 in Kenya and $ 13.39 in Tanzania , and that targeting a population with HIV-1 prevalence of 45 % decreased the cost per DALY saved to $ 8.36 in Kenya and $ 11.74 in Tanzania . INTERPRETATION HIV-1 VCT is highly cost-effective in urban east African setting s , but slightly less so than interventions such as improvement of sexually transmitted disease services and universal provision of nevirapine to pregnant women in high-prevalence setting s. With the targeting of VCT to population s with high HIV-1 prevalence and couples the cost-effectiveness of VCT is improved significantly Objective : Due to high rates of undiagnosed and untreated HIV infection in Africa , we compared HIV counseling and testing ( VCT ) uptake among household members of patients receiving antiretroviral therapy . Methods : HIV-infected persons attending an AIDS clinic were r and omized to a home-based or clinic-based antiretroviral therapy program including VCT for household members . Clinic arm participants were given free VCT vouchers and encouraged to invite their household members to the clinic for VCT . Home arm participants were visited , and their household members offered VCT using a 3-test rapid finger-stick testing algorithm . VCT uptake and HIV prevalence were compared . Findings : Of 7184 household members , 3974 ( 55.3 % ) were female and 4798 ( 66.8 % ) were in the home arm . Home arm household members were more likely to receive VCT than those from the clinic arm ( 55.8 % vs. 10.9 % , odds ratio : 10.41 , 95 % confidence interval : 7.89 to 13.73 ; P < 0.001 ) , although the proportion of HIV-infected household members was higher in the clinic arm ( 17.3 % vs. 7.1 % , odds ratio : 2.76 , 95 % confidence interval : 1.97 to 3.86 , P < 0.001 ) . HIV prevalence among all household members tested in the home arm was 56 % compared with 27 % in the clinic arm . Of 148 spouses of HIV-infected patients , 69 ( 46.6 % ) were uninfected . Persons aged 15 - 24 were less likely to test than other age groups , and in the home arm , women were more likely to test than men . Conclusions : Home-based VCT for household members of HIV-infected persons was feasible , associated with lower prevalence , higher uptake , and increased identification of HIV-infected persons than clinic-based provision BACKGROUND Male circumcision could provide substantial protection against acquisition of HIV-1 infection . Our aim was to determine whether male circumcision had a protective effect against HIV infection , and to assess safety and changes in sexual behaviour related to this intervention . METHODS We did a r and omised controlled trial of 2784 men aged 18 - 24 years in Kisumu , Kenya . Men were r and omly assigned to an intervention group ( circumcision ; n=1391 ) or a control group ( delayed circumcision , 1393 ) , and assessed by HIV testing , medical examinations , and behavioural interviews during follow-ups at 1 , 3 , 6 , 12 , 18 , and 24 months . HIV seroincidence was estimated in an intention-to-treat analysis . This trial is registered with Clinical Trials.gov , with the number NCT00059371 . FINDINGS The trial was stopped early on December 12 , 2006 , after a third interim analysis review ed by the data and safety monitoring board . The median length of follow-up was 24 months . Follow-up for HIV status was incomplete for 240 ( 8.6 % ) participants . 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped . The 2-year HIV incidence was 2.1 % ( 95 % CI 1.2 - 3.0 ) in the circumcision group and 4.2 % ( 3.0 - 5.4 ) in the control group ( p=0.0065 ) ; the relative risk of HIV infection in circumcised men was 0.47 ( 0.28 - 0.78 ) , which corresponds to a reduction in the risk of acquiring an HIV infection of 53 % ( 22 - 72 ) . Adjusting for non-adherence to treatment and excluding four men found to be seropositive at enrollment , the protective effect of circumcision was 60 % ( 32 - 77 ) . Adverse events related to the intervention ( 21 events in 1.5 % of those circumcised ) resolved quickly . No behavioural risk compensation after circumcision was observed . INTERPRETATION Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa . Where appropriate , voluntary , safe , and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible Purpose To improve the slow uptake of HIV counseling and testing , the World Health Organization ( WHO ) and the Joint United Nations Programme on HIV/AIDS ( UNAIDS ) have developed draft guidelines on provider-initiated testing and counseling ( PITC ) . Both in low- and high-income countries , mainly from outpatient clinics and tuberculosis setting s , indicates that the direct offer of HIV testing by health providers can result in significant improvements in test uptake . In Ethiopia , there were limited numbers of studies conducted regarding PITC in outpatient clinics . Therefore , in this study , we have assessed the factors affecting the acceptance of PITC among outpatient clients in selected health facilities in Harar , Harari Region State , Ethiopia . Material s and methods Institutional-based , cross-sectional quantitative and qualitative studies were conducted from February 12–30 , 2011 in selected health facilities in Harar town , Harari Region State , Ethiopia . The study participants were recruited from the selected health facilities of Harar using a systematic r and om sampling technique . The collected data were double entered into a data entry file using Epi Info version 3.5.1 . The data were transferred to SPSS software version 16 and analyzed according to the different variables . Results A total of 362 ( 70.6 % ) clients accepted PITC , and only 39.4 % of clients had heard of PITC in the outpatient department service . Age , occupation , marital status , anyone who wanted to check their HIV status , and the importance of PITC were the variables that showed significant associations with the acceptance of PITC upon bivariate and multivariate analyses . The main reasons given for not accepting the tests were self-trust , not being at risk for HIV , not being ready , needing to consult their partners , a fear of the results , a shortage of staff , a busy work environment , a lack of private rooms , and a lack of refresher training , which were identified as the main barriers for PITC . Conclusion There is evidence of the relatively increased acceptability of PITC services by outpatient department clients . A program needs to be strengthened to enhance the use of PITC ; the Ministry of Health , Regional Health Bureau , and other responsible bodies – including health facilities – should design and strengthen information education and communication/behavioral change and communication interventions and promote activities related to PITC and HIV counseling and testing in both health facilities and the community at large BACKGROUND Although several interventions have shown reduced HIV incidence in clinical trials , the community-level effect of effective interventions on the epidemic when scaled up is unknown . We investigated whether a multicomponent , multilevel social and behavioural prevention strategy could reduce HIV incidence , increase HIV testing , reduce HIV risk behaviour , and change social and behavioural norms . METHODS For this phase 3 cluster-r and omised controlled trial , 34 communities in four sites in Africa and 14 communities in Thail and were r and omly allocated in matched pairs to receive 36 months of community-based voluntary counselling and testing for HIV ( intervention group ) or st and ard counselling and testing alone ( control group ) between January , 2001 , and December , 2011 . The intervention was design ed to make testing more accessible in communities , engage communities through outreach , and provide support services after testing . R and omisation was done by a computer-generated code and was not masked . Data were collected at baseline ( n=14 567 ) and after intervention ( n=56.683 ) by cross-sectional r and om surveys of community residents aged 18 - 32 years . The primary outcome was HIV incidence and was estimated with a cross-sectional multi-assay algorithm and antiretroviral drug screening assay . Thail and was excluded from incidence analyses because of low HIV prevalence . This trial is registered at Clinical Trials.gov , number NCT00203749 . FINDINGS The estimated incidence of HIV in the intervention group was 1.52 % versus 1.81 % in the control group with an estimated reduction in HIV incidence of 13.9 % ( relative risk [ RR ] 0.86 , 95 % CI 0.73 - 1.02 ; p=0.082 ) . HIV incidence was significantly reduced in women older than 24 years ( RR=0.70 , 0.54 - 0.90 ; p=0.0085 ) , but not in other age or sex subgroups . Community-based voluntary counselling and testing increased testing rates by 25 % overall ( 12 - 39 ; p=0.0003 ) , by 45 % ( 25 - 69 ; p<0·0001 ) in men and 15 % ( 3 - 28 ; p=0.013 ) in women . No overall effect on sexual risk behaviour was recorded . Social norms regarding HIV testing were improved by 6 % ( 95 % CI 3 - 9 ) in communities in the intervention group . INTERPRETATION These results are sufficiently robust , especially when taking into consideration the combined results of modest reductions in HIV incidence combined with increases in HIV testing and reductions in HIV risk behaviour , to recommend the Project Accept approach as an integral part of all interventions ( including treatment as prevention ) to reduce HIV transmission at the community level . FUNDING US National Institute of Mental Health , the Division of AIDS of the US National Institute of Allergy and Infectious Diseases , and the Office of AIDS Research of the US National Institutes of Health Background Timely diagnosis and treatment of tuberculosis ( TB ) and HIV is important to reduce morbidity and mortality , and break the cycle of ongoing transmission . Methods We performed an implementation research study to develop a model for systematic TB symptom screening and HIV counseling and testing ( HCT ) for all adult clients at a primary care clinic and prospect ively evaluate the 6-month coverage and yield , and 18-month sustainability at a primary care clinic in Johannesburg , South Africa . Results During the first 6 months , 26,515 visits occurred among 12,078 adults . The proportion of adults aware of their HIV status was 43.7 % at the start of the first visit , increased to 84.6 % at the end of the first visit , and to 90 % at end of any visit during the first 6 months . During these 6 months , 1042 clients were newly diagnosed with HIV . HIV prevalence was 22.9 % among those newly tested , and 58.9 % among all adult clinic clients . High coverage of systematic HCT was sustained across all 18 months . Coverage of systematic HIV-stratified TB symptom screening during first 6-months was also high ( 89.6 % ) but only 35.0 % of those symptomatic were screened by sputum . During these 6-months , 90 clients had a positive Xpert MTB/RIF assay , corresponding to a TB prevalence of 0.4 % among all 23,534 clients TB symptom-screened and 2.8 % among the 3,284 clients with a positive TB symptom screen . The initial high coverage of TB symptom screening was not sustained , with coverage of TB symptom screening dropping after the first six months to 70 % and assessment by sputum dropping to 15 % . Conclusion Routine , systematic HCT and HIV-stratified TB symptom screening is feasible at primary care level . Systematic HCT doubled the proportion of clients with known HIV status . While HCT was sustainable , coverage of systematic TB screening dropped significantly after the first 6 months of implementation Background We examined linkage to care for patients with sexually transmitted infection who were diagnosed HIV-positive via the provider-initiated HIV testing and counselling ( PITC ) approach , as compared to the voluntary counselling and testing ( VCT ) approach , as little is known about the impact of exp and ed testing strategies on linkage to care . Methods In a controlled trial on PITC ( Cape Town , 2007 ) , we compared HIV follow-up care for a nested cohort of 930 HIV-positive patients . We cross-referenced HIV testing and laboratory records to determine access to CD4 and viral load testing as primary outcomes . Secondary outcomes were HIV immune status and time taken to be linked to HIV care . Logistic regression was performed to analyse the difference between arms . Results There was no difference in the main outcomes of patients with a record of CD4 testing ( 69.9 % in the intervention , 65.2 % in control sites , OR 0.82 ( CI : 0.44 - 1.51 ; p = 0.526 ) and viral load testing ( 14.9 % intervention versus 10.9 % control arm ; OR 0.69 ( CI : 0.42 - 1.12 ; p = 0.131 ) . In the intervention arm , ART-eligible patients ( based on low CD4 test result ) , accessed viral load testing approximately 2.5 months sooner than those in the control arm ( 214 days vs. 288 days , HR : 0.417 , 95 % CI : 0.221 - 0.784 ; p = 0.007 ) . Conclusion The PITC intervention did not improve linkage to CD4 testing , but shortened the time to viral load testing for ART-eligible patients . Major gaps found in follow-up care across both arms , indicate the need for more effective linkage-to-HIV care strategies . Trial registration Current Controlled Trials IS RCT OBJECTIVES To assess the age and gender differences of clients accessing mobile HIV counselling and testing ( HCT ) compared with clients accessing facility-based testing , and to determine the difference in HIV prevalence and baseline CD4 counts . METHODS This was a prospect i ve observational cross-sectional study of 3 different HIV testing services in Cape Town . We compared data on age , sex , HIV status and CD4 counts collected between August and December 2008 from a mobile testing service ( known as the Tutu Tester ) , a primary health care clinic , and a district hospital . RESULTS A total of 3 820 individuals were tested : 2 499 at the mobile , 657 at the clinic , and 664 at the hospital . Age and sex distribution differed across services , with the mobile testing more men and older individuals . HIV prevalence was lowest at the mobile ( 5.9 % ) compared with the clinic ( 18.0 % ) and hospital ( 23.3 % ) . Of the HIV-infected individuals from the mobile service , 75 % had a CD4 count higher than 350 cells/µl compared with 48 % and 32 % respectively at the clinic and hospital . Age- and sex-adjusted risk for HIV positivity was 3.5 and 4.9 times higher in the clinic-based and hospital-based services compared with the mobile service . CONCLUSION Mobile services are accessed by a different population compared with facility-based services . Mobile service clients were more likely to be male and less likely to be HIV-positive , and those infected presented with earlier disease Objective : To explore the role of primary health centers in provision of voluntary counseling and testing ( VCT ) in Kenya . Design and Setting : Prospect i ve service evaluation at 3 ( 1 urban and 2 rural ) government health centers . Subjects : Consecutive adult clients . Main Outcome Measures : Uptake of services , user characteristics , quality of service . Results : Counseling services received 2315 new clients over 26 months . The last quarter averaged 101 clients per clinic . More than 80 % of clients lived locally . Overall 93 % opted to test , 91 % receiving results , 82 % on the same day . Most clients tested HIV negative ( 81 % ) . Youth and men were well represented . Few couples ( 10 % ) attended . Seventeen percent of women were pregnant . Self-referral was common and illness was an uncommon reason for testing ( < 20 % ) . Thirty-one percent of clients were referred from VCT to other health center services . Counseling was perceived as high quality by users and providers . Validation of the test algorithm showed a sensitivity of 98.0 % and specificity of 98.7 % . Conclusion : Government health centers in Kenya can be appropriate providers of VCT . This pilot helped initiate a new strategy of health center-based VCT in Kenya and this has facilitated rapid expansion and more equitable provision for Kenyans Background : Experimental evidence has shown that treatment of HIV infection with antiretroviral therapy ( ART ) prevents heterosexual transmission of HIV to an uninfected partner . However , the “ real-world ” application of this strategy to key population s such as men who have sex with men ( MSM ) has been limited . We report findings on acceptability of a treatment as prevention ( TasP ) strategy among HIV-infected MSM at a Trusted Community Center providing comprehensive HIV prevention and treatment services to MSM in Abuja , Nigeria . Methods : Using respondent-driven sampling ( RDS ) , MSM who were 16 years and older and have engaged in either receptive or insertive anal intercourse within the previous 12 months were recruited into a prospect i ve combination HIV prevention and treatment study ( TRUST ) . Two weeks after enrollment , HIV testing and counseling was conducted . At each 3-month follow-up visits , HIV-infected individuals underwent clinical and laboratory evaluation , including CD4 count , plasma HIV viral load , immediate 3 weekly sessions of ART preparation , and then ART initiation per TasP strategy irrespective of CD4 count . Reasons for not engaging in pre-TasP preparation and TasP were documented . Characteristics associated with TasP engagement and loss to follow-up ( LTFU ) were determined using logistic and Cox regression , respectively . Results : Of 186 HIV-positive MSM enrolled , 58 ( 31.2 % ) were on ART at the time of recruitment , whereas 128 ( 68.8 % ) were ART-naive and provided opportunity for engaging TasP. Of these , 70 ( 54.7 % ) engaged in TasP. Compared with MSM who did not engage in TasP , those who engaged had significantly lower mean CD4 count ( P = 0.001 ) , were more likely to be Christian ( P = 0.01 ) , and had disclosed being MSM to family ( P = 0.02 ) or health care providers ( P = 0.02 ) . In multivariate models , disclosure of being MSM to health care providers remained significantly associated with uptake of TasP. Among individuals engaged in TasP , 10 % were LTFU in care at 18 months since enrollment . Being engaged in TasP ( relative hazards = 0.08 , P < 0.001 ) and on ART ( relative hazards = 0.17 , P < 0.001 ) were associated with decreased risk of LTFU . Conclusions : Although there was high acceptance of HIV testing and low LTFU among individuals who were already on ART or engaged in TasP , a higher than expected proportion did not engage in TasP , suggesting the need for customized treatment preparation and an increase in enabling environments to support HIV treatment access with this key population Background Antiretroviral therapy ( ART ) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission . It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level . This trial aims to evaluate the effect of ART initiated immediately after identification /diagnosis of HIV-infected individuals , regardless of CD4 count , on HIV incidence in the surrounding population . The primary outcome of the overall trial will be HIV incidence over two years . Secondary outcomes will include i ) socio-behavioural outcomes ( acceptability of repeat HIV counselling and testing , treatment acceptance and linkage to care , sexual partnerships and quality of life ) ; ii ) clinical outcomes ( mortality and morbidity , retention into care , adherence to ART , virologic failure and acquired HIV drug resistance ) , iii ) cost-effectiveness of the intervention . The first phase will specifically focus on the trial ’s secondary outcomes . Methods / design A cluster-r and omised trial in 34 ( 2 × 17 ) clusters within a rural area of northern KwaZulu-Natal ( South Africa ) , covering a total population of 34,000 inhabitants aged 16 years and above , of whom an estimated 27,200 would be HIV-uninfected at start of the trial . The first phase of the trial will include ten ( 2 × 5 ) clusters . Consecutive rounds of home-based HIV testing will be carried out . HIV-infected participants will be followed in dedicated trial clinics : in intervention clusters , they will be offered immediate ART initiation regardless of CD4 count and clinical stage ; in control clusters they will be offered ART according to national treatment eligibility guidelines ( CD4 < 350 cells/μL , World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis ) . Following proof of acceptability and feasibility from the first phase , the trial will be rolled out to further clusters . Discussion We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level . Data collected from the participants at home and in the clinics will inform underst and ing of socio-behavioural , economic and clinical impacts of the intervention as well as feasibility and generalizability . Trial registration Clinical trials.gov : NCT01509508 ; South African Trial Register : DOH-27 - 0512 - 3974 Background Underst and ing the epidemiological HIV context is critical in building effective setting -specific preventive strategies . We examined HIV prevalence patterns in selected communities of men and women aged 15–59 years in Zambia . Methods Population -based HIV surveys in 1995 ( n = 3158 ) , 1999 ( n = 3731 ) and 2003 ( n = 4751 ) were conducted in selected communities using probability proportional to size stratified r and om-cluster sampling . Multivariate logistic regression and trend analyses were stratified by residence , sex and age group . Absence , < 30 % in men and < 15 % in women in all rounds , was the most important cause of non-response . Saliva was used for HIV testing , and refusal was < 10 % . Results Among rural groups aged 15–24 years , prevalence declined by 59.2 % ( 15.7 % to 6.4 % , P < 0.001 ) in females and by 44.6 % ( 5.6 % to 3.1 % , P < 0.001 ) in males . In age-group 15–49 years , declines were less than 25 % . In the urban groups aged 15–24 , prevalence declined by 47 % ( 23.4 % to 12.4 % , P < 0.001 ) among females and 57.3 % ( 7.5 % to 3.2 % , P = 0.001 ) among males but were 32 % and 27 % in men and women aged 15–49 , respectively . Higher educated young people in 2003 had lower odds of infection than in 1995 in both urban [ men : AOR 0.29(95%CI 0.14–0.60 ) ; women : AOR 0.38(95%CI 0.19–0.79 ) ] and rural groups [ men : AOR 0.16(95%CI 0.11–0.25 ) , women : AOR 0.10(95%CI 0.01–7.34 ) ] . Although higher mobility was associated with increased likelihood of infection in men overall , AOR , 1.71(95%CI 1.34–2.19 ) , prevalence declined in mobile groups also ( OR 0.52 95%CI 0.31–0.88 ) . In parallel , urban young people with ≥11 school years were more likely to use condoms during the last casual sex ( OR 2.96 95%CI 1.93–4.52 ) and report less number of casual sexual partners ( AOR 0.33 95%CI 0.19–0.56 ) in the last twelve months than lower educated groups . ConclusionS teep HIV prevalence declines in young people , suggesting continuing declining incidence , were masked by modest overall declines . The concentration of declines in higher educated groups suggests a plausible association with behavioural change BACKGROUND We conducted a prospect i ve study to evaluate methods of detecting clients with sexually transmitted diseases ( STDs ) who were acutely coinfected with human immunodeficiency virus ( HIV ) in Lilongwe , Malawi . METHODS After informed consent was obtained , all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests . Sample s from rapid test-negative or -discordant subjects were pooled ( 50 : 5 : 1 ) and tested for HIV RNA . Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA . A subset of specimens received p24 antigen testing with st and ard and /or ultrasensitive methods . Patients with possible acute HIV infection were followed to confirm seroconversion . RESULTS A total of 1450 clients ( 34 % female and 66 % male ) agreed to testing , of whom 588 ( 40.55 % ) had established HIV infection and 21 ( 1.45 % ) had acute infection . Discordant rapid antibody tests identified 7 of 21 ( 33.3 % sensitivity ) , st and ard p24 antigen identified 12 of 16 ( 75 % sensitivity ) , and ultrasensitive p24 antigen identified 15 of 17 ( 88 % sensitivity ) acute cases . By definition , the sensitivity of the RNA assay was 100 % . CONCLUSIONS Real-time pooled RNA testing for the detection of acute HIV infection is feasible in re source -limited setting s. However , parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90 % of acute cases Introduction Routine provider-initiated HIV testing and counselling ( PITC ) may increase HIV testing rates , but whether PITC is acceptable to health facility ( HF ) attendees is unclear . In the course of a PITC intervention study in Rw and a , we assessed the acceptability of PITC , reasons for being or not being tested and factors associated with HIV testing . Methods Attendees were systematic ally interviewed in March 2009 as they left the HF , regarding knowledge and acceptability of PITC , history of testing and reasons for being tested or not . Subsequently , PITC was introduced in 6 of the 8 HFs and a second round of interviews was conducted . Independent factors associated with testing were analysed using logistic regression . R and omly selected health care workers ( HCWs ) were also interviewed . Results 1772 attendees were interviewed . Over 95 % agreed with the PITC policy , both prior to and after implementation of PITC policy . The most common reasons for testing were the desire to know one ’s HIV status and having been offered an HIV test by an HCW . The most frequent reasons for not being tested were known HIV status and test not being offered . In multivariable analysis , PITC , age ≥15 years , and not having been previously tested were factors significantly associated with testing . Although workload was increased by PITC , HIV testing rates increased and HCWs overwhelmingly supported the policy . Conclusion Among attendees and HCWs in Rw and an clinics , the acceptability of PITC was very high . PITC appeared to increase testing rates and may be helpful in prevention and early access to treatment RATIONALE South Africa has a high prevalence of tuberculosis ( TB ) and HIV-coinfected adults in whom TB is often diagnosed late in the course of disease . OBJECTIVES Improved case-finding approaches for TB and HIV are needed to reduce mortality and prevent transmission . METHODS We identified newly diagnosed index TB cases in a rural district and enrolled their households in a TB-HIV contact-tracing study . A group of r and omly selected control households were enrolled to determine community prevalence of undetected TB and HIV . Field teams screened participants for TB symptoms , collected sputum specimens for smear microscopy and culture , provided HIV counseling and testing , and collected blood for CD4 testing . Participants were referred to public clinics for TB treatment and antiretroviral therapy . MEASUREMENTS AND MAIN RESULTS We evaluated 2,843 household contacts of 727 index patients with TB and 983 r and omly selected control household members . The prevalence of TB in household contacts was 6,075 per 100,000 ( 95 % confidence interval , 5,789 - 6,360 per 100,000 ) , whereas the prevalence detected in r and omly selected households was 407 per 100,000 ( 95 % confidence interval , 0 - 912 per 100,000 ; prevalence difference , 5,668 per 100,000 ; P < 0.001 ) . TB detected among contacts was less likely to be smear-positive than in the index patients ( 6 % vs. 22 % ; P < 0.001 ) . Most contacts with culture-confirmed TB were asymptomatic . At least one case of undiagnosed TB was found in 141 ( 19 % ) of 727 contact versus 4 ( 1 % ) of 312 control households . HIV testing was positive in 166 ( 11 % ) of 1,568 contacts tested versus 76 ( 14 % ) of 521 control participants tested ( odds ratio , 1.48 ; P = 0.02 ) . CONCLUSIONS Active case finding in TB contact households should be considered to improve TB and HIV case detection in high-prevalence setting s , but sensitive diagnostic tools are necessary Objective : To evaluate the yield of a routine voluntary HIV testing program compared with traditional provider-referred voluntary counseling and testing ( VCT ) in a hospital-affiliated outpatient department ( OPD ) in Durban , South Africa . Design and Methods : In a prospect i ve 14-week “ st and ard of care ” period , we compared OPD physician logs documenting patient referrals to the hospital VCT site with HIV test registers to measure patient completion of HIV test referral . The st and ard of care period was followed by a 12-week intervention during which all patients who registered at the OPD were given an educational intervention and offered a rapid HIV test at no charge as part of routine care . Results : During the st and ard of care period , OPD physicians referred 435 patients aged ≥18 years for HIV testing ; 137 ( 31.5 % ) of the referred patients completed testing at the VCT site within 4 weeks . Among those tested , 102 ( 74.5 % ) were HIV infected . During the intervention period , 1414 adults accepted HIV testing and 1498 declined . Of those tested , 463 ( 32.7 % , 95 % confidence interval : 30.3 to 35.3 ) were HIV infected . Routine HIV testing in the OPD identified 39 new HIV cases per week compared with 8 new cases per week with st and ard of care testing based on physician referral to a VCT site ( P < 0.0001 ) . Conclusions : Routine voluntary HIV testing in an OPD in South Africa leads to significantly higher rates of detection of HIV disease . This strategy should be implemented more widely in high HIV prevalence areas where treatment is available OBJECTIVE The aim of the study was to compare the yields of newly diagnosed cases of HIV infection and advanced immunodeficiency between individuals attending a mobile HIV counselling and testing ( HCT ) service as participants in a population -based HIV seroprevalence survey and those accessing the same service as volunteers for routine testing . METHODS The study was conducted in a peri-urban township within the Cape Metropolitan Region , South Africa . Survey participants ( recruited testers ) were r and omly selected , visited at home and invited to attend the mobile HCT service . They received 70 South African R and food vouchers for participating in the survey , but could choose to test anonymously . The yield of HIV diagnoses was compared with that detected in members of the community who voluntarily attended the same HIV testing facility prior to the survey and did not receive incentives ( voluntary testers ) . RESULTS A total of 1813 individuals were included in the analysis ( 936 recruited and 877 voluntary testers ) . The prevalence of newly diagnosed HIV infection was 10.9 % [ 95 % confidence interval ( CI ) 9.0 - 13.1 % ] among recruited testers and 5.0 % ( 3.7 - 6.7 % ) among voluntary testers . The prevalence of severe immune deficiency ( CD4 count ≤ 200 cells/ μL ) among recruited and voluntary testers was 17.8 % ( 10.9 - 26.7 % ) and 4.6 % ( 0.0 - 15.4 % ) , respectively . Linkage to HIV care in recruited testers with CD4 counts ≤ 350 cells/ μL was 78.8 % . CONCLUSION Compared with routine voluntary HCT , selection and invitation in combination with incentives doubled the yield of newly diagnosed HIV infections and increased the yield almost fourfold of individuals needing antiretroviral therapy . This may be an important strategy to increase community-based HIV diagnosis and access to care Abstract : The optimal approach of provider-initiated HIV testing and counseling ( PITC ) for in patients in high-burden setting s is unknown . We prospect ively evaluated the implementation of task shifting from clinician-referral to counselor-initiated PITC on the medical wards of Kamuzu Central Hospital , Malawi . Most of patients ( 1905/3154 , 60.4 % ) had an unknown admission HIV status . Counselors offered testing to 66.6 % ( 1268/1905 ) . HIV prevalence was 39.3 % . Counselor-initiated PITC significantly increased HIV testing by 79 % ( 643/2957 vs. 1228/3154 ) , result ing in an almost 2-fold increase in patients with known HIV status ( 2447/3154 vs. 1249/3154 ) ( both P < 0.0001 ) , with 18.4 % of those tested receiving a new diagnosis of HIV OBJECTIVE Antiretroviral therapy ( ART ) significantly decreases HIV-associated morbidity , mortality , and HIV transmission through HIV viral load suppression . In high HIV prevalence setting s , outreach strategies are needed to find asymptomatic HIV positive persons , link them to HIV care and ART , and achieve viral suppression . METHODS We conducted a prospect i ve intervention study in two rural communities in KwaZulu-Natal , South Africa , and Mbabara district , Ug and a. The intervention included home HIV testing and counseling ( HTC ) , point-of-care CD4 count testing for HIV positive persons , referral to care , and one month then quarterly lay counselor follow-up visits . The outcomes at 12 months were linkage to care , and ART initiation and viral suppression among HIV positive persons eligible for ART ( CD4≤350 cells/μL ) . FINDINGS 3,393 adults were tested for HIV ( 96 % coverage ) , of whom 635 ( 19 % ) were HIV positive . At baseline , 36 % of HIV positive persons were newly identified ( 64 % were previously known to be HIV positive ) and 40 % were taking ART . By month 12 , 619 ( 97 % ) of HIV positive persons visited an HIV clinic , and of 123 ART eligible participants , 94 ( 76 % ) initiated ART by 12 months . Of the 77 participants on ART by month 9 , 59 ( 77 % ) achieved viral suppression by month 12 . Among all HIV positive persons , the proportion with viral suppression ( < 1,000 copies/mL ) increased from 50 % to 65 % ( p=<0.001 ) at 12 months . INTERPRETATION Community-based HTC in rural South Africa and Ug and a achieved high testing coverage and linkage to care . Among those eligible for ART , a high proportion initiated ART and achieved viral suppression , indicating high adherence . Implementation of this HTC approach by existing community health workers in Africa should be evaluated to determine effectiveness and costs Background : Sexual partners of persons with newly diagnosed HIV infection require HIV counseling , testing and , if necessary , evaluation for therapy . However , many African countries do not have a st and ardized protocol for partner notification , and the effectiveness of partner notification has not been evaluated in developing countries . Methods : Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe , Malawi , were r and omized to 1 of 3 methods of partner notification : passive referral , contract referral , or provider referral . The passive referral group was responsible for notifying their partners themselves . The contract referral group was given seven days to notify their partners , after which a health care provider contacted partners who had not reported for counseling and testing . In the provider referral group , a health care provider notified partners directly . Results : Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252 . Among locatable partners , 107 returned for HIV counseling and testing ; 20 of 82 [ 24 % ; 95 % confidence interval ( CI ) : 15 % to 34 % ] partners returned in the passive referral arm , 45 of 88 ( 51 % ; 95 % CI : 41 % to 62 % ) in the contract referral arm , and 42 of 82 ( 51 % ; 95 % CI : 40 % to 62 % ) in the provider referral arm ( P < 0.001 ) . Among returning partners ( n = 107 ) , 67 ( 64 % ) of were HIV infected with 54 ( 81 % ) newly diagnosed . Discussion : This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa . Active partner notification was feasible , acceptable , and effective among sexually transmitted infections clinic patients . Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners Home-based voluntary HIV counselling and testing ( HB-VCT ) has been reported to have a high uptake , but it has not been rigorously evaluated . We design ed a model for HB-VCT appropriate for wider scale-up , and investigated the acceptance of home-based counselling and testing , equity in uptake and negative life events with a cluster-r and omized trial . Thirty six rural clusters in southern Zambia were pair-matched based on baseline data and r and omly assigned to the intervention or the control arm . Both arms had access to st and ard HIV testing services . Adults in the intervention clusters were offered HB-VCT by local lay counsellors . Effects were first analysed among those participating in the baseline and post-intervention surveys and then as intention-to-treat analysis . The study was registered with www.controlled-trials.com , number IS RCT N53353725 . A total of 836 and 858 adults were assigned to the intervention and control clusters , respectively . In the intervention arm , counselling was accepted by 85 % and 66 % were tested ( n = 686 ) . Among counselled respondents who were cohabiting with the partner , 62 % were counselled together with the partner . At follow-up eight months later , the proportion of adults reporting to have been tested the year prior to follow-up was 82 % in the intervention arm and 52 % in the control arm ( Relative Risk ( RR ) 1.6 , 95 % CI 1.4 - 1.8 ) , whereas the RR was 1.7 ( 1.4 - 2.0 ) according to the intention-to-treat analysis . At baseline the likelihood of being tested was higher for women vs. men and for more educated people . At follow-up these differences were found only in the control communities . Measured negative life events following HIV testing were similar in both groups . In conclusion , this HB-VCT model was found to be feasible , with a very high acceptance and to have important equity effects . The high couple counselling acceptance suggests that the home-based approach has a particularly high HIV prevention potential Background : We investigated HIV testing practice s at baseline among pregnant women and their partners within a multicountry r and omized trial aim ing to evaluate the effect of enhanced prenatal posttest HIV counseling on men 's involvement . Methods : In Yaoundé , Cameroon , 484 pregnant women with stable partners were recruited on their first antenatal care visit . We analyzed the coverage of previous HIV testing among women and their partners and looked for the factors associated with previous HIV testing , using multivariable logistic regression . Results : Among 476 pregnant women who completed the baseline question naire , 408 ( 85.7 % ) reported having been tested for HIV already once in their life , 48.3 % of them during a previous pregnancy . Women previously tested for HIV were more likely to be in a stable relationship for > 5 years than those never tested ( P < 0.001 ) . In multivariable analysis , tested women were more likely to be aged between 25 and 30 years compared with women < 20 years [ odds ratio ( OR ) 5.5 , 95 % confidence interval ( CI ) : 1.4 to 22.1 ] , to be able to say whether they felt at risk for HIV infection ( OR 2.1 , CI : 1.1 to 3.9 ) , and to have ever discussed about HIV with their partner ( OR 2.7 , CI : 1.1 to 6.4 ) . Most women ( 85.1 % ) reported that their partner had already been tested for HIV . Reasons for partner HIV testing were related to self-motivation ( 30.0 % ) and clinical symptoms ( 12.7 % ) . Conclusions : Strategies aim ing at improving knowledge and couple communication about HIV risks need to be considered to address the remaining barriers to HIV testing and contribute to a couple approach to HIV prevention The objective of this study is to describe HIV-testing among men in rural Lusaka Province , Zambia , using a population -based survey for a cluster-r and omized trial . Households ( N = 120 ) were r and omly selected from each of the 42 clusters , defined as a health facility catchment area . Individuals aged 15–60 years were invited to complete question naires regarding demographics and HIV-testing history . Men testing in the last year were defined as recent-testers . After question naire completion adults were offered home-based rapid HIV-testing . Of the 2,828 men , 53 % reported ever-testing and 25 % recently-testing . Factors independently associated with ever- and recent-testing included age 20 + years , secondary /higher education , being married or widowed , a history of TB-treatment and higher socioeconomic position . 53 % of never-testers and 57 % of men who did not report a recent-test accepted home-based HIV-testing . Current HIV-testing approaches are inadequate in this high prevalence setting . Alternative strategies , including self-testing , mobile- or workplace-testing , may be required to complement facility-based services Background : Routine opt-out provider-initiated HIV testing and counseling ( PITC ) remains underutilized in sub-Saharan Africa . By selectively targeting clients who either volunteer or have clinical indications of HIV disease , st and ard approaches to HIV counseling and testing are presumed more cost-efficient than PITC . Methods : One thous and two hundred twenty-one patients aged 15 - 49 years were seen by 22 practitioners in a mobile clinic in southern Zambia . A r and om sample of physicians was assigned to administer PITC , whereas the remaining practitioners offered st and ard non-PITC ( ie , voluntary or diagnostic ) . Question naires assessed patient demographics and attitudes toward HIV . HIV detection rates were stratified by referral type , demographics , and HIV-related knowledge and attitudes . Results : HIV prevalence was 10.6 % . Infection rates detected using PITC [ 11.1 % ; 95 % confidence interval ( CI ) : 8.8 % to 13.5 % ] and st and ard non-PITC ( 10.0 % ; 95 % CI : 7.5 % to 12.5 % ) did not significantly differ ( odds ratio = 1.01 ; 95 % CI : 0.67 to 1.52 ; P = 0.95 ) . Patients who did not request testing or demonstrate clinical indicators of HIV did not have significantly higher HIV prevalence than those who did ( odds ratio = 0.83 ; 95 % CI : 0.55 to 1.24 ; P = 0.36 ) . Implementation of PITC was highly acceptable and produced a 3-fold increase in patients tested per practitioner compared with st and ard non-PITC ( 114 vs. 34 patients per practitioner , respectively ) . Conclusions : PITC detected a comparable HIV infection rate as a st and ard non-PITC approach among rural adults seeking primary care services . Widespread implementation of PITC may therefore lead to significantly more cases of HIV detected OBJECTIVES To describe the methodology used in a recent survey of HIV/AIDS in South Africa and to present the response rates . METHODS A cross-sectional , national household-based survey was conducted using second-generation surveillance procedures . A complex multistage sampling technique was used to create a master sample of 1,000 census enumerator areas out of a total of 86,000 nationally . Aerial photographs were taken and used to r and omly select more than 10,197 households and ultimately 13,518 individuals from a sampling frame of 31,321 people . Phase 1 of the study involved notifying the household residents about the study and collecting key demographic information on respondents aged 2 years and older . This information was used to r and omly select up to 3 respondents from each household : 1 adult ( 25 years and older ) , 1 youth ( 15 - 24 years ) , and 1 child ( 2 - 14 years ) . In phase 2 nurses interviewed respondents and collected oral fluid specimens for HIV testing . In the case of children aged 2 - 11 years , parents or guardians were interviewed , but HIV testing was performed on the selected children . Question naire data were anonymously linked with HIV test results . RESULTS A total of 9,963 persons agreed to be interviewed and 8,840 were tested for HIV , yielding a response rate of 73.7 % and 65.4 % respectively . However , only 8,428 ( 62.3 % ) HIV test results were correctly matched with behavioural data . The results showed that those tested for HIV did not differ from those not tested in terms of key determinants . CONCLUSION It is possible to use community-based surveys to study the prevalence of HIV in the general population Provider-initiated routine HIV testing is being scaled up throughout the world , however , little is known about the outcomes of routine HIV testing on subsequent behavior . This study examined the initial outcomes of provider-initiated routine HIV testing at a rural Ug and an hospital regarding partner HIV testing , sexual risk behavior , disclosure , and HIV care seeking . In a prospect i ve cohort study , 245 out patients receiving routine HIV testing completed baseline and 3-month follow-up interviews . After receiving routine HIV testing the percentage of participants engaging in risky sex decreased from 70.1 % to 50.3 % among HIV-negative and from 75.0 % to 53.5 % among HIV-positive participants , the percentage knowing their partner(s ) ' HIV status increased from 18.7 % to 34.3 % of HIV-negative and from 14.3 % to 35.7 % of HIV-positive participants . Among those reporting risky sex at baseline , HIV-positive participants were more likely to eliminate risky sex in general and specifically to become abstinent at follow-up than were HIV-negative participants . Similarly , unmarried participants who were risky at baseline were more likely to become safe in general , become abstinent , and start 100 % condom use than were married/cohabitating participants . Rates of disclosure were high . Over 85 % of those who tested HIV positive enrolled in care . Routine HIV testing in this setting may promote earlier HIV diagnosis and access to care but leads to only modest reductions in risky sexual behavior . To fully realize the potential HIV prevention benefits of routine HIV testing an emphasis on tailored risk-reduction counseling may be necessary BACKGROUND In developing countries , most people infected with HIV do not know their infection status . We aim ed to assess whether HIV testing could be increased by combination of community mobilisation , mobile community-based voluntary counselling and testing ( VCT ) , and support after testing . METHODS Project Accept is underway in ten communities in Tanzania , eight in Zimbabwe , and 14 in Thail and . Communities at each site were paired according to similar demographic and environmental characteristics , and one community from each pair was r and omly assigned to receive st and ard clinic-based VCT ( SVCT ) , and the other community was assigned to receive community-based VCT ( CBVCT ) plus access to SVCT . R and omisation and assignment of communities to intervention groups was done by the statistics centre by computer ; no one was masked to treatment assignment because the interventions were community based . Intervention was provided for about 3 years ( 2006 - 09 ) . The primary endpoint of HIV incidence is pending completion of assessment s after the intervention . In this interim analysis , we examined the secondary endpoint of uptake in HIV testing , differences in characteristics of clients receiving their first HIV test , and repeat testing . Analyses were limited to clients aged 16 - 32 years . This study is registered with Clinical Trials.gov , number NCT00203749 . FINDINGS The proportion of clients receiving their first HIV test during the study was higher in CBVCT communities than in SVCT communities in Tanzania ( 2341 [ 37 % ] of 6250 vs 579 [ 9 % ] of 6733 ) , Zimbabwe ( 5437 [ 51 % ] of 10,700 vs 602 [ 5 % ] of 12,150 ) , and Thail and ( 7802 [ 69 % ] of 11,290 vs 2319 [ 23 % ] 10,033 ) . The mean difference in the proportion of clients receiving HIV testing between CBVCT and SVCT communities was 40·2 % ( 95 % CI 15·8 - 64·7 ; p=0·019 ) across three community pairs ( one per country ) . HIV prevalence was higher in SVCT communities than in CBVCT communities , but CBVCT detected almost four times more HIV cases than did SVCT across the three study sites ( 952 vs 264 ; p=0·003 ) . Repeat HIV testing in CBVCT communities increased in all sites to reach 28 % of all those testing for HIV by the end of the intervention period . INTERPRETATION CBVCT should be considered as a viable intervention to increase detection of HIV infection , especially in regions with restricted access to clinic-based VCT and support services after testing . FUNDING US National Institute of Mental Health , HIV Prevention Trials Network ( via US National Institute of Allergy and Infectious Diseases ) , and US National Institutes of Health Background The linkage and barriers of linkage to facility-based HIV care from a mobile HIV testing unit have not previously been described . Methods A stratified r and om sample ( N = 192 ) was drawn of all eligible , newly diagnosed , HIV-infected individuals with a laboratory CD4 count result on a mobile unit between August 2008 and December 2009 . All individuals with CD4 counts ⩽350 cells per microliter and 30 % of individuals with CD4 counts > 350 cells per microliter were sample d. Linkage to care was assessed during April to June 2010 in those who received their CD4 count result . A participant who accessed HIV care at least once after testing was regarded as having linked to care . Binomial regression models were used to identify clinical and socio-demographic factors associated with receiving a CD4 count result and linking to care . Results Forty-three ( 27 % ) individuals did not receive their CD4 count result . A lower CD4 count , being female , and the availability of a phone number increased the likelihood of receiving this result . Follow-up was attempted in the remaining 145 individuals . Ten refused to participate , and contact was unsuccessful in 42.4 % . Linkage was 100 % in patients with CD4 counts ⩽200 cells per microliter , 66.7 % in individuals with CD4 counts 201–350 cells per microliter , and 36.4 % in those with CD4 counts > 350 cells per microliter . A lower CD4 count , disclosure , symptoms of tuberculosis , and unemployment increased the likelihood of linking to care . Conclusion Linkage to care was best among those eligible for antiretroviral therapy . Interventions design ed at improving linkage among employed individuals are urgently warranted OBJECTIVES To examine factors affecting readiness for and acceptability of voluntary HIV counselling and testing ( VCT ) . METHODS Participants in a population -based HIV survey conducted in an urban population in Zambia in 1996 were offered VCT . Although 29 % of them expressed interest in being tested ( readiness ) , only 4 % of this group used the services ( i.e. acceptability ) . When the survey was repeated 3 years later , VCT was design ed differently to assess acceptability . At the cluster level the participants were r and omly allocated to VCT either at the local clinic ( similar to 1996 , n = 1102 ) or at an optional location ( n = 1343 ) . RESULTS Readiness varied significantly by age group ( 47 % in age group 20 - 24 years vs. 18 % in age group 40 - 49 years ) . There were contrasts between young ( 15 - 24 years ) and older age groups ( 25 - 49 years ) regarding the main factors associated with readiness . Whereas self-perceived risk of being HIV infected was the only significant factor among the young , poor self-rated health and ever HIV tested were important factors among the older . The acceptability was 11.8 % among the group allocated to VCT at the local clinic compared with 55.8 % for the group allocated to an optional location ( RR , 4.7 ) . CONCLUSIONS Perceived risk of HIV infection had a major influence on VCT readiness among young people , whereas declining general health status , as indicated by self-rated health , was most evident among those of older age . A strong effect of placement on acceptability of VCT was demonstrated , indicating this barrier to be important in explaining low dem and s for VCT in the past . Differences in perceptions of how confidentiality is h and led at the two locations might be an important underlying factor Objective To assess the effect of home based HIV counselling and testing on the prevalence of HIV testing and reported behavioural changes in a rural subdistrict of South Africa . Design Cluster r and omised controlled trial . Setting 16 communities ( clusters ) in uMzimkhulu subdistrict , KwaZulu-Natal province , South Africa . Participants 4154 people aged 14 years or more who participated in a community survey . Intervention Lay counsellors conducted door to door outreach and offered home based HIV counselling and testing to all consenting adults and adolescents aged 14 - 17 years with guardian consent . Control clusters received st and ard care , which consisted of HIV counselling and testing services at local clinics . Main outcome measures Primary outcome measure was prevalence of testing for HIV . Other outcomes were HIV awareness , stigma , sexual behaviour , vulnerability to violence , and access to care . Results Overall , 69 % of participants in the home based HIV counselling and testing arm versus 47 % in the control arm were tested for HIV during the study period ( prevalence ratio 1.54 , 95 % confidence interval 1.32 to 1.81 ) . More couples in the intervention arm had counselling and testing together than in the control arm ( 2.24 , 1.49 to 3.03 ) . The intervention had broader effects beyond HIV testing , with a 55 % reduction in multiple partners ( 0.45 , 0.33 to 0.62 ) and a stronger effect among those who had an HIV test ( 0.37 , 0.24 to 0.58 ) and a 45 % reduction in casual sexual partners ( 0.55 , 0.42 to 0.73 ) . Conclusions Home based HIV counselling and testing increased the prevalence of HIV testing in a rural setting with high levels of stigma . Benefits also included higher uptake of couple counselling and testing and reduced sexual risk behaviour . Trial registration Current Controlled Trials IS RCT N31271935 IMPORTANCE Self-testing for HIV infection may contribute to early diagnosis of HIV , but without necessarily increasing antiretroviral therapy ( ART ) initiation . OBJECTIVE To investigate whether offering optional home initiation of HIV care after HIV self-testing might increase dem and for ART initiation , compared with HIV self-testing accompanied by facility-based services only . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized trial conducted in Blantyre , Malawi , between January 30 and November 5 , 2012 , using restricted 1:1 r and omization of 14 community health worker catchment areas . Participants were all adult ( ≥16 years ) residents ( n = 16,660 ) who received access to home HIV self-testing through resident volunteers . This was a second-stage r and omization of clusters allocated to the HIV self-testing group of a parent trial . INTERVENTIONS Clusters were r and omly allocated to facility-based care or optional home initiation of HIV care ( including 2 weeks of ART if eligible ) for participants reporting positive HIV self-test results . MAIN OUTCOMES AND MEASURES The preplanned primary outcome compared between groups the proportion of all adult residents who initiated ART within the first 6 months of HIV self-testing availability . Secondary outcomes were uptake of HIV self-testing , reporting of positive HIV self-test results , and rates of loss from ART at 6 months . RESULTS A significantly greater proportion of adults in the home group initiated ART ( 181/8194 , 2.2 % ) compared with the facility group ( 63/8466 , 0.7 % ; risk ratio [ RR ] , 2.94 , 95 % CI , 2.10 - 4.12 ; P < .001 ) . Uptake of HIV self-testing was high in both the home ( 5287/8194 , 64.9 % ) and facility groups ( 4433/8466 , 52.7 % ; RR , 1.23 ; 95 % CI , 0.96 - 1.58 ; P = .10 ) . Significantly more adults reported positive HIV self-test results in the home group ( 490/8194 [ 6.0 % ] vs the facility group , 278/8466 [ 3.3 % ] ; RR , 1.86 ; 95 % CI , 1.16 - 2.97 ; P = .006 ) . After 6 months , 52 of 181 ART initiators ( 28.7 % ) and 15 of 63 ART initiators ( 23.8 % ) in the home and facility groups , respectively , were lost from ART ( adjusted incidence rate ratio , 1.18 ; 95 % CI , 0.62 - 2.25 , P = .57 ) . CONCLUSIONS AND RELEVANCE Among Malawian adults offered HIV self-testing , optional home initiation of care compared with st and ard HIV care result ed in a significant increase in the proportion of adults initiating ART . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01414413 OBJECTIVE To describe a participatory approach to implement and evaluate ways to integrate and train community care workers ( CCWs ) to enhance collaborative TB/HIV/PMTCT activities , and home-based HIV counseling and testing ( HCT ) at community level . METHODS The intervention study was conducted in Sisonke , a rural district of KwaZulu Natal , South Africa . A baseline household ( HH ) survey was conducted in 11 villages . Six villages were r and omly selected into intervention and control clusters . Training was provided first to CCWs from the intervention cluster ( IC ) followed by the control cluster ( CC ) . Routine monthly data from CCWs were collected from March-December 2010 . The data was subjected to bivariate tests . RESULTS The baseline HH survey revealed that of 3012 HH members visited by CCWs in 2008 , 21 % were screened for TB symptoms , 7 % were visited for TB adherence support and 2 % for ART adherence , and 1.5 % were counselled on infant feeding options . A total of 89 CCWs were trained . Data show that during the study period in IC , 684 adults were offered HCT by CCWs , 92 % accepted HCT and tested and 7 % tested HIV-positive and were referred to the clinic for further care . Of 3556 adults served in IC , 44 % were screened for TB symptoms and 32 % for symptoms of sexually transmitted infections ( STIs ) and 37 % of children were traced as TB contact . Out of 6226 adults served in CC , 10 % were screened for TB symptoms and 7 % for STI symptoms . The differences in uptake of services between IC and CC were statistically significant ( p<0.05 ) . CONCLUSION The findings of this study suggest higher uptake of TB and STI symptoms screening , TB contact tracing and home based HCT in the intervention clusters . This study suggests that up-skilling CCWs could be one avenue to enhance TB/HIV case finding , TB contact tracing and linkages to care |
10,829 | 27,257,858 | Meta-analyses for pain scores and functional outcomes revealed statistical superiority of back schools vs no intervention for some comparisons but not others .
No meta- analysis was feasible for the comparison of back schools vs other active treatments .
Adverse events were poorly reported so that no reliable conclusions regarding the safety of back schools can be drawn , although some limited reassurance in this regard may be derived from the fact that few adverse events and no serious adverse events were reported in the back school groups in the studies that did report on safety .
Overall , the evidence base for the use of back schools to treat chronic low back pain is weak ; in nearly a half-century since back schools were first trialled , no unequivocal evidence of benefit has emerged | Back schools are interventions that comprise exercise and education components .
We aim ed to systematic ally review the r and omized controlled trial evidence on back schools for the treatment of chronic low back pain . | Study Design . A r and omized trial . Objective . To evaluate the effectiveness of a semi-intensive multidisciplinary rehabilitation for patients with chronic low back pain in an outpatient setting . Summary and Background Data . Systematic review s have shown that there is strong evidence that intensive multidisciplinary treatment ( > 100 hours ) , which includes functional restoration , improves function among chronic patients with low back pain , and moderate evidence that it reduces pain but contradictory evidence regarding improvement of working ability . However , there is paucity of data whether semi-intensive outpatient multidisciplinary rehabilitation in groups is more effective than individual physiotherapy . Material s and Methods . A total of 120 women employed as healthcare and social care professionals with nonspecific chronic low back pain were recruited from two occupational healthcare centers . The patients were r and omized into two intervention programs . Multidisciplinary rehabilitation ( n = 59 ) was conducted in groups and comprised of physical training , workplace interventions , back school , relaxation training , and cognitive-behavioral stress management methods for 70 hours . The individual physiotherapy ( n = 61 ) included physical exercise and passive treatment methods administered for 10 hours . Main outcome measures were : back pain and sciatic pain intensity , disability , sick leaves , healthcare consumption , symptoms of depression , and beliefs of working ability after 2 years . Results . There were no statistically significant differences between the two treatment groups in main outcome measures just after rehabilitation , at 6- , at 12- , or 24-month follow-up . In both intervention arms , however , the before- and -after comparison showed favorable effects , and the effects were still maintained at 2 years follow-up . Conclusions . The results of this study indicate that semilight outpatient multidisciplinary rehabilitation program for female chronic low back pain patients does not offer incremental benefits when compared with rehabilitation carried out by a physiotherapist having a cognitive-behavioral way of administering the treatment OBJECTIVES To evaluate the effectiveness of a back school program in pain , functional status , quality of life , and in anxiety and depression in patients with non-specific low back pain . METHODS Sixty patients with low back pain were r and omized to an intervention and control group . The intervention group underwent a five-weekly back school program . The control group was seen in weekly medical visits , without educative approaches . Both groups took acetaminophen as analgesic medication . All subjects were evaluated by a blind physiotherapist after r and omization , 30 , 60 and 120 days . Roll and -Morris , SF-36 , STAI and Beck question naires , pain visual analogical scale and Schober 's test were applied . Non-steroidal anti-inflammatory drugs ( NSAID ) consumption was considered co-intervention . The statistical analyses were performed using Pearson 's Chi-Square analysis and Student 's t-test to compare the baseline characteristics of the groups and the analysis of variance ( ANOVA ) with repeated measures to assess changes inter/intra groups . RESULTS There were no significant differences in the baseline characteristics between the two groups . Fifty-five patients completed the study . The intervention group showed a significant improvement in the general health domain , assessed by SF-36 , and also in the reduction of acetaminophen and NSAID intake . There was no significant difference between the groups in pain , functional status , anxiety or depression . CONCLUSION The back school program was more effective than any educational intervention in general health status and in decreasing acetaminophen and NSAID intake . It was ineffective in the other quality of life domains , in pain , functional status , anxiety and depression OBJECTIVE To evaluate the effectiveness of the addition of back school to exercise and physical treatment modalities in relieving pain and improving the functional status of patients with chronic low back pain . DESIGN A r and omized controlled trial . PATIENTS A total of 146 patients with chronic low back pain were enrolled in the study . METHODS Subjects were divided into 2 groups : the back school group received exercise , physical treatment modalities and a back school programme ; and the control group received exercise and physical treatment modalities . Treatment efficacy was evaluated at the end of treatment and 3 months post-treatment , in terms of pain , measured with the Visual Analogue Scale , and functional status , measured with the Oswestry Low Back Pain Disability Question naire . RESULTS In both groups , Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire were significantly reduced after therapy ( p < 0.01 ) , but the difference between the scores at the end of treatment and 3 months post-treatment was not significant . There was a significant improvement in Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire in the back school group compared with the control group at the end of therapy and 3 months post-treatment ( p < 0.05 ) . CONCLUSION The addition of back school was more effective than exercise and physical treatment modalities alone in the treatment of patients with chronic low back pain Background Different interventions can reduce the burden of the chronic low back pain . One example is the use of a ' Back School Programme ' . This is a brief therapy that uses a health education method to empower participants through a procedure of assessment , education and skill development . This study aim ed to evaluate to what extent the programme could improve quality of life in those who suffer from the condition . Methods This was a r and omized controlled trial . One-hundred and two female patients with low back pain ( n = 102 ) were r and omly allocated into two groups , matched in terms of age , weight , education , socioeconomic status , occupation and some aspects of risk behavior . Group 1 ( back school group , n = 50 ) but not group 2 ( clinic group , n = 52 ) received the ' Back School Programme ' . Then quality of life using the Short Form Health Survey ( SF-36 ) was assessed at two time points : at baseline and at three months follow-up . The findings were compared both within and between two groups . Results The ' Back School Programme ' was effective in improving patients ' quality of life ; significant differences were found on all eight subscales of the SF-36 for group 1 . In the clinic group ( group 2 ) , improvement was observed on three scales ( bodily pain , vitality and mental health ) but these improvements were less than in group 1 . The mean improvement over all eight subscales of the SF-36 was significantly better for the ' Back School Programme ' group . Conclusion The ' Back School Programme ' is an effective intervention and might improve the quality of life over a period of 3 months in patients who experience chronic low back pain Intensive group training using principles of grade d activity has been proven to be effective in occupational care for workers with chronic low back pain . Objective of the study was to compare the effects of an intensive group training protocol aim ed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain . The study was design ed as pragmatic r and omised controlled trial with a setup of 105 primary care physiotherapists in 49 practice s and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study . In the intensive group training protocol exercise therapy , back school and operant-conditioning behavioural principles are combined . Patients were treated during 10 individual sessions along 20 group sessions . Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain . Main outcome measures were functional disability ( Rol and Morris disability question naire ) , pain intensity , perceived recovery and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 and 52 weeks . Both an intention-to-treat analysis and a per- protocol analysis were performed . Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period , with one exception . After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group , but this difference was absent after 52 weeks . We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain Study Design . R and omized , single blind , controlled trial . Objective . To determine the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back disorder . Summary of Background Data . Musculoskeletal physiotherapy encompasses many treatment methods , however , manual therapy and exercises to rehabilitate spinal stabilization are the most frequently used . Despite their popularity , scant evidence supports their use on subjects with chronic low back disorder . Methods . A total of 346 subjects were r and omized to manual therapy , a 10-week spinal stabilization rehabilitation program , or a minimal intervention control group . Data were collected at baseline , and 3 , 6 , 12 , and 24 months after intervention . Outcome measures recorded intensity of low back pain , disability , h and icap , medication , and quality of life . There were 4 main variables combined in a primary component analysis to form a single outcome measure ( i.e. , a measure of dysfunction ) . Results . The results indicated statistically significant improvements in favor of the spinal stabilization group at the 6-month stage in pain ( 65.9 % reduction in symptoms ) and dysfunction ( combined mean reduction of 134 , st and ard error 23.84 ) , and at the 1-year stage in medication ( 34.3 % reduction in medication ) , dysfunction ( combined mean reduction of 134 , st and ard error 18.2 ) , and disability ( mean difference in change 15.71 Oswestry Disability Index , 95 % confidence interval 19.3–10.01 ) . Conclusions . As a component of musculoskeletal physiotherapy , the spinal stabilization program is more effective than manually applied therapy or an education booklet in treating chronic low back disorder over time . Both manual therapy and the spinal stabilization program are significantly effective in pain reduction in comparison to an active control . To our knowledge and up until now , this result has not been shown in patients with chronic low back disorder OBJECTIVE To evaluate a progressive fitness programme for patients with chronic low back pain . DESIGN Single blind r and omised controlled trial . Assessment s were carried out before and after treatment by an observer blinded to the study and included a battery of vali date d measures . All patients were followed up by postal question naire six months after treatment . SETTING Physiotherapy department of orthopaedic hospital . SUBJECTS 81 patients with chronic low back pain referred from orthopaedic consultants for physiotherapy . The patients were r and omly allocated to a fitness programme or control group . INTERVENTION Both groups were taught specific exercises to carry out at home and referred to a back-school for education in back care . Patients allocated to the fitness class attended eight exercise classes over four weeks in addition to the home programme and backschool . RESULTS Significant differences between the groups were shown in the changes before and after treatment in scores on the Oswestry low back pain disability index ( P < 0.005 ) , pain reports ( sensory P < 0.05 and affective P < 0.005 ) , self efficacy reports ( P < 0.05 ) , and walking distance ( P < 0.005 ) . No significant differences between the groups were found by the general health question naire or question naire on pain locus of control . A benefit of about 6 percentage points on the disability index was maintained by patients in the fitness group at six months . CONCLUSION There is a role for supervised fitness programmes in the management of moderately disabled patients with chronic low back pain . Further clinical trials , however , need to be established in other centres to confirm these findings BACKGROUND AND OBJECTIVES The aim of this trial is to search effectiveness of specifically adapted exercise programs on its own and with low back school on pain , disability , trunk and quadriceps muscle strength , walking performance , spinal mobility , quality of life ( QOL ) , and depression in the patients with chronic low back pain ( CLBP ) . MATERIAL AND METHOD A total of 121 patients with definite CLBP were included in this study . The patients were r and omized into two groups . Group 1 ( n=60 ) was given exercises only and accepted as the control group . Group 2 ( n=61 ) received back school program and exercises . The exercise treatment was performed 3 days a week , for 3 months . The pain ( visual analog scale , VAS ) , disability ( Oswestry Disability Question naire , ODQ ) , walking performance ( 6 minute walking test , 6MWT ) , depression ( Beck Depression Inventory scores , BDI ) , and QOL ( Short Form 36 , SF-36 ) of all participants were evaluated . The trunk and knee muscle strength were measured with a h and held dynamometer . Patients were assessed at baseline ( BT ) , at the end of treatment ( AT ) , and at the six month follow-up ( F ) . RESULTS Statistically significant improvements were found between groups regarding all of the clinical parameters over time . Pain , disability , muscle strength , endurance , 6MWT , mobility , QOL , and depression of both groups also showed improvements AT . These improvements persisted at 6-months follow-ups ( P < 0.05 ) . There were statistically significant differences between the groups for pain , disability , muscle strength , endurance , 6MWT , QOL , and depression regarding the change scores between AT-BT test and F-BT test ( P < 0.05 ) . Group 2 improved more than group 1 except for mobility . CONCLUSION Exercise programs can be modified and used successfully in CLBP and this effect can be increased with addition of back school further . LEVEL OF EVIDENCE Diagnostic study Level-I-I ( prospect i ve study ) Inpatient and outpatient treatments were compared with a control intervention in 288 men and 168 women , aged 35 - 54 , who were at work , but suffered from chronic or recurrent low back pain . Physical measurements and back pain assessment s were carried out before the intervention and at a 3-month follow-up . Physical fitness improved most in the in patients , but the out patients did not differ from the controls . Correlations between back pain and physical measurements indicated that increase of lumbar and hip mobility was more important than increase of trunk strength for subjective progress in these patients . Increased trunk extension strength correlated significantly with subjective progress in women , who also had higher correlations between improved physical fitness and progress than men Ninety-two chronic low back pain patients were r and omly allocated to two groups to evaluate the effectiveness of a back school compared with an exercise-only regimen according to specified outcome variables . The data from 78 patients with 7 years mean duration of symptoms was analyzed . Three assessment s were made : before treatment and 6 and 16 weeks after treatment . Changes in patients ' levels of pain , functional disability , and other related variables were compared in the two groups . Almost all variables showed an improvement at 6 weeks . At 16 weeks , functional disability and pain levels showed a significant difference . Back school patients continued to make an improvement . This method of managing low back pain makes maximal use of limited re sources and appears to be effective , especially in the longer term BACKGROUND Low back pain is a worldwide health problem , affecting up to 80 % of adult population . Psychological factors are involved in its development and maintenance . Many clinical trials have evaluated the efficacy of different interventions for chronic non-specific low back pain . In this field , Back School program has been demonstrated effective for people with chronic non-specific low back . AIM To evaluate the relationship between the effects of the Back School treatment and psychological features measured by MMPI-II of patients with chronic non-specific low back pain . DESIGN A r and omised controlled trial with three and six-month follow-up . SETTING Ambulatory rehabilitative university centre . POPULATION Fifty patients with chronic non-specific low back pain out of 77 screened patients . METHODS Patients were r and omly placed in a 3:2 form and were allocated into two groups ( Treatment versus Control ) . The Treatment Group participated to an intensive multidisciplinary Back School program ( BSG , N.=29 ) , while the Control Group received medical assistance ( CG , N.=21 ) . Medication was the same in both groups . Then , patients were subgrouped in those with at least an elevation in one scale of MMPI-II , and those without it . The Short Form 36 Health Status Survey for the assessment of quality of life ( primary outcome measure ) , pain Visual Analogue Scale , Waddel Index and Oswestry Disability Index were collected at baseline , at the end of treatment , and at the three and six-month follow-up . RESULTS Only the two treated subgroups showed a significant improvements in terms of quality of life , disability and pain . Among treated subjects , only those with at least one scale elevation in MMPI-II showed also a significant improvement in terms of Short Form 36 mental composite score and relevant subscores . CONCLUSION These results suggest that Back School program has positive effects , even in terms of mental components of quality of life in patients with scale elevations of MMPI-II . Probably these findings are due to its educational and cognitive-behavioural characteristics . CLINICAL REHABILITATION IMPACT Because of its educational purpose s , the Back School treatment can have positive effects also on the mental status of patients with low back pain when it affects their psychological features The long-term outcome results of inpatient and outpatient treatment of low back pain ( LBP ) were studied in 476 subjects ( aged 35 - 54 , 63 % men ) r and omly assigned to three study groups : in patients ( n = 157 ) , out patients ( n = 159 ) , and controls ( n = 160 ) . The study included changes in the severity of low back pain , grade and disability , compliance with self-care , data on disability pensions , and days of sickness allowance during a 2.5-year follow-up period . These variables were used as outcome criteria . Pain and disability had decreased significantly in the two treated groups up to the 3-month follow-up . LBP was still a little slighter in the in patients at the 1.5-year and 22-month follow-ups , but there were no significant differences between the groups in disability caused by LBP . The refresher programme carried out 1.5 years after the first one did not bring about as clear short-term improvement in pain and disability as the first treatment . During the whole 2.5-year follow-up compliance with self-care was better in the two treated groups , especially in the in patients . Days of sickness allowance had increased somewhat more in the controls than in the in patients during the follow-up . No differences between the groups were found in the number of disability pensions granted Objectives A back school is a m and atory part of the multimodal rehabilitation program for patients with chronic low back pain in Germany . However , no st and ardized and evaluated back school program has been available for routine use . In this study , we report the evaluation of a new back school that was developed based on theories of health behavior , treatment evidence , practice guidelines , and quality criteria for patient education . Methods R and omized controlled trial of patients with low back pain ( n=360 ) in inpatient orthopedic rehabilitation clinic in Germany . Intervention patients received the new back school , whereas control patients a traditional back school ( usual care ) . Illness knowledge ( primary outcome ) and secondary behavioral and health outcomes were assessed at admission , discharge , and 6 and 12 months follow-up . Results Results showed a significant medium between-group treatment effect in patients ' knowledge about back pain at discharge ( & eegr;2=0.081 ) , after 6 ( & eegr;2=0.056 ) , and 12 months ( & eegr;2=0.026 ) . Furthermore , small-to-medium effects were observed among the secondary self-management behaviors , such as physical activity , back exercises , back posture habits , and coping with pain , after 6 and 12 months . Discussion The superior effectiveness of the back school based on a biopsychosocial approach was demonstrated with regard to illness knowledge and self-management behaviors up to 1 year . Thus , the program may be recommended for dissemination within medical rehabilitation In a r and omized , blinded study , we compared the outcome from a full-time functional restoration program with the outcome from shorter active rehabilitation programs for patients with chronic , disabling low back pain . The study initially included 132 patients , r and omized into one of three treatment programs : ( 1 ) an intensive 3-week multidisciplinary program ; ( 2 ) active physical training and back school ; or ( 3 ) psychological pain management and active physical training . Nine of the r and omized patients never started in any program , so the studied population consisted of 123 patients . Of these , 14 patients ( 11 % ) dropped out . The results presented here are at 1 year following treatment , where we achieved a 92 % response rate , including the drop-outs . The functional restoration program was superior to the shorter programs as to work-ready rate , health care contacts , back pain level , disability level , staying physically active , and reduction in analgesics . There was no significant difference between Programs 2 and 3 in most of these parameters . As for sick leave and leg pain , there was no significant difference between Programs 1 and 2 , although a difference was observed when comparing Program 3 with each of the other two . Conclusively , it seems that there is human , as well as economical , benefit from a functional restoration program compared to less intensive programs for these patients Study Design . A r and omized controlled trial . Objective . To examine the effects of the back school program on quality of life in women with chronic low back pain . Summary of Background Data . There is a controversial debate whether back school program might improve quality of life in back pain patients . This study aim ed to address this issue . Methods . One hundred and two eligible women were r and omly allocated into 2 groups . The 2 groups including back school group who received the back school program plus medication ( n = 50 ) and clinic group who received just medication ( n = 52 ) were compared at 4 points in time . Data were collected at baseline and at 3 , 6 , and 12 months follow-up using the SF-36 question naire . Repeated measures analysis was performed to compare quality of life scores in 2 groups . Results . Quality of life scores were significantly different between 2 groups throughout the study ( P < 0.0001 ) indicating a better quality of life among intervention group . Conclusion . The back school program might improve the quality of life score in women with chronic low back pain Patients with chronic low back pain have a worse posture , probably related to poor control of the back muscles and altered perception of the trunk midline . The aim of this study was to evaluate the efficacy of a perceptive rehabilitation in terms of stability and pain relief in patients with chronic nonspecific low back pain . Thirty patients were enrolled and r and omized into two groups : 15 patients received rehabilitation , on the basis of a specific tool to perform perceptive exercises [ perceptive group ( PG ) ] , and 15 patients received a back school programme [ back school group ( BG ) ] . Both groups were assessed using stabilometry and the McGill Pain Question naire before and at the end of treatment . For the reference values of stabilometric parameters , 15 healthy individuals were enrolled . Significant reductions in sway length ( P=0.019 ) and laterolateral sway velocity ( P=0.038 ) were observed in the PG . The anteroposterior sway velocity was reduced in both the groups , but significantly only for BG ( P=0.048 ) . The percentage of sway length reduction was inversely and significantly correlated with the initial sway length value for PG ( R=−0.708 , P=0.003 ) , but not for BG ( R=−0.321 , P=0.243 ) . In the PG , the sagittal arrows and bi-acromial and bi-spinoiliac lines ’ angles were all significantly reduced . General pain relief was reported after treatment , without a significant difference ( P=0.436 ) . Our results suggest that a perceptive rehabilitation can improve the postural stability for the realignment of the trunk , controlling the back pain . The use of cognitive exercises may strengthen the usual rehabilitation of low back pain , avoiding the recurrence of symptoms . Patienten mit chronischen Kreuzschmerzen weisen eine schlechtere Körperhaltung auf , wahrscheinlich aufgrund der schlechten Kontrolle der Rückenmuskulatur und einer abweichenden Wahrnehmung der Mittellinie ihres Rumpfes . Ziel der vorliegenden Studie war die Evaluierung der Wirksamkeit einer perzeptiven Rehabilitation von Patienten mit chronischen unspezifischen Kreuzschmerzen , was Stabilität und Schmerzlinderung anbelangt . An der Studie nahmen insgesamt 30 Patienten teil , die r and omisiert in zwei Gruppen aufgeteilt wurden : 15 Patienten erhielten Rehabilitation auf der Grundlage eines spezifischen Tools zur Durchführung eines sensomotorisch-perzeptiven Trainings [ perzeptive Gruppe ( PG ) ] , die and eren 15 Patienten Rückenschulübungen [ Rückenschulgruppe ( RG ) ] . Beide Gruppen wurden vor und nach der Beh and lung mit Hilfe von Stabilometrie und dem McGill-Schmerz-Fragebogen evaluiert . Zu Referenzzwecken bei den stabilometrischen Parametern wurden 15 gesunde Prob and en in die Studie aufgenommen . In der PG wurden signifikante Reduktionen der Schwankungslänge ( P=0,019 ) und der laterolateralen Schwankungsgeschwindigkeit ( P=0,038 ) beobachtet . Die anteroposteriore Schwankungsgeschwindigkeit war in beiden Gruppen reduziert , wobei sie nur in der BG signifikant reduziert war ( P=0,048 ) . Der Prozentsatz der Schwankungslängenreduktion korrelierte umgekehrt und signifikant mit dem Wert der anfänglichen Schwankungslänge bei der PG ( R=−0,708 , P=0,003 ) , nicht aber bei der BG ( R=−0,321 , P=0,243 ) . In der PG waren die Sagittalebene und die Winkel der beidseitig akromialen und spinal-iliakalen Linien alle signifikant reduziert . Eine allgemeine Schmerzlinderung wurde nach der Beh and lung ohne signifikanten Unterschied ( P=0,436 ) berichtet . Unsere Ergebnisse legen den Schluss nahe , dass eine perzeptive Rehabilitation die Haltungsstabilität bei der Neuausrichtung des Rumpfes zu verbessern und somit Rückenschmerzen zu kontrollieren vermag . Die Anwendung kognitiver Übungen kann die übliche Rehabilitation bei Kreuzschmerzen unterstützen und somit ein erneutes Auftreten der Symptome vermeiden . Los pacientes con dolor lumbar crónico poseen una postura incorrecta , probablemente relacionada con la falta de control de los músculos lumbares y la percepción alterada de la línea media del tronco . El objetivo de este estudio fue evaluar la eficacia de la rehabilitación perceptiva en términos de estabilidad y alivio del dolor en pacientes con dolor lumbar crónico no específico . Treinta pacientes participaron en el estudio y fueron distribuidos en dos grupos de forma aleatoria : quince pacientes recibieron sesiones de rehabilitación utiliz and o una herramienta específica para la realización de ejercicios de percepción [ grupo perceptivo ] y los otros quince participaron en un programa de escuela de espalda [ grupo de escuela de espalda ] . Ambos grupos se evaluaron mediante estabilometría y el cuestionario del dolor McGill antes y después del tratamiento . Quince individuos sanos participaron en el estudio como valor de referencia de los parámetros estabilométricos . En el grupo perceptivo se observaron reducciones significativas en la longitud del balanceo ( P=0,019 ) y en la velocidad de balanceo latero-lateral ( P=0,038 ) . La velocidad de balanceo anteroposterior se vio reducida en ambos grupos , pero solo de forma significativa en el grupo de escuela de espalda ( P=0,048 ) . El porcentaje de la reducción de la longitud del balanceo mostró una correlación inversa y significativa con el valor inicial de la longitud del balanceo del grupo perceptivo ( R=−0,708 , P=0,003 ) pero no del grupo de escuela de espalda ( R=−0,321 , P=0,243 ) . En el grupo perceptivo , las flechas verticales y los ángulos de las líneas biacromiales y biespinailíacas se vieron reducidos de forma significativa . Tras el tratamiento se registró el alivio general del dolor sin ninguna diferencia significativa ( P=0,436 ) . Los result ados de este estudio sugieren que la rehabilitación perceptiva puede mejorar la estabilidad postural de la alineación del tronco mediante el control del dolor lumbar . El uso de ejercicios cognitivos puede reforzar la rehabilitación del dolor lumbar y evitar la recurrencia de los síntomas . Les patients atteints de lombalgie chronique adoptent une plus mauvaise posture , probablement liée à un mauvais contrôle des muscles du dos et la perception altérée de la ligne médiane du tronc . Cette étude avait pour objet d'évaluer l'efficacité d'une rééducation de la perception en termes de stabilité et de soulagement de la douleur chez les patients atteints de douleur chronique lombaire non spécifique . Trente patients ont été recrutés et r and omisés en deux groupes : 15 patients ont reçu une rééducation basée sur un outil spécifique destiné à effectuer des exercices de perception [ groupe de perception ( GP ) , et 15 patients ont reçu un programme d'exercice pour le dos ( GD ) . Les deux groupes ont été évalués par stabilométrie et par le question naire de McGill Pain avant et à la fin du traitement . Pour les valeurs de référence des paramètres stabilométriques , 15 individus en bonne santé ont été inclus . Des réductions significatives de longueur de balancement ( P = 0,019 ) et de la vitesse de balancement latérolatéral ( P = 0,038 ) ont été observées chez le GP . La vitesse de balancement antéro-postérieur a été réduite dans les deux groupes , mais uniquement de façon significative pour GE ( P = 0,048 ) . Le pourcentage de réduction de la longueur de balancement présentait une corrélation inverse significative avec la valeur de la longueur initiale pour GP ( R = −0,708 , P = 0,003 ) , mais pas pour GE ( R = 0,321 , P = 0,243 ) . Dans le GP , les flèches sagittales et biacromiales et les angles des lignes bi-spinoiliaques présentaient tous une réduction significative . Un soulagement général de la douleur a été signalé après le traitement , sans différence significative ( P = 0,436 ) . Nos résultats suggèrent que la rééducation de la perception peut améliorer la stabilité posturale pour le réalignement du tronc en contrôlant la douleur au dos . L'utilisation d'exercices cognitifs peut renforcer la rééducation habituelle de la douleur lombaire , en évitant la réapparition des symptômes Objective : To evaluate the efficacy of a perceptive rehabilitative approach , based on a new device , with regard to pain and disability in patients with chronic nonspecific low back pain . Design : Single blind , r and omized , controlled trial . Setting : An outpatient academic hospital . Patients : Seventy-five patients with chronic low back pain . Interventions : Patients were r and omized into three groups . Twenty-five subjects received 10 sessions in one month , based on specific perceptive exercises that were performed on a suitably developed device . Twenty-five patients entered a Back School programme . Twenty-five patients comprised a control group that received the same medical and pharmacological assistance as the other groups . Main outcome measures : Pain was assessed using the Visual Analogue Scale and McGill Pain Question naire . Disability was evaluated using the Oswestry Disability Index and Waddell Disability Index . All measurements were recorded before treatment , at the end of the study , and at 12 and 24 weeks . Results : General pain relief was recorded in all the groups , which was elicited more quickly in the perceptive treatment group ; significant differences in pain scores were observed at the end of treatment ( P < 0.001 for visual analogue scale and P = 0.001 for Question naire ) versus the other groups . Disability scores in the perceptive group did not differ significantly from those in the other group , whereas these scores significantly differed between Back School and control groups at the follow-ups ( P < 0.01 for both scales ) . Conclusion : Perceptive rehabilitation has immediate positive effects on pain . Back School reduces disabilities at follow-up Background Back School and McKenzie methods are popular active treatment approaches that include both exercises and information for patients with chronic nonspecific low back pain . Objective The purpose of this study was to compare the effectiveness of Back School and McKenzie methods in patients with chronic nonspecific low back pain . Design The study was a prospect ively registered , 2-arm r and omized controlled trial with a blinded assessor . Setting The study was conducted in the outpatient physical therapy clinic in São Paulo , Brazil . Patients The study participants were 148 patients with chronic nonspecific low back pain . Interventions The 4-week treatment program ( one session/week ) was based on the Back School ( delivered to the group ) or McKenzie ( delivered individually ) principles . The participants also were instructed to perform a daily set of home exercises . Measurements Clinical outcomes were assessed at follow-up appointments at 1 , 3 , and 6 months after r and omization . Primary outcome measures were pain intensity ( measured by the 0–10 pain numerical rating scale ) and disability ( measured by the 24-item Rol and -Morris Disability Question naire ) 1 month after r and omization . Secondary outcome measures were pain intensity and disability at 3 and 6 months after r and omization , quality of life ( measured by the World Health Organization Quality of Life – BREF instrument ) at 1 , 3 , and 6 months after r and omization , and trunk flexion range of motion measured by an inclinometer at 1 month after r and omization . The data were collected by a blinded assessor . Results Participants allocated to the McKenzie group had greater improvements in disability at 1 month ( mean effect=2.37 points , 95 % confidence interval=0.76 to 3.99 ) but not for pain ( mean effect=0.66 points , 95 % confidence interval=−0.29 to 1.62 ) . No between-group differences were observed for all secondary outcome measures . Limitations It was not possible to monitor the home exercise program . Therapists and participants were not blinded . Conclusions The McKenzie method ( a more re source -intensive intervention ) was slightly more effective than the Back School method for disability , but not for pain intensity immediately after treatment in participants with chronic low back pain Objective : To investigate the effects of a multidisciplinary back school programme ( Roessingh Back Rehabilitation Programme , RRP ) compared with usual care , as well as differences in treatment outcome between subgroups defined using two multiaxial assessment instruments : the Multidimensional Pain Inventory ( MPI-DLV ) and lumbar dynamometry . Design : R and omized controlled trial . Setting : Rehabilitation . Subjects : One hundred and sixty-three patients with chronic , aspecific low back pain . Intervention : All subjects were r and omly assigned either to a multidisciplinary , physically oriented group treatment or to their usual care . Main outcome measures : The Rol and Disability Question naire and health-related quality of life ( EuroQol , EQ5-D ) were measured as primary outcomes before r and omization and after eight weeks and six months follow-up . Result : Only 30 - 50 % of the patients in the RRP group showed improvement and this number is not significantly different from the control group . Subgroup analyses give some first indications that multiaxial measurement instruments can be used to identify subgroups with differences in treatment effects . Conclusion : The overall effect of a multidisciplinary treatment is disappointing , however multiaxial assessment before admission might be valuable in clinical practice , result ing in more effective treatments for patients with chronic low back pain STUDY DESIGN A three and six months follow-up in a r and omized controlled trial . BACKGROUND Back School has become a widespread exercise program for low back pain ( LBP ) , since its introduction in 1969 . Back School could improve quality of life ( QoL ) , but there are controversial data regarding its effectiveness . AIM To evaluate the effects of the Back School program on quality of life ( primary outcome ) , disability and pain perceptions ( secondary outcomes ) in patients with chronic and non-specific low back pain . SETTING Rehabilitative specialized centre . POPULATION Seventy four patients with chronic non-specific LBP . METHODS Patients were r and omly placed in a 3:2 form and were allocated into 2 groups ( treated-control ) . Treatment group participated in a intensive multidisciplinary Back School program including brief education and active back exercises ( BSG , N.=41 ) , while the control group received medical assistance ( CG , N.=29 ) . Medication was the same in both groups . The Short Form 36 Health Status Survey , Waddel Index , Oswestry Disability Index and Visual Analogue Scale were collected at baseline , at the end of treatment , and at the three and six month follow-up . RESULTS Quality of life significantly improved along time more in BSG , both in Physical and Mental Composite Score ( repeated measure Anova : interaction time per group : P<0.001 and P=0.002 , respectively ) . We also observed a significant improvement in disability scores along time ( P<0.001 ) in BSG with significant differences between groups at three and at six months for Waddell Index ( P=0.006 and P=0.009 respectively ) and for Oswestry Disability Index ( P=0.018 and 0.011 respectively ) . Moreover , pain perception score VAS showed a reduction in both groups , but it was significantly lower in BSG at end of treatment and both follow-ups ( P<0.001 ) . CONCLUSION Our Back School program can be considered an effective treatment in people with chronıc non-specıfıc LBP Objective : To compare spinal manipulation , back school and individual physiotherapy in the treatment of chronic low back pain . Design : R and omized trial , 12-month follow-up . Setting : Outpatient rehabilitation department . Participants : 210 patients with chronic , non-specific low back pain , 140/210 women , age 59 ± 14 years . Interventions : Back school and individual physiotherapy scheduled 15 1-hour-sessions for 3 weeks . Back school included : group exercise , education/ ergonomics ; individual physiotherapy : exercise , passive mobilization and soft-tissue treatment . Spinal manipulation , given according to Manual Medicine , scheduled 4 to 6 20’-sessions once-a-week . Outcome : Rol and Morris Disability Question naire ( scoring 0 - 24 ) and Pain Rating Scale ( scoring 0 - 6 ) were assessed at baseline , discharge 3 , 6 , and 12 months . Results : 205 patients completed the study . At discharge , disability score decreased by 3.7 ± 4.1 for back school , 4.4 ± 3.7 for individual physiotherapy , 6.7 ± 3.9 for manipulation ; pain score reduction was 0.9 ± 1.1 , 1.1 ± 1.0 , 1.0 ± 1.1 , respectively . At 12 months , disability score reduction was 4.2 ± 4.8 for back school , 4.0 ± 5.1 for individual physiotherapy , 5.9 ± 4.6 for manipulation ; pain score reduction was 0.7 ± 1.2 , 0.4 ± 1.3 , and 1.5 ± 1.1 , respectively . Spinal manipulation was associated with higher functional improvement and long-term pain relief than back school or individual physiotherapy , but received more further treatment at follow-ups ( P<0.001 ) ; pain recurrences and drug intake were also reduced compared to back school ( P < 0.05 ) or individual physiotherapy ( P < 0.001 ) . Conclusions : Spinal manipulation provided better short and long-term functional improvement , and more pain relief in the follow-up than either back school or individual physiotherapy Outcome of inpatient and outpatient treatment of low back pain was studied in 459 patients ( aged 35 - 54 years , 63 % men ) ; 156 in patients , 150 out patients and 153 controls . Changes in low back pain and in disability caused by it , and adherence and accomplishment of back exercises were used as short-term outcome criteria . The overall results showed a significant decrease in pain and disability and better compliance in the two treated groups when compared to the controls . There was also a significant difference in treatment gains between the in patients and out patients ; i.e. the decrease in pain was greater and the frequency of back exercises higher in the in patients . The in patients also estimated their treatment benefits more positively than the out patients THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard BACKGROUND Reporting of all serious adverse events ( SAEs ) is a requirement for regulatory approval of a drug . Can equally rigorous reporting st and ards be expected in studies of non-drug treatments and how can underreporting , if any , be detected and proven ? Using data from our large-scale prospect i ve cohort study of acupuncture on out patients , we examine the use of an internal st and ard , a principle taken from laboratory medicine , to quantify real event rates . METHODS A total of 190,924 patients ( 68.6 % women ) seeking treatment for chronic pain ( headache , low back pain , coxarthrosis or gonarthrosis ) from 12,000 physicians in private practice in Germany were observed during a six-month period ending in May 2002 . Most received ten sessions of body acupuncture . Mean treatment time was six weeks . All practitioners were certified in acupuncture and received written instructions on completing forms for basic patient data and SAE monitoring . They were also informed that payment by insurers would be made only upon return of the completed form . All SAEs occurring between start of the first acupuncture session and end of the last one were to be reported , whether causally related to the treatment or not . Multiple minor adverse events ( AEs ) per single patient were to be reported only once . As the internal st and ard we chose the expected number of deaths , based on the death rate for the German population , adjusted for age , sex distribution and mean observation time of our study patients . RESULTS 45 SAEs and 14,404 AEs were reported ( i.e. 2.4 SAEs and 754 AEs per 10,000 patients ) . The number of reported deaths ( 9 ) was only 5 % of the statistically expected number ( 180 ) . Applying the result ing correction factor of 20 to all reported SAEs , result ed in 900 expected SAEs ( versus 45 reported ) or 47 per 10,000 patients . CONCLUSIONS Without verifying the accuracy of a measurement , results remain speculative . Our internal st and ard for the first time provides a means of verifying the accuracy of the reported SAE rate and correcting it to the statistically expected SAE rate The use of an education program for patients with chronic low back pain ( Back School ) has been investigated . The effect evaluation is based on a pretest-post-test-control group design , including a follow-up after 8 weeks . The Maastricht Back School is based on the theory that pain is also maintained by emotional , cognitive and environmental factors . Information and training are given on these and physical factors . The purpose of the course is to teach patients to manage their own pain problem . The results suggest that the Back School program for patients with chronic low back pain can have a positive effect BACKGROUND AND AIM OF THE WORK Chronic low back pain ( CLBP ) is a major cause of disability , for which clinical practice guidelines suggest exercise programs , such as Back School program ( stretching and selective muscle reinforcement techniques ) and Hydrotherapy technique , as an effective treatment to reduce pain intensity and disability . METHODS We enrolled 56 elderly individuals , affected by non-specific CLBP , whose pain had worsened in the last three months , which were r and omly allocated to Back School ( group A ) or to Hydrotherapy program ( group B ) . Each group underwent two one-hour-treatment sessions per week , over a 12-week period . Each patient was evaluated using the Rol and Morris Disability Question naire ( RMDQ ) and the 36-Item Short Form Health Survey ( SF-36 ) V2.0 at the beginning ( T0 ) , at the end of treatment ( T1 ) and at the 3-month follow-up ( T2 ) . RESULTS At T1 and T2 we observed a highly significant statistical difference in the values measured in both groups : at T1 in group A RMDQ improvement of 3.26±1.02 ( p<0.001 ) and SF-36 of 13.30±1.44 ( p<0.001 ) ; in group B RMDQ improvement of 4.96±0.71 ( p<0.001 ) and SF-36 of 14.19±1.98 ( p<0.001 ) . We have also evaluated the difference in effectiveness of the two programs and no significant statistical differences were found between the two groups . CONCLUSIONS Back School program and Hydrotherapy could be valid treatment options in the rehabilitation of non-specific CLBP in elderly people . Both therapies proved to be effective and can be used in association with other rehabilitation programs . We believe that Back School program should be favored for its simplicity and the small number of re sources required & NA ; The aim of this study was to assess the long‐term effect of a supervised fitness programme on patients with chronic low back pain . The design of the study was a single blind r and omised controlled trial with follow‐up , by postal question naire , 2 years after intervention . The Oswestry Low Back Pain Disability Index was used as the outcome measure to assess daily activity affected by back pain . Eighty‐one patients with chronic low back pain , who were referred to the physiotherapy department of a National Health Service orthopaedic hospital , were r and omised to either a supervised fitness programme or a control group . Patients in the intervention group and control group were taught specific exercises to be continued at home and referred to a backschool for back care education . In addition , the intervention group attended eight sessions of a supervised fitness programme . Sixty‐two patients ( 76 % ) with a mean age of 37 years , returned the Oswestry Low Back Pain Disability Index question naire . Of these , 29 were in the intervention group and 31 in the control group . Patients in the intervention group demonstrated a mean reduction of 7.7 % in the Oswestry Low Back Pain Disability Index score ( 95 % confidence interval of mean paired difference 3.9 , 11.6 P<0.001 ) , compared with only 2.4 % in the control group ( 95 % confidence interval of mean paired difference −2.0 , 6.9 P>0.05 ) . Between group comparisons demonstrated a statistically significant difference in disability scores between the treatment and control group ( mean difference 5.8 , 95 % confidence interval 0.3 , 11.4 P<0.04 ) . This study supports the current trend towards a more active treatment approach to low back pain . We have demonstrated clinical effectiveness of a fitness programme 2 years after treatment but this needs to be replicated in a larger study which should include a cost effectiveness analysis , further analysis of objective functional status and a placebo intervention group |
10,830 | 19,770,788 | No significant differences were found when comparing different drugs ( omeprazole , ranitidine , sucralfate , famotidine , amalgate ) , doses , or regimens for main outcomes ( deaths , endoscopic findings of erosion or ulcers , upper gastrointestinal bleeding , or pneumonia ) . | OBJECTIVE To identify and evaluate the quality of evidence supporting prophylactic use of treatments for stress ulcers and upper gastrointestinal bleeding .
Stress ulcers , erosions of the stomach and duodenum , and upper gastrointestinal bleeding are well-known complications of critical illness in children admitted to the pediatric intensive care unit . | Sixty children aged 6 wk to 10 yr were studied . The children were undergoing cardiopulmonary bypass ( CPB ) for correction of congenital heart defects . The aim of the study was to provide prophylaxis for stress-induced gastric ulceration by elevating the gastric pH to at least 3.5 . Two infusion regimes of ranitidine were compared : 0.1 and 0.2 mg/kg.h . The period of study was from induction of anesthesia until the end of the first 24 h after surgery . Both regimes were effective . The 0.2-mg/kg.h infusion produced a significantly higher plasma concentration of ranitidine throughout the study period without any additional clinical benefit . Both regimes produced , within 3 h of cessation of CPB , a significant elevation in mean gastric pH to at least 5.3 . This paper concludes that 0.1-mg/kg.h infusion of ranitidine is a safe and efficacious regime for the critically ill pediatric patient Objective : To identify the incidence and factors related to upper gastrointestinal ( UGI ) bleeding in children requiring mechanical ventilation for longer than 48 hrs . Design : Prospect i ve analytic study . Setting : Ten-bed-pediatric intensive care unit of a tertiary care University Hospital . Patients : A total of 110 patients requiring mechanical ventilation for longer than 48 hrs from January 1 , 2005 to December 31 , 2005 . Measurements and Results : UGI bleeding was defined by evidence of blood in nasogastric aspirates , hematemesis , or melena within 5 days of pediatric intensive care unit admission . We prospect ively collected data on patient demographics , admission diagnosis , operative status , and pediatric risk of mortality score . UGI bleeding and the potential risk factors including organ failure , coagulopathy , maximum ventilator setting , enteral feeding , stress ulcer prophylaxis as well as sedation were daily monitored . Of the 110 patients who required mechanical ventilation for > 48 hrs , the incidence of UGI bleeding was 51.8 % , in which 3.6 % of the cases presented with clinical ly significant bleeding ( shock , requiring blood transfusion and /or surgery ) . Significant risk factors were thrombocytopenia , prolonged partial thromboplastin time , organ failure , high pressure ventilator setting ≥25 cm H2O , and pediatric risk of mortality score ≥ 10 using univariate analysis . However , the independent factors of UGI bleeding in the multivariate analysis were organ failure ( relative risk = 2.85 , 95 % confidence interval 1.18–6.92 ) and high pressure ventilator setting ≥25 cm H2O ( relative risk = 3.73 , 95 % confidence interval 1.59–8.72 ) . Conclusion : The incidence of UGI bleeding is high in children requiring mechanical ventilation . Organ failure and high pressure ventilator setting are significant risk factors for UGI bleeding Objective To estimate the mortality and length of stay in the intensive care unit ( ICU ) attributable to clinical ly important gastrointestinal bleeding in mechanically ventilated critically ill patients . Design Three strategies were used to estimate the mortality attributable to bleeding in two multicentre data bases . The first method matched patients who bled with those who did not ( matched cohort ) , using duration of ICU stay prior to the bleed , each of six domains of the Multiple Organ Dysfunction Score ( MODS ) measured 3 days prior to the bleed , APACHE II score , age , admitting diagnosis , and duration of mechanical ventilation . The second approach employed Cox proportional hazards regression to match bleeding and non-bleeding patients ( model-based matched cohort ) . The third method , instead of matching , derived estimates based on regression modelling using the entire population ( regression method ) . Three parallel analyses were conducted for the length of ICU stay attributable to clinical ly important bleeding . Setting Sixteen Canadian university-affiliated ICUs . Patients A total of 1666 critically ill patients receiving mechanical ventilation for at least 48 hours . Measurements We prospect ively collected data on patient demographics , APACHE II score , admitting diagnosis , daily MODS , clinical ly important bleeding , length of ICU stay , and mortality . Independent adjudicators determined the occurrence of clinical ly important gastrointestinal bleeding , defined as overt bleeding in association with haemodynamic compromise or blood transfusion . Results Of 1666 patients , 59 developed clinical ly important gastrointestinal bleeding . The mean APACHE II score was 22.9 ± 8.6 among bleeding patients and 23.3 ± 7.7 among non-bleeding patients . The risk of death was increased in patients with bleeding using all three analytic approaches ( matched cohort method : relative risk [RR]= 2.9 , 95 % confidence interval (CI)= 1.6–5.5 ; model-based matched cohort method : RR = 1.8 , 95 % CI = 1.1–2.9 ; and the regression method : RR = 4.1 , 95 % CI = 2.6–6.5 ) . However , this was not significant for the adjusted regression method ( RR = 1.0 , 95 % CI = 0.6–1.7 ) . The median length of ICU stay attributable to clinical ly important bleeding for these three methods , respectively , was 3.8 days ( 95 % CI = -0.01 to 7.6 days ) , 6.7 days ( 95 % CI = 2.7–10.7 days ) , and 7.9 days ( 95 % CI = 1.4–14.4 days ) . Conclusions Clinical ly important upper gastrointestinal bleeding has an important attributable morbidity and mortality , associated with a RR of death of 1–4 and an excess length of ICU stay of approximately 4–8 days Background No surveys of stress ulcer prophylaxis prescribing in the USA havebeen conducted since 1995 . Since that time , the most comprehensive meta- analysis and largest r and omized study to date concerning stress ulcer prophylaxis havebeen published . Results Three hundred sixty-eight surveys were sent to all members of theSection of Pharmacy and Pharmacology of the Society of Critical Care Medicine . One hundred fifty-three ( 42 % ) surveys were returned . Representatives from 86%of institutions stated that medications for stress ulcer prophylaxis are usedin a majority ( > 90 % ) of patients admitted to the intensive care unit (ICU).Twenty-two per cent of institutions have recommendations for both ICU and non-ICU setting s. Fifty-eight per cent of institutions stated that there wasone preferred medication for stress ulcer prophylaxis , and in 77 % of thesehistamine-2-antagonists were the most popular . Conclusions There are wide variations in prescribing practice s for stressulcer prophylaxis . Institutions should consult published literature and usepre-existing guidelines as templates for developing their own guidelines We determined the ranitidine dosage necessary to maintain gastric pH at or above 4 in 40 critically ill children . The patients were divided into four groups of ten patients each . They were treated with ranitidine in the following dosages : a ) 2 mg/kg by NG tube every 12 h ; b ) 4 mg/kg by NG tube every 12 h ; c ) 0.75 mg/kg iv every 6 h ; d ) 1.5 mg/kg iv every 6 h. The fourth group had a higher median pH than the other groups , in spite of also having the highest risk of acute gastric mucosal damage ( AGMD ) . Eight ( 80 % ) of ten patients in the fourth group had a pH greater than or equal to 4 or more than 80 % of the study period . We recommend 1.5 mg/kg iv every 6 h for gastric acid inhibition in AGMD prophylaxis in children OBJECTIVE To determine whether the dose of ranitidine recommended in commonly used pediatric drug dosage h and books ( 2 to 4 mg/kg/day i.v . ) results in successful gastric pH control ( pH of > 4 ) in critically ill children . DESIGN Prospect i ve sample . SETTING Pediatric intensive care unit in a tertiary care children 's hospital . PATIENTS Fifty consecutive patients who received > 24 hrs of scheduled intermittent intravenous ranitidine for stress ulcer prophylaxis were enrolled in the study . Patients with renal or hepatic dysfunction and those who received enteral nutrition through the nasogastric tube were excluded from enrollment . INTERVENTION Gastric pH was determined at the end of the ranitidine dosing interval , 1 hr after the dose , and at the midpoint between doses . All pH measurements were made from a sample of nasogastric aspirate , using pH sensitive paper . Gastric pH control with ranitidine was considered unsuccessful ( poorly controlled ) if the pH was < 4 for any of the three measurements . MEASUREMENTS AND MAIN RESULTS Forty-five patients ( median age 36 mos ; range 2 wks to 264 mos ) were included in the analysis . Eighty-two percent of the patients were mechanically ventilated , 16 % were pharmacologically paralyzed , 18 % required vasoactive infusions , 36 % were nourished via transpyloric feeding tubes , and 7 % received total parenteral nutrition . Gastric pH was poorly controlled in 36 % of patients . Among these patients , the pH at the end of the dosing interval was significantly lower than the pH measured at 1 hr or at the midpoint between doses ( p < .05 ) . Seventy-one percent of patients who received <3 mg/kg/day of ranitidine had poor gastric pH control as compared with 19 % who received a minimum of 3 mg/kg/day ( p < .05 ) . Poor control of gastric pH was not associated with feeding , intubation status , presence of pharmacologic paralysis , use of vasoactive infusions , or age ( p > .05 ) . CONCLUSIONS The minimum ranitidine dose recommended in commonly used pediatric drug references result ed in unsuccessful gastric pH control in a high percentage of pediatric intensive care unit patients . Critically ill children with normal renal and hepatic function should be treated with a minimum 3 mg/kg/day of intravenous ranitidine and the dose should be titrated to a gastric pH of > or = 4 Objectives . To determine the incidence , risk factors , and complications associated with or attributable to clinical ly significant upper gastrointestinal ( GI ) bleeding acquired in a pediatric intensive care unit ( ICU ) . Methods . Prospect i ve , descriptive epidemiologic study in a multidisciplinary pediatric ICU of a tertiary-care university hospital . Upper GI bleeding was considered to be present if hematemesis occurred or blood was present in the gastric tube . An upper GI bleed was qualified as clinical ly significant if two or three review ers independently assessed that at least one of the six complications considered for analysis was attributable to the upper GI bleed . Results . A cohort of 1114 consecutive admissions was enrolled ; 108 ( 9.7 % ) were excluded mostly ( 37.0 % ) because they already had an upper GI bleed at entry to the pediatric ICU . The final sample included 1006 admissions ( 881 patients ) ; 103 upper GI bleeds ( 10.2 % ) were diagnosed , including 16 clinical ly significant upper GI bleeds ( 1.6 % ) . Complications attributed to an upper GI bleed included : decreased hemoglobin concentration ( 10 cases ) , transfusion ( 10 ) , hypotension ( 3 ) , and surgery ( 1 ) . Three independent risk factors for clinical ly significant upper GI bleeding were retained by multivariate analysis : respiratory failure , coagulopathy , and pediatric risk of mortality score ≥10 . Nine of the 16 cases ( 56.3 % ) with clinical ly significant upper GI bleeding had three risk factors , 14 ( 87.5 % ) had two , and 1 ( 6.3 % ) had none . Conclusions . Clinical ly significant upper GI bleeds are rare in critically ill children . Prophylaxis to prevent them may be limited to patients who present with at least two risk factors PURPOSE The purpose of the study was to evaluate the effects of sucralfate , ranitidine , and omeprazole use on incidence of ventilatory-associated pneumonia ( VAP ) and mortality in ventilated pediatric critical care patients . MATERIAL S AND METHODS This prospect i ve study was conducted at the pediatric intensive care unit ( PICU ) between August 2000 and February 2002 . A total of 160 patients who needed mechanical ventilation were r and omized into 4 groups according to the computer-generated r and om number table : group ( S ) , ( n = 38 ) received sucralfate suspension 60 mg/kg/d in 4 doses via the nasogastric tube that was flushed with 10 mL of sterile water ; group ( R ) , ( n = 42 ) received ranitidine 2 mg/kg/d intravenously in 4 doses ; group ( O ) , ( n = 38 ) received omeprazole 1 mg/kg/d intravenously in 2 doses ; and group ( P ) , ( n = 42 ) did not receive any medication for stress ulcer prophylaxis . Treatment was begun within 6 hours of PICU admission . RESULTS Seventy patients ( 44 % ) developed VAP . VAP rate was 42 % ( 16 of 38 ) in the sucralfate group , 48 % ( 20 of 42 ) in the ranitidine group , 45 % ( 17 of 38 ) in the omeprazole group , and 41 % ( 17 of 42 ) in the nontreated group . Overall mortality rate was 22 % ( 35 of 160 ) ; it was 21 % ( 8 of 38 ) in the sucralfate group , 23 % ( 10 of 42 ) in the ranitidine group , 21 % ( 8 of 38 ) in the omeprazole group , and 21 % ( 9 of 42 ) in the nontreated group . Our results did not show any difference in the incidence of VAP and mortality in mechanically ventilated PICU patients treated with ranitidine , omeprazole , or sucralfate , or nontreated subjects ( P = .963 , confidence interval [ CI ] = 0.958 - 0.968 ; P = .988 , CI = 0.985 - 0.991 , respectively ) . Nine patients ( 5.6 % ) had macroscopic bleeding . There was no statistically significant difference in macroscopic bleeding between groups . CONCLUSIONS Our results did not show any difference in the incidence of VAP , macroscopic stress ulcer bleeding , and mortality in the mechanically ventilated PICU patients treated with ranitidine , omeprazole , or sucralfate , or nontreated subjects . None of the treatment regimens increased VAP compared with the nontreated group . Because there is insufficient data about stress ulcer prophylaxis and VAP in the pediatric age group , more studies with larger numbers of patients are needed BACKGROUND --Stress lesions of the upper gastrointestinal tract are well recognised in adult patients in intensive care . There are no controlled studies of the incidence of these lesions and the effects or side effects of prophylactic treatment in high risk paediatric patients . METHODS --79 paediatric patients in intensive care were studied prospect ively after operation for congenital heart disease . All patients had at least one endoscopic examination . The first 36 patients were not given prophylactic medication : later 43 children were treated r and omly either with pirenzepine ( n = 21 ) or with famotidine ( n = 22 ) . Gastric and tracheal secretions were taken daily for culture in those patients given prophylactic medication . RESULTS --Severe inflammation or ulceration of the upper gastrointestinal tract was less common in those patients who were given prophylactic medication ( 18 % v 44 % ) . Prophylactic treatment did not , however , reduce the total incidence of postoperative stress lesions : it shifted the severity of these changes towards mild lesions and reduced the incidence of ulcerations from 25 % to 2 % . None of the patients developed a pneumonia caused by an organism previously isolated from the stomach . CONCLUSIONS --The incidence of stress lesions in children after cardiac surgery resembles that in high risk adult patients . Children in intensive care after cardiac surgery should be treated prophylactically with famotidine or pirenzepine until they can be fed by mouth Objective To test the influence of continuously administered enteral feeding on gastric pH and gastric colonization in patients receiving or not receiving topical antimicrobial prophylaxis of the oropharynx and stomach , including sucralfate as stress ulcer prophylaxis . Design Prospect i ve , open trial Setting Two university hospital general intensive care units ( ICUs ) . Patients Patients ( n = 95 ) with an ICU stay for at least 5 days . Interventions Thirty-one patients received antimicrobial agents into the stomach and oropharynx in combination with sucralfate ( 1 g/6 hrs ) as stress ulcer prophylaxis . Sixty-four other patients did not receive antimicrobial prophylaxis or sucralfate , but instead received gastric pH-increasing stress ulcer prophylactic agents , if indicated . Gastric colonization and gastric pH were measured on admission and subsequently at least two times a week . Forty-eight patients ( 14 receiving and 34 not receiving antimicrobial prophylaxis ) received enteral feeding . Measurements and Main Results Both enteral feeding and gastric pH-increasing stress ulcer prophylaxis independently increased gastric pH : the risks for a gastric pH of > 3.5 were , respectively , 4.54 and 2.04 ( odds ratios ) . Enteral feeding also increased the risk for gastric colonization by potentially pathogenic microorganisms ( odds ratio = 4.52 ) . Patients receiving both topical antimicrobial prophylaxis and sucralfate remained free of gastric colonization for a longer period than those patients receiving gastric pH-increasing stress ulcer prophylaxis . In these two groups , patients without enteral feeding remained free of gastric colonization for a longer period than those patients receiving enteral feeding . Conclusions Topical antimicrobial prophylaxis , including sucralfate , successfully prevented gastric colonization with potentially pathogenic microorganisms and was correlated with lower gastric pH values . However , the efficacy was markedly decreased when continuous enteral feeding was administered simultaneously . ( Crit Care Med 1994 ; 22:939–944 To determine the effect of illness severity and acute central nervous system injury on the control and variability of gastric pH in pediatric intensive care unit ( ICU ) patients receiving ranitidine . Design : Prospect i ve , descriptive study . Setting : Pediatric ICU of a children 's hospital . Patients : Fourteen pediatric ICU patients . Interventions : Ranitidine ( 4 mg/kg/day ) was administered to all patients . Measurements and Main Results : Patients enrolled in the study were divided into two groups based on illness type and severity . Illness severity was measured by the Pediatric Risk of Mortality ( PRISM ) score , with a PRISM score of > 20 defining severe illness . Illness type was design ated as central nervous system or non central nervous system . Gastric pH was continuously monitored in all patients using an intragastric , pH-sensitive electrode . Poor control of gastric pH was defined as a pH of < 4.0 for > 20 % of the time monitored . The statistical significance of the differences between groups was measured using the Wilcoxon two- sample test or Fisher 's exact test . Patients with severe illness or acute central nervous system injury had a lower mean gastric pH than all other patients ( 4.6 vs. 6.4;p = .008 ) and spent more time with a gastric pH of < 4.0 than other patients ( 47.5 % of time monitored vs. 12.5 % of time monitored ; p = .003 ) . Poor control of gastric pH occurred in 100 % of patients with severe illness or acute central nervous system injury , while only 20 % of the remaining patients had poor control of gastric pH ( p = .01 ) . Using power-spectrum analysis to evaluate gastric pH variability , gastric pH in patients receiving bolus ranitidine was more variable than gastric pH in patients receiving ranitidine continuously ( p = .045 ) . Illness severity or type had no effect on gastric pH variability ( p = .78 ) . Conclusions : a ) Continuous infusion of ranitidine decreases variability of gastric pH in pediatric ICU patients ; b ) gastric pH variability may make intermittent monitoring of gastric pH inaccurate ; c ) children with acute central nervous system injury or PRISM scores of ≥20 have poor control of gastric pH ; d ) type of injury and PRISM scores predict response to ranitidine therapy . ( Crit Care Med 1993 ; 21:1850–1855 OBJECTIVE To assess endoscopically the effect of prophylactic short-term ranitidine treatment in the prevention of stress-induced gastric lesions in neonatal intensive care unit ( ICU ) patients . DESIGN Prospect i ve , r and omized study . SETTING Department of Neonatal Intensive Care , University Hospital of Tampere . PATIENTS Fifty-three infants were enrolled in a r and omized , controlled study . Forty-eight ( 90 % ) of these patients underwent endoscopic examination and were evaluated . INTERVENTIONS A histamine-2-receptor blocker , ranitidine , was given prophylactically after birth for 4 days to infants mechanically ventilated and treated in the neonatal ICU . The gastric mucosa was both visually and histologically evaluated after 3 to 6 days , and the outcome of the infants was registered . MEASUREMENTS AND MAIN RESULTS In the 23 infants prophylactically treated with ranitidine , the gastric mucosa was visually classified as normal in 14 ( 61 % ) infants as compared with five ( 20 % ) of 25 controls ( p < .004 ) . Histologic lesions showed parallel results ( 57 % vs. 16 % , p < .004 ) . Eight gastric ulcers were diagnosed endoscopically in the control group vs. none in the treatment group . The ulcers were all clinical ly " silent " at the time of endoscopy . According to logistic regression modeling , the decreased risk for gastric mucosal lesions in infants receiving prophylactic ranitidine was 0.03 ( 95 % confidence interval 0.003 to 0.178 ) . Surfactant treatment for infant respiratory distress syndrome also decreased the risk for stress-induced gastric mucosal lesions ( odds ratio 0.083 ; 95 % confidence interval 0.009 to 0.788 ) , whereas other variables ( birth weight , gestational age , Apgar scores , cord blood pH , and duration of intubation ) had no significant effect . No side effects could be attributed to the ranitidine treatment . CONCLUSION We conclude that short-term prophylactic ranitidine treatment prevents gastric mucosal lesions in newborn infants under stress Objective To determine the occurrence of upper gastrointestinal hemorrhage in critically ill children , and the efficacy of prophylaxis with almagate ( antacid ) , ranitidine , and sucralfate . Design Prospect i ve , r and omized , controlled trial . Setting Pediatric ICU of a tertiary care pediatric hospital . Patients During a 2-yr study period , 165 patients with one or more upper gastrointestinal hemorrhage risk factors were r and omized into one of four groups . Twenty-five patients were excluded because of protocol violations . A total of 140 patients completed the study , with 35 patients in each group . Interventions Patients received no treatment in the control group . The antacid group received almagate 0.25 to 0.5 mL/kg every 2 hrs by nasogastric tube . The ranitidine group received 1.5 mg/kg every 6 hrs iv . The sucralfate group received 0.5 to 1 g every 6 hrs by nasogastric tube . Methods Gastric pH and macroscopic bleeding were determined every 2 hrs in all patients until the end of the study . Macroscopic bleeding was classified as nonhemorrhage , slight , or important . Microscopic gastric bleeding was research ed with guaiac testing in 72 patients ( 680 sample s ) . The severity of illness was evaluated by using the Therapeutic Intervention Scoring System , Physiologic Stability Index , and the Multiorgan System Failure scores . The risk of upper gastrointestinal hemorrhage was evaluated by the Zinner and Tryba indices , and was modified for children . Measurements and Main Results The occurrence rate of important upper gastrointestinal hemorrhage was higher ( by 20 % ) in the control group than in the rest of the groups ( 5.7 % ) , p < .01 . There were no differences between the other groups ( almagate 5.7 % , ranitidine 8.5 % , and sucralfate 2.8 % ) . There was a statistically significant correlation between the occurrence rate of important upper gastrointestinal hemorrhage , the scores of severity of illness indices ( Therapeutic Intervention Scoring System , Physiologic Stability Index , and the Multiorgan System Failure scoring system ) , the risk of upper gastrointestinal hemorrhage indices ( Zinner and Tryba ) , and mortality rate . The Zinner index better classified the patients in relation to the onset of important upper gastrointestinal hemorrhage ( sensitivity 76.9 % , specificity 85.8 % ) . Conclusions Upper gastrointestinal hemorrhage is an important complication in critically ill children . Prophylaxis with almagate , ranitidine , or sucralfate reduces the occurrence rate of clinical ly important gastrointestinal hemorrhage . ( Crit Care Med 1992 ; 20:1082–1089 Objective To determine the frequency of upper gastrointestinal ( GI ) bleeding in pediatric ICUs . Design Prospect i ve , descriptive study . Setting Pediatric ICU in a university hospital . Patients All children admitted to a pediatric ICU over a 55-wk period . InterventionNone . Measurements and Main Results Upper GI bleeding was considered to be present if there was an episode of hematemesis or if any amount of blood was seen in drainage from a nasogastric tube . Sixty-three ( 6.4 % ) upper GI bleeds were detected among 984 patients : 5.2 % in 698 patients who did not receive upper GI bleeding prophylaxis , and 9.4 % in 286 patients who did receive some prophylaxis . Density was defined as the number of events/1000 days patient . The mean density was 10.8 GI bleeding episodes/1000 days patient in a pediatric ICU . A multivariate analysis detected four independent risk factors or risk markers for upper GI bleeding : high Pediatric Risk of Mortality score , coagulopathy , pneumonia , and multitrauma . Age , sex , hepatic and respiratory failures were identified as confounding variables . An upper GI bleeding episode was defined as being clinical ly important if hypotension , death , or transfusion occurred within 24 hrs after the bleeding . There were four clinical ly important GI bleeding epidodes . All were caused , at least in part , by a coagulopathy . The GI bleeding was associated with a need for transfusion in four children , and with hypotension in two . Conclusions The frequency of upper GI bleeding is substantial , but the rate of occurrence of clinical ly important upper GI bleeding is low , even in a pediatric ICU where most patients do not receive any prophylaxis . ( Crit Care Med 1992 ; 20:35 AIM To determine the optimal doses of ranitidine for both preterm and term infants . METHOD The effect of ranitidine treatment was measured from the long term intraluminal gastric pH in 16 preterm ( gestational age under 37 weeks ) and term infants treated in neonatal intensive care . The infants received three different bolus doses of ranitidine : 0.5 mg , 1.0 mg , and 1.5 mg per kilogram of body weight to keep the intraluminal gastric pH above 4 on a 24 hour basis . RESULTS Critically ill neonates , including very low birth weight infants , were capable of gastric acid formation , and ranitidine treatment increased the intraluminal gastric pH. The effect of a single dose lasted longer in preterm than in term infants . The time needed for reaching the maximum gastric pH was significantly longer in preterm than in term infants . The ranitidine given correlated with the duration of increased gastric pH in a dose dependent manner both in preterm and term infants . CONCLUSION Preterm infants need significantly smaller doses of ranitidine than term neonates to keep their intraluminal gastric pH over 4 . The required optimal dose of ranitidine for preterm infants is 0.5 mg/kg/body weight twice a day and that for term infants 1.5 mg/kg body weight three times a day Essai controle en double-insu des effets de la cimetidine ( n=19 ) contre placebo ( n=21 ) , chez des enfants de 10 jours a 14 ans . La cimetidine accroit le pH du suc gastrique dans les 3 heures apres la 1ere injection intraveineuse mais ne previent pas les saignements macroscopiques gastro-intertinaux ( SMGI ) chez les sujets a risque . Le type de prophylaxie est conteste et les transfusions sanguines demeurent indiquees chez les sujets a Gastric bleeding from stress ulcers in acutely sick infants frequently signals impending mortality . This study was carried out to evaluate the efficacy of cimetidine in preventing and treating stress ulcers in such neonates . One hundred babies were included in this study . Out of this , 32 babies were given prophylactic cimetidine and 68 neonates acted as controls . It was observed that the babies on prophylactic cimetidine fared better than controls . In the second part of study , 77 neonates with clinical evidence of hemorrhage were included , 43 were put on cimetidine and 34 acted as controls . It was observed that babies on cimetidine therapy showed a better response . The gastric bleeding stopped earlier , and more babies responded favourably to this therapy . Use of cimetidine in stress induced bleeding in high risk neonates is recommended Objectives : To determine the efficacy of nasogastric administration of omeprazole suspension in raising the gastric pH > 4 in critically ill pediatric patients and to determine the most appropriate dosing regimen for this indication . Design : Open-label pharmacodynamic study . Setting : Twenty-six bed tertiary-care pediatric intensive care unit . Patients : Mechanically ventilated children aged 1–18 yrs with an additional risk factor for stress ulcer formation . Interventions : Continuous gastric pH monitoring was performed during administration and dose titration of omeprazole suspension to achieve the goal of gastric pH > 4 for greater than 75 % of the dosing interval . Measurements and Main Results : Data were collected from 18 patients . Subjects were categorized based on the pharmacologic response to nasogastric administration of 1 mg/kg omeprazole suspension ( maximum 20 mg ) as rapid ( n = 9 ) , late ( n = 5 ) , and nonresponders ( n = 4 ) . Rapid responders required 0.72 mg/kg per day omeprazole suspension to achieve adequate gastric pH elevation for stress ulcer prophylaxis . Late responders required 1.58 mg/kg per day . Nonresponders did not achieve adequate elevation of gastric pH for stress ulcer prophylaxis . Conclusions : Nasogastric administration of omeprazole suspension has variable efficacy in critically ill pediatric patients . Half of the studied subjects either required significant dose titrations to achieve gastric acid suppression or did not respond to nasogastric administration of omeprazole suspension Objective To determine the occurrence of , and risk factors for , the development of upper gastrointestinal ( GI ) tract bleeding in critically ill pediatric patients . Design Prospect i ve , descriptive , comparative study . Setting ICU in a tertiary care pediatric hospital affiliated with a university . Patients All patients < 19 yrs of age who were admitted to the ICU for a 4-month period ( n = 429 ) were eligible for inclusion . A total of 221 patients were excluded for reasons listed below . Thus , 208 patients were studied . InterventionNone . Measurements and Main Results Patients were evaluated for overt upper GI bleeding as indicated by coffee ground material or bright red blood in gastric aspirates or black , tarry stools . Excluded were patients who were transferred out of the ICU within 24 hrs of admission , were receiving medications that would alter their risk for upper GI bleeding , or had a GI tract surgical procedure . Patients were categorized by diagnoses and analyzed for relative risk for upper GI bleeding . Of the 208 patients included , 25 % had evidence of upper GI bleeding . There was no association between upper GI bleeding and age , weight , race , or sex . Diagnoses independently associated with an increased risk for upper GI bleeding were : circulatory shock , an operative procedure 3 hrs in duration , and trauma . No clinical ly important sequelae were directly attributable to upper GI bleeding in this group of patients ; however , intervention with antacids and histamine-2 receptor ( H-2 ) antagonists likely decreased the progression of GI bleeding . Conclusions Overt evidence of upper GI bleeding is not uncommon in critically ill pediatric patients . Certain diagnoses or risk factors may predispose these patients to develop upper GI bleeding BACKGROUND Gastric bleeding in children is associated with critical illness , shock , and physical trauma . Histamine-2 receptor antagonist therapy is used prophylactically to treat gastric bleeding , but it is not known whether bolus dosing or continuous infusion dosing is more effective . OBJECTIVES To compare the effects of continuous infusion intravenous ranitidine and intravenous bolus dosing of ranitidine on gastric pH in critically ill children and to look for correlation between illness severity scores and gastric pH. METHODS Sixteen critically ill children were r and omized into two groups . Children in group 1 received bolus dosing on day 1 and continuous infusion of ranitidine on day 2 . Group 2 received the continuous infusion on day 1 and bolus dosing on day 2 . Equivalent doses of ranitidine were based on weight . Continuous infusion regimen : ranitidine bolus of 0.15 mg/kg followed by continuous infusion at 0.15 mg/kg per hour for 12 hours . Bolus regimen : 1 mg/kg , two doses 6 hours apart . Pediatric risk of mortality scores were recorded upon admission to the study . RESULTS There was no statistically significant difference between regimens . Both raised gastric pH values above 4.0 during the treatment phase . There was no correlation between illness severity scores and gastric pH values . CONCLUSIONS Both bolus dosing and continuous infusion dosing of 4 mg/kg per day of intravenous ranitidine were effective at raising and maintaining gastric pH in critically ill children We examined the efficacy of intravenous ranitidine and famotidine on raising intragastric pH in each of 10 critically ill pediatric patients . The severity of illness was assessed by using the modified zinner index score . The study had 3 phases and each phase took 24 hours . Intragastric pH was measured by continuous pH monitoring digitrapper for 72 hours . In phase 1 and 3 , the patients did not receive any H2 blockers . In phase 2 , they were r and omized to receive intravenous ranitidine or famotidine . The majority of cases had intragastric pH < 4 in day 1 ( base line ) . Ranitidine and famotidine increased total time of intragastric pH > or = 4 from the base line during day 2 , 38.2 + /- 16.9 per cent and 60.3 + /- 24.8 per cent respectively ( P0.004 ) , but there was no statistical difference between the 2 medications in both Zinner index score 1 and score greater than 1 group ( P 0.08 , 0.45 ) . Three cases in the famotidine group had successful prophylaxis with total time pH > or = 4 more than 80 per cent . Famotidine appeared to have a trend toward increasing intragastric pH in critically ill pediatric patients Objective To determine the pharmacokinetics and pharmacodynamics of ranitidine in critically ill children and to design a dosage regimen that achieves a gastric pH ≥4 . Design Prospect i ve , open-label , pharmacokinetic-pharmacodynamic study . Setting Pediatric intensive care unit in a tertiary care children ’s hospital . Patients Mechanically ventilated , critically ill children ≥10 kg who required intravenous ranitidine for stress ulcer prophylaxis . Interventions Ranitidine pharmacokinetics were determined after a single intravenous dose . Gastric pH was monitored hourly via nasogastric pH probe . After the last blood sample , patients received an intravenous bolus of ranitidine ( 0.5 mg/kg ) followed by a continuous infusion ( 0.1 mg·kg−1·hr−1 ) . The infusion was increased incrementally ( 0.05 mg·kg−1·hr−1 ) until reaching gastric pH ≥4 for ≥75 % of a 24-hr period , after which steady-state plasma concentrations were measured . Plasma concentrations were analyzed by high-pressure liquid chromatography . Measurements and Main Results Twenty-three children ( ranging in age from 1.4 to 17.1 yrs ) were studied . Pharmacokinetic variables included a clearance of 511.7 ± 219.7 mL·kg−1·hr−1 , volume of distribution of 1.53 ± 0.99 L/kg , and half-life of 3.01 ± 1.35 hrs . After the single intravenous dose ( 1.52 ± 0.47 mg/kg ) , gastric pH increased from 1.6 ± 1.0 to 5.1 ± 1.1 ( p < .001 ) , which was associated with a plasma concentration of 373 ± 257 ng/mL. Based on the pharmacokinetic variables , the dose of intravenous ranitidine required to target 373 ng/mL as the average steady-state concentration is 1.5 mg/kg administered every 8 hrs . During the continuous infusion , the mean steady-state ranitidine concentration associated with gastric pH ≥4 was 287 ± 133 ng/mL. This concentration may be achieved with an intravenous loading dose of 0.45 mg/kg followed by a continuous infusion of 0.15 mg·kg−1·hr−1 . Conclusions The pharmacokinetics of ranitidine in critically ill children are variable . The description of ranitidine ’s pharmacokinetics and pharmacodynamics in this study may used to design an initial ranitidine dosage regimen that targets a gastric pH ≥4 . Thereafter , gastric pH should be monitored and the dose of ranitidine adjusted accordingly UNLABELLED In the prophylaxis of stress ulcers with antacids in young infants there are no recommendations of dosages that consider the physiologic maturation of gastric acid secretion . During the first six month of life the amount of gastric acid secretion in relation to body weight and body surface area increases exponentially . Therefore adult dosages of antacids can not be transferred to infants . METHODS In a cross over study 12 infants aged between 4 and 174 days , who had been undergoing a cardiosurgical intervention with the heart lung machine , were treated during 48 hours with 2 different antacid regimens over a period of 24 hours each , monitoring the gastric pH continuously . The used antacid consisted of an aluminium-magnesium complex ( Al(OH)3 , 90 mg/ml and Mg(OH)2 , 60 mg/ml ) : Regimen A : 6 x 0.5 ml per kg body weight . Regimen B : 0.25 ml per kg body weight at a gastric pH less than 3 , with the pH read every 30 minutes . RESULTS Compared to 28 applications under regimen B , 72 single doses were given under regimen A , 58 of them at a gastric pH of higher than 3 . Thus , the mean administered dose was significant lower under regimen B ( 2.2 ml ) than under regimen A ( 12.0 ml ) . Consequently , the mean level of gastric pH was higher under regimen A ( median : 5.96 + /- 1.31 versus 4.94 + /- 1.16 ) . pH-values lower than 3 were more often measured under regimen B , whereas the phases at this pH-level were longer under regimen A. CONCLUSION The usual body weight related dosage of antacids seems to be to high for early infancy . In the face of the discrepancy of the administered antacid quantity comparing regimen A with regimen B , it seems to be reasonable for the studied age group to reduce the single antacid dose to 0.25 ml/kg body weight while adhering to a high application frequency of 6 times a day OBJECTIVES To determine if the administration of ranitidine to neonates leads to an increase in gastric pH to > or = 4 and if this increase in gastric pH correlates with gastric colonization . STUDY DESIGN 628 pH measurements and 276 gastric cultures were obtained from 86 neonates . Twenty-three patients received ranitidine and 63 patients served as controls . RESULTS Treated patients had a mean gastric pH of 5.6 compared with a control mean pH of 4.4 ( p < 0.0001 ) . Gastric pH was significantly affected by feeding and postnatal age . 54 patients were colonized with pathogenic bacteria and /or yeast ( n = 20 treated , n = 34 control ) . Length of hospitalization ( p < 0.0001 ) , increase in gastric pH ( p < 0.01 ) , days of antibiotics before culture ( p < 0.0001 ) , and ranitidine use ( p < 0.0001 ) were associated with an increased rate of colonization . CONCLUSIONS The use of ranitidine did lead to a significant increase in gastric pH and with this increase in gastric pH gastric colonization rates increased . No increased frequency of infection was found in ranitidine-treated infants |
10,831 | 26,109,870 | The corresponding cumulative meta-analyses of the rates of overall response rate , complete response and near complete response , and grade s 3 and 4 peripheral neuropathy supported the superiority of bortezomib-based maintenance therapy over consolidation therapy .
Bortezomib-based therapy after autologous stem cell transplantation , with tolerable AEs , could obviously improve the response as well as the outcome of multiple myeloma patients , particularly when bortezomib was administered as maintenance therapy | OBJECTIVE To evaluate the efficacy and safety of bortezomib-based vs non-bortezomib-based post-transplantation therapy in patients with multiple myeloma . | In patients with multiple myeloma ( MM ) , risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches . In the present study , we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial . Because of the 2-arm design of the study , we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation ( arm B ) compared with st and ard treatment without bortezomib ( arm A ) . For allanalyzed chromosomal aberrations , progression-free survival ( PFS ) and overall survival ( OS ) were at least equal or superior in the bortezomib arm compared with the st and ard arm . Strikingly , patients with del(17p13 ) benefited the most from the bortezomib-containing treatment : the median PFS in arm A was 12.0 months and in arm B it was 26.2 months ( P = .024 ) ; the 3 year-OS for arm A was 17 % and for arm B it was 69 % ( P = .028 ) . After multivariate analysis , del(17p13 ) was an independent predictor for PFS ( P < .0001 ) and OS ( P < .0001 ) in arm A , whereas no statistically significant effect on PFS ( P = .28 ) or OS ( P = .12 ) was seen in arm B. In conclusion , the adverse impact of del(17p13 ) on PFS and OS could be significantly reduced by bortezomib-based treatment , suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13 ) BACKGROUND Thalidomide plus dexamethasone ( TD ) is a st and ard induction therapy for myeloma . We aim ed to assess the efficacy and safety of addition of bortezomib to TD ( VTD ) versus TD alone as induction therapy before , and consolidation therapy after , double autologous stem-cell transplantation in newly diagnosed multiple myeloma . METHODS Patients ( aged 18 - 65 years ) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May , 2006 , and April , 2008 , and data collection continued until June 30 , 2010 . Patients were r and omly allocated ( 1:1 ratio ) by a web-based system to receive three 21-day cycles of thalidomide ( 100 mg daily for the first 14 days and 200 mg daily thereafter ) plus dexamethasone ( 40 mg daily on 8 of the first 12 days , but not consecutively ; total of 320 mg per cycle ) , either alone or with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , and 11 ) . The r and omisation sequence was computer generated by the study coordinating team and was stratified by disease stage . After double autologous stem-cell transplantation , patients received two 35-day cycles of their assigned drug regimen , VTD or TD , as consolidation therapy . The primary endpoint was the rate of complete or near complete response to induction therapy . Analysis was by intention to treat . Patients and treating physicians were not masked to treatment allocation . This study is still underway but is not recruiting participants , and is registered with Clinical Trials.gov , number NCT01134484 , and with EudraCT , number 2005 - 003723 - 39 . FINDINGS 480 patients were enrolled and r and omly assigned to receive VTD ( n=241 patients ) or TD ( n=239 ) . Six patients withdrew consent before start of treatment , and 236 on VTD and 238 on TD were included in the intention-to-treat analysis . After induction therapy , complete or near complete response was achieved in 73 patients ( 31 % , 95 % CI 25·0 - 36·8 ) receiving VTD , and 27 ( 11 % , 7·3 - 15·4 ) on TD ( p<0·0001 ) . Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD ( n=132 , 56 % ) than in those on TD ( n=79 , 33 % ; p<0·0001 ) , with a higher occurrence of peripheral neuropathy in patients on VTD ( n=23 , 10 % ) than in those on TD ( n=5 , 2 % ; p=0·0004 ) . Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD , and in three of five patients on TD . INTERPRETATION VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response , and represents a new st and ard of care for patients with multiple myeloma who are eligible for transplant . FUNDING Seràgnoli Institute of Haematology at the University of Bologna , Bologna , Italy The role of maintenance therapy in multiple myeloma is controversial . Recent studies have shown an improvement in both progression-free and overall survival for patients receiving maintenance treatment with a combination of interferon and glucocorticoids , compared with interferon alone . The role of glucocorticoids alone as maintenance therapy has not been previously addressed . We compared alternate-day , oral prednisone at 2 different dose levels ( 10 mg versus 50 mg ) for remission maintenance among previously untreated myeloma patients following a response to induction with st and ard-dose vincristine , doxorubicin , and dexamethasone with prednisone ( VAD-P ) or VAD-P plus quinine ( VAD-P/Q ) . There were 250 eligible patients registered on Southwest Oncology Group study 9210 and r and omized to receive VAD-P or VAD-P/Q. There were 125 patients achieving at least a 25 % tumor reduction following induction therapy who were r and omized to either physiologic ( 10 mg ) or pharmacologic ( 50 mg ) doses of alternate-day , oral prednisone until disease progression . At the time of study entry , patient characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms r and omized to maintenance therapy . After a median follow-up of 53 months , there was no difference in either progression-free or overall survival between the 2 induction regimens . However , from the time of maintenance r and omization , both progression-free ( 14 versus 5 months ; P = .003 ) and overall survival ( 37 versus 26 months ; P = .05 ) were significantly improved in patients receiving 50 mg as compared with 10 mg alternate-day prednisone . There was no difference in treatment-related adverse events between the groups . Thus , 50 mg , oral , alternate-day prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy . ( Blood . 2002;99:3163 - 3168 Background and Objectives The proteasome inhibitor bortezomib is approved for the treatment of multiple myeloma ( MM ) and , in the US , for the treatment of mantle cell lymphoma following at least one prior therapy ; the recommended dose and schedule is 1.3 mg/m2 on days 1 , 4 , 8 and 11 of 21-day cycles , and the approved routes of administration in the US prescribing information are by intravenous and , following a recent up date , subcutaneous injection . Findings from a phase III study demonstrated that subcutaneous administration of bortezomib , using the same dose and schedule , result ed in similar efficacy with an improved systemic safety profile ( including significantly lower rates of peripheral neuropathy ) versus intravenous bortezomib in patients with relapsed MM . The objectives of this report were to present a comprehensive analysis of the pharmacokinetics and pharmacodynamics of subcutaneous versus intravenous bortezomib , and to evaluate the impact of the subcutaneous administration site , subcutaneous injection concentration and demographic characteristics on bortezomib pharmacokinetics and pharmacodynamics . Patients and Methods Data were analysed from the pharmacokinetic sub study of the r and omized phase III MMY-3021 study and the phase I CAN-1004 study of subcutaneous versus intravenous bortezomib in patients aged ≥18 ( MMY-3021 ) or ≤75 ( CAN-1004 ) years with symptomatic relapsed or refractory MM after 1–3 ( MMY-3021 ) or ≥1 ( CAN-1004 ) prior therapies . Patients received up to eight 21-day cycles of subcutaneous or intravenous bortezomib 1.3 mg/m2 on days 1 , 4 , 8 and 11 . Pharmacokinetic and pharmacodynamic ( 20S proteasome inhibition ) parameters of bortezomib following subcutaneous or intravenous administration were evaluated on day 11 , cycle 1 . Results Bortezomib systemic exposure was equivalent with subcutaneous versus intravenous administration in MMY-3021 [ mean area under the plasma concentration – time curve from time zero to the last quantifiable timepoint ( AUClast ) : 155 vs. 151 ng·h/mL ; geometric mean ratio 0.992 ( 90 % CI 80.18 , 122.80 ) ] and comparable in CAN-1004 ( mean AUClast : 195 vs. 241 ng·h/mL ) ; maximum ( peak ) plasma drug concentration ( Cmax ) was lower with subcutaneous administration in both MMY-3021 ( mean 20.4 vs. 223 ng/mL ) and CAN-1004 ( mean 22.5 vs. 162 ng/mL ) , and time to Cmax ( tmax ) was longer with subcutaneous administration in both studies ( median 30 vs. 2 min ) . Blood 20S proteasome inhibition pharmacodynamic parameters were also similar with subcutaneous versus intravenous bortezomib : mean maximum effect ( Emax ) was 63.7 versus 69.3 % in MMY-3021 and 57.0 versus 68.8 % in CAN-1004 , and mean area under the effect – time curve from time zero to 72 h was 1,714 versus 1,383 % · h in MMY-3021 and 1,619 versus 1,283 % · h in CAN-1004 . Time to Emax was longer with subcutaneous administration in MMY-3021 ( median 120 vs. 5 min ) and CAN-1004 ( median 120 vs. 3 min ) . Concentration of the subcutaneous injected solution had no appreciable effect on pharmacokinetic or pharmacodynamic parameters . There were no apparent differences in bortezomib pharmacokinetic and pharmacodynamic parameters between subcutaneous administration in the thigh or abdomen . There were also no apparent differences in bortezomib exposure related to body mass index , body surface area or age . ConclusionS ubcutaneous administration results in equivalent bortezomib plasma exposure to intravenous administration , together with comparable blood 20S proteasome inhibition pharmacodynamic effects . These findings , together with the non-inferior efficacy of subcutaneous versus intravenous bortezomib demonstrated in MMY-3021 , support the use of bortezomib via the subcutaneous route across the setting s of clinical use in which the safety and efficacy of intravenous bortezomib has been established In a r and omized , phase 3 study , superior complete/near-complete response ( CR/nCR ) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone ( VTD ) versus thalidomide-dexamethasone ( TD ) as induction therapy before , and consolidation after , double autologous stem cell transplantation for newly diagnosed myeloma patients ( intention-to-treat analysis ; VTD , n = 236 ; TD , n = 238 ) . This per- protocol analysis ( VTD , n = 160 ; TD , n = 161 ) specifically assessed the efficacy and safety of consolidation with VTD or TD . Before starting consolidation , CR/nCR rates were not significantly different in the VTD ( 63.1 % ) and TD arms ( 54.7 % ) . After consolidation , CR ( 60.6 % vs 46.6 % ) and CR/nCR ( 73.1 % vs 60.9 % ) rates were significantly higher for VTD-treated versus TD-treated patients . VTD consolidation significantly increased CR and CR/nCR rates , but TD did not ( McNemar test ) . With a median follow-up of 30.4 months from start of consolidation , 3-year progression-free survival was significantly longer for the VTD group ( 60 % vs 48 % for TD ) . Grade 2 or 3 peripheral neuropathy ( 8.1 % vs 2.4 % ) was more frequent with VTD ( grade 3 , 0.6 % ) versus TD consolidation . The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation . VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients r and omly assigned to the VTD arm of the study . The study is registered at www . clinical trials.gov as # NCT01134484 The Nordic Myeloma Study Group conducted an open r and omized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation ( ASCT ) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma . Overall , 370 patients were central ly r and omly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation . The hypothesis was that consolidation therapy would prolong progression-free survival ( PFS ) . The PFS after r and omization was 27 months for the bortezomib group compared with 20 months for the control group ( P = .05 ) . Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after r and omization ( P = .007 ) . No difference in overall survival was seen . Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality -of-life ( QOL ) question naires , whereas no other major differences in QOL were recorded between the groups . Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response ( VGPR ) but not for patients in the ≥ VGPR category at r and omization . Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL . This trial was registered at www . clinical trials.gov as # NCT00417911 Renal impairment is frequent in patients with multiple myeloma and is correlated with an inferior prognosis . This analysis evaluates the prognostic role of renal impairment in patients with myeloma treated with bortezomib before and after autologous stem cell transplantation within a prospect i ve r and omized phase III trial . Eight hundred and twenty-seven newly diagnosed myeloma patients in the HOVON-65/GMMG-HD4 trial were r and omized to receive three cycles of vincristine , adriamycin , dexamethasone ( VAD ) or bortezomib , adriamycin , dexamethasone ( PAD ) followed by autologous stem cell transplantation and maintenance with thalidomide 50 mg daily ( VAD-arm ) or bortezomib 1.3 mg/m2 every 2 weeks ( PAD-arm ) . Baseline serum creatinine was less than 2 mg/dL ( Durie-Salmon-stage A ) in 746 patients and 2 mg/dL or higher ( stage B ) in 81 . In myeloma patients with a baseline creatinine ≥2 mg/dL the renal response rate was 63 % in the VAD-arm and 81 % in the PAD-arm ( P=0.31 ) . The overall myeloma response rate was 64 % in the VAD-arm versus 89 % in the PAD-arm with 13 % complete responses in the VAD-arm versus 36 % in the PAD-arm ( P=0.01 ) . Overall survival at 3 years for patients with a baseline creatinine ≥2 mg/dL was 34 % in the VAD-arm versus 74 % in the PAD-arm ( P<0.001 ) with a progression-free survival rate at 3 years of 16 % in the VAD-arm versus 48 % in the PAD-arm ( P=0.004 ) . Overall and progression-free survival rates in the PAD-arm were similar in patients with a baseline creatinine ≥2 mg/dL or < 2 mg/dL. We conclude that a bortezomib-containing treatment before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in patients with newly diagnosed multiple myeloma . The trial was registered at www.trialregister.nl as NTR213 and at www.controlled-trials.com as IS RCT N The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone ( VTD ) versus thalidomide/dexamethasone ( TD ) versus vincristine , BCNU , melphalan , cyclophosphamide , prednisone/vincristine , BCNU , doxorubicin , dexamethasone/bortezomib ( V BMC P/VBAD/B ) in patients aged 65 years or younger with multiple myeloma . The primary endpoint was complete response ( CR ) rate postinduction and post-autologous stem cell transplantation ( ASCT ) . Three hundred eighty-six patients were allocated to VTD ( 130 ) , TD ( 127 ) , or V BMC P/VBAD/B ( 129 ) . The CR rate was significantly higher with VTD than with TD ( 35 % vs 14 % , P = .001 ) or with V BMC P/VBAD/B ( 35 % vs 21 % , P = .01 ) . The median progression-free survival ( PFS ) was significantly longer with VTD ( 56.2 vs 28.2 vs 35.5 months , P = .01 ) . In an intention-to-treat analysis , the post-ASCT CR rate was higher with VTD than with TD ( 46 % vs 24 % , P = .004 ) or with V BMC P/VBAD/B ( 46 % vs 38 % , P = .1 ) . Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups . In conclusion , VTD result ed in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics . Our results support the use of VTD as a highly effective induction regimen prior to ASCT . The study was registered with http://www . clinical trials.gov ( NCT00461747 ) and Eudra CT ( no. 2005 - 001110 - 41 ) A multicenter phase III study for untreated multiple myeloma was conducted to investigate a switch-induction chemotherapy with melphalan-prednisolone and vincristine-doxorubicin-dexamethasone followed by r and omization on maintenance therapy for patients achieving plateau . Between November 2002 and November 2005 , 34 patients were registered . The study was closed early because of poor accrual . Thirty-three eligible patients , with a median age of 65 years ( range : 47 - 77 years ) were analyzed for the secondary purpose . For induction therapy , 16 patients were treated with vincristine-doxorubicin-dexamethasone and 17 with melphalan-prednisolone initially . In eight cases , induction therapy was switched because of a poor response . Both regimens were well tolerated , but neutropenia , anorexia , constipation and infection with neutropenia were more frequent for vincristine-doxorubicin-dexamethasone . Best response rates were 44 % ( 95 % confidence interval , 20 - 70 ) and 47 % ( 95 % confidence interval , 23 - 72 ) , respectively , for vincristine-doxorubicin-dexamethasone and melphalan-prednisolone . Vincristine-doxorubicin-dexamethasone/melphalan-prednisolone switch-induction therapy might be feasible and effective for Japanese patients with multiple myeloma We present a pooled up date of two large , multicenter MM-009 and MM-010 placebo-controlled r and omized phase III trials that included 704 patients and assessed lenalidomide plus dexamethasone versus dexamethasone plus placebo in patients with relapsed/refractory multiple myeloma ( MM ) . Patients in both studies were r and omized to receive 25 mg daily oral lenalidomide or identical placebo , plus 40 mg oral dexamethasone . In this pooled analysis , using data up to unblinding ( June 2005 for MM-009 and August 2005 for MM-010 ) , treatment with lenalidomide plus dexamethasone significantly improved overall response ( 60.6 vs 21.9 % , P<0.001 ) , complete response rate ( 15.0 vs 2.0 % , P<0.001 ) , time to progression ( median of 13.4 vs 4.6 months , P<0.001 ) and duration of response ( median of 15.8 months vs 7 months , P<0.001 ) compared with dexamethasone-placebo . At a median follow-up of 48 months for surviving patients , using data up to July 2008 , a significant benefit in overall survival ( median of 38.0 vs 31.6 months , P=0.045 ) was retained despite 47.6 % of patients who were r and omized to dexamethasone-placebo receiving lenalidomide-based treatment after disease progression or study unblinding . Low β2-microglobulin and low bone marrow plasmacytosis were associated with longer survival . In conclusion , these data confirm the significant response and survival benefit with lenalidomide and dexamethasone BACKGROUND The effect of interferon-alpha 2b ( IFN-alpha-2b ) on progression-free and overall survival as well as quality of life ( QoL ) was studied in mainly elderly patients with multiple myeloma ( MM ) , who reached a plateau phase after melphalan/prednisone induction . PATIENTS AND METHODS In an open phase III trial , 262 patients , median age 69 years ( range 34 - 91 ) , received at least 10 monthly courses of melphalan/prednisone followed by response evaluation . Plateau phase was reached by 128 patients . Next , 90 patients were r and omized between IFN-alpha-2b and no maintenance therapy . Reasons for non-r and omization were : refusal ( 18 ) , concomitant disease ( nine ) , protocol violation ( six ) , WHO performance status > 2 ( four ) and allogeneic transplantation ( one ) RESULTS At a median follow-up from diagnosis of 97 months ( 0 - 140 ) for those patients alive , IFN-alpha-2b therapy was associated with improved progression-free survival ( median 13.5 versus 8.4 months from r and omization ) , although this did not translate in a better overall survival ( 41 versus 38.4 months ) . One-third of patients discontinued IFN-alpha due to toxicity . No differences were observed between patient groups in QoL. CONCLUSIONS IFN maintenance therapy in MM prolongs progression-free survival and , provided that the burden of toxicity is not too high , does not adversely affect PURPOSE To evaluate the effect of bortezomib as induction therapy before autologous transplantation , followed by lenalidomide as consolidation-maintenance in myeloma patients . PATIENTS AND METHODS Newly diagnosed patients age 65 to 75 years were eligible . Induction ( bortezomib , doxorubicin , and dexamethasone [ PAD ] ) included four 21-day cycles of bortezomib ( 1.3 mg/m(2 ) on days 1 , 4 , 8 , and 11 ) , pegylated liposomal doxorubicin ( 30 mg/m(2 ) on day 4 ) , and dexamethasone ( 40 mg/d ; cycle 1 : days 1 to 4 , 8 to 11 , and 15 to 18 ; cycles 2 to 4 : days 1 to 4 ) . Autologous transplantation was t and em melphalan 100 mg/m(2 ) ( MEL100 ) and stem-cell support . Consolidation included four 28-day cycles of lenalidomide ( 25 mg/d on days 1 to 21 every 28 days ) plus prednisone ( 50 mg every other day ) , followed by maintenance with lenalidomide ( LP-L ; 10 mg/d on days 1 to 21 ) until relapse . Primary end points were safety ( incidence of grade 3 to 4 adverse events [ AEs ] ) and efficacy ( response rate ) . Results A total of 102 patients were enrolled . In a per- protocol analysis , after PAD , 58 % of patients had very good partial response ( VGPR ) or better , including 13 % with complete response ( CR ) ; after MEL100 , 82 % of patients had at least VGPR and 38 % had CR ; and after LP-L , 86 % of patients had at least VGPR and 66 % had CR . After median follow-up time of 21 months , the 2-year progression-free survival rate was 69 % , and the 2-year overall survival rate was 86 % . During induction , treatment-related mortality was 3 % ; grade 3 to 4 AEs included thrombocytopenia ( 17 % ) , neutropenia ( 10 % ) , peripheral neuropathy ( 16 % ) , and pneumonia ( 10 % ) . During consolidation-maintenance , grade 3 to 4 AEs were neutropenia ( 16 % ) , thrombocytopenia ( 6 % ) , pneumonia ( 5 % ) , and cutaneous rash ( 4 % ) . CONCLUSION Bortezomib as induction before autologous transplantation , followed by lenalidomide as consolidation-maintenance , is an effective regimen Incorporation of novel agents has result ed in an improved response rate and reduced side effects in multiple myeloma . This has prompted combining novel agents in induction chemotherapy in patients with newly diagnosed multiple myeloma . Our patients received 2 cycles of vincristine , adriamycin , dexamethasone ( VAD ) and then 2 cycles of bortezomib , thalidomide , dexamethasone ( VTD ) chemotherapy as an induction treatment . Subsequently , autologous stem cell transplantation was performed , and bortezomib was administered as a consolidation therapy . Seventy-one patients were enrolled , and 65 were evaluable for response . After 2 cycles of VAD , the overall response rate was 69 % . After VTD , the response rate improved to 97 % with a complete response ( CR ) and near CR rate of 27 % . Importantly , patients with cytogenetics , having poor prognostic features , all responded after VTD . Autologous stem cells were successfully collected in all 58 patients with a median CD34 + cell count of 7.12 × 106/kg ( range , 1.94–44.7 × 106/kg ) , except in 1 patient ( 2 % ) . After ASCT , 36 patients completed bortezomib maintenance with a combined CR and near CR rate approaching 75 % . Median time to response was rapid ( 1.6 months ) . With a median follow-up duration of 52.7 months , the median TTP was 29.4 months and median OS was not reached . Toxicities proved manageable . In conclusion , sequential VAD and VTD induction therapy in patients with newly diagnosed multiple myeloma was active with manageable toxicity and excellent stem cell yields . The incorporation of bortezomib as a consolidation therapy improved the clinical outcome with the expense of rather frequent development of peripheral neuropathy BACKGROUND Intravenous injection is the st and ard administration route of bortezomib ; however , subcutaneous administration is an important alternative . We compared the efficacy and safety of subcutaneous versus intravenous bortezomib at the approved 1·3 mg/m(2 ) dose and twice per week schedule in patients with relapsed multiple myeloma . METHODS This r and omised , phase 3 study was undertaken at 53 centres in ten countries in Europe , Asia , and South America . Patients aged 18 years and older with relapsed multiple myeloma after one to three previous lines of therapy were r and omly assigned to receive up to eight 21-day cycles of bortezomib 1·3 mg/m(2 ) , on days 1 , 4 , 8 , and 11 , by subcutaneous injection or intravenous infusion . R and omisation was by an interactive voice response system based on a computer-generated r and omisation schedule , stratified by number of previous lines and disease stage . Patients and treating physicians were not masked to treatment allocation . The primary objective was to show non-inferiority of subcutaneous versus intravenous bortezomib in terms of overall response rate ( ORR ) after four cycles in all patients with a diagnosis of measurable , secretory multiple myeloma who received one or more dose of drug ( response-evaluable population ) . Non-inferiority was defined as retaining 60 % of the intravenous treatment effect . This study is registered with Clinical Trials.gov , number NCT00722566 , and is ongoing for long-term follow-up . FINDINGS 222 patients were r and omly assigned to receive subcutaneous ( n=148 ) or intravenous ( n=74 ) bortezomib . The response-evaluable population consisted of 145 patients in the subcutaneous group and 73 in the intravenous group . Patients received a median of eight cycles ( range one to ten ) in both groups . ORR after four cycles was 42 % in both groups ( 61 patients in subcutaneous group and 31 in intravenous group ; ORR difference -0·4 % , 95 % CI -14·3 to 13·5 ) , showing non-inferiority ( p=0·002 ) . After a median follow-up of 11·8 months ( IQR 7·9 - 16·8 ) in the subcutaneous group and 12·0 months ( 8·1 - 15·6 ) in the intravenous group , there were no significant differences in time to progression ( median 10·4 months , 95 % CI 8·5 - 11·7 , vs 9·4 months , 7·6 - 10·6 ; p=0·387 ) and 1-year overall survival ( 72·6 % , 95 % CI 63·1 - 80·0 , vs 76·7 % , 64·1 - 85·4 ; p=0·504 ) with subcutaneous versus intravenous bortezomib . Grade 3 or worse adverse events were reported in 84 ( 57 % ) patients in the subcutaneous group versus 52 ( 70 % ) in the intravenous group ; the most common were thrombocytopenia ( 19 [ 13 % ] vs 14 [ 19 % ] ) , neutropenia ( 26 [ 18 % ] vs 13 [ 18 % ] ) , and anaemia ( 18 [ 12 % ] vs six [ 8 % ] ) . Peripheral neuropathy of any grade ( 56 [ 38 % ] vs 39 [ 53 % ] ; p=0·044 ) , grade 2 or worse ( 35 [ 24 % ] vs 30 [ 41 % ] ; p=0·012 ) , and grade 3 or worse ( nine [ 6 % ] vs 12 [ 16 % ] ; p=0·026 ) was significantly less common with subcutaneous than with intravenous administration . Subcutaneous administration was locally well tolerated . INTERPRETATION Subcutaneous bortezomib offers non-inferior efficacy to st and ard intravenous administration , with an improved safety profile . FUNDING Johnson & Johnson Pharmaceutical Research and Development , and Millennium Pharmaceuticals The frequency , characteristics and reversibility of bortezomib‐associated peripheral neuropathy were evaluated in the phase III APEX ( Assessment of Proteasome Inhibition for Extending Remissions ) trial in patients with relapsed myeloma , and the impact of a dose‐modification guideline on peripheral neuropathy severity and reversibility was assessed . Patients received bortezomib 1·3 mg/m2 ( days 1 , 4 , 8 , 11 , eight 21‐d cycles , then days 1 , 8 , 15 , 22 , three 35‐d cycles ) ; bortezomib was held , dose‐reduced or discontinued depending on peripheral neuropathy severity , according to a protocol ‐specified dose‐modification guideline . Overall , 124/331 patients ( 37 % ) had treatment‐emergent peripheral neuropathy , including 30 ( 9 % ) with grade ≥3 ; incidence and severity were not affected by age , number/type of prior therapies , baseline glycosylated haemoglobin level , or diabetes history . Grade ≥3 incidence appeared lower versus phase II trials ( 13 % ) that did not specifically provide dose‐modification guidelines . Of patients with grade ≥2 peripheral neuropathy , 58/91 ( 64 % ) experienced improvement or resolution to baseline at a median of 110 d , including 49/72 ( 68 % ) who had dose modification versus 9/19 ( 47 % ) who did not . Efficacy did not appear adversely affected by dose modification for grade ≥2 peripheral neuropathy . Bortezomib‐associated peripheral neuropathy is manageable and reversible in most patients with relapsed myeloma . Dose modification using a specific guideline improves peripheral neuropathy management without adversely affecting outcome PURPOSE This prospect i ve multicenter phase III study compared the efficacy and safety of a triple combination ( bortezomib-thalidomide-dexamethasone [ VTD ] ) versus a dual combination ( thalidomide-dexamethasone [ TD ] ) in patients with multiple myeloma ( MM ) progressing or relapsing after autologous stem-cell transplantation ( ASCT ) . PATIENTS AND METHODS Overall , 269 patients were r and omly assigned to receive bortezomib ( 1.3 mg/m(2 ) intravenous bolus ) or no bortezomib for 1 year , in combination with thalidomide ( 200 mg per day orally ) and dexamethasone ( 40 mg orally once a day on 4 days once every 3 weeks ) . Bortezomib was administered on days 1 , 4 , 8 , and 11 with a 10-day rest period ( day 12 to day 21 ) for eight cycles ( 6 months ) , and then on days 1 , 8 , 15 , and 22 with a 20-day rest period ( day 23 to day 42 ) for four cycles ( 6 months ) . RESULTS Median time to progression ( primary end point ) was significantly longer with VTD than TD ( 19.5 v13.8 months ; hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.80 ; P = .001 ) , the complete response plus near-complete response rate was higher ( 45 % v 21 % ; P 0.001 ) , and the median duration of response was longer ( 17.9 v 13.4 months ; P.04 ) [corrected].The 24-month survival rate was in favor of VTD ( 71 % v 65 % ; P = .093 ) . Grade 3 peripheral neuropathy was more frequent with VTD ( 29 % v 12 % ; P = .001 ) as were the rates of grade s 3 and 4 infection and thrombocytopenia . CONCLUSION VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity PURPOSE We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma ( MM ) . PATIENTS AND METHODS In all , 827 eligible patients with newly diagnosed symptomatic MM were r and omly assigned to receive induction therapy with vincristine , doxorubicin , and dexamethasone ( VAD ) or bortezomib , doxorubicin , and dexamethasone ( PAD ) followed by high-dose melphalan and autologous stem-cell transplantation . Maintenance consisted of thalidomide 50 mg ( VAD ) once per day or bortezomib 1.3 mg/m(2 ) ( PAD ) once every 2 weeks for 2 years . The primary analysis was progression-free survival ( PFS ) adjusted for International Staging System ( ISS ) stage . RESULTS Complete response ( CR ) , including near CR , was superior after PAD induction ( 15 % v 31 % ; P < .001 ) and bortezomib maintenance ( 34 % v 49 % ; P < .001 ) . After a median follow-up of 41 months , PFS was superior in the PAD arm ( median of 28 months v 35 months ; hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.62 to 0.90 ; P = .002 ) . In multivariate analysis , overall survival ( OS ) was better in the PAD arm ( HR , 0.77 ; 95 % CI , 0.60 to 1.00 ; P = .049 ) . In high-risk patients presenting with increased creatinine more than 2 mg/dL , bortezomib significantly improved PFS from a median of 13 months to 30 months ( HR , 0.45 ; 95 % CI , 0.26 to 0.78 ; P = .004 ) and OS from a median of 21 months to 54 months ( HR , 0.33 ; 95 % CI , 0.16 to 0.65 ; P < .001 ) . A benefit was also observed in patients with deletion 17p13 ( median PFS , 12 v 22 months ; HR , 0.47 ; 95 % CI , 0.26 to 0.86 ; P = .01 ; median OS , 24 months v not reached at 54 months ; HR , 0.36 ; 95 % CI , 0.18 to 0.74 ; P = .003 ) . CONCLUSION Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS |
10,832 | 20,956,649 | Moderate- quality evidence suggests that daily use of oral finasteride increases hair count and improves patient and investigator assessment of hair appearance , while increasing the risk of sexual dysfunction | CONTEXT And rogenetic alopecia is the most common form of alopecia in men .
OBJECTIVE To determine the efficacy and safety of finasteride therapy for patients with and rogenetic alopecia . | BACKGROUND And rogenetic alopecia ( male pattern hair loss ) is caused by and rogen-dependent miniaturization of scalp hair follicles , with scalp dihydrotestosterone ( DHT ) implicated as a contributing cause . Finasteride , an inhibitor of type II 5alpha-reductase , decreases serum and scalp DHT by inhibiting conversion of testosterone to DHT . OBJECTIVE Our purpose was to determine whether finasteride treatment leads to clinical improvement in men with male pattern hair loss . METHODS In two 1-year trials , 1553 men ( 18 to 41 years of age ) with male pattern hair loss received oral finasteride 1 mg/d or placebo , and 1215 men continued in blinded extension studies for a second year . Efficacy was evaluated by scalp hair counts , patient and investigator assessment s , and review of photographs by an expert panel . RESULTS Finasteride treatment improved scalp hair by all evaluation techniques at 1 and 2 years ( P < .001 vs placebo , all comparisons ) . Clinical ly significant increases in hair count ( baseline = 876 hairs ) , measured in a 1-inch diameter circular area ( 5.1 cm2 ) of balding vertex scalp , were observed with finasteride treatment ( 107 and 138 hairs vs placebo at 1 and 2 years , respectively ; P < .001 ) . Treatment with placebo result ed in progressive hair loss . Patients ' self- assessment demonstrated that finasteride treatment slowed hair loss , increased hair growth , and improved appearance of hair . These improvements were corroborated by investigator assessment s and assessment s of photographs . Adverse effects were minimal . CONCLUSION In men with male pattern hair loss , finasteride 1 mg/d slowed the progression of hair loss and increased hair growth in clinical trials over 2 years BACKGROUND Finasteride , a type II 5alpha-reductase inhibitor , reduces scalp and serum dihydrotestosterone and has been shown to be effective in men with and rogenetic alopecia ( AGA ) . OBJECTIVE The purpose of this study was to determine the effect of finasteride on scalp hair weight in men with AGA . METHODS Sixty-six men with AGA received finasteride , 1 mg/d , or placebo in a 48-week study , and 49 men continued in a 48-week extension . Efficacy was assessed by scalp hair weights and hair counts . RESULTS As expected , hair counts improved with finasteride ( net mean percent change + /- SE [ 95 % CI ] compared with placebo = 9.2 % + /- 2.8 % [ 3.8 , 14.6 ] and 15.4 % + /- 3.2 % [ 9.1 , 21.7 ] at 48 and 96 weeks , respectively ; P < .01 for both time points ) , and net improvements in hair weight were greater ( 25.6 % + /- 3.6 % [ 18.5 , 32.7 ] and 35.8 % + /- 4.6 % [ 26.7 , 44.8 ] at 48 and 96 weeks , respectively ; P < .001 for both time points ) . Finasteride was generally well tolerated . CONCLUSION In this study , finasteride , 1 mg , increased hair weight in men with AGA . Hair weight increased to a larger extent than hair count , implying that factors other than the number of hairs , such as increased growth rate ( length ) and thickness of hairs , contribute to the beneficial effects of finasteride in treated men BACKGROUND Finasteride , a specific inhibitor of type II 5alpha-reductase , decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss . OBJECTIVE This study evaluated the efficacy of finasteride 1 mg/day in men with frontal ( anterior/mid ) scalp hair thinning . METHODS This was a 1-year , double-blind , placebo-controlled study followed by a 1-year open extension . Efficacy was assessed by hair counts ( 1 cm2 circular area ) , patient and investigator assessment s , and global photographic review . RESULTS There was a significant increase in hair count in the frontal scalp of finasteride-treated patients ( P < .001 ) , as well as significant improvements in patient , investigator , and global photographic assessment s. Efficacy was maintained or improved throughout the second year of the study . Finasteride was generally well tolerated . CONCLUSION In men with hair loss in the anterior/mid area of the scalp , finasteride 1 mg/day slowed hair loss and increased hair growth BACKGROUND Male pattern hair loss ( MPHL ) is a potentially reversible condition in which dihydrotestosterone is an important etiologic factor . OBJECTIVE Our aim was to evaluate the efficacy of the type 1 and 2 5alpha-reductase inhibitor dutasteride in men with MPHL . METHODS Four hundred sixteen men , 21 to 45 years old , were r and omized to receive dutasteride 0.05 , 0.1 , 0.5 or 2.5 mg , finasteride 5 mg , or placebo daily for 24 weeks . RESULTS Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks . Expert panel photographic review and investigator assessment of hair growth confirmed these results . Scalp and serum dihydrotestosterone levels decreased , and testosterone levels increased , in a dose-dependent fashion with dutasteride . LIMITATIONS The study was limited to 24 weeks . CONCLUSION Dutasteride increases scalp hair growth in men with MPHL . Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of MPHL Background Finasteride is a competitive inhibitor of 5 alpha-reductase enzyme , and is used for treatment of benign prostatic hyperplasia and and rogenetic alopecia . Animal studies have shown that finasteride might induce behavioral changes . Additionally , some cases of finasteride-induced depression have been reported in humans . The purpose of this study was to examine whether depressive symptoms or anxiety might be induced by finasteride administration . Methods One hundred and twenty eight men with and rogenetic alopecia , who were prescribed finasteride ( 1 mg/day ) were enrolled in this study . Information on depressed mood and anxiety was obtained by Beck Depression Inventory ( BDI ) , and Hospital Anxiety and Depression Scale ( HADS ) . Participants completed BDI and HADS question naires before beginning the treatment and also two months after it . Results Mean age of the subjects was 25.8(± 4.4 ) years . At baseline , mean BDI and HADS depression scores were 12.11(± 7.50 ) and 4.04(± 2.51 ) , respectively . Finasteride treatment increased both BDI ( p < 0.001 ) and HADS depression scores significantly ( p = 0.005 ) . HADS anxiety scores were increased , but the difference was not significant ( p = 0.061 ) . Conclusion This preliminary study suggests that finasteride might induce depressive symptoms ; therefore this medication should be prescribed cautiously for patients with high risk of depression . It seems that further studies would be necessary to determine behavioral effects of this medication in higher doses and in more susceptible patients A 24-month double-blind , r and omized , placebo-controlled , parallel-group , multicenter study of 424 men was conducted to determine the efficacy and tolerability of finasteride 1 mg on hair growth/loss in men aged 41 to 60 years with mild-to-moderate , predominantly vertex male pattern hair loss . Efficacy was evaluated by review of global photographs of the vertex scalp taken at baseline and at Months 6 , 12 , 18 , and 24 and by patient self- assessment s and investigator clinical assessment s of change from baseline in hair growth/loss collected at Months 6 , 12 , 18 , and 24 . Safety analyses included assessment of clinical and laboratory adverse experiences , including sexual adverse experiences . Analysis of global photographic assessment data showed significant improvement in hair growth for men in the finasteride group compared with those taking placebo beginning at Month 6 ( p < 0.001 ) and maintained through Month 24 ( p < 0.001 ) . Results of the patient self- assessment and investigator assessment s were consistent with those from the global photographic assessment . Finasteride 1 mg improved scalp hair growth in men aged 41 to 60 years with predominantly vertex male pattern hair loss compared with results seen with placebo . Improvement was evident by 6 months of treatment and continued through 24 months . Treatment with finasteride 1 mg was generally well tolerated BACKGROUND And rogenetic alopecia is a common condition of adult men . Finasteride , a type 2 5alpha-reductase inhibitor , decreases the formation of dihydrotestosterone from testosterone . OBJECTIVE Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition . METHODS Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5 , 1 , 0.2 , or 0.01 mg/day or placebo based on r and om assignment . Efficacy was determined by scalp hair counts , patient self- assessment , investigator assessment , and assessment of clinical photographs . Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences . RESULTS Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher , with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses . Efficacy of the 0.01 mg dose was similar to placebo . No significant safety issues were identified in the trials . CONCLUSION Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development BACKGROUND Data suggest that and rogenetic alopecia is a process dependent on dihydrotestosterone ( DHT ) and type 2 5alpha-reductase . Finasteride is a type 2 5alpha-reductase inhibitor that has been shown to slow further hair loss and improve hair growth in men with and rogenetic alopecia . OBJECTIVE We attempted to determine the effect of finasteride on scalp skin and serum and rogens . METHODS Men with and rogenetic alopecia ( N = 249 ) underwent scalp biopsies before and after receiving 0.01 , 0.05 , 0.2 , 1 , or 5 mg daily of finasteride or placebo for 42 days . RESULTS Scalp skin DHT levels declined significantly by 13.0 % with placebo and by 14.9 % , 61.6 % , 56 . 5 % , 64.1 % , and 69.4 % with 0.01 , 0.05 , 0.2 , 1 , and 5 mg doses of finasteride , respectively . Serum DHT levels declined significantly ( P < .001 ) by 49.5 % , 68.6 % , 71.4 % , and 72.2 % in the 0.05 , 0.2 , 1 , and 5 mg finasteride treatment groups , respectively . CONCLUSION In this study , doses of finasteride as low as 0.2 mg per day maximally decreased both scalp skin and serum DHT levels . These data support the rationale used to conduct clinical trials in men with male pattern hair loss at doses of finasteride between 0.2 and 5 mg BACKGROUND Finasteride 1 mg ( Propecia ) is indicated for the treatment of men with and rogenetic alopecia ( male pattern hair loss , MPHL ) . However , the long-term ( > 2 years ) efficacy and safety of finasteride in this population has not been previously reported . Objectives . To assess the efficacy and safety of finasteride in men with MPHL compared to treatment with placebo over five years . METHODS In two 1-year , Phase III trials , 1,553 men with MPHL were r and omized to receive finasteride 1 mg/day or placebo , and 1,215 men continued in up to four 1-year , placebo-controlled extension studies . Efficacy was evaluated by hair counts , patient and investigator assessment s , and panel review of clinical photographs . RESULTS Treatment with finasteride led to durable improvements in scalp hair over five years ( p 3/4 0.001 versus placebo , all endpoints ) , while treatment with placebo led to progressive hair loss . Finasteride was generally well tolerated and no new safety concerns were identified during long-term use . CONCLUSIONS In men with MPHL , long-term treatment with finasteride 1 mg/day over five years was well tolerated , led to durable improvements in scalp hair growth , and slowed the further progression of hair loss that occurred without treatment BACKGROUND Our practical experience indicates that sexual side-effects in subjects taking finasteride 1 mg ( Propecia ) for and rogenetic alopecia are much less common than reported in the literature . OBJECTIVE To evaluate the sexual function in subjects taking finasteride ( 1 mg ) compared with age-matched controls using the International Index of Erectile Function ( IIEF ) . METHODS The IIEF , a brief , reliable question naire , was self-administered to 236 patients taking Propecia and 236 age-matched males attending the Department of Dermatology of the University of Bologna . RESULTS Statistical analysis showed no differences between scores obtained with the IIEF in subjects taking finasteride and controls . CONCLUSIONS The sexual and erectile function of subjects taking finasteride does not significantly differ from that of age-matched controls . This is consistent with the experience of many dermatologists who do not see sexual or erectile dysfunction in patients taking Propecia Finasteride is a type 2 5 alpha-reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone , a key mediator of male pattern hair loss ( and rogenetic alopecia ) . The objective of this study was to identify the optimal dosage of finasteride and to evaluate its efficacy and safety in the treatment of Japanese men with male pattern hair loss . In this double- blind r and omized study , 414 Japanese men with male pattern hair loss received finasteride 1 mg ( n = 139 ) , finasteride 0.2 mg ( n = 137 ) , or placebo ( n = 38 ) once daily for 48 weeks . Efficacy was evaluated by global photographic assessment , patient self- assessment , and investigator assessment . All efficacy endpoints showed significant improvement with finasteride therapy by 12 weeks ( p < 0.05 versus placebo ) . At 48 weeks , 58 % , 54 % , and 6 % of men in the finasteride 1 mg , finasteride 0.2 mg , and placebo groups , respectively , had improved based on assessment s of global photographs . All efficacy endpoints were numerically superior for the 1 mg dose over the 0.2 mg dose at 48 weeks . Finasteride treatment was generally well tolerated . Finasteride 1 mg\day slows hair loss and improves hair growth in Japanese men with male pattern hair loss Twenty-eight men with AGA , aged 53 - 76 years ( mean , 65 years ) , were selected to participate in this trial from a double blind , placebo controlled , multicenter study of subjects with moderate symptoms of BPH . Patients received either finasteride 5 mg or placebo daily for 24 months . Hair counts were performed at entry to the study and at 6 , 12 , 18 , and 24 months . Hair counts were made directly on the scalp in a circular target area 1 in in diameter , located in the center of a template . The template was applied in such a way that its counting window fell on the most balding scalp area , which remained the same for each patient.11 At each hair counting session , patients were asked about side-effects and question ed about their sex life . Time trend and differences between groups were examined using a one-way ( treatment ) MANOVA with repeated measures ( baseline , 6 , 12 , 18 , and 24 months ) . Additional two-tailed t-tests were performed to compare the two groups at each point of time . P < 0.05 was considered to be significant BACKGROUND We previously reported the effects of finasteride on scalp hair weight and count over a 2-year period in men with and rogenetic alopecia ( AGA ) . OBJECTIVE Our purpose was to evaluate the effects of finasteride on hair weight and count over 4 years in men with AGA . METHODS Men with AGA were r and omized to receive finasteride ( 1 mg/d ) or placebo for 192 weeks . Results of the second ( weeks 96 - 144 ) and third ( weeks 144 - 192 ) extension periods are reported . RESULTS Finasteride increased hair weight at 144 and 192 weeks ( week 192 : finasteride , 21.6 % increase from baseline ; placebo , 24.5 % decrease from baseline ; net increase in hair weight for finasteride vs placebo = 46.0 % , P < .001 ) . Hair count also increased with finasteride at 144 and 192 weeks ( week 192 : finasteride , 7.2 % increase from baseline ; placebo , 13.0 % decrease from baseline ; net increase in hair count for finasteride vs placebo = 20.3 % , P < .05 ) . Finasteride was generally well tolerated . LIMITATIONS Because this study was extended from its original 48-week duration to nearly 4 years , the sample size available for analysis decreased with time . CONCLUSION Long-term finasteride treatment led to sustained improvement in hair weight compared with placebo . Hair weight increased to a larger extent than hair count , implying that factors other than the number of hairs , such as increased growth rate ( length ) and thickness of hairs , contribute to the beneficial effects of finasteride in treated men Background The growth of scalp hair is a cyclical process of successive phases of growth ( anagen ) and rest ( telogen ) . In previous clinical trials in men with and rogenetic alopecia , treatment with finasteride increased scalp hair counts in a defined area ( i.e. increased hair density ) . Objectives The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle . Patients / Methods Two hundred and twelve men , age 18–40 years , with and rogenetic alopecia were r and omized to receive finasteride 1 mg daily or placebo for 48 weeks . At baseline and at 24 and 48 weeks , macrophotographs were taken to measure total and anagen hair count in a 1‐cm2 target area of the scalp . Results At baseline , mean total and anagen hair counts in the finasteride group were 200 and 124 hairs , respectively ( % anagen = 62 % ) and the anagen to telogen ratio was 1·74 ( geometric mean ) . In the placebo group , the respective values were 196 and 119 hairs ( % anagen = 60 % ) and 1·57 . At week 48 , the finasteride group had a net improvement ( mean ± SE ) compared with placebo in total and anagen hair counts of 17·3 ± 2·5 hairs ( 8·3 % ± 1·4 % ) and 27·0 ± 2·9 hairs ( 26 % ± 3·1 % ) , respectively ( P < 0·001 ) . Furthermore , treatment with finasteride result ed in a net improvement in the anagen to telogen ratio of 47 % ( P < 0·001 ) . In this study , treatment with finasteride 1 mg day−1 for 48 weeks increased both total and anagen hair counts , and improved the anagen to telogen ratio . Conclusions These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase . These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients OBJECTIVES This study compared the efficacy of finasteride with placebo in the treatment of male pattern hair loss ( and rogenetic alopecia ) in nine pairs of male identical twins . METHODS In this r and omized , double-blind , placebo-controlled , single-center study , one twin from each identical twin pair received finasteride 1 mg/day for one year while the other received placebo . Hair growth was evaluated from st and ardized clinical photographs , hair counts and patient self- assessment question naires . Serum dihydrotestosterone and testosterone levels were analyzed and adverse events recorded . RESULTS Finasteride significantly improved hair growth at one year compared to placebo ( p < 0.05 ) based on analysis of photographs of the vertex and superior-frontal scalp . These results were consistent with the hair count change measured in the finasteride group , which was superior ( p < 0.05 ) to the change measured in the placebo group . Patient self- assessment demonstrated that treatment with finasteride , in comparison to placebo , led to improvements in scalp hair growth and patients ' satisfaction with appearance of hair . No drug-related adverse events were reported during the study . CONCLUSION Through the use of identical twins , this study provides further evidence that finasteride significantly reduces hair loss progression and restores hair growth in men with male pattern hair loss Background The improved scalp coverage achieved by hair transplant for men with and rogenetic alopecia can be diminished by continued miniaturization and loss of preexisting , nontransplanted hairs . Objectives To evaluate whether finasteride 1 mg , administered daily from 4 weeks before until 48 weeks after hair transplant , improves scalp hair and growth of nontransplanted hair in areas surrounding the transplant and to evaluate the safety and tolerability of finasteride for men undergoing hair transplant . Methods In this r and omized , double-blind , placebo-controlled study , 79 men with and rogenetic alopecia ( 20–45 years of age ) were assigned to treatment with finasteride 1 mg ( n = 40 ) or placebo ( n = 39 ) once daily from 4 weeks before until 48 weeks after hair transplant . Efficacy was evaluated by review of global photographs by an expert dermatologist and by macrophotography for scalp hair counts . Results Treatment with finasteride result ed in significant improvements from baseline , compared with placebo , in scalp hair based on global photographic assessment ( p < .01 ) and hair counts ( p < .01 ) at week 48 . Visible increases in superior/frontal scalp hair post-transplant were recorded for 94 % and 67 % of patients in the finasteride and placebo groups , respectively . Finasteride treatment was generally well tolerated . Conclusion For men with and rogenetic alopecia , therapy with finasteride 1 mg daily from 4 weeks before until 48 weeks after hair transplant improves scalp hair surrounding the hair transplant and increases hair density |
10,833 | 23,943,471 | The strongest evidence currently exists for mindfulness-based interventions and St. John ’s Wort ( SJW ) as monotherapies , and there is relatively strong evidence to support the use of omega-3 fatty acids and exercise as adjunct therapies .
However , there remains an overall lack of method ologically rigorous research to support the efficacy of many other IntM techniques . | Integrative medicine ( IntM ) is a growing medical trend combining conventional medical approaches with evidence -based complementary therapies to promote well-being .
Over half of individuals with depression use some form of IntM for symptom management .
The purpose of the current study was to critically review the scientific evidence for IntM techniques in treating adult unipolar depression . | BACKGROUND Nearly two-thirds of elderly patients treated for depression fail to achieve symptomatic remission and functional recovery with first-line pharmacotherapy . In this study , we ask whether a mind-body exercise , Tai Chi Chih ( TCC ) , added to escitalopram will augment the treatment of geriatric depression design ed to achieve symptomatic remission and improvements in health functioning and cognitive performance . METHODS : One hundred twelve older adults with major depression age 60 years and older were recruited and treated with escitalopram for approximately 4 weeks . Seventy-three partial responders to escitalopram continued to receive escitalopram daily and were r and omly assigned to 10 weeks of adjunct use of either 1 ) TCC for 2 hours per week or 2 ) health education ( HE ) for 2 hours per week . All participants underwent evaluations of depression , anxiety , resilience , health-related quality of life , cognition , and inflammation at baseline and during 14-week follow-up . RESULTS Subjects in the escitalopram and TCC condition were more likely to show greater reduction of depressive symptoms and to achieve a depression remission as compared with those receiving escitalopram and HE . Subjects in the escitalopram and TCC condition also showed significantly greater improvements in 36-Item Short Form Health Survey physical functioning and cognitive tests and a decline in the inflammatory marker , C-reactive protein , compared with the control group . CONCLUSION : Complementary use of a mind-body exercise , such as TCC , may provide additional improvements of clinical outcomes in the pharmacologic treatment of geriatric depression Objective This study examined the feasibility , safety , and efficacy of using tai chi for treating major depressive disorder . Design Thirty-nine Chinese Americans with major depressive disorder were r and omized into a 12-wk tai chi intervention or a waitlisted control group in a 2:1 ratio . The key outcome measurement was the 17-item Hamilton Rating Scale for Depression . Positive response was defined as a decrease of 50 % or more on the 17-item Hamilton Rating Scale for Depression , and remission was defined as a score of 7 or lower on the 17-item Hamilton Rating Scale for Depression . Results Of the participants ( n = 39 ) , 77 % were women , and mean ( SD ) age was 55 ( 10 ) years . There were 26 ( 67 % ) participants in the tai chi intervention group and 13 ( 33 % ) in the control group . Of the participants in the tai chi group , 73 % completed the intervention ; no adverse events were reported . We observed trends toward improvement in the tai chi intervention group , compared with the control group , in positive treatment-response rate ( 24 % vs. 0 % ) and remission rate ( 19 % vs. 0 % ) , although the differences in our small sample did not reach statistical significance . Conclusions A r and omized controlled trial of tai chi is feasible and safe in Chinese American patients with major depressive disorder . These promising pilot study results inform the design of a more definitive trial BACKGROUND There appears to be consensus that patients with only one or two prior depressive episodes do not benefit from treatment with mindfulness-based cognitive therapy ( MBCT ) . AIMS To investigate whether the effect of MBCT on residual depressive symptoms is contingent on the number of previous depressive episodes ( trial number NTR1084 ) . METHOD Currently non-depressed adults with residual depressive symptoms and a history of depression ( ≤2 prior episodes : n = 71 ; ≥3 episodes : n = 59 ) were r and omised to MBCT ( n = 64 ) or a waiting list ( control : n = 66 ) in an open-label , r and omised controlled trial . The main outcome measured was the reduction in residual depressive symptoms ( Hamilton Rating Scale for Depression , HRSD-17 ) . RESULTS Mindfulness-based cognitive therapy was superior to the control condition across subgroups ( β = -0.56 , P<0.001 ) . The interaction between treatment and subgroup was not significant ( β = 0.45 , P = 0.16 ) . CONCLUSIONS Mindfulness-based cognitive therapy reduces residual depressive symptoms irrespective of the number of previous episodes of major depression Mental health problems continue topresent a global challenge and contributesignificantly to the global burden ofhuman disease ( DALYs ) . Depression isthe most common psychiatric disorder and is thought to affect 121 million adultsworldwide , and as such was rated as thefourth leading cause of disease burden in2000 ( Moussavi et al. , 2007 ) , projected tobecome the highest cause of disease bur-den by 2020 . Antidepressant drugs are aneffective and commonly used treatmentfor depression in primary care ( Arrollet al. , 2009 ) , although almost half of thosetreated do not achieve full remission oftheir symptoms , and there remains a riskof residual symptoms , relapse/recurrence(Fava and Ruini , 2002 ) . In those patients who do demonstrate improvements indepressive symptoms with antidepres-sant therapies , a time-lag in the onset oftherapeutic effects is frequently reported . Antidepressant drugs are associated withadverse side effects ( Agency for Health Research and Quality ( AHRQ ) , 2012 ) and an increased risk of cardiovascu-lar disease , particularly in those withpre-existing cardiovascular conditions ormajor cardiovascular risk factors ( Waring,2012 ) . Furthermore , adherence to antide-pressant medications is often poor and patients often prematurely discontinuetheir antidepressant therapy ; it has beensuggested that approximately 50 % of psy-chiatric patients and 50 % of primary care patients are non-adherent when assessed6-months after the initiation of treatment(Sansone and Sansone , 2012).Psychological treatments for depres-sion have been recommended in theUK National Institute for Health and Clinical Excellence ( NICE ) guidelines ( NICE , 2009 ) and are becoming morecommonplace for helping to reducesymptoms in depressed adults ( Ambresinet al. , 2012 ; Brakemeier and Frase , 2012),with even brief psychosocial interven-tions showing promise for improvingadherence to depression medication treat-ment in primary care setting s ( Sirey et al.,2010).However , attendance atpsychologi-cal intervention sessions can be poor sincemany depressed adults who may benefitfromsuch treatments choosenotto attendmental health clinics due to the perceivedstigma ofpsychological therapies . As such there has been an increasinginterest in the role of alternative inter-ventions for depression . Physical exercisehas been proposed as a complementarytreatment which may help to improveresidual symptoms of depression and pre-vent relapse ( Trivedi et al. , 2006 ) . Exercisehas been proposed by many as a poten-tial treatment for depression and meta- analysis has demonstrated that effect sizesin intervention studies range from -0.80to -1.1 ( Rethorst et al. , 2009 ) . However , the evidence is not always consistent;recent research has shown that that pro-vision of tailored advice and encourage-ment for physical activity did not improvedepression outcome or antidepressant usein depressed adults when compared withusual care ( Chalder et al. , 2012 ) . Other research ers have failed to find an antide-pressant effect of exercise in patients with major depression but have foundshort term positive effects on physical outcomes , body composition and mem-ory ( Krogh et al. , 2012 ) . Others haveargued that the nature of exercise deliv-ery is an important factor , with exer-cise of preferred ( rather than prescribed)intensity shown to improve psychological , physiological and social outcomes , and exercise participation rates in depressedindividuals(Callaghanet al. , 2011 ) . Research findings have beensummarized by a recent Cochrane review whichreportedthefindingsof32r and om-ized controlled trials in which exercisewas compared to st and ard treatment , no treatment or a placebo treatment inadults ( aged 18 and over ) with depression(Rimeretal.,2012).This review concludedthat exercise seems to improve depressivesymptoms in people with a diagnosis ofdepression when compared with no treat-ment or control intervention , althoughhighlighted that this should be interpretedwith caution since the positive effects ofexercise were smaller in method ologi-cally robust trials . Similarly , a systematic review found that physical exercise pro-grams obtain clinical ly relevant outcomes in the treatment of depressive symptomsin depressed older people Although cognitive-behavioural programmes for preventing depression have produced promising findings , their administration requires extensive training . Relaxation techniques are more straightforward psychological strategies , but they have not been investigated in the prevention of depression . This trial aim ed to compare the results of relaxation training ( RT ) with that of a cognitive-behavioural programme ( CBT ) for prevention of depression in university students with elevated depressive symptoms . The 133 participants ( mean age 23.3 years , 82 % women ) were r and omly assigned to CBT or RT . Both programmes were administered to groups of 5 or 6 participants in eight weekly 90-min sessions . Participants were evaluated by independent raters before , immediately after , and 3 and 6 months after taking part in the programmes . By itself , intervention type had no significant effect on either depression or anxiety scores . The scores were lower at the follow-up time points with respect to pre-intervention scores . Effect size was greatest between pre- and immediately post-intervention scores for CBT , d = 1.32 , 95 % CI [ 1.00 , 1.64 ] , and between pre- and 6-month post-intervention scores for RT , d = 0.75 , 95 % CI [ 0.47 , 1.03 ] . Anxiety symptoms were significantly improved by both interventions at 3-month follow-up , and by CBT at 6-month follow-up also . In the medium term ( 3 - 6 months ) , relaxation training produced similar reductions in depressive and anxiety symptoms as a more complex cognitive-behavioural programme CONTEXT Mindfulness-based cognitive therapy ( MBCT ) is a group-based psychosocial intervention design ed to enhance self-management of prodromal symptoms associated with depressive relapse . OBJECTIVE To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy , the current st and ard of care . DESIGN Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were r and omized to receive maintenance antidepressant medication , MBCT , or placebo and were followed up for 18 months . SETTING Outpatient clinics at the Centre for Addiction and Mental Health , Toronto , Ontario , Canada , and St Joseph 's Healthcare , Hamilton , Ontario . PARTICIPANTS One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes . Of these , 84 achieved remission ( 52.5 % ) and were assigned to 1 of the 3 study conditions . INTERVENTIONS Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT , continued taking their therapeutic dose of antidepressant medication , or discontinued active medication and were switched to placebo . MAIN OUTCOME MEASURE Relapse was defined as a return , for at least 2 weeks , of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV . RESULTS Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in r and omized patients ( P = .03 ) . Among unstable remitters ( 1 or more Hamilton Rating Scale for Depression score > 7 during remission ) , patients in both MBCT and maintenance treatment showed a 73 % decrease in hazard compared with placebo ( P = .03 ) , whereas for stable remitters ( all Hamilton Rating Scale for Depression scores ≤7 during remission ) there were no group differences in survival . CONCLUSIONS For depressed patients achieving stable or unstable clinical remission , MBCT offers protection against relapse/recurrence on a par with that of maintenance antidepressant pharmacotherapy . Our data also highlight the importance of maintaining at least 1 long-term active treatment in unstable remitters This study evaluated mindfulness-based cognitive therapy ( MBCT ) , a group intervention design ed to train recovered recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that may mediate relapse/recurrence . Recovered recurrently depressed patients ( n = 145 ) were r and omized to continue with treatment as usual or , in addition , to receive MBCT . Relapse/recurrence to major depression was assessed over a 60-week study period . For patients with 3 or more previous episodes of depression ( 77 % of the sample ) , MBCT significantly reduced risk of relapse/recurrence . For patients with only 2 previous episodes , MBCT did not reduce relapse/recurrence . MBCT offers a promising cost-efficient psychological approach to preventing relapse/recurrence in recovered recurrently depressed patients OBJECTIVE To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode ( MDE ) . METHOD Inclusive , double-blind , r and omized , controlled , 8-week , parallel-group trial , conducted October 17 , 2005 through January 30 , 2009 in 8 Canadian academic and psychiatric clinics . Adult out patients ( N = 432 ) with MDE ( Mini-International Neuropsychiatric Interview , version 5.0.0 , criteria ) lasting at least 4 weeks , including 40.3 % taking antidepressants at baseline , were r and omly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid ( EPA ) and 150 mg/d of docosahexaenoic acid ( DHA ) or matched sunflower oil placebo ( 2 % fish oil ) . The primary outcome was the self-report Inventory of Depressive Symptomatology ( IDS-SR(30 ) ) ; the secondary outcome was the clinician-rated Montgomery-Åsberg Depression Rating Scale ( MADRS ) . RESULTS The adjusted mean difference between treatment and placebo was 1.32 points ( 95 % CI , -0.20 to 2.84 ; P = .088 ) on the IDS-SR(30 ) and 0.97 points ( 95 % CI , -0.012 to 1.95 ; P = .053 ) on the MADRS . Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group ( P = .035 ) . For patients without comorbid anxiety disorders ( n = 204 ) , omega-3 supplementation was superior to placebo , with an adjusted mean difference of 3.17 points on the IDS-SR(30 ) ( 95 % CI , 0.89 to 5.45 ; P = .007 ) and 1.93 points ( 95 % CI , 0.50 to 3.36 ; P = .008 ) on the MADRS . CONCLUSIONS In this heterogeneous sample of patients with MDE , there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms . However , there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders . TRIAL REGISTRATION controlled-trials.com Identifier : IS RCT N47431149 Objective : To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder . Methods : In the present double-blind , r and omized , placebo-controlled trial , 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were r and omly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks . Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale ( HDRS ) as a primary outcome measure and the 21-item Beck Depression Inventory ( BDI ) as a secondary outcome measure . Serum 25(OH ) vitamin D was measured at baseline and after intervention . Results : Forty patients completed the trial . A two-way repeated- measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention , with a significant difference between the two groups . The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment . Conclusions : In the present 8-week trial , the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms AIMS Aims were to determine the effectiveness of acupuncture and Chinese herbs as treatments for depression , and to assess beliefs , attitudes and treatment experience . METHOD Participants received acupuncture or acupuncture and Chinese herbs combined for five weeks . Acupuncture was given for 30 min twice a week and herbs taken three times a day . A Beliefs and Attitudes question naire was administered at baseline and Treatment Experience question naire post treatment . Outcome measure was improvement in depressive symptoms at the end of treatment period . RESULTS Nineteen participants completed 5 weeks of treatment , 12 in the acupuncture group and 7 in the combined group . Treatment significantly improved depressive symptoms , however , there were no differences between groups . At baseline , participants were positive about the perceived effectiveness of treatment , and treatment experiences were positive . CONCLUSIONS Acupuncture was effective in reducing depressive symptoms . However , herbs did not have an additional treatment effect . Beliefs and attitudes were positive Major depressive disorder ( MDD ) is a common , debilitating chronic condition in the United States and worldwide . Particularly in women , depressive symptoms are often accompanied by high levels of stress and ruminations , or repetitive self-critical negative thinking . There is a research and clinical imperative to evaluate complementary therapies that are acceptable and feasible for women with depression and that target specific aspects of depression in women , such as ruminations . To begin to address this need , we conducted a r and omized , controlled , mixed- methods community-based study comparing an 8-week yoga intervention with an attention-control activity in 27 women with MDD . After controlling for baseline stress , there was a decrease in depression over time in both the yoga group and the attention-control group , with the yoga group having a unique trend in decreased ruminations . Participants in the yoga group reported experiencing increased connectedness and gaining a coping strategy through yoga . The findings provide support for future large scale research to explore the effects of yoga for depressed women and the unique role of yoga in decreasing rumination INTRODUCTION Trials of acupuncture for the treatment of depression have produced mixed results . We examined the effectiveness of laser acupuncture compared with placebo acupuncture for the treatment of major depression . METHODS A r and omised , double blinded , placebo controlled trial was conducted in Sydney , Australia . Participants aged 18 - 50 years with DSM-IV major depressive disorder were eligible to join the study . Forty-seven participants were r and omised to receive laser acupuncture or placebo laser at acupoints LR14 , CV14 , LR8 , HT7 and KI3 . The intervention was administered twice a week for 4 weeks and once a week for another four weeks , for a total of 12 sessions . The primary outcome assessed the change in severity of depression using the Hamilton-Depression Rating Scale ( HAM-D ) , and secondary outcomes assessed the change in severity of depression using the Quick Inventory for Depression-Self Reporting ( QID-SR ) , the Quick Inventory for Depression-Clinician ( QIDS-CL ) , with outcomes assessed at eight weeks . The treatment response ( greater than 50 % improvement in HAM-D ) and remission ( HAM-D<8 ) were analysed . RESULTS At eight weeks participants showed greater improvement in the active laser group on the primary and clinician-rated secondary outcome measures ( HAM-D ( mean 9.28 ( SD 6.55 ) vs. mean 14.14 ( SD 4.78 p<0.001 ) ; QIDS-CL ( mean 8.12 ( SD 6.61 versus 12.68 ( mean SD 3.77 ) ) p<0.001 ) . The self-report QIDS-SR scores improved in both groups but did not differ significantly between the groups . In the active laser group , QIDS-SR scores remained significantly lower than baseline at 3 months follow-up . Response rates ( active laser , placebo laser ) on ITT ( intention to treat ) analyses were 72.0 % and 18.2 % ( p<0.001 ) , respectively . Remission rates on ITT analyses ( active laser , placebo laser ) were 56.0 % and 4.5 % ( p<0.001 ) . Transient fatigue was the only adverse effect reported . LIMITATIONS There was no follow-up for the placebo group at one and 3 months . CONCLUSION Laser acupuncture showed a clinical ly and statistically significant benefit with reducing symptoms of depression on objective measures AIM To examine the comparative effectiveness of Mindfulness-Based Cognitive Therapy ( MBCT ) and Cognitive Behaviour Therapy ( CBT ) as treatments for non-melancholic depression . METHOD Participants who met criteria for a current episode of major depressive disorder were r and omly assigned to either an 8-week MBCT ( n=19 ) or CBT ( n=26 ) group therapy condition . They were assessed at pre-treatment , 8-week post-group , and 6- and 12-month follow-ups . RESULTS There were significant improvements in pre- to post-group depression and anxiety scores in both treatment conditions and no significant differences between the two treatment conditions . However , significant differences were found when participants in the two treatment conditions were dichotomized into those with a history of four or more episodes of depression vs those with less than four . In the CBT condition , participants with four or more previous episodes of depression demonstrated greater improvements in depression than those with less than four previous episodes . No such differences were found in the MBCT treatment condition . No significant differences in depression or anxiety were found between the two treatment conditions at 6- and 12-month follow-ups . LIMITATIONS Small sample sizes in each treatment condition , especially at follow-up . CONCLUSIONS MBCT appears to be as effective as CBT in the treatment of current depression . However , CBT participants with four or more previous episodes of depression derived greater benefits at 8-week post-treatment than those with less than four episodes |
10,834 | 27,693,228 | Limited data suggest that BN , BED and obesity are associated with increased TD , whilst data in AN are mixed .
Aberrant neural activity in frontostriatal circuitry is implicated .
TD tasks vary widely and TD in ED/obesity may vary according to factors such as illness stage .
Our findings suggest altered self-regulatory control in ED and obesity . | OBJECTIVE Eating Disorders ( ED ) and obesity are suggested to involve a spectrum of self-regulatory control difficulties .
Temporal discounting ( TD ) tasks have been used to explore this idea .
This systematic review examines behavioural and neuroimaging TD data in ED and obesity . | The aim of the present proof-of-concept study was to test a novel cognitive bias modification ( CBM ) programme in an analogue sample of people with sub clinical bulimic eating disorder ( ED ) psychopathology . Thirty participants with high levels of trait food craving were trained to make avoidance movements in response to visual food stimuli in an implicit learning paradigm . The intervention comprised ten 15-minute sessions over a 5-week course . At baseline , participants showed approach and attentional biases towards high-caloric palatable food that were both significantly reduced and turned into avoidance biases after the training . Participants also reported pronounced reductions in both trait and cue-elicited food craving and in ED symptoms as well . The overall evaluation of the training by the participants was positive . The specific CBM programme tested in this pilot trial promises to be an effective and feasible way to alter automatic action tendencies towards food in people suffering from bulimic ED psychopathology BACKGROUND Excessive discounting of future rewards has been observed in a variety of disorders and has been linked both to valuation of the past and to memory of past events . METHODS To explore the functionality of discounting and memory , we examined whether training of working memory would result in less discounting of future rewards . In this study , 27 adults in treatment for stimulant use were r and omly assigned to receive either working memory training or control training according to a yoked experimental design . Measures of delay discounting and several other cognitive behaviors were assessed pre- and posttraining . RESULTS Rates of discounting of delayed rewards were significantly reduced among those who received memory training but were unchanged among those who received control training ; other cognitive assessment s were not affected by memory training . Discount rates were positively correlated with memory training performance measures . CONCLUSIONS To our knowledge , this is the first study demonstrating that neurocognitive training on working memory decreases delay discounting . These results offer further evidence of a functional relationship between delay discounting and working memory The mere sight of foods may activate the brain ’s reward circuitry , and humans often experience difficulties in inhibiting urges to eat upon encountering visual food signals . Imbalance between the reward circuit and those supporting inhibitory control may underlie obesity , yet brain circuits supporting volitional control of appetite and their possible dysfunction that can lead to obesity remain poorly specified . Here we delineated the brain basis of volitional appetite control in healthy and obese individuals with functional magnetic resonance imaging ( fMRI ) . Twenty-seven morbidly obese women ( mean BMI = 41.4 ) and fourteen age-matched normal-weight women ( mean BMI = 22.6 ) were scanned with 1.5 Tesla fMRI while viewing food pictures . They were instructed to inhibit their urge to eat the foods , view the stimuli passively or imagine eating the foods . Across all subjects , a frontal cortical control circuit was activated during appetite inhibition versus passive viewing of the foods . Inhibition minus imagined eating ( appetite control ) activated bilateral precunei and parietal cortices and frontal regions spanning anterior cingulate and superior medial frontal cortices . During appetite control , obese subjects had lower responses in the medial frontal , middle cingulate and dorsal cau date nuclei . Functional connectivity of the control circuit was increased in morbidly obese versus control subjects during appetite control , which might reflect impaired integrative and executive function in obesity OBJECTIVE Obesity is largely attributable to excess caloric intake , in particular from " junk " foods , including salty snack foods . Evidence suggests that neurobiological preferences to consume highly hedonic foods translate ( via implicit processes ) into poor eating choices , unless overturned by inhibitory mechanisms or interrupted by explicit processes . The primary aim of the current study was to test the independent and combinatory effects of a computerized inhibitory control training ( ICT ) and a mindful decision-making training ( MDT ) design ed to facilitate de-automatization . METHODS We r and omized 119 habitual salty snack food eaters to one of four short , training conditions : MDT , ICT , both MDT and ICT , or neither ( i.e. , psychoeducation ) . For 7 days prior to the intervention and 7 days following the intervention , participants reported on their salty snack food consumption 2 times per day , on 3 portions of their days , using a smartphone-based ecological momentary assessment system . Susceptibility to emotional eating cues was measured at baseline . RESULTS Results indicated that the effect of MDT was consistent across levels of trait emotional eating , whereas the benefit of ICT was apparent only at lower levels of emotional eating . No synergistic effect of MDT and ICT was detected . CONCLUSIONS These results provide qualified support for the efficacy of both types of training for decreasing hedonically-motivated eating . Moderation effects suggest that those who eat snack foods for reasons unconnected to affective experiences ( i.e. , lower in emotional eating ) may derive benefit from a combination of ICT and MDT . Future research should investigate the additive benefit of de-automization training to st and ard weight loss interventions The choice of small immediate rewards as opposed to larger delayed rewards , or delay discounting , is an important dimension of impulsive decision making . The inability to delay gratification is related to obesity , as well as other maladaptive behaviors such as substance abuse , problem drinking , smoking , pathological gambling , and risky HIV behaviors . One way to reduce delay discounting ( DD ) may be to use prospect i ve imagery in the form of episodic future thinking ( EFT ) during inter-temporal decision making . We have recently shown that EFT reduces DD and ad libitum energy intake in obese individuals . However , no studies have examined whether the magnitude of the EFT effect differs between lean and overweight/obese individuals . We conducted a within-subject design experiment to compare the efficacy of EFT versus a control task in reducing DD between lean ( N=24 ) and overweight/obese ( N=24 ) women . Participants attended two sessions in which they engaged in either EFT or control episodic thinking during a DD task . We also examined whether individual differences such as trait time perspective , behavioral inhibition or behavioral activation moderated the EFT effect on DD . Results showed EFT reduced DD similarly for lean and overweight/obese individuals . The EFT effect was moderated by behavioral activation . This suggests EFT is just as effective in reducing impulsive decision making in obese individuals as it is in lean individuals and may be useful in reducing other impulsive obesity related behaviors Impulsive delayed reward discounting ( DRD ) is an important behavioral process in alcohol use disorders ( AUDs ) , reflecting incapacity to delay gratification . Recent work in neuroeconomics has begun to unravel the neural mechanisms supporting DRD , but applications of neuroeconomics in relation to AUDs have been limited . This study examined the neural mechanisms of DRD preferences in AUDs , with emphasis on dissociating activation patterns based on DRD choice type and level of cognitive conflict . Heavy drinking adult men with ( n = 13 ) and without ( n = 12 ) a diagnosis of an AUD completed a monetary DRD task during a functional magnetic resonance imaging scan . Participant responses were coded based on choice type ( impulsive versus restrained ) and level of cognitive conflict ( easy versus hard ) . AUD+ participants exhibited significantly more impulsive DRD decision‐making . Significant activation during DRD was found in several decision‐making regions , including dorsolateral prefrontal cortex ( DLPFC ) , insula , posterior parietal cortex ( PPC ) , and posterior cingulate . An axis of cognitive conflict was also observed , with hard choices associated with anterior cingulate cortex and easy choices associated with activation in supplementary motor area . AUD+ individuals exhibited significant hyperactivity in regions associated with cognitive control ( DLPFC ) and prospect i ve thought ( PPC ) and exhibited less task‐related deactivation of areas associated with the brain 's default network during DRD decisions . This study provides further clarification of the brain systems supporting DRD in general and in relation to AUDs OBJECTIVE The current study sought to examine executive function ( EF ) in overweight individuals with and without loss-of-control ( LOC ) eating . METHOD Eighty overweight and obese individuals entering a behavioural weight loss trial with ( n=18 ) and without ( n=62 ) LOC eating were administered a clinical interview and neuropsychological battery design ed to assess self-regulatory control , planning , delayed discounting and working memory . RESULTS After controlling for age , IQ and depression , individuals with LOC eating performed worse on tasks of planning and self-regulatory control and did not differ in performance on other tasks . DISCUSSION Results indicate that overweight individuals with LOC eating display relative deficits in EF compared with overweight individuals without LOC eating . Planning and self-regulatory control deficits in particular may contribute to dysregulated eating patterns , increasing susceptibility to LOC episodes . Future research should examine how EF deficits relate to treatment outcome Background Research has shown that obese individuals have cognitive deficiencies in executive function , leading to poor planning and impulse control , and decision-making difficulties . An intervention that could help reduce these deficits and in turn help weight loss maintenance is Cognitive Remediation Therapy for Obesity ( CRT-O ) . We aim to examine the efficacy of manualised CRT-O , which is intended to improve executive function , enhance reflective practice and help weight loss maintenance . Methods / Design A r and omised controlled trial ( registered with the Australian New Zeal and Clinical Trials Registry ) will be conducted . First , 90 obese adults ( body mass index > 30 kg/m2 ) in the community will receive three weekly sessions of a group Behaviour Weight Loss Treatment ( BWLT ) , and then will be r and omised either to receive CRT-O or to enter a no-treatment control group . CRT-O training will comprise twice-weekly sessions of 45 minutes over a 4 to 6 week period , for a total of eight sessions . Measurement points will be at baseline , post CRT-O ( or 4 to 6 weeks after BWLT for the no-treatment control ) , 3 months post treatment and 1 year post treatment . The primary outcome will be executive function and secondary outcome measures will include participants ’ body mass index , hip to waist ratio , eating behaviours and quality of life . Discussion This is the first study of its kind to examine the efficacy of Cognitive Remediation Therapy for obese adults through a r and omised controlled trial . Trial Registration Australian New Zeal and Clinical Trials Registry number : 12613000537752 . Date of registration : 14 May 2013 Obese individuals tend to behave more impulsively than healthy weight individuals across a variety of measures , but it is unclear whether this pattern can be altered . The present study examined the effects of a mindful eating behavioral strategy on impulsive and risky choice patterns for hypothetical food and money . In Experiment 1 , 304 participants completed computerized delay and probability discounting tasks for food-related and monetary outcomes . High percent body fat ( PBF ) predicted more impulsive choice for food , but not small-value money , replicating previous work . In Experiment 2 , 102 r and omly selected participants from Experiment 1 were assigned to participate in a 50-min workshop on mindful eating or to watch an educational video . They then completed the discounting tasks again . Participants who completed the mindful eating session showed more self-controlled and less risk-averse discounting patterns for food compared to baseline ; those in the control condition discounted similarly to baseline rates . There were no changes in discounting for money for either group , suggesting stimulus specificity for food for the mindful eating condition Although higher delay discounting rates have been linked to cigarette smoking , little is known about the stability of delay discounting , whether delay discounting promotes smoking acquisition , whether smoking contributes to impulsive choices , or if different relationships exist in distinct subgroups . This study sought to fill these gaps within a prospect i ve longitudinal cohort study ( N=947 ) spanning mid-adolescence to young adulthood ( age 15 - 21 years old ) . Smoking and delay discounting were measured across time . Covariates included peer and household smoking , academic performance , depression , novelty seeking , inattention and hyperactivity/impulsivity symptoms , and alcohol and marijuana use . The associated processes latent growth curve modeling ( LGCM ) with paths from the delay discounting level factor ( baseline measure ) and the trend factor ( slope ) to the smoking trend factor ( slope ) fit the data well , chi(2)((19,n=947 ) ) = 15.37 , p=.70 , CFI=1.00 , RMSEA=0 , WRMR=.36 . The results revealed that delay discounting did not change significantly across time . Baseline delay discounting had a significant positive effect on smoking trend ( beta=.08 , z=2.16 , p=.03 ) . A st and ard deviation ( SD=1.41 ) increase in baseline delay discounting result ed in an 11 % increase ( OR=1.11 , 95 % CI=1.03 , 1.23 ) in the odds of smoking uptake . The alternative path LCGM revealed that smoking did not significantly impact delay discounting ( p's>.05 ) . Growth mixture modeling identified three smoking trajectories : nonsmokers , early/fast smoking adopters , and slow smoking progressors . Delay discounting was higher in the smoking versus nonsmoking trajectories , but did not discriminate between the smoking trajectories , despite different acquisition patterns . Delay discounting may provide a variable by which to screen for smoking vulnerability and help identify subgroups to target for more intensive smoking prevention efforts that include novel behavioral components directed toward aspects of impulsivity OBJECTIVE A positive association between delay discounting and substance use has been documented ; substance users tend to discount future rewards more than non-users . However , studies detailing the responsiveness of delay discounting to interventions are lacking , and few have examined how any behavioral intervention affects delay discounting and whether these effects moderate changes in substance abuse . This study assesses the effectiveness of a money management intervention , Advisor-Teller Money Manager ( ATM ) , in reducing delay discounting over time and the relationship of these effects to changes in cocaine use . METHOD Ninety psychiatric patients with histories of cocaine and /or alcohol use were r and omly assigned to 36-weeks of ATM treatment or to a minimal-attention control condition . Delay discounting and cocaine use were measured throughout the intervention with a 52-week follow up measure of cocaine use . Analyses were conducted of ( a ) the effect of ATM on slopes of delay discounting and cocaine abstinence and ( b ) the relationship between change in delay discounting and change in cocaine abstinence . RESULTS The ATM intervention was associated with significantly less delay discounting and less cocaine use over time relative to controls . Increases in delay discounting were associated with decreased abstinence from cocaine . CONCLUSIONS ATM treatment decreased delay discounting rates and these effects extended to cocaine use . Concrete conceptualizations of future events , as occur in financial planning , with higher perceived probability may account for higher valuation of future rewards in counseled patients Background Methamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting ( DD ) tasks . Human and animal data implicate ventral ( amygdala , ventral striatum , ventrolateral prefrontal cortex insula ) and dorsal ( dorsolateral prefrontal cortex , dorsal anterior cingulate cortex and posterior parietal cortex ) systems in DD decisions . The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice . Methods We used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls . Results Hard DD choices were associated with greatest activation in bilateral middle cingulate , posterior parietal cortex ( PPC ) , and the right rostral insula . Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right cau date nucleus , anterior cingulate cortex ( ACC ) , and dorsolateral prefrontal cortex ( DLPFC ) . Magnitude of discounting was correlated with activity in the amygdala , DLPFC , posterior cingulate cortex and PPC . Conclusions Our findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions . Patients addicted to MA , who strongly prefer smaller immediate over larger delayed rewards , activate the dorsal cognitive control system in order to overcome their preference . Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting , suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls To determine whether reduction of smoking via contingency management in depen-dent smokers would decrease the discounting of delayed reinforcers compared with smokers who did not reduce their smoking , moderate to heavy cigarette smokers were r and omly assigned to one of two conditions : a contingency management condi-tion and a control condition . In three phases ( baseline discounting determination for hypothetical money and cigarettes , implementation of a contingency management or control condition , and postintervention discounting determination ) , the procedure to reinforce reduction in cigarette smoking produced CO decreases in all subjects exposed to that procedure . Discounting decreased significantly for both cigarettes and money among the group for whom smoking reductions were reinforced , whereas the control group showed no significant change for either commodity . Reductions in smoking can lead to reductions in discounting , and increased discounting in current smokers may be a reversible effect of nicotine dependence BACKGROUND The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . METHODS Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975 - 85 ] , mean BMI 25 [ SD 4 ] kg/m(2 ) ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . FINDINGS In both sexes , mortality was lowest at about 22.5 - 25 kg/m(2 ) . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m(2 ) higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m(2 ) [ HR ] 1.29 [ 95 % CI 1.27 - 1.32 ] ) : 40 % for vascular mortality ( HR 1.41 [ 1.37 - 1.45 ] ) ; 60 - 120 % for diabetic , renal , and hepatic mortality ( HRs 2.16 [ 1.89 - 2.46 ] , 1.59 [ 1.27 - 1.99 ] , and 1.82 [ 1.59 - 2.09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1.10 [ 1.06 - 1.15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1.20 [ 1.07 - 1.34 ] and 1.20 [ 1.16 - 1.25 ] , respectively ) . Below the range 22.5 - 25 kg/m(2 ) , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . INTERPRETATION Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22.5 - 25 kg/m(2 ) . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30 - 35 kg/m(2 ) , median survival is reduced by 2 - 4 years ; at 40 - 45 kg/m(2 ) , it is reduced by 8 - 10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22.5 kg/m(2 ) is due mainly to smoking-related diseases , and is not fully explained |
10,835 | 25,925,483 | Furthermore , in the subset of stage III/IV patients , the addition of radiotherapy statistically significantly improved local control and progression-free survival/eventfree survival , and yielded a trend toward improved OS . | As appropriately discussed by the authors , the National Comprehensive Cancer Center Network ( NCCN ) guidelines accepts 6 cycles of R-CHOP alone as being adequate treatment for many stage I – II patients , with design ation that radiotherapy could be included or excluded and should be considered for bulky patients .
Radiotherapy is listed as one of several options for bulky stage III/IV patients along with observation and transplant for high-risk patients after a complete response to 6 cycles of R-CHOP .
Since these trials were published , additional trials demonstrating the increased efficacy of adding rituximab to CHOP [ 9–11 ] have led many to believe that the marginal In this issue of Acta Haematologica , Hu et al. [ 1 ] present a systematic review and meta- analysis of recently published series comparing the role of 6–8 cycles of R-CHOP chemotherapy with or without the addition of consolidative radiotherapy for patients with diffuse large B cell lymphoma , stages I – IV . | BACKGROUND The role of rituximab in combination with different CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined . We aim ed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients . METHODS 824 patients who were from 18 countries ; aged 18 - 60 years ; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index ( IPI ) , stage II-IV disease , or stage I disease with bulk were enrolled . These patients were r and omly assigned to six cycles of CHOP-like chemotherapy and rituximab ( n=413 ) or to six cycles of CHOP-like chemotherapy alone ( n=411 ) . Bulky and extranodal sites received additional radiotherapy . The primary endpoint was event-free survival ; secondary endpoints were response , progression under therapy , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat and per protocol . This trial is registered at http://www . clinical trials.gov , NCT 00064116 . FINDINGS After a median follow-up of 34 months ( range 0.03 - 61 ) , patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone ( 79 % [ 95 % CI 75 - 83 ] vs 59 % [ 54 - 64 ] ; difference between groups 20 % [ 13 - 27 ] , log-rank p<0.0001 ) , and had increased 3-year overall survival ( 93 % [ 90 - 95 ] vs 84 % [ 80 - 88 ] ; difference between groups 9 % [ 3 - 13 ] , log-rank p=0.0001 ) . Event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI : after chemotherapy and rituximab , a favourable subgroup ( ie , IPI=0 , no bulk ) could be defined from a less-favourable subgroup ( ie , IPI=1 or bulk , or both ) . Groups did not differ in the frequency of adverse events . INTERPRETATION Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients PURPOSE To compare low-dose ( 30 Gy ) radiotherapy ( RT ) with observation ( OBS ) in limited-stage aggressive lymphoma patients achieving complete remission ( CR ) after chemotherapy , and to measure conversion from partial response ( PR ) to CR with high-dose ( 40 Gy ) RT . PATIENTS AND METHODS From 1984 to 1992 , stage I ( with risk factors ) and II adults with diffuse aggressive lymphoma in CR after eight cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) were r and omly assigned to 30 Gy involved-field RT or OBS . PR patients received 40 Gy RT . RESULTS Among 172 CR patients , the 6-year disease-free survival ( DFS ) was 73 % for low-dose RT versus 56 % for OBS ( two-sided P = .05 ) . Failure-free survival ( two-sided P = .06 ) , and time to progression ( two-sided P = .06 ) also favored RT . Intent-to-treat analyses yielded similar results . No survival differences were observed . Three RT versus 15 OBS patients relapsed in initial disease sites . At 6 years , failure-free survival was 63 % in PR patients ; conversion to CR did not significantly influence clinical outcome . CONCLUSION For patients in CR after CHOP , low-dose RT prolonged DFS and provided local control , but no survival benefit was observed . The majority of PR patients were event-free at 6 years despite residual radiographic abnormalities . Future efforts should be directed toward improved imaging and more effective systemic therapies BACKGROUND The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma . Extended follow-up was needed to establish long-term effects . METHODS In the r and omised open-label MInT study , patients from 18 countries ( aged 18 - 60 years with none or one risk factor according to the age-adjusted International Prognostic Index [ IPI ] , stage II-IV disease or stage I disease with bulk ) were r and omly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab . Bulky and extranodal sites received additional radiotherapy . R and omisation was done central ly with a computer-based tool and was stratified by centre , bulky disease , age-adjusted IPI , and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component . Patients and investigators were not masked to treatment allocation . The primary endpoint was event-free survival . Analyses were by intention to treat . This observational study is a follow-up of the MInT trial , which was stopped in 2003 , and is registered at Clinical Trials.gov , number NCT00400907 . FINDINGS The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab . After a median follow-up of 72 months ( range 0·03 - 119 ) , 6-year event-free survival was 55·8 % ( 95 % CI 50·4 - 60·9 ; 166 events ) for patients assigned to chemotherapy alone and 74·3 % ( 69·3 - 78·6 ; 98 events ) for those assigned to chemotherapy plus rituximab ( difference between groups 18·5 % , 11·5 - 25·4 , log-rank p<0·0001 ) . Multivariable analyses showed that event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only . After chemotherapy and rituximab , a favourable subgroup ( IPI=0 , no bulk ) could be defined from a less favourable subgroup ( IPI=1 or bulk , or both ; event-free survival 84·3 % [ 95 % CI 74·2 - 90·7 ] vs 71·0 % [ 65·1 - 76·1 ] , log-rank p=0·005 ) . 18 ( 4·4 % , 95 % CI 2·6 - 6·9 ) second malignancies occurred in the chemotherapy-alone group and 16 ( 3·9 % , 2·2 - 6·2 ) in the chemotherapy and rituximab group ( Fisher 's exact p=0·730 ) . INTERPRETATION Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone . FUNDING Hoffmann-La Roche PURPOSE To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98 - 5 ( LNH98 - 5 ) comparing cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) to rituximab plus CHOP ( R-CHOP ) in elderly patients with diffuse large B-cell lymphoma . PATIENTS AND METHODS LNH98 - 5 was a r and omized study that included 399 previously untreated patients , age 60 to 80 years , with diffuse large B-cell lymphoma . Patients received eight cycles of classical CHOP ( cyclophosphamide 750 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , vincristine 1.4 mg/m(2 ) , and prednisone 40 mg/m(2 ) for 5 days ) every 3 weeks . In R-CHOP , rituximab 375 mg/m(2 ) was administered the same day as CHOP . Survivals were analyzed using the intent-to-treat principle . RESULTS Median follow-up is 5 years at present . Event-free survival , progression-free survival , disease-free survival , and overall survival remain statistically significant in favor of the combination of R-CHOP ( P = .00002 , P < .00001 , P < .00031 , and P < .0073 , respectively , in the log-rank test ) . Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination . No long-term toxicity appeared to be associated with the R-CHOP combination . CONCLUSION Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma , with significant survival benefit maintained during a 5-year follow-up . This combination should become the st and ard for treating these patients PURPOSE R-CHOP ( rituximab plus cyclophosphamide , doxorubicin , vincristine , and prednisone ) is st and ard care for aggressive B-cell lymphoma . A prospect i ve trial was conducted to investigate the role of additive radiotherapy ( RT ) to bulky and extralymphatic disease . PATIENTS AND METHODS The best arm of the RICOVER-60 trial ( 6 × R-CHOP-14 + 2R [ R-CHOP administered once every 2 weeks plus two additional applications of rituximab ] plus involved-field RT [ 36 Gy ] to sites of initial bulky [ ≥ 7.5 cm ] disease and extralymphatic involvement ) was compared with a cohort receiving the same immunochemotherapy but without RT in an amendment to the RICOVER-60 trial ( RICOVER-noRTh ) in a prospect i ve fashion . RESULTS After a median observation time of 39 months , 164 of 166 RICOVER-noRTh patients were evaluable . In a multivariable analysis of the intention-to-treat population adjusting for International Prognostic Index risk factors and age ( > 70 years ) , event-free survival ( EFS ) of patients with bulky disease was inferior without additive RT ( hazard ratio [ HR ] , 2.1 ; 95 % CI , 1.3 to 3.5 ; P = .005 ) , with trends for inferior progression-free ( PFS ; HR , 1.8 ; 95 % CI , 1.0 to 3.3 ; P = .058 ) and overall survival ( OS ; HR , 1.6 ; 95 % CI , 0.9 to 3.1 ; P = .127 ) . In a per- protocol analysis with 11 patients in RICOVER-noRTh excluded for receiving unplanned RT , multivariable analysis revealed HRs of 2.7 ( 95 % CI , 1.3 to 5.9 ; P = .011 ) for EFS , 4.4 ( 95 % CI , 1.8 to 10.6 ; P = .001 ) for PFS , and 4.3 ( 95 % CI , 1.7 to 11.1 ; P = .002 ) for OS for patients not receiving RT to bulky disease . CONCLUSION Additive RT to bulky sites abrogates bulky disease as a risk factor and improves outcome of elderly patients with aggressive B-cell lymphoma . Whether RT can be spared in patients with ( metabolic ) complete remission after immunochemotherapy must be addressed in appropriately design ed prospect i ve trials BACKGROUND Chemoradiotherapy is st and ard treatment for localized aggressive lymphoma . To determine the optimal therapy for nonelderly persons with low-risk localized lymphoma , we conducted a r and omized trial comparing chemoradiotherapy with chemotherapy alone . METHODS Previously untreated patients less than 61 years old with localized stage I or II aggressive lymphoma and no adverse prognostic factors according to the International Prognostic Index were r and omly assigned to three cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) plus involved-field radiotherapy ( 329 patients ) or chemotherapy alone with dose-intensified doxorubicin , cyclophosphamide , vindesine , bleomycin , and prednisone ( ACVBP ) plus sequential consolidation ( 318 patients ) . RESULTS With a median follow-up of 7.7 years , event-free and overall survival rates were significantly higher in the group given chemotherapy alone than in the group given CHOP plus radiotherapy ( P<0.001 and P=0.001 , respectively ) . The five-year estimates of event-free survival were 82 percent ( 95 percent confidence interval , 78 to 87 percent ) for patients receiving chemotherapy alone and 74 percent ( 95 percent confidence interval , 69 to 78 percent ) for those receiving chemoradiotherapy . The respective five-year estimates of overall survival were 90 percent ( 95 percent confidence interval , 87 to 93 percent ) and 81 percent ( 95 percent confidence interval , 77 to 86 percent ) . In a multivariate analysis , event-free and overall survival rates were affected by treatment group , independently of tumor stage and the presence or absence of bulky disease . CONCLUSIONS In patients under 61 years of age , chemotherapy with three cycles of ACVBP followed by sequential consolidation is superior to three cycles of CHOP plus radiotherapy for the treatment of low-risk localized lymphoma BACKGROUND Patients with clinical ly localized , intermediate- or high- grade non-Hodgkin 's lymphoma usually receive initial treatment with a doxorubicin-containing regimen such as cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) . Pilot studies suggest that eight cycles of CHOP alone or three cycles of CHOP followed by involved-field radiotherapy are effective in such patients . METHODS We compared these two approaches in a prospect i ve , r and omized , multi-institutional study . The end points were progression-free survival , overall survival , and life-threatening or fatal toxic effects . Two hundred eligible patients were r and omly assigned to receive CHOP plus radiotherapy , and 201 received CHOP alone . RESULTS Patients treated with three cycles of CHOP plus radiotherapy had significantly better progression-free survival ( P=0.03 ) and overall survival ( P=0.02 ) than patients treated with CHOP alone . The five-year estimates of progression-free survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 77 percent and 64 percent , respectively . The five-year estimates of overall survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 82 percent and 72 percent , respectively . The adverse effects included one death in each treatment group . Life-threatening toxic effects of any type were seen in 61 of 200 patients treated with CHOP plus radiotherapy and in 80 of 201 patients treated with CHOP alone ( P=0.06 ) . The left ventricular function was decreased in seven patients who received CHOP alone , whereas no cardiac events were recorded in the group receiving CHOP plus radiotherapy ( P=0.02 ) . CONCLUSIONS Three cycles of CHOP followed by involved-field radiotherapy are superior to eight cycles of CHOP alone for the treatment of localized intermediate- and high- grade non-Hodgkin 's lymphoma |
10,836 | 30,310,287 | In conclusion , the concurrent use of trastuzumab and anthracycline-based NAC for certain HER2-positive locally advanced breast cancers significantly improves the pCR rates without obvious increases in the cardiotoxicity | The concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy ( NAC ) has been proposed to improve the pathologic complete response ( pCR ) rate , although there are conflicting views about its efficacy and safety .
The purpose of this study was to evaluate the efficacy and cardiac safety of the concurrent use of trastuzumab and anthracycline-based NAC for human epidermal growth factor receptor 2 (HER2)-positive locally advanced breast cancer . | This trial was design ed to compare the efficacy and safety between epirubicin ( E ) and carboplatin ( C ) in combination with paclitaxel ( P ) and trastuzumab ( H ) in neoadjuvant setting . In 13 Chinese cancer centers , 100 patients with HER2-positive , locally advanced breast cancer were 1:1 r and omized to receive medication as follows : trastuzumab and paclitaxel weekly combined with carboplatin weekly for PCH group , or epirubicin every 3 weeks for PEH group . Patients were given 4 to 6 cycles of chemotherapy . The primary endpoint was pathologic complete response ( pCR ) rate , which was no significant difference in PCH and PEH regimen ( 39.1 % vs. 48.8 % ; p=0.365 ) . However , PEH regimen achieved higher pCR in luminal-B ( HER2-poitive ) subgroup ( 55.0 % vs. 24.0 % ; p = 0.033 ) , but not in ERBB2 + subgroup ( 42.9 % vs. 57.1 % ; p = 0.355 ) . PEH regimen showed a favorable efficacy in PIK3CA mutated subgroup ( 69.2 % vs.23.5 % , p=0.012 ) . No significant difference was observed in the subgroup analysis of TP53 mutation status , PTEN expression , FCGR2A SNP and FCGR3A SNP . Both regimens as neoadjuvant chemotherapy achieve similar efficacy and safety . PEH might improve pCR rate , especially in the luminal-B subtype and PIK3CA mutation subtype . PEH is feasible and less likely to increase the incidence of acute cardiac events compared to PCH BACKGROUND We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy . METHODS In the GeparQuinto r and omised phase 3 trial , patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7 , 2007 , and July 9 , 2010 . Patients were eligible if their tumours were classified as cT3/4a-d , or hormone receptor (HR)-negative , HR-positive with clinical ly node-positive and cT2 disease ( cT2 cN+ ) , or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease ( cT1 pN(SLN+ ) ) . Patients were r and omly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC ( epirubicin [ 90 mg/m(2 ) intravenously ] plus cyclophosphamide [ 600 mg/m(2 ) intravenously ] , every 3 weeks ) , and four cycles of docetaxel ( 100 mg/m(2 ) intravenously every 3 weeks ) with either trastuzumab ( 6 mg/kg intravenously , with a starting loading dose of 8 mg/kg , for eight cycles , every 3 weeks ) or lapatinib ( 1000 - 1250 mg per day orally ) throughout all cycles before surgery . R and omisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site , HR status , and extent of disease ( cT1 - 3 cN0 - 2 vs T4 or N3 ) . The primary endpoint was pathological complete response ( defined as ypT0 and ypN0 ) and was analysed in all patients who received at least one cycle of EC . Participants and investigators were not masked to treatment assignment . Pathologists in centres assessing surgery outcomes were masked to group assignment . This trial is registered with Clinical Trials.gov , number NCT00567554 . FINDINGS Of 620 eligible patients , 309 were r and omly assigned to chemotherapy with trastuzumab ( ECH-TH group ) and 311 to chemotherapy with lapatinib ( ECL-TL group ) . Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery . 93 ( 30·3 % ) of 307 patients in the ECH-TH group and 70 ( 22·7 % ) of 308 patients in the ECL-TL group had a pathological complete response ( odds ratio [ OR ] 0·68 [ 95%CI 0·47 - 0·97 ] ; p=0·04 ) . Chemotherapy with trastuzumab was associated with more oedema ( 119 [ 39·1 % ] vs 88 [ 28·7 % ] ) and dyspnoea ( 90 [ 29·6 % ] vs 66 [ 21·4 % ] ) , and ECL-TL with more diarrhoea ( 231 [ 75·0 % ] vs 144 [ 47·4 % ] ) and skin rash ( 169 [ 54·9 % ] vs 97 [ 31·9 % ] ) . 43 ( 14·0 % ) patients discontinued in the ECH-TH group and 102 ( 33·1 % ) in the ECL-TL group . 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group . INTERPRETATION This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab . Unless long-term outcome data show different results , lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy . FUNDING GlaxoSmithKline , Roche , and Sanofi-Aventis To report the results of the DECT trial , a phase II study of locally advanced or operable HER2‐positive breast cancer ( BC ) treated with taxanes and concurrent anthracyclines and trastuzumab . Eligible patients ( stage IIA‐IIIB HER2‐positive BC , 18–75 years , normal organ functions , ECOG ≤1 , and left ventricular ejection fraction ( LVEF ) ≥55 % ) received four cycles of neoadjuvant docetaxel , 100 mg/m2 intravenously , plus trastuzumab 6 mg/kg ( loading dose 8 mg/kg ) every 3 weeks , followed by four 3‐weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide , 600 mg/m2 , plus trastuzumab . Primary objective was pathologic complete response ( pCR ) rate , defined as ypT0/is ypN0 at definitive surgery . We enrolled 45 consecutive patients . All but six patients ( 13.3 % ) completed chemotherapy and all underwent surgery . pCR was observed in 28 patients ( 62.2 % ) overall and in 6 ( 66.7 % ) from the inflammatory subgroup . The classification and regression tree analysis showed a 100 % pCR rate in patients with BMI ≥25 and with hormone negative disease . The median follow up was 46 months ( 8–78 ) . Four‐year recurrence‐free survival was 74.7 % ( 95%CI , 58.2–91.2 ) . Seven patients ( 15.6 % ) recurred and one died . Treatment was well tolerated , with limiting toxicity being neutropenia . No clinical cardiotoxicity was observed . Six patients ( 13.4 % ) showed a transient LVEF decrease ( < 10 % ) . In one patient we observed a ≥10 % asymptomatic LVEF decrease persisting after surgery . Notwithst and ing their limited applicability due to the current guidelines , our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile , including cardiotoxicity . Results on BMI may invite further assessment in future studies . J. Cell . Physiol . 231 : 2541–2547 , 2016 . © 2016 The Authors . Journal of Cellular Physiology Published by Wiley Periodicals , Objective A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide ( TC ) regimen was inferior to docetaxel , anthracycline and cyclophosphamide ( TAC ) in neoadjuvant treatment of triple-negative breast cancer ( TNBC ) and human epidermal growth factor receptor-2-(HER2)-positive breast cancer in a short-term follow-up . Herein , long-term follow-up survival outcomes have been investigated . Methods TNBC or HER2-positive patients were r and omized to receive 6 cycles of TC or TAC neoadjuvant treatment . The primary endpoint was pathological complete remission ( pCR ) . Secondary endpoints included clinical response rate , event-free survival ( EFS ) , and overall survival ( OS ) . Results A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm . With a median follow-up period of 53 ( range , 8–76 ) months , the patients achieving pCR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without pCR ( P<0.05 ) . TAC treatment result ed in consistently better EFS than TC treatment : the estimated 5-year EFS was 66.1 % vs. 29.8 % ( P=0.002 ) . Moreover , the estimated 5-year OS was also in favor of TAC : 88.4 % vs. 51.6 % ( P<0.001 ) . Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor , and patients treated with TAC had a superior EFS [ hazard ratio ( HR ) , 0.48 ; 95 % confidence interval ( 95 % CI ) , 0.26–0.90 ; P=0.021 ] and OS ( HR , 0.20 ; 95 % CI , 0.08–0.60 ; P=0.003 ) . Conclusions The up date d long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment , indicating that anthracycline is an essential and effective drug in this clinical trial Purpose Combining anthracyclines and taxanes are to date the most active cytotoxic treatment option in the neoadjuvant and palliative therapy of breast cancer patients . Adding trastuzumab to these cytotoxic agents can improve outcome for women with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer . We conducted a pilot study of preoperative epidoxorubicin and docetaxel plus trastuzumab in outpatient patients suffering from breast cancer . Patients and methods Fourteen consecutive patients were enrolled in this prospect i ve clinical pilot trial . Preoperative treatment consisted of weekly trastuzumab ( 4 mg/kg body-weight loading dose , 2 mg/kg/week maintenance dose ) , in combination with weekly epidoxorubicin ( 30 mg/m2 body surface area [ BSA ] ) and docetaxel ( 35 mg/m2 BSA ) once a week for 6 weeks followed by 1 week off therapy . Results Patients received a total of 30 cycles ( median : 2 cycles , range : 2–3 cycles ) of this therapeutic regimen . Outpatient epidoxorubicin and docetaxel plus trastuzumab were well tolerated . A major response to this preoperative therapy regimen could be demonstrated in 12 of 14 patients ( 86 % ) leading to breast-conserving surgery in 11 of 14 patients ( 79 % ) . Conclusions We conclude that outpatient epidoxorubicin and docetaxel plus trastuzumab are safe in the neoadjuvant treatment of patients suffering from breast cancer , based on a favorable side-effect and activity profile . Thus , this regimen can be considered for further clinical trials BACKGROUND The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early , operable , and metastatic breast cancer that has HER2 ( also known as ERBB2 ) overexpression or amplification . We aim ed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab . METHODS We compared 1 year of treatment with trastuzumab ( given as neoadjuvant and adjuvant treatment ; n=117 ) with no trastuzumab ( 118 ) , in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin , paclitaxel , cyclophosphamide , methotrexate , and fluorouracil . R and omisation was done with a computer program and minimisation technique , taking account of geographical area , disease stage , and hormone receptor status . Investigators were informed of treatment allocation . A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen . Primary endpoint was event-free survival . Analysis was by intention to treat . This study is registered , number IS RCT N86043495 . FINDINGS Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer ( 3-year event-free survival , 71 % [ 95 % CI 61 - 78 ; n=36 events ] with trastuzumab , vs 56 % [ 46 - 65 ; n=51 events ] without ; hazard ratio 0.59 [ 95 % CI 0.38 - 0.90 ] ; p=0.013 ) . Trastuzumab was well tolerated and , despite concurrent administration with doxorubicin , only two patients ( 2 % ) developed symptomatic cardiac failure . Both responded to cardiac drugs . INTERPRETATION The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival , survival , and clinical and pathological tumour responses . FUNDING F Hoffmann-La Roche A previously published prospect i ve r and omized phase 3 trial showed that administration of 24 weeks of primary systemic chemotherapy ( PST ) with paclitaxel and FEC75 ( fluorouracil , epirubicin , cyclophosphamide ) concurrently with trastuzumab in patients with HER2‐positive primary breast cancer result ed in a 60 % pathologic complete response rate ( PCR ) with no associated severe cardiac toxicity . The purpose of this study was to review the efficacy and safety of a similar regimen outside the setting of a clinical trial Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions PURPOSE The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response ( pCR ) rate in patients with human epidermal growth factor receptor 2 ( HER2 ) -positive disease . PATIENTS AND METHODS Forty-two patients with HER2-positive disease with operable breast cancer were r and omly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil , epirubicin , and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks . The primary objective was to demonstrate a 20 % improvement in pCR ( assumed 21 % to 41 % ) with the addition of trastuzumab to chemotherapy . The planned sample size was 164 patients . RESULTS Prognostic factors were similar in the two groups . After 34 patients had completed therapy , the trial 's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy . pCR rates were 25 % and 66.7 % for chemotherapy ( n = 16 ) and trastuzumab plus chemotherapy ( n = 18 ) , respectively ( P = .02 ) . The decision was based on the calculation that , if study continued to 164 patients , there was a 95 % probability that trastuzumab plus chemotherapy would be superior . Of the 42 r and omized patients , 26 % in the chemotherapy arm achieved pCR compared with 65.2 % in the trastuzumab plus chemotherapy arm ( P = .016 ) . The safety of this approach is not established , although no clinical congestive heart failure was observed . A more than 10 % decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms , respectively . CONCLUSION Despite the small sample size , these data indicate that adding trastuzumab to chemotherapy , as used in this trial , significantly increased pCR without clinical congestive heart failure Abstract Background Based on previous results obtained with non-pegylated liposomal-encapsulated doxorubicin ( TLC-D99 ) together with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer ( BC ) , a similar regimen was evaluated in the neoadjuvant setting in a prospect ively selected series of consecutive patients with clinical stage II – III BC . Primary and secondary objectives included the rate of pathologic complete response ( pCR ) , safety , and predictive factors of pCR . Methods Patients received six cycles of TLC-D99 ( 50 mg/m2 every 3 weeks ) , paclitaxel ( 80 mg/m2 weekly ) and trastuzumab ( 4 mg/kg initial dose and 2 mg/kg weekly ) . All patients underwent surgery after treatment . pCR was defined as the absence of invasive cancer cells in the breast and the axilla . Results Sixty-two patients with a median age of 46.6 years were analyzed . Stage IIIA was diagnosed in 43.5 % of patients and 14.5 % had inflammatory BC . Conservative surgery was performed in 46.8 % of the patients and pCR was achieved in 63 % ( 95 % CI 50.5–75.5 ) . Patients with estrogen receptor (ER)-negative tumors presented a significantly higher pCR rate than patients with ER-positive tumors ( 74.4 vs 43.5 % ; P = 0.028 ) . Forty-five patients ( 72.6 % ) completed study treatment and 80.6 % received at least five treatment cycles . No patients developed congestive heart failure and 14.5 % of patients showed a ≥10 % decrease in the left ventricular ejection fraction . Conclusion The triple combination therapy assessed is effective and safe , offering a high pCR rate in patients with HER2-positive BC PURPOSE Trastuzumab , a humanized antibody against the human epidermal growth factor receptor type 2 ( HER2 ) , has shown high efficacy in breast cancer . We prospect ively investigated its efficacy given simultaneously with anthracycline-taxane-based neoadjuvant chemotherapy . PATIENTS AND METHODS Patients with operable or locally advanced , HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine ( EC-T[X ] ) and trastuzumab 6 mg/kg ( with a loading dose of 8 mg/kg ) every 3 weeks during all chemotherapy cycles . Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group . Results Of 1,509 participants , 445 had HER2-positive tumors treated with trastuzumab and chemotherapy . Pathologic complete response ( pCR ; defined as no invasive or in situ residual tumors in the breast ) rate was 31.7 % , which was 16 % higher than that in the reference group ( 15.7 % ) . HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6 % ( 3.3 % in the reference group ) . Breast conservation rate was 63.1 % and comparable to that of the reference group ( 64.7 % ) . EC-T(X ) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis , but with a comparable short-term cardiac toxicity profile as the reference group . CONCLUSION This trial confirms that combining trastuzumab with anthracycline-taxane-based neoadjuvant chemotherapy results in a high pCR rate without clinical ly relevant early toxicity . Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer PURPOSE To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer . PATIENTS AND METHODS Patients with central ly confirmed HER2-overexpressing breast cancer ( ≥ 2 cm or inflammatory ) received four 3-week cycles epirubicin and cyclophosphamide ( 90/600 mg/m(2 ) ) followed by four 3-week cycles paclitaxel ( 175 mg/m(2 ) ) and trastuzumab ( 6 mg/kg ) before surgery . Trastuzumab was continued after surgery to complete 1 year of treatment . Primary end point was pathologic complete response ( pCR ) defined as no residual invasive tumor in breast and lymphatic tissue . RESULTS Thirty-nine percent of 217 enrolled patients achieved a pCR . Breast conservation was possible in 64 % of patients . Three-year disease-free survival ( DFS ) was 88 % in patients with pCR compared to 73 % in patients without pCR ( P = .01 ) . Three-year overall survival ( OS ) was 96 % in patients with pCR compared to 86 % in patients without pCR ( P = .025 ) . pCR was the only significant prognostic factor for DFS ( hazard ratio [ HR ] 2.5 ; 95 % CI , 1.2 to 5.1 ; P = .013 ) and OS ( HR , 4.9 ; 95 % CI , 1.4 to 17.4 ; P = .012 ) in multivariable analysis . Cardiac toxicity was reported in eight patients ( 3.7 % ) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure . CONCLUSION Neoadjuvant combination of trastuzumab and chemotherapy result ed in a high pCR rate in HER2-overexpressing primary breast cancer . Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome . Patients without a pCR had an increased risk for relapse and death |
10,837 | 26,268,692 | Trans fats are associated with all cause mortality , total CHD , and CHD mortality , probably because of higher levels of intake of industrial trans fats than ruminant trans fats . | OBJECTIVE To systematic ally review associations between intake of saturated fat and trans unsaturated fat and all cause mortality , cardiovascular disease ( CVD ) and associated mortality , coronary heart disease ( CHD ) and associated mortality , ischemic stroke , and type 2 diabetes . | BACKGROUND Previous observational studies of self-reported dairy product consumption and stroke risk have reported mixed findings . Few studies have used circulating biomarkers that provide objective measures of dairy fat intake . OBJECTIVES We tested the hypothesis that the circulating biomarkers of dairy fat , pentadecanoic acid ( 15:0 ) , heptadecanoic acid ( 17:0 ) , and trans palmitoleate ( trans 16:1n-7 ) , were associated with lower incidence of stroke , especially ischemic stroke . Secondarily , we evaluated 14:0 , which is obtained from dairy products and beef , and also endogenously synthesized . DESIGN In participants from 2 large US cohorts ( the Health Professionals Follow-Up Study : 51,529 men ; the Nurses ' Health Study : 121,700 women ) with stored blood sample s in 1993 - 1994 ( n = 18,225 ) and 1989 - 1990 ( n = 32,826 ) , respectively , we prospect ively identified 594 incident stroke cases ( median follow-up : 8.3 y ) and matched them 1:1 to risk-set- sample d control subjects by age , sex , race , and smoking . Total plasma and red blood cell ( RBC ) fatty acids were measured by using gas-liquid chromatography . Covariates were assessed by using vali date d question naires . Stroke events and subtypes were adjudicated by using medical records or other supporting documentation . We used conditional logistic regression to estimate associations of fatty acids with incident stroke , and cohort-specific findings were combined by inverse-variance weights . RESULTS After adjustment for demographic characteristics , lifestyle , cardiovascular disease risk factors , diet , and other circulating fatty acids , no significant associations with total stroke were seen for plasma 15:0 ( pooled HR for highest compared with lowest quartiles : 0.85 ; 95 % CI : 0.54 , 1.33 ) , 17:0 ( 0.99 ; 0.67 , 1.49 ) , trans 16:1 n-7 ( 0.89 ; 0.55 , 1.45 ) , or 14:0 ( 1.05 ; 0.62 , 1.78 ) . Results were similar for ischemic and hemorrhagic stroke subtypes , for RBC fatty acids , and in several different sensitivity analyses . CONCLUSION In 2 large prospect i ve cohorts , circulating biomarkers of dairy fat were not significantly associated with stroke Background It may be useful to examine associations of fat intakes with total mortality as a basis for dietary recommendations . We aim ed to eluci date associations between dietary fat and total mortality among Japanese population s with low fat intake . Methods We conducted a prospect i ve study consisting of 58,672 men and women aged 40 to 79 years . Fat intakes were estimated using a food frequency question naire . Multivariate-adjusted hazard ratios ( HRs ) for mortality by sex were computed according to quintiles of energy-adjusted fat intakes . Results During the follow-up period ( median duration , 19.3 years ) , 11,656 deaths were recorded . In men , we found no clear association between total fat and total mortality . HRs across quintiles of total fat intake were 1.00 , 1.03 ( 95 % confidence interval [ CI ] , 0.95–1.12 ) , 1.02 ( 0.94–1.10 ) , 0.98 ( 0.90–1.07 ) , and 1.07 ( 0.98–1.17 ) . No significant association was detected in regard to types of fat . In women , HR was lowest in the fourth quintile of total fat intake followed by the top quintile ; HRs across quintiles were 1.00 , 1.03 ( 0.94–1.11 ) , 1.00 ( 0.92–1.09 ) , 0.88 ( 0.81–0.96 ) , and 0.94 ( 0.86–1.03 ) . Regarding types of fat in women , total mortality was inversely associated with intakes of saturated fatty acids ( SFA ) , monounsaturated fatty acids ( MUFA ) , and polyunsaturated fatty acids ( PUFA ) ; the lowest HR was in the top quintile of intake for SFA , MUFA , and PUFA : 0.91 ( 95 % CI , 0.83–1.00 ) , 0.91 ( 0.83–0.99 ) and 0.88 ( 0.80 - 0.97 ) , respectively ( trend P across quintiles , 0.020 , 0.012 , and 0.029 , respectively ) . Causes of death other than cancer and cardiovascular disease contributed most to decreases in HRs for total and types of fat . In women , analysis with finer categories revealed that the lowest risk for total mortality appeared at total fat intake of 28 % of energy . Conclusions Our findings from a large cohort study among population s with relatively low fat intake provide evidence regarding optimal levels of fat intakes Recently , there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat , but results have been inconsistent . We identified 8 prospect i ve studies that met predefined criteria and analyzed their primary data using a st and ardized approach . Holding total energy intake constant , we calculated relative risks for increments of 5 % of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat . We combined study -specific relative risks using a r and om effects model . In the pooled data base , 7,329 incident invasive breast cancer cases occurred among 351,821 women . The pooled relative risks ( 95 % confidence intervals [ CI ] ) for an increment of 5 % of energy were 1.09 ( 1.00 - 1.19 ) for saturated , 0.93 ( 0.84 - 1.03 ) for monounsaturated and 1.05 ( 0.96 - 1.16 ) for polyunsaturated fat compared with equivalent energy intake from carbohydrates . For a 5 % of energy increment , the relative risks were 1.18 ( 95 % CI 0.99 - 1.42 ) for substituting saturated for monounsaturated fat , 0.98 ( 95 % CI 0.85 - 1.12 ) for substituting saturated for polyunsaturated fat and 0.87 ( 95 % CI 0.73 - 1.02 ) for substituting monounsaturated for polyunsaturated fat . No associations were observed for animal or vegetable fat intakes . These associations were not modified by menopausal status . These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption ; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption Aims /hypothesis . The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders . Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans . Methods . The KANWU study included 162 healthy subjects chosen at r and om to receive a controlled , isoenergetic diet for 3 months containing either a high proportion of saturated ( SAFA diet ) or monounsaturated ( MUFA diet ) fatty acids . Within each group there was a second assignment at r and om to supplements with fish oil ( 3.6 g n-3 fatty acids/d ) or placebo . Results . Insulin sensitivity was significantly impaired on the saturated fatty acid diet ( -10 % , p = 0.03 ) but did not change on the monounsaturated fatty acid diet ( + 2 % , NS ) ( p = 0.05 for difference between diets ) . Insulin secretion was not affected . The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion . The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median ( 37E % ) . Here , insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively ( p = 0.03 ) . Low density lipoprotein cholesterol ( LDL ) increased on the saturated fatty acid diet ( + 4.1 % , p < 0.01 ) but decreased on the monounsaturated fatty acid diet ( MUFA ) ( –5.2 , p < 0.001 ) , whereas lipoprotein ( a ) [ Lp(a ) ] increased on a monounsaturated fatty acid diet by 12 % ( p < 0.001 ) . Conclusions /interpretation . A change of the proportions of dietary fatty acids , decreasing saturated fatty acid and increasing monounsaturated fatty acid , improves insulin sensitivity but has no effect on insulin secretion . A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E % ) . [ Diabetologia ( 2001 ) 44 : 312–319 Objectives To investigate the association between long term intake of individual saturated fatty acids ( SFAs ) and the risk of coronary heart disease , in two large cohort studies . Design Prospect i ve , longitudinal cohort study . Setting Health professionals in the United States . Participants 73 147 women in the Nurses ’ Health Study ( 1984 - 2012 ) and 42 635 men in the Health Professionals Follow-up Study ( 1986 - 2010 ) , who were free of major chronic diseases at baseline . Main outcome measure Incidence of coronary heart disease ( n=7035 ) was self-reported , and related deaths were identified by search ing National Death Index or through report of next of kin or postal authority . Cases were confirmed by medical records review . Results Mean intake of SFAs accounted for 9.0 - 11.3 % energy intake over time , and was mainly composed of lauric acid ( 12:0 ) , myristic acid ( 14:0 ) , palmitic acid ( 16:0 ) , and stearic acid ( 18:0 ; 8.8 - 10.7 % energy ) . Intake of 12:0 , 14:0 , 16:0 and 18:0 were highly correlated , with Spearman correlation coefficients between 0.38 and 0.93 ( all P<0.001 ) . Comparing the highest to the lowest groups of individual SFA intakes , hazard ratios of coronary heart disease were 1.07 ( 95 % confidence interval 0.99 to 1.15 ; Ptrend=0.05 ) for 12:0 , 1.13 ( 1.05 to 1.22 ; Ptrend<0.001 ) for 14:0 , 1.18 ( 1.09 to 1.27 ; Ptrend<0.001 ) for 16:0 , 1.18 ( 1.09 to 1.28 ; Ptrend<0.001 ) for 18:0 , and 1.18 ( 1.09 to 1.28 ; Ptrend<0.001 ) for all four SFAs combined ( 12:0 - 18:0 ) , after multivariate adjustment of lifestyle factors and total energy intake . Hazard ratios of coronary heart disease for isocaloric replacement of 1 % energy from 12:0 - 18:0 were 0.92 ( 95 % confidence interval 0.89 to 0.96 ; P<0.001 ) for polyunsaturated fat , 0.95 ( 0.90 to 1.01 ; P=0.08 ) for monounsaturated fat , 0.94 ( 0.91 to 0.97 ; P<0.001 ) for whole grain carbohydrates , and 0.93 ( 0.89 to 0.97 ; P=0.001 ) for plant proteins . For individual SFAs , the lowest risk of coronary heart disease was observed when the most abundant SFA , 16:0 , was replaced . Hazard ratios of coronary heart disease for replacing 1 % energy from 16:0 were 0.88 ( 95 % confidence interval 0.81 to 0.96 ; P=0.002 ) for polyunsaturated fat , 0.92 ( 0.83 to 1.02 ; P=0.10 ) for monounsaturated fat , 0.90 ( 0.83 to 0.97 ; P=0.01 ) for whole grain carbohydrates , and 0.89 ( 0.82 to 0.97 ; P=0.01 ) for plant proteins . Conclusions Higher dietary intakes of major SFAs are associated with an increased risk of coronary heart disease . Owing to similar associations and high correlations among individual SFAs , dietary recommendations for the prevention of coronary heart disease should continue to focus on replacing total saturated fat with more healthy sources of energy BACKGROUND Substitution of dietary polyunsaturated for saturated fat has long been recommended for the primary prevention of cardiovascular disease ( CVD ) , but only a few prospect i ve cohort studies have provided support for this advice . METHODS We assessed the association of dietary linoleic and total polyunsaturated fatty acid ( PUFA ) intake with cardiovascular and overall mortality in a population -based cohort of 1551 middle-aged men . Dietary fat composition was estimated with a 4-day food record and serum fatty acid composition . RESULTS During the 15-year follow-up , 78 men died of CVD and 225 of any cause . Total fat intake was not related to CVD or overall mortality . Men with an energy-adjusted dietary intake of linoleic acid ( relative risk [ RR ] 0.39 ; 95 % confidence interval [ CI ] , 0.21 - 0.71 ) and PUFA ( RR , 0.38 ; 95 % CI , 0.20 - 0.70 ) in the upper third were less likely to die of CVD than men with intake in the lower third after adjustment for age . Multivariate adjustment weakened the association somewhat . Mortality from CVD was also lower for men with proportions of serum esterified linoleic acid ( RR , 0.42 ; 95 % CI , 0.21 - 0.80 ) and PUFA ( RR , 0.25 ; 95 % CI , 0.12 - 0.50 ) in the upper vs lower third , with some attenuation in multivariate analyses . Serum and to a lesser extent dietary linoleic acid and PUFA were also inversely associated with overall mortality . CONCLUSIONS Dietary polyunsaturated and more specifically linoleic fatty acid intake may have a substantial cardioprotective benefit that is also reflected in overall mortality . Dietary fat quality seems more important than fat quantity in the reduction of cardiovascular mortality in men Background Evidence regarding the role of dairy fat intake in cardiovascular disease ( CVD ) has been mixed and inconclusive . Most earlier studies have used self‐reported measures of dietary intake and focused on relatively racially homogeneous population s. Circulating biomarkers of dairy fat in a multiethnic cohort provide objective measures of dairy fat intake and facilitate conclusions relevant to population s with different diets and susceptibility to CVD . Methods and Results In a multiethnic cohort of 2837 US adults aged 45 to 84 years at baseline ( 2000–2002 ) , phospholipid fatty acids including 15:0 , 14:0 , and trans‐16:1n7 were measured using st and ardized methods , and the incidence of CVD prospect ively adjudicated . Self‐reported whole‐fat dairy and butter intakes had strongest associations with 15:0 , rather than 14:0 or trans‐16:1n7 . In multivariate models including demographics and lifestyle and dietary habits , each SD‐unit of 15:0 was associated with 19 % lower CVD risk ( hazard ratio [ 95 % CI ] 0.81 [ 0.68 to 0.98 ] ) and 26 % lower coronary heart disease ( CHD ) risk ( 0.74 [ 0.60 to 0.92 ] ) . Associations were strengthened after mutual adjustment for 14:0 and trans‐16:1n‐7 and were similar after adjustment for potential mediators . Plasma phospholipid 14:0 and trans‐16:1n‐7 were not significantly associated with incident CVD or CHD . All findings were similar in white , black , Hispanic , and Chinese American participants . Conclusion Plasma phospholipid 15:0 , a biomarker of dairy fat , was inversely associated with incident CVD and CHD , while no association was found with phospholipid 14:0 and trans‐16:1n‐7 . These findings support the need for further investigation of CVD effects of dairy fat , dairy‐specific fatty acids , and dairy products in general BACKGROUND Whether elevated intakes of trans fatty acids ( TFAs ) increase the risk of stroke remains unclear . Except for the Women 's Health Initiative-Observational Study , most studies that directly assessed the association between TFA intake and stroke yielded null results . OBJECTIVE The aim of this study was to investigate the association between TFA intake and stroke incidence . DESIGN We prospect ively investigated the association between TFA intake and stroke incidence in black and white men and women ( n = 17,107 ) from the REasons for Geographic And Racial Differences in Stroke ( REGARDS ) cohort . Participants were recruited between 2003 and 2007 from the continental United States and followed for incident stroke . Diet was assessed by using the Block 1998 food-frequency question naire . Cox regression was used to test whether energy-adjusted TFA intake in 1-SD increments was associated with incident stroke . RESULTS During a median follow-up of 7 y , 479 strokes were identified , including 401 ischemic strokes . Sex modified the association between TFA intake and stroke ( P-interaction = 0.06 ) , and thus the results were stratified by sex . In fully adjusted models , a 1-SD ( 2-g/d ) increase in TFA intake was associated with an increased risk of any stroke in men ( HR : 1.14 ; 95 % CI : 1.02 , 1.28 ) but not in women ( HR : 0.93 ; 95 % CI : 0.79 , 1.11 ) . Similarly , our results showed an increased risk of ischemic stroke in men ( HR : 1.13 ; 95 % CI : 1.00 , 1.28 ) but not in women ( HR : 0.93 ; 95 % CI : 0.77 , 1.12 ) . CONCLUSIONS We show that sex modifies the association between TFA intake and stroke ; for every 2-g/d increase in TFA intake , there was a 14 % increase in the risk of stroke in men but not in women . Our findings provide further evidence to support the concerted effort to minimize TFAs in the diet Summary Background Conflicting evidence exists regarding the association between saturated fatty acids ( SFAs ) and type 2 diabetes . In this longitudinal case-cohort study , we aim ed to investigate the prospect i ve associations between objective ly measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants . Methods The EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up ( the EPIC study ) . Incident type 2 diabetes was ascertained until Dec 31 , 2007 , by a review of several sources of evidence . Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids ( mol% ) ; sample s from people with type 2 diabetes and subcohort participants were processed in a r and om order by centre , and laboratory staff were masked to participant characteristics . We estimated country-specific hazard ratios ( HRs ) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression , which is weighted for case-cohort sampling , and pooled our findings using r and om-effects meta- analysis . Findings SFAs accounted for 46 % of total plasma phospholipid fatty acids . In adjusted analyses , different individual SFAs were associated with incident type 2 diabetes in opposing directions . Even-chain SFAs that were measured ( 14:0 [ myristic acid ] , 16:0 [ palmitic acid ] , and 18:0 [ stearic acid ] ) were positively associated with incident type 2 diabetes ( HR [ 95 % CI ] per SD difference : myristic acid 1·15 [ 95 % CI 1·09–1·22 ] , palmitic acid 1·26 [ 1·15–1·37 ] , and stearic acid 1·06 [ 1·00–1·13 ] ) . By contrast , measured odd-chain SFAs ( 15:0 [ pentadecanoic acid ] and 17:0 [ heptadecanoic acid ] ) were inversely associated with incident type 2 diabetes ( HR [ 95 % CI ] per 1 SD difference : 0·79 [ 0·73–0·85 ] for pentadecanoic acid and 0·67 [ 0·63–0·71 ] for heptadecanoic acid ) , as were measured longer-chain SFAs ( 20:0 [ arachidic acid ] , 22:0 [ behenic acid ] , 23:0 [ tricosanoic acid ] , and 24:0 [ lignoceric acid ] ) , with HRs ranging from 0·72 to 0·81 ( 95 % CIs ranging between 0·61 and 0·92 ) . Our findings were robust to a range of sensitivity analyses . Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions , which suggests that SFAs are not homogeneous in their effects . Our findings emphasise the importance of the recognition of subtypes of these fatty acids . An improved underst and ing of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed . Funding EU FP6 programme , Medical Research Council Epidemiology Unit , Medical Research Council Human Nutrition Research , and Cambridge Lipidomics Biomarker Research Initiative The authors aim ed to evaluate the association of the traditional Mediterranean diet and major food groups with incidence of and mortality from cerebrovascular disease ( CBVD ) in a Mediterranean population . The study population was a cohort of 23,601 participants from the Greek segment of the EPIC Study ( European Prospect i ve Investigation into Cancer and Nutrition ) who were free of cardiovascular diseases and cancer at baseline ( 1994 - 1999 ) . Diet was assessed by means of a vali date d food frequency question naire . A 10-point scale integrating key Mediterranean diet characteristics was used to assess the participants ' degree of adherence to this diet . During a median follow-up period of 10.6 years ( 1994 - 2009 ) , 395 confirmed incident cases and 196 deaths from CBVD were recorded . Using Cox proportional hazards regression and adjusting for potential confounders , increased adherence to the Mediterranean diet , as measured by 2-point increments in score , was inversely associated with CBVD incidence ( adjusted hazard ratio = 0.85 , 95 % confidence interval : 0.74 , 0.96 ) and mortality ( adjusted hazard ratio = 0.88 , 95 % CI : 0.73 , 1.06 ) . These inverse trends were mostly evident among women and with respect to ischemic rather than hemorrhagic CBVD and were largely driven by consumption of vegetables , legumes , and olive oil . These data provide support for an inverse association of adherence to the Mediterranean diet with CBVD incidence and mortality BACKGROUND Little is known about the effects of the amount and type of carbohydrates on risk of coronary heart disease ( CHD ) . OBJECTIVE The objective of this study was to prospect ively evaluate the relations of the amount and type of carbohydrates with risk of CHD . DESIGN A cohort of 75521 women aged 38 - 63 y with no previous diagnosis of diabetes mellitus , myocardial infa rct ion , angina , stroke , or other cardiovascular diseases in 1984 was followed for 10 y. Each participant 's dietary glycemic load was calculated as a function of glycemic index , carbohydrate content , and frequency of intake of individual foods reported on a vali date d food-frequency question naire at baseline . All dietary variables were up date d in 1986 and 1990 . RESULTS During 10 y of follow-up ( 729472 person-years ) , 761 cases of CHD ( 208 fatal and 553 nonfatal ) were documented . Dietary glycemic load was directly associated with risk of CHD after adjustment for age , smoking status , total energy intake , and other coronary disease risk factors . The relative risks from the lowest to highest quintiles of glycemic load were 1.00 , 1.01 , 1 . 25 , 1.51 , and 1.98 ( 95 % CI : 1.41 , 2.77 for the highest quintile ; P for trend < 0.0001 ) . Carbohydrate classified by glycemic index , as opposed to its traditional classification as either simple or complex , was a better predictor of CHD risk . The association between dietary glycemic load and CHD risk was most evident among women with body weights above average ¿ ie , body mass index ( in kg/m(2 ) ) > /= 23 . CONCLUSION These epidemiologic data suggest that a high dietary glycemic load from refined carbohydrates increases the risk of CHD , independent of known coronary disease risk factors BACKGROUND Dietary trans fatty acids ( FAs ) , which are formed during the process of hydrogenating vegetable oil , are known to increase plasma LDL-cholesterol concentrations . However , their effect on LDL particle size has yet to be investigated . OBJECTIVE We investigated the effect of trans FA consumption on the electrophoretic characteristics of LDL particles . DESIGN Eighteen women and 18 men each consumed 5 experimental diets in r and om order for 35-d periods . Fat represented 30 % of total energy intake in each diet , with two-thirds of the fat in the form of semiliquid margarine ( 0.6 g trans FAs/100 g fat ) , soft margarine ( 9.4 g trans FAs/100 g fat ) , shortening ( 13.6 g trans FAs/100 g fat ) , stick margarine ( 26.1 g trans FAs/100 g fat ) , or butter , which was low in trans FAs ( 2.6 g trans FAs/100 g fat ) but rich in saturated fat . LDL particle size and distribution were characterized by nondenaturing , 2 - 16 % polyacrylamide gradient gel electrophoresis . RESULTS Relative to the LDL particle size observed after consumption of the butter-enriched diet , LDL particle size decreased significantly and in a dose-dependent fashion with increasing amounts of dietary trans FAs ( P < 0.001 ) . Cholesterol concentrations in large ( > 260 A ) and medium-sized ( 255 - 260 A ) LDL particles also increased proportionately to the amount of trans FAs in the diet . CONCLUSION Consumption of dietary trans FAs is associated with a deleterious increase in small , dense LDL , which further reinforces the importance of promoting diets low in trans FAs to favorably affect the lipoprotein profile BACKGROUND Dietary fatty acids may be associated with diabetes but are difficult to measure accurately . OBJECTIVE We aim ed to investigate the associations of fatty acids in plasma and diet with diabetes incidence . DESIGN This was a prospect i ve case-cohort study of 3737 adults aged 36 - 72 y. Fatty acid intake ( /kJ ) and plasma phospholipid fatty acids ( % ) were measured at baseline , and diabetes incidence was assessed by self-report 4 y later . Logistic regression excluding ( model 1 ) and including ( model 2 ) body mass index and waist-hip ratio was used to calculate odds ratios ( ORs ) for plasma phospholipid and dietary fatty acids . RESULTS In plasma phospholipid , positive associations with diabetes were seen for stearic acid [ OR model 1 , highest versus lowest quintile : 4.14 ( 95 % CI : 2.65 , 6.49 ) , P for trend < 0.0001 ] and total saturated fatty acids [ OR model 1 : 3.76 ( 2.43 , 5.81 ) , P for trend < 0.0001 ] , whereas an inverse association was seen for linoleic acid [ OR model 1 : 0.22 ( 0.14 , 0.36 ) , P for trend < 0.0001 ] . Dietary linoleic [ OR model 1 : 1.77 ( 1.19 , 2.64 ) , P for trend = 0.002 ] , palmitic [ OR model 1 : 1.65 ( 1.12 , 2.43 ) , P for trend = 0.012 ] , and stearic [ OR model 1 : 1.46 ( 1.00 , 2.14 ) , P for trend = 0.030 ] acids were positively associated with diabetes incidence before adjustment for body size . Within each quintile of linoleic acid intake , cases had lower baseline plasma phospholipid linoleic acid proportions than did controls . CONCLUSIONS Dietary saturated fat intake is inversely associated with diabetes risk . More research is required to determine whether linoleic acid is an appropriate dietary substitute BACKGROUND The quantity and quality of fats consumed in the diet influence the risk of cardiovascular disease ( CVD ) . Although the effect of diet on plasma lipids and lipoproteins is well documented , less information exists on the role of fats on blood pressure ( BP ) . OBJECTIVE The objective was to evaluate the effects of different types of dietary fat on BP in healthy subjects . DESIGN Healthy subjects ( n = 162 ) were r and omly assigned for 3 mo to follow 1 of 2 isoenergetic diets : 1 rich in monounsaturated fatty acids ( MUFA diet ) and the other rich in saturated fatty acids ( SFA diet ) . Each group was further r and omly assigned to receive supplementation with fish oil ( 3.6 g n-3 fatty acids/d ) or placebo . RESULTS Systolic BP ( SBP ) and diastolic BP ( DBP ) decreased with the MUFA diet [ -2.2 % ( P = 0.009 ) and -3.8 % ( P = 0.0001 ) , respectively ] but did not change with the SFA diet [ -1.0 % ( P = 0.2084 ) and -1.1 % ( P = 0.2116 ) ] . The MUFA diet caused a significantly lower DBP than did the SFA diet ( P = 0.0475 ) . Interestingly , the favorable effects of MUFA on DBP disappeared at a total fat intake above the median ( > 37 % of energy ) . The addition of n-3 fatty acids influenced neither SBP nor DBP . CONCLUSIONS Changing the proportions of dietary fat by decreasing SFAs and increasing MUFAs decreased diastolic BP . Interestingly , the beneficial effect on BP induced by fat quality was negated by the consumption of a high total fat intake . The addition of n-3 fatty acids to the diet had no significant effect on BP BACKGROUND Metabolic studies suggest that saturated fatty acids differ in their effects on blood lipids . OBJECTIVE The objective was to examine the associations between intakes of individual saturated fatty acids and their food sources in relation to the risk of coronary heart disease ( CHD ) . DESIGN This was a prospect i ve cohort study of 80082 women in the Nurses ' Health Study aged 34 - 59 y. Subjects had no known cardiovascular disease , cancer , hypercholesterolemia , or diabetes , and completed vali date d food-frequency question naires in 1980 . RESULTS During 14 y of follow-up , we documented 939 incident cases of major CHD events . In multivariate analyses in which age , smoking , and other covariates were controlled for , intakes of short- to medium-chain saturated fatty acids ( 4:0 - 10:0 ) were not significantly associated with the risk of CHD . In contrast , intakes of longer-chain saturated fatty acids ( 12:0 - 18:0 ) were each separately associated with a small increase in risk . The multivariate RR for a 1 % energy increase from stearic acid was 1.19 ( 95 % CI : 1.02 , 1.37 ) . The ratio of polyunsaturated to saturated fat was strongly and inversely associated with CHD risk ( multivariate RR for a comparison of the highest with the lowest deciles : 0.58 ; 95 % CI : 0.41 , 0.83 ; P for trend < 0.0001 ) . Conversely , higher ratios of red meat to poultry and fish consumption and of high-fat to low-fat dairy consumption were associated with significantly greater risk . CONCLUSION A distinction between stearic acid and other saturated fats does not appear to be important in dietary advice to reduce CHD risk , in part because of the high correlation between stearic acid and other saturated fatty acids in typical diets BACKGROUND The effect of individual dietary fatty acids on emerging risk factors for cardiovascular disease that are associated with sub clinical inflammation is unknown . OBJECTIVE The goal was to evaluate the role of dietary fat and specific fatty acids , especially trans fatty acids , in altering concentrations of markers of inflammation in humans fed controlled diets . DESIGN In a r and omized crossover design , 50 men consumed controlled diets for 5 wk that provided 15 % of energy from protein , 39 % of energy from fat , and 46 % of energy from carbohydrate . Eight percent of fat or fatty acids was replaced across diets with the following : cholesterol , oleic acid , trans fatty acids ( TFAs ) , stearic acid ( STE ) , TFA+STE ( 4 % of energy each ) , and 12:0 - 16:0 saturated fatty acids ( LMP ) . RESULTS Fibrinogen concentrations were higher after consumption of the diet enriched in stearic acid than after consumption of the carbohydrate diet . C-reactive protein concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet , but were not significantly different after consumption of the TFA and TFA+STE diets than after consumption of the LMP diet . Interleukin 6 concentrations were lower after consumption of the oleic acid diet than after consumption of the LMP , TFA , and STE diets . E-selectin concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet . Consumption of the TFA but not the TFA+STE diet result ed in higher E-selectin concentrations than did the LMP diet . CONCLUSIONS These data provide evidence that dietary fatty acids can modulate markers of inflammation . Although stearic acid minimally affects LDL cholesterol , it does appear to increase fibrinogen concentrations BACKGROUND Acute alcohol intake is associated with changes in plasma lipid concentrations and whole-body lipid balances in humans . The quantitative roles of hepatic de novo lipogenesis ( DNL ) and plasma acetate production in these changes have not been established , however . OBJECTIVE We used stable-isotope mass spectrometric methods with indirect calorimetry to establish the metabolic basis of changes in whole-body lipid balances in healthy men after consumption of 24 g alcohol . DESIGN Eight healthy subjects were studied and DNL ( by mass-isotopomer distribution analysis ) , lipolysis ( by dilution of [1,2,3,4-(13)C(4)]palmitate and [(2)H(5)]glycerol ) , conversion of alcohol to plasma acetate ( by incorporation from [1-(13)C(1)]ethanol ) , and plasma acetate flux ( by dilution of [1-(13)C(1)]acetate ) were measured . RESULTS The fractional contribution from DNL to VLDL-triacylglycerol palmitate rose after alcohol consumption from 2 + /- 1 % to 30 + /- 8 % ; nevertheless , the absolute rate of DNL ( 0.8 g/6 h ) represented < 5 % of the ingested alcohol dose ; 77 + /- 13 % of the alcohol cleared from plasma was converted directly to acetate entering plasma . Acetate flux increased 2.5-fold after alcohol consumption . Adipose release of nonesterified fatty acids into plasma decreased by 53 % and whole-body lipid oxidation decreased by 73 % . CONCLUSIONS We conclude that the consumption of 24 g alcohol activates the hepatic DNL pathway modestly , but acetate produced in the liver and released into plasma inhibits lipolysis , alters tissue fuel selection , and represents the major quantitative fate of ingested ethanol BACKGROUND Nutritional therapy is a cornerstone of diabetes management , but no epidemiologic studies have investigated the relation between specific dietary fatty acids and cholesterol and cardiovascular disease ( CVD ) risk among diabetic patients . OBJECTIVE This study assessed the relation between specific dietary fatty acids and cholesterol and CVD risk among women with type 2 diabetes . DESIGN Among 5672 women with type 2 diabetes from the Nurses ' Health Study , diet was assessed prospect ively and up date d periodically . Relative risks of CVD were estimated from Cox proportional hazards analysis after adjustment for potential confounders . RESULTS Between 1980 and 1998 , we identified 619 new cases of CVD ( nonfatal myocardial infa rct ion , fatal coronary heart disease , and stroke ) . The relative risk ( RR ) of CVD for an increase of 200 mg cholesterol/1000 kcal was 1.37 ( 95 % CI : 1.12 , 1.68 ; P = 0.003 ) . Each 5 % of energy intake from saturated fat , as compared with equivalent energy from carbohydrates , was associated with a 29 % greater risk of CVD ( RR : 1.29 ; 95 % CI : 1.02 , 1.63 ; P = 0.04 ) . The ratio of polyunsaturated to saturated fat ( P : S ) was inversely associated with the risk of fatal CVD . We estimated that replacement of 5 % of energy from saturated fat with equivalent energy from carbohydrates or monounsaturated fat was associated with a 22 % or 37 % lower risk of CVD , respectively . CONCLUSIONS A higher intake of cholesterol and saturated fat and a low P : S were related to increased CVD risk among women with type 2 diabetes . Among diabetic persons , replacement of saturated fat with monounsaturated fat may be more effective in lowering CVD risk than is replacement with carbohydrates BACKGROUND The long-term relations between specific types of dietary fat and risk of type 2 diabetes remain unclear . OBJECTIVE Our objective was to examine the relations between dietary fat intakes and the risk of type 2 diabetes . DESIGN We prospect ively followed 84204 women aged 34 - 59 y with no diabetes , cardiovascular disease , or cancer in 1980 . Detailed dietary information was assessed at baseline and up date d in 1984 , 1986 , and 1990 by using vali date d question naires . Relative risks of type 2 diabetes were obtained from pooled logistic models adjusted for nondietary and dietary covariates . RESULTS During 14 y of follow-up , 2507 incident cases of type 2 diabetes were documented . Total fat intake , compared with equivalent energy intake from carbohydrates , was not associated with risk of type 2 diabetes ; for a 5 % increase in total energy from fat , the relative risk ( RR ) was 0.98 ( 95 % CI : 0.94 , 1.02 ) . Intakes of saturated or monounsaturated fatty acids were also not significantly associated with the risk of diabetes . However , for a 5 % increase in energy from polyunsaturated fat , the RR was 0.63 ( 0.53 , 0.76 ; P < 0.0001 ) and for a 2 % increase in energy from trans fatty acids the RR was 1.39 ( 1.15 , 1.67 ; P = 0.0006 ) . We estimated that replacing 2 % of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40 % lower risk ( RR : 0.60 ; 95 % CI : 0.48 , 0.75 ) . CONCLUSIONS These data suggest that total fat and saturated and monounsaturated fatty acid intakes are not associated with risk of type 2 diabetes in women , but that trans fatty acids increase and polyunsaturated fatty acids reduce risk . Substituting nonhydrogenated polyunsaturated fatty acids for trans fatty acids would likely reduce the risk of type 2 diabetes substantially Background Recently , some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians . The aim of this study was to examine the association of red meat , processed meat , and poultry consumption with the risk of early death in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . Methods Included in the analysis were 448,568 men and women without prevalent cancer , stroke , or myocardial infa rct ion , and with complete information on diet , smoking , physical activity and body mass index , who were between 35 and 69 years old at baseline . Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality . Results As of June 2009 , 26,344 deaths were observed . After multivariate adjustment , a high consumption of red meat was related to higher all-cause mortality ( hazard ratio ( HR ) = 1.14 , 95 % confidence interval ( CI ) 1.01 to 1.28 , 160 + versus 10 to 19.9 g/day ) , and the association was stronger for processed meat ( HR = 1.44 , 95 % CI 1.24 to 1.66 , 160 + versus 10 to 19.9 g/day ) . After correction for measurement error , higher all-cause mortality remained significant only for processed meat ( HR = 1.18 , 95 % CI 1.11 to 1.25 , per 50 g/d ) . We estimated that 3.3 % ( 95 % CI 1.5 % to 5.0 % ) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day . Significant associations with processed meat intake were observed for cardiovascular diseases , cancer , and ' other causes of death ' . The consumption of poultry was not related to all-cause mortality . Conclusions The results of our analysis support a moderate positive association between processed meat consumption and mortality , in particular due to cardiovascular diseases , but also to cancer IMPORTANCE Red meat consumption has been consistently associated with an increased risk of type 2 diabetes mellitus ( T2DM ) . However , whether changes in red meat intake are related to subsequent T2DM risk remains unknown . OBJECTIVE To evaluate the association between changes in red meat consumption during a 4-year period and subsequent 4-year risk of T2DM in US adults . DESIGN AND SETTING Three prospect i ve cohort studies in US men and women . PARTICIPANTS We followed up 26,357 men in the Health Professionals Follow-up Study ( 1986 - 2006 ) , 48,709 women in the Nurses ' Health Study ( 1986 - 2006 ) , and 74,077 women in the Nurses ' Health Study II ( 1991 - 2007 ) . Diet was assessed by vali date d food frequency question naires and up date d every 4 years . Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios with adjustment for age , family history , race , marital status , initial red meat consumption , smoking status , and initial and changes in other lifestyle factors ( physical activity , alcohol intake , total energy intake , and diet quality ) . Results across cohorts were pooled by an inverse variance-weighted , fixed-effect meta- analysis . MAIN OUTCOMES AND MEASURES Incident T2DM cases vali date d by supplementary question naires . RESULTS During 1,965,824 person-years of follow-up , we documented 7540 incident T2DM cases . In the multivariate-adjusted models , increasing red meat intake during a 4-year interval was associated with an elevated risk of T2DM during the subsequent 4 years in each cohort ( all P < .001 for trend ) . Compared with the reference group of no change in red meat intake , increasing red meat intake of more than 0.50 servings per day was associated with a 48 % ( pooled hazard ratio , 1.48 ; 95 % CI , 1.37 - 1.59 ) elevated risk in the subsequent 4-year period , and the association was modestly attenuated after further adjustment for initial body mass index and concurrent weight gain ( 1.30 ; 95 % CI , 1.21 - 1.41 ) . Reducing red meat consumption by more than 0.50 servings per day from baseline to the first 4 years of follow-up was associated with a 14 % ( pooled hazard ratio , 0.86 ; 95 % CI , 0.80 - 0.93 ) lower risk during the subsequent entire follow-up through 2006 or 2007 . CONCLUSIONS AND RELEVANCE Increasing red meat consumption over time is associated with an elevated subsequent risk of T2DM , and the association is partly mediated by body weight . Our results add further evidence that limiting red meat consumption over time confers benefits for T2DM prevention BACKGROUND Few population -based longitudinal studies on diet and stroke have been conducted , and associations between dietary fat and fish intake and risk of stroke are unclear . OBJECTIVES To prospect ively examine relationships between intakes of total fat , saturated fat , unsaturated fat , white fish and oily fish and risk of stroke in a well-defined population of 2710 middle-aged men . STUDY DESIGN Prospect i ve cohort study . METHODS Detailed information on health and lifestyle factors was collected via interview , and diet was assessed on three occasions using a food frequency question naire . Stroke ascertainment was by self-report and inspection of clinical records . Extracted data were assessed by two independent experts . RESULTS During a median follow-up of 18 years , 225 strokes ( 209 ischaemic and 19 haemorrhagic ) were eligible for inclusion in the analyses . For most recent diet ( i.e. food frequency question naire data collected immediately prior to the stroke event ) , there was a slightly lower risk of stroke with higher intakes of unsaturated fat and oily fish . Multiple adjusted hazard ratios ( HRs ) for the lowest vs highest quintiles of unsaturated fat and oily fish intakes were 0.66 [ 95 % confidence interval ( CI ) 0.41 - 1.05 , P trend = 0.13 ] and 0.66 ( 95 % CI 0.41 - 1.05 , P trend = 0.09 ) , respectively . Baseline and cumulative diets showed a slightly higher risk of stroke with higher intake of white fish ; HRs for the lowest vs highest quintiles were 1.16 ( 95 % CI 0.76 - 1.77 , P trend = 0.22 ) and 1.28 ( 95 % CI 0.77 - 2.13 , P trend = 0.48 ) , respectively . CONCLUSIONS Overall , strong associations were not found between intakes of different types of fat and fish and risk of stroke in middle-aged men . The inverse associations between unsaturated fat and oily fish intakes and risk of stroke were weak , but the direction of association was broadly consistent with other studies ; however , these relatively weak associations were not conventionally statistically significant Background — Intake of trans fatty acids is associated with increased risk of coronary heart disease . Whether different classes of trans fatty acids show similar associations is unclear . We previously reported an association of sudden cardiac death with red cell membrane trans-18:2 but not trans-18:1 fatty acids . To extend these findings , we investigated the associations of plasma phospholipid trans fatty acids with fatal ischemic heart disease ( IHD ) and sudden cardiac death . Methods and Results — We conducted a case-control study nested in the Cardiovascular Health Study . We identified 214 cases of fatal IHD ( fatal myocardial infa rct ion and coronary heart disease death ) between 1992 and 1998 . We r and omly selected 214 controls , matched to cases on demographics , prevalent cardiovascular disease , and timing of blood draw . Plasma phospholipid fatty acids were assessed in blood sample s collected earlier . Higher levels of plasma phospholipid trans-18:2 fatty acids were associated with higher risk of fatal IHD ( odds ratio [ OR ] for interquintile range 1.68 , 95 % confidence interval [ CI ] 1.21 to 2.33 ) after adjustment for risk factors and trans-18:1 levels . Trans-18:1 levels above the 20th percentile were associated with lower risk ( OR 0.34 , 95 % CI 0.18 to 0.63 ) . In analyses limited to cases of sudden cardiac death ( n=95 ) , higher levels of trans-18:2 fatty acids were associated with higher risk ( OR 2.34 , 95 % CI 1.27 to 4.31 ) and higher trans-18:1 with lower risk ( OR 0.18 , 95 % CI 0.06 to 0.54 ) . Conclusions — Higher levels of trans-18:2 and lower levels of trans-18:1 fatty acids are associated with higher risks of fatal IHD and sudden cardiac death . If confirmed , these findings suggest that current efforts at decreasing trans fatty acid intake in foods should take into consideration the trans-18:2 content Background : The association of individual fatty acids with ischemic stroke has not been thoroughly studied , and results have been inconsistent . Few prospect i ve studies have systematic ally explored the association of biomarkers of fatty acid intake with stroke . The aim of this study was to explore which individual plasma fatty acids would be associated with higher risk of ischemic stroke among whites . Methods : We studied 3,870 white men and women from the Minneapolis field center of the Atherosclerosis Risk in Communities ( ARIC ) Study , aged 45 - 64 years at baseline ( 1987 - 1989 ) , who had plasma cholesterol ester ( CE ) and phospholipid ( PL ) fatty acids measured . Participants were followed through 2008 for incident ischemic stroke . Hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) across quartiles of each fatty acid , measured as the percentage of total fatty acids , were calculated using the Cox proportional hazards model . Results : During a maximum of 22 years of follow-up , we identified 168 cases of ischemic stroke . After adjustment for age and sex , plasma levels of saturated fatty acids were associated positively : HR ( 95 % CI ) of the highest versus the lowest quartile for CE fraction was 1.93 ( 1.23 - 3.04 , p for trend = 0.01 ) and that for PL fraction was 1.64 ( 1.05 - 2.57 , p for trend = 0.03 ) . There was also a positive linear association with monounsaturated fatty acids , especially with palmitoleic acid : HR ( 95 % CI ) of the highest versus the lowest quartile for CE fraction was 1.86 ( 1.20 - 2.87 , p for trend = 0.003 ) and that for PL fraction was 1.52 ( 0.99 - 2.34 , p for trend = 0.005 ) . No associations of ω-3 and ω-6 polyunsaturated fatty acids with ischemic stroke were observed , but linoleic acid was inversely and nonlinearly associated with ischemic stroke : HR ( 95 % CI ) of the highest versus the lowest quartile for CE fraction was 0.64 ( 0.43 - 0.97 , p for trend = 0.13 ) and that for PL fraction was 0.69 ( 0.45 - 1.05 , p for trend = 0.24 ) . These associations were generally unchanged after adjustment for cardiovascular risk factors . Conclusions : In this US cohort of whites , we found significant positive associations of plasma saturated and monounsaturated fatty acids , especially of palmitoleic acid , with ischemic stroke . We also found an inverse nonlinear association between linoleic acid and ischemic stroke OBJECTIVE To investigate the association between macronutrient intake and type 2 diabetes risk in middle-aged Australian women . DESIGN A prospect i ve cohort study , with 6 years ( 2002 - 2007 ) of follow up . Dietary intake was assessed with a vali date d FFQ . Relative risks with 95 % confidence intervals were used to examine risk associations . SETTING Australian Longitudinal Study on Women 's Health , Australia . SUBJECTS Australian women ( n 8370 ) from the Australian Longitudinal Study on Women 's Health aged 45 - 50 years and free of type 2 diabetes at baseline . RESULTS After 6 years of follow-up , 311 women developed type 2 diabetes . After adjusting for sociodemographic , lifestyle and other dietary risk factors , MUFA , total n-3 PUFA , α-linolenic acid and total n-6 PUFA intakes were positively associated with the incidence of type 2 diabetes . The relative risks for type 2 diabetes for the highest compared with the lowest quintiles were 1·64 ( 95 % CI 1·06 , 2·54 ) , P = 0·04 for MUFA ; 1·55 ( 95 % CI 1·03 , 2·32 ) , P = 0·01 for n-3 PUFA ; 1·84 ( 95 % CI 1·25 , 2·71 ) , P < 0·01 for α-linolenic acid ; and 1·60 ( 95 % CI 1·03 , 2·48 ) , P = 0·04 for n-6 PUFA . Other dietary macronutrients were not significantly associated with diabetes risk . CONCLUSIONS The data indicate that consumption of MUFA , n-3 PUFA and n-6 PUFA may influence the risk of developing type 2 diabetes in women Aim /hypothesisThe aim of this study was to investigate the association between total and types of dairy product intake and risk of developing incident type 2 diabetes , using a food diary . Methods A nested case-cohort within the EPIC-Norfolk Study was examined , including a r and om subcohort ( n = 4,000 ) and cases of incident diabetes ( n = 892 , including 143 cases in the subcohort ) followed-up for 11 years . Diet was assessed using a prospect i ve 7-day food diary . Total dairy intake ( g/day ) was estimated and categorised into high-fat ( ≥3.9 % ) and low-fat ( < 3.9 % fat ) dairy , and by subtype into yoghurt , cheese and milk . Combined fermented dairy product intake ( yoghurt , cheese , sour cream ) was estimated and categorised into high- and low-fat . Prentice-weighted Cox regression HRs were calculated . Results Total dairy , high-fat dairy , milk , cheese and high-fat fermented dairy product intakes were not associated with the development of incident diabetes . Low-fat dairy intake was inversely associated with diabetes in age- and sex-adjusted analyses ( tertile [ T ] 3 vs T1 , HR 0.81 [ 95 % CI 0.66 , 0.98 ] ) , but further adjustment for anthropometric , dietary and diabetes risk factors attenuated this association . In addition , an inverse association was found between diabetes and low-fat fermented dairy product intake ( T3 vs T1 , HR 0.76 [ 95 % CI 0.60 , 0.99 ] ; ptrend = 0.049 ) and specifically with yoghurt intake ( HR 0.72 [ 95 % CI 0.55 , 0.95 ] ; ptrend = 0.017 ) in multivariable adjusted analyses . Conclusions /interpretationGreater low-fat fermented dairy product intake , largely driven by yoghurt intake , was associated with a decreased risk of type 2 diabetes development in prospect i ve analyses . These findings suggest that the consumption of specific dairy types may be beneficial for the prevention of diabetes , highlighting the importance of food group subtypes for public health messages BACKGROUND Dairy product intake may be inversely associated with risk of type 2 diabetes , but the evidence is inconclusive for total dairy products and sparse for types of dairy products . OBJECTIVE The objective was to investigate the prospect i ve association of total dairy products and different dairy subtypes with incidence of diabetes in population s with marked variation of intake of these food groups . DESIGN A nested case-cohort within 8 European countries of the European Prospect i ve Investigation into Cancer and Nutrition Study ( n = 340,234 ; 3.99 million person-years of follow-up ) included a r and om subcohort ( n = 16,835 ) and incident diabetes cases ( n = 12,403 ) . Baseline dairy product intake was assessed by using dietary question naires . Country-specific Prentice-weighted Cox regression HRs were calculated and pooled by using a r and om-effects meta- analysis . RESULTS Intake of total dairy products was not associated with diabetes ( HR for the comparison of the highest with the lowest quintile of total dairy products : 1.01 ; 95 % CI : 0.83 , 1.34 ; P-trend = 0.92 ) in an analysis adjusted for age , sex , BMI , diabetes risk factors , education , and dietary factors . Of the dairy subtypes , cheese intake tended to have an inverse association with diabetes ( HR : 0.88 ; 95 % CI : 0.76 , 1.02 ; P-trend = 0.01 ) , and a higher combined intake of fermented dairy products ( cheese , yogurt , and thick fermented milk ) was inversely associated with diabetes ( HR : 0.88 ; 95 % CI : 0.78 , 0.99 ; P-trend = 0.02 ) in adjusted analyses that compared extreme quintiles . CONCLUSIONS This large prospect i ve study found no association between total dairy product intake and diabetes risk . An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested , which merits further study BACKGROUND The issue of whether saturated fats and trans fats are superior predictors of all-cause death and cardiovascular disease than n-3 polyunsaturated fatty acids , such as eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , remains a matter of contention . Furthermore , few studies have examined the relationship between fatty acids and the outcomes of cardiovascular disease ( CVD ) in Asian population s. The aim of this study was to compare the effectiveness of various plasma fatty acids as predictors for all-cause death and CVD events in an ethnic Chinese population . METHODS This study assembled a community-based prospect i ve cohort , comprising 1833 participants ( 60.6 ± 10.5 yrs , 44.5 % women ) who underwent a comprehensive evaluation of fatty acids in blood using gas chromatography . None of the subjects had a history of CVD at the time of recruitment . RESULTS A total of 568 individuals died and 275 individuals developed CVD during the follow-up period ( median of 9.6 years ; interquartile range of 8.9 - 10.5 years ) . Following adjustment for established cardiovascular risk factors , the relative risk of all-cause death in the highest quartile , compared with the lowest quartile , was 1.33 for saturated fats ( 95 % confidence interval [ CI ] , 1.01 - 1.75 , test for trend , P = 0.015 ) , 1.71 for trans fats ( 95 % CI , 1.27 - 2.31 , test for trend , P = 0.0003 ) , 0.77 for EPA ( 95 % CI , 0.59 - 1.00 , test for trend , P = 0.048 ) , and 0.89 for DHA ( 95 % CI , 0.68 - 1.18 , test for trend , P = 0.354 ) . Similar patterns were observed for CVD events . Trans fats presented the largest area under the receiver operator characteristic curve ( 0.740 , 95 % CI , 0.716 - 0.766 ) for the prediction of all-cause death . A mutually adjusted two-marker model indicated that saturated fats and trans fats were significant predictors of all-cause death and CVD ; however , the other fatty acids were not . In addition , trans fats presented the greatest improvement in net reclassification for all-cause death ( 7.7 % , P = 0.003 ) , followed by EPA ( 3.8 % , P = 0.033 ) . Saturated fats presented the greatest improvement in net reclassification for CVD events ( 5.6 % , P = 0.039 ) . CONCLUSIONS Our data provides strong evidence to support that plasma saturated fats and trans fats can predict all-cause death and CVD more effectively than other fatty acid markers OBJECTIVE To evaluate diet as a risk factor for myocardial infa rct ion . DESIGN Community based case-control study . SETTING University Hospital , Oporto . PARTICIPANTS First time consecutive cases of acute myocardial infa rct ion ( n = 100 ) and 198 community controls , older than 39 years and living in Oporto , were compared . METHODS Data were collected by trained interviewers using a structured question naire design ed to obtain information on socio-demographic , medical and behavioural aspects , emphasising the description of diet and food habits ( using a semi-quantitative food frequency question naire ) . Controls were selected by r and om digit dialing with a participation rate of 70 % . Odds ratios and 95 % confidence intervals ( CI ) according to quartiles of nutrient ingestion were calculated using unconditional logistic regression . RESULTS Female controls presented significantly higher mean intakes of protein , omega-3 fatty acids , fiber , cholesterol and vitamin C. Male controls had a significantly higher mean daily intake of fiber , vitamin C , vitamin E , and carotenes . After adjusting for age , sex , education , body mass index , ethanol , smoking and total energy intake , there was a protective effect of vitamin C ( OR = 0.2 , 95 % CI : 0.1 - 0.6 , for the 4th quartile ) , vitamin E ( OR = 0.3 , 95 % CI : 0.1 - 0.9 for the 4th quartile ) and total fiber ( OR = 0.3 , 95 % CI : 0.1 - 0.9 ) for the 4th quartile ) . No significant effect was found for trans-fatty acids , but there was a higher risk with increased energy intake . CONCLUSIONS This study showed that diet has an important independent effect on myocardial infa rct ion , a protective independent role for anti-oxidant vitamin C and E was verified Objective : The paper aims to investigate the relationships of dietary fats to subsequent coronary heart disease ( CHD ) mortality in men and women while taking account of other CHD-related behaviours . Design : A cohort of r and omly selected men and women were interviewed in 1984–85 and monitored subsequently for 16 y for deaths . The interview covered health , health-related behaviours , physical measurements , socio-demographic details and a dietary question naire . Appropriate exclusions left 1225 men and 1451 women aged 40–75 with 98 and 57 CHD deaths , respectively . Saturated , polyunsaturated and total fat intakes were estimated . Setting : The sample was r and omly selected from households in Great Britain . The interviews took place in participants ' own homes . Results : Not consuming alcohol , smoking , not exercising and being socially disadvantaged were related to high saturated fat intake and CHD death . Cox survival analyses adjusting for these factors found that a level of saturated fat 100 g per week higher corresponded to a relative risk for CHD death for men of 1.00 ( 0.86–1.18 ) and 1.40 ( 1.09–1.79 ) for women . This difference between the effects of saturated fat in men and women was statistically significant ( P=0.019 ) . Results are also reported for total fat and the relative effects of polyunsaturated and saturated fats . Conclusions : Strong evidence was found for the within cohort relationship of dietary fat and CHD death in women while no evidence was found for a relationship in men . Possible explanations for this are discussed . Sponsorship : This study was supported by University of Hertfordshire using funding made available by the UK Higher Education Funding Council H istorically , nutrition principles and recommendations for diabetes and related complications have been based on scientific evidence and diabetes knowledge when available and , when evidence was not available , on clinical experience and expert consensus . Often it has been difficult to discern the level of evidence used to construct the nutrition principles and recommendations . Furthermore , in clinical practice , many nutrition recommendations that have no scientific supporting evidence have been and are still being given to individuals with diabetes . To address these problems and to incorporate the research done in the past 8 years , this 2002 technical review provides principles and recommendations classified according to the level of evidence available . It review s the evidence from r and omized , controlled trials ; cohort and case-controlled studies ; and observational studies , which can also provide valuable evidence ( 1,2 ) , and takes into account the number of studies that have provided consistent outcomes of support . In this review , nutrition principles are grade d into four categories based on the available evidence : those with strong supporting evidence , those with some supporting evidence , those with limited supporting evidence and those based on expert consensus . Evidence -based nutrition recommendations attempt to translate research data and clinical ly applicable evidence into nutrition care . However , the best available evidence must still be moderated by individual circumstances and preferences . The goal of evidence -based recommendations is to improve the quality of clinical judgments and facilitate costeffective care by increasing the awareness of clinicians and patients with diabetes of the evidence supporting nutrition services and the strength of that evidence , both in quality and quantity . Before 1994 , the American Diabetes Association ’s ( ADA ’s ) nutrition principles and recommendations attempted to define an “ ideal ” nutrition prescription that would apply to everyone with diabetes ( 3–5 ) . Although individualization was a major principle of all recommendations , it was usually done within defined limits for recommended energy intake and macronutrient composition . The 1994 nutrition recommendations shifted this focus to one that emphasized effects of nutrition therapy on metabolic control ( 6,7 ) . The nutrition prescription is determined considering treatment goals and lifestyle changes the diabetic patient is willing and able to make , rather than predetermined energy levels and percentages of carbohydrate , protein , and fat . The goal of nutrition intervention is to assist and facilitate individual lifestyle and behavior changes that will lead to improved metabolic control . This focus continues with the 2002 nutrition principles and recommendations . Medical nutrition therapy ( MNT ) is an integral component of diabetes management ( 8,9 ) and diabetes sel fmanagement education ( 10 ) . ( Medical nutrition therapy is the preferred term and should replace other terms , such as diet , diet therapy , and dietary management . ) MNT for diabetes includes the process and the system by which nutrition care is provided for diabetic individuals and the specific lifestyle recommendations for that care . However , recommendations should not only be based on scientific evidence but should also take into consideration lifestyle changes the ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● The study deals with 412 men , aged 30 to 64 years , r and omized 1 to 2 years after a first myocardial infa rct ion . For the experimental group a diet low in saturated fats and cholesterol , and high in polyunsaturated fats was recommended . After 5 years , as reported previously , the incidence of fatal and nonfatal myocardial reinfa rct ion was found to be significantly reduced . “ Sudden death ” was uninfluenced . Major coronary heart disease ( CHD ) relapses , including fatal and nonfatal events ( MI ) , were significantly reduced ( P = 0.05).After 11 years , death from all causes had occurred in 101 of the original dieters and 108 controls . A significantly reduced myocardial infa rct ion mortality in the original diet group was found ( 32 versus 57 , P = 0.004 ) . The total number of coronary deaths ( fatal myocardial infa rct ion and sudden death ) was 79 in the diet group and 94 in the control group ( P = 0.097).The CHD mortality was correlated with age , serum cholesterol level , blood pressure , body weight , smoking habits , and a combination of these risk factors Background and Purpose — A traditional diet that is poor in animal products is thought to explain the high rate of stroke in Asian population s. The purpose of the present study was to examine the effect of a diet rich in animal protein , animal fat , and cholesterol on the risk of cerebral infa rct ion mortality in a Japanese population . Methods — A prospect i ve study of 3731 Japanese men and women aged 35 to 89 years was conducted from 1984 to 2001 . Nutrient intake was estimated at baseline from the responses to a 24-hour diary . During the follow-up period , cases of cerebral infa rct ion deaths ( as entered on death certificates ) were monitored . Results — During the follow-up period , 60 deaths were attributed to cerebral infa rct ion . A high intake of animal fat and cholesterol was significantly associated with a reduced risk of cerebral infa rct ion death . The risk was reduced by 62 % ( CI , 82 % to 18 % ) for those in the third tertile of animal fat intake , compared with those in the first tertile , with a significant linear dose-response relationship ( P = 0.0073 ) . The risk of death from infa rct ion was reduced by 63 % ( CI , 82 % to 22 % ) in the high cholesterol consumption group , compared with the low consumption group . A significant linear dose – response relationship was observed . Animal protein was not significantly associated with infa rct ion mortality after adjustment for animal fat and cholesterol . Conclusions — This study suggests that in Japan , where animal product intake is lower than in Western countries , a high consumption of animal fat and cholesterol was associated with a reduced risk of cerebral infa rct ion death The authors assessed the association between serum phospholipid fatty acids as biomarkers of fatty acid intake and breast cancer risk among women in the E3N Study ( 1989 - 2002 ) , the French component of the European Prospect i ve Investigation into Cancer and Nutrition . During an average of 7 years of follow-up , 363 cases of incident invasive breast cancer were documented among 19,934 women who , at baseline ( 1995 - 1998 ) , had completed a diet history question naire and provided serum sample s. Controls were r and omly matched to cases by age , menopausal status at blood collection , fasting status at blood collection , date , and collection center . Serum phospholipid fatty acid composition was assessed by gas chromatography . Adjusted odds ratios for risk of breast cancer with increasing levels of fatty acids were calculated using conditional logistic regression . An increased risk of breast cancer was associated with increasing levels of the trans-monounsaturated fatty acids palmitoleic acid and elaidic acid ( highest quintile vs. lowest : odds ratio = 1.75 , 95 % confidence interval : 1.08 , 2.83 ; p-trend = 0.018 ) . cis-Monounsaturated fatty acids were unrelated to breast cancer risk . A high serum level of trans-monounsaturated fatty acids , presumably reflecting a high intake of industrially processed foods , is probably one factor contributing to increased risk of invasive breast cancer in women In a prospect i ve epidemiologic study of 1001 middle-aged men , we examined the relation between dietary information collected approximately 20 years ago and subsequent mortality from coronary heart disease . The men were initially enrolled in three cohorts : one of men born and living in Irel and , another of those born in Irel and who had emigrated to Boston , and the third of those born in the Boston area of Irish immigrants . There were no differences in mortality from coronary heart disease among the three cohorts . In within- population analyses , those who died of coronary heart disease had higher Keys ( P = 0.06 ) and modified Hegsted ( P = 0.02 ) dietary scores than did those who did not ( a high score indicates a high intake of saturated fatty acids and cholesterol and a relatively low intake of polyunsaturated fatty acids ) . These associations were significant ( P = 0.03 for the Keys and P = 0.04 for the modified Hegsted scores ) after adjustment for other risk factors for coronary heart disease . Fiber intake ( P = 0.04 ) and a vegetable-foods score , which rose with increased intake of fiber , vegetable protein , and starch ( P = 0.02 ) , were lower among those who died from coronary heart disease , though not significantly so after adjustment for other risk factors . A higher Keys score carried an increased risk of coronary heart disease ( relative risk , 1.60 ) , and a higher fiber intake carried a decreased risk ( relative risk , 0.57 ) . Overall , these results tend to support the hypothesis that diet is related , albeit weakly , to the development of coronary heart disease OBJECTIVE The aim of this study was to prospect ively assess the relation between red meat intake and incidence of type 2 diabetes . RESEARCH DESIGN AND METHODS Over an average of 8.8 years , we evaluated 37,309 participants in the Women 's Health Study aged > /=45 years who were free of cardiovascular disease , cancer , and type 2 diabetes and completed vali date d semiquantitative food frequency question naires in 1993 . RESULTS During 326,876 person-years of follow-up , we documented 1,558 incident cases of type 2 diabetes . After adjusting for age , BMI , total energy intake , exercise , alcohol intake , cigarette smoking , and family history of diabetes , we found positive associations between intakes of red meat and processed meat and risk of type 2 diabetes . Comparing women in the highest quintile with those in the lowest quintile , the multivariate-adjusted relative risks ( RRs ) of type 2 diabetes were 1.28 for red meat ( 95 % CI 1.07 - 1.53 , P < 0.001 for trend ) and 1.23 for processed meat intake ( 1.05 - 1.45 , P = 0.001 for trend ) . Furthermore , the significantly increased diabetes risk appeared to be most pronounced for frequent consumption of total processed meat ( RR 1.43 , 95 % CI 1.17 - 1.75 for > /=5/week vs. < 1/month , P < 0.001 for trend ) and two major subtypes , which were bacon ( 1.21 , 1.06 - 1.39 for > /=2/week vs. < 1/week , P = 0.004 for trend ) and hot dogs ( 1.28 , 1.09 - 1.50 for > /=2/week vs. < 1/week , P = 0.003 for trend ) . These results remained significant after further adjustment for intakes of dietary fiber , magnesium , glycemic load , and total fat . Intakes of total cholesterol , animal protein , and heme iron were also significantly associated with a higher risk of type 2 diabetes . CONCLUSIONS Our data indicate that higher consumption of total red meat , especially various processed meats , may increase risk of developing type 2 diabetes in women Some evidence suggests that diets high in animal fat or red meat may increase the risk of colon cancer , whereas high intake of fiber or vegetables may be protective . Frequently , intake of red meat has been a stronger risk factor than total fat . Because data from prospect i ve cohort studies are sparse , we examined fat , meat , fiber , and vegetable intake in relation to risk of colon cancer in a cohort of 47,949 U.S. male health professionals who were free of diagnosed cancer in 1986 . At baseline , these men , 40 to 75 years of age , completed a vali date d food frequency question naire and provided detailed information on other lifestyle and health-related factors . Between 1986 and 1992 , 205 new cases of colon cancer were diagnosed in these men . Intakes of total fat , saturated fat , and animal fat were not related to risk of colon cancer . However , an elevated risk of colon cancer was associated with red meat intake ( relative risk , 1.71 ; 95 % confidence interval , 1.15 - 2.55 between high and low quintiles ; P = 0.005 for trend ) . Men who ate beef , pork , or lamb as a main dish five or more times per week had a relative risk of 3.57 ( 95 % confidence interval , 1.58 - 8.06 ; P = 0.01 for trend ) compared to men eating these foods less than once per month . The association with red meat was not confounded appreciably by other dietary factors , physical activity , body mass , alcohol intake , cigarette smoking , or aspirin use . Other sources of animal fat , including dairy products , poultry , and fish as well as vegetable fat , were slightly inversely related to risk of colon cancer . No clear association existed between fiber or vegetable intake and risk of colon cancer . These data support the hypothesis that intake of red meat is related to an elevated risk of colon cancer Kay-Tee Khaw and colleagues analyze data from a prospect i ve cohort study and show associations between plasma concentrations of saturated phospholipid fatty acids and risk of coronary heart disease , and an inverse association between omega-6 polyunsaturated phospholipid fatty acids and risk of coronary heart disease Objective To investigate dietary determinants of ischaemic heart disease ( IHD ) in health conscious individuals to explain the reduced risk in vegetarians , and to examine the relation between IHD and body mass index ( BMI ) within the normal range . Design Prospect i ve observation of vegetarians , semi-vegetarians , and meat eaters for whom baseline dietary data , reported weight and height information , social class , and smoking habits were recorded . Subjects 10 802 men and women in the UK aged between 16 and 79 , mean duration of follow up 13.3 years . Main outcome measures Death rate ratios for IHD and total mortality in relation to dietary and other characteristics recorded at recruitment ( reference category death rate = 100 ) . Results IHD mortality was less than half that expected from the experience reported for all of Engl and and Wales . An increase in mortality for IHD was observed with increasing intakes of total and saturated animal fat and dietary cholesterol — death rate ratios in the third tertile compared with the first tertile : 329 , 95 % confidence interval ( CI ) 150 to 721 ; 277 , 95 % CI 125 to 613 ; 353 , 95 % CI 157 to 796 , respectively . No protective effects were observed for dietary fibre , fish or alcohol . Within the study , death rate ratios were increased among those in the upper half of the normal BMI range ( 22.5 to < 25 ) and those who were overweight ( BMI ⩾ 25 ) compared with those with BMI 20 to < 22.5 . Conclusions In these relatively health conscious individuals the deleterious effects of saturated animal fat and dietary cholesterol appear to be more important in the aetiology of IHD than the protective effect of dietary fibre . Reduced intakes of saturated animal fat and cholesterol may explain the lower rates of IHD among vegetarians compared with meat eaters . Increasing BMI within the normal range is associated with increased risk of IHD . The results have important public health implication Aims Although dietary saturated fatty acids ( SFA ) are considered atherogenic , associations between SFAs intake and stroke and coronary heart disease are still debated . We sought to test the hypothesis that SFA intake is associated inversely with risk of stroke and its subtypes and positively with coronary heart disease among Japanese , whose average SFA intake is lower than that of Westerners . Methods and results The Japan Public Health Center-based prospect i ve Study involves two subcohorts : Cohort I , aged 45 - 64 in 1995 and followed-up through 2009 , and Cohort II , aged 45 - 74 in 1998 and followed-up through 2007 . A total of 38 084 men and 43 847 women were included in this report . Hazards ratios for incident total stroke , ischaemic stroke , intraparhenchymal haemorrhage , subarachnoid haemorrhage , myocardial infa rct ion , and sudden cardiac death across quintiles of dietary SFAs were examined . We found inverse associations between SFA intake and total stroke [ multivariable hazard ratio ( 95 % confidence interval ) for the highest vs. lowest quintiles = 0.77 ( 0.65 - 0.93 ) , trend P = 0.002 ] , intraparenchymal haemorrhage [ 0.61 ( 0.43 - 0.86 ) , P for trend = 0.005 ] , and ischaemic stroke [ 0.84 ( 0.67 - 1.06 ) , trend P = 0.08 ] , primarily for deep intraparenchymal haemorrhage [ 0.67 ( 0.45 - 0.99 ) , P for trend = 0.04 ] and lacunar infa rct ion [ 0.75 ( 0.53 , 1.07 ) , trend P = 0.02 ] . We also observed a positive association between SFAs intake and myocardial infa rct ion [ 1.39 ( 0.93 - 2.08 ) , trend P = 0.046 ] primarily among men . No associations were observed between SFAs intake and incidence of subarachnoid haemorrhage or sudden cardiac death . Conclusions In this Japanese population , SFAs intake was inversely associated with deep intraparenchymal haemorrhage and lacunar infa rct ion and positively associated with myocardial infa rct ion The role of dietary fat in the etiology of type 2 diabetes remains uncertain . The authors investigated the association between dietary fat composition and risk of clinical type 2 diabetes in the European Prospect i ve Investigation of Cancer-Norfolk study and identified food consumption patterns associated with dietary fat composition . Diet was assessed at baseline ( 1993 - 1997 ) using a semiquantitative food frequency question naire . From multiple sources of information , 414 incident cases of diabetes were identified among 23,631 men and women aged 40 - 78 years during 3 - 7 years of follow-up . The capture-recapture ascertainment level was 99 % . The energy-adjusted dietary polyunsaturated : saturated fat ratio was inversely associated with the risk of diabetes ( odds ratio ( OR ) = 0.84 per st and ard deviation change , 95 % confidence interval ( CI ) : 0.75 , 0.94 ) . Adjustment for age , sex , family history of diabetes , smoking , physical activity , total fat , protein , and alcohol attenuated the association ( OR = 0.88 , 95 % CI : 0.78 , 0.99 ) , and it was no longer statistically significant after including body mass index and the waist : hip ratio ( OR = 0.91 , 95 % CI : 0.81 , 1.03 ) . This prospect i ve study showed that an increased dietary polyunsaturated : saturated fat ratio was associated with a reduced risk of diabetes , independent of age , sex , family history of diabetes , and other lifestyle factors OBJECTIVE To examine the associations between reported intakes of dietary fat and incident type 2 diabetes . RESEARCH DESIGN AND METHODS We studied the relation between dietary fatty acids and diabetes in a prospect i ve cohort study of 35,988 older women who initially did not have diabetes . Diet was assessed with a food frequency question naire at baseline , and 1,890 incident cases of diabetes occurred during 11 years of follow-up . RESULTS After adjusting for age , smoking , alcohol consumption , BMI , waist-to-hip ratio , physical activity , demographic factors , and dietary magnesium and cereal fiber , diabetes incidence was negatively associated with dietary polyunsaturated fatty acids , vegetable fat , and trans fatty acids and positively associated with omega-3 fatty acids , cholesterol , and the Keys score . After simultaneous adjustment for other dietary fat , only vegetable fat remained clearly related to diabetes risk . Relative risks across quintiles of vegetable fat intake were 1.00 , 0.90 , 0.87 , 0.84 , and 0.82 ( P = 0.02 ) . Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score . CONCLUSIONS These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol Aims /hypothesisLow adherence to recommendations for dietary saturated fatty acid ( SFA ) and fibre intake in patients with type 1 diabetes mellitus may heighten their increased risk of cardiovascular disease ( CVD ) and mortality . We examined the relationship of SFA and total , soluble and insoluble fibre with incident CVD and all-cause mortality in type 1 diabetic patients . Methods A prospect i ve cohort analysis was performed in 2,108 European type 1 diabetic patients aged 15–60 years who were free of CVD at baseline and enrolled in the EURODIAB Prospect i ve Complications Study ( 51 % male ) . Diet was assessed from a st and ardised 3 day dietary record . HR were calculated using Cox proportional hazards models . Results During a mean follow-up of 7.3 years , 148 incident cases of fatal and non-fatal CVD and 46 all-cause deaths were documented . No statistically significant association was found between SFA and CVD and all-cause mortality . Total dietary fibre , per 5 g/day , was associated with lower all-cause mortality risk ( HR 0.72 ; 95 % CI 0.55 , 0.95 ) . This association was stronger for soluble fibre ( per 5 g/day , HR 0.34 ; 95 % CI 0.14 , 0.80 ) compared with insoluble fibre ( per 5 g/day ; HR 0.66 ; 95 % CI 0.45 , 0.97 ) . Similar results were found for the association with CVD . Conclusions /interpretationThis study suggests that reported dietary SFA is not significantly associated with CVD and all-cause mortality in type 1 diabetic patients . On the contrary , higher dietary fibre consumption , especially soluble fibre , within the range commonly consumed by type 1 diabetic patients , may contribute to the prevention of CVD and all-cause mortality in type 1 diabetic patients Objective : To investigate the consumption of industrial trans-fatty acids ( TFAs ) in Iranian homes and the proportion of coronary heart disease ( CHD ) events in Iran attributable to such intake . Design , setting and participants : The consumption of industrial TFAs was determined using ( 1 ) detailed in-home assessment s of dietary intake among 7158 urban and rural households containing 35 924 individuals and ( 2 ) gas chromatography to determine TFA contents of the most commonly consumed partially hydrogenated oils . The population -attributable risk for CHD owing to TFA consumption was calculated on the basis of ( 1 ) documented effects of TFAs on total : high-density lipoprotein ( HDL ) cholesterol in r and omized controlled dietary trials and ( 2 ) relationships of TFA intake with incidence of CHD in prospect i ve observational studies . Results : Partially hydrogenated oils were used extensively for cooking in Iranian homes with average per-person intake of 14 g/1000 kcal . TFAs accounted for 33 % of fatty acids in these products , or 4.2 % of all calories consumed ( 12.3 g/day ) . On the basis of total : HDL cholesterol effects alone , 9 % of CHD events would be prevented by replacement of TFA in Iranian homes with cis-unsaturated fats ( 8 % by replacement with saturated fats ) . On the basis of relationships of TFA intake with CHD incidence in prospect i ve studies , 39 % of CHD events would be prevented by replacement of TFA with cis-unsaturated fats ( 31 % by replacement with saturated fats ) . These population -attributable risks may be overestimates owing to competing risks and because not all the fat used for cooking might actually be consumed . If actual TFA consumption were only half as large , the estimated proportion of CHD events prevented by TFA elimination would be 5 % on the basis of total : HDL cholesterol effects and replacement with cis-unsaturated ( 4 % for replacement with saturated fats ) , and 22 % on the basis of prospect i ve studies and replacement with cis-unsaturated fats ( 17 % for replacement with saturated fats ) . These estimates do not include possible additional benefits derived from replacing TFAs with vegetable oils containing n-3 fatty acids . Conclusions : Intake of TFAs is high in Iranian homes and contributes to a sizeable proportion of CHD events . Replacement of partially hydrogenated oils with unhydrogenated oils would likely produce substantial reductions in CHD incidence . Sponsorship : National Heart , Lung and Blood Institute , National Institutes of Health , USA . National Nutrition & Food Technology Research Institute , Tehran , Iran The influence of risk factors on CHD and all-cause mortality rates in 35- to 57-year-old men is examined by means of data on 325,348 white men who were screened for the MRFIT . This large data set permits an unusually detailed analysis of factors associated with the 6968 deaths , including 2426 ascribed to CHD , that were detected in the Social Security Administration data set during 6 years of follow-up . Simple cross classification of the data confirms the independent effect of serum cholesterol concentration , diastolic blood pressure , and cigarette smoking as risk factors for CHD and all-cause mortality rates . A distinct escalation of risk is noted for combinations of these risk factors . The strength of the association of each of the risk factors with CHD and all-cause mortality rates diminished with increasing age , although the number of excess deaths attributable to the risk factors increased because of the higher death rates in older men . Comparison of these findings with those observed in the five population s studied in the Pooling Project revealed an overall similarity in the risk relationships . It is estimated that elimination of these risk factors has the potential for reducing the CHD mortality rate by two thirds in 35- to 45-year old men , and by one half in 46- to 57-year-old men BACKGROUND Evidence on the relation between trans fatty acid intake and coronary heart disease is limited . We investigated this relation in a Dutch population with a fairly high trans fatty acid intake , including trans fatty acids from partly hydrogenated fish oils . METHODS We prospect ively studied 667 men of the Zutphen Elderly Study aged 64 - 84 years and free of coronary heart disease at baseline . We used dietary surveys to establish the participants ' food consumption patterns . Information on risk factors and diet was obtained in 1985 , 1990 , and 1995 . After 10 years of follow-up from 1985 - 95 , there were 98 cases of fatal or non-fatal coronary heart disease . FINDINGS Between 1985 and 1995 , average trans fatty acid intake decreased from 4.3 % to 1.9 % of energy . After adjustment for age , body mass index , smoking , and dietary covariates , trans fatty acid intake at baseline was positively associated with the 10-year risk of coronary heart disease . The relative risk for a difference of 2 % of energy in trans fatty acid intake at baseline was 1.28 ( 95 % CI 1.01 - 1.61 ) . INTERPRETATION A high intake of trans fatty acids ( all types of isomers ) contributes to the risk of coronary heart disease . The substantial decrease in trans fatty acid intake , mainly due to industrial lowering of trans contents in Dutch edible fats , could therefore have had a large public-health impact OBJECTIVE To evaluate the validity of the Northern Sweden eighty-four-item FFQ to estimate intake of fatty acids relative to 24 h diet recalls ( 24-HDR ) and fatty acids in erythrocyte membranes . DESIGN Participants , r and omly recruited from the population -based Västerbotten Intervention Project , answered the eighty-four-item FFQ . During the following year each participant carried out ten 24-HDR . Intake of fatty acids measured by the FFQ was compared with intake by the 24-HDR and fatty acid levels in erythrocytes . SETTING The county of Västerbotten in northern Sweden . SUBJECTS Ninety-six men and ninety-nine women . RESULTS Spearman correlation coefficients ( rs ) between intakes of the fatty acids 14 : 0 , 15 : 0 , 16 : 0 , 17 : 0 , 18 : 2n-6 , 18 : 3n-3 , 20 : 5n-3 and 22 : 6n-3 estimated by the FFQ and the 24-HDR were all significant and ranged from 0.29 ( 22 : 6n-3 in men and women ) to 0.60 ( 16 : 0 in men ) , whereas significant correlations between FFQ-estimated intake and erythrocyte membrane content were only seen for milk fatty acids 14 : 0 , 15 : 0 and 17 : 0 ( rs = 0.23 - 0.34 ) and fish fatty acids 20 : 5n-3 and 22 : 6n-3 ( rs = 0.42 - 0.51 ) . CONCLUSION The Northern Sweden eighty-four-item FFQ gives a satisfactory estimate of the intake of fish fatty acids ( 20 : 5n-3 and 22 : 6n-3 ) and milk fatty acids ( 15 : 0 and 17 : 0 ) , whereas its validity for fatty acids 18 : 2n-6 and 18 : 3n-3 , derived mainly from vegetable oils , can not be shown BACKGROUND Epidemiologic evidence for the association between types of fatty acid and risk of type 2 diabetes is inconsistent . This may in part be due to the limitations of fatty acid measurement methods . OBJECTIVE The objective was to use 3 different measures of fatty acid to estimate the prospect i ve association between fatty acid composition and development of incident diabetes . DESIGN We analyzed 199 cases of clinical ly incident diabetes and 184 noncases aged 40 - 79 y at baseline in the EPIC ( European Prospect i ve Investigation into Cancer and Nutrition)-Norfolk study . Fatty acids were derived from a food-frequency question naire ( FFQ ) and measured in plasma phospholipid ( P-FA ) and erythrocyte-membrane phospholipid ( Ery-FA ) fractions by gas chromatography . RESULTS There were stronger associations with diabetes risk with the use of objective ly measured fatty acids ( P-FA and Ery-FA ) than with the FFQ in analyses adjusted for age , sex , and potential confounders . Positive associations with diabetes were greater in magnitude with the use of P-FA than with Ery-FA ( highest : lowest tertiles ) : for example , the palmitic acid odds ratios ( ORs ) were 2.47 ( 95 % CI : 1.37 , 4.46 ) and 1.96 ( 95 % CI : 1.10 , 3.49 ) , respectively . Inverse associations with diabetes were also stronger with the use of P-FA than with Ery-FA : for example , the OR for linoleic acid was 0.50 ( 95 % CI : 0.28 , 0.91 ) compared with 0.77 ( 95 % CI : 0.43 , 1.37 ) , respectively . CONCLUSIONS The objective measurement of fatty acids with the use of either P-FA or Ery-FA identifies important associations with diabetes incidence that may be missed when assessed by FFQ . Fatty acids measured in P-FA appear to be more strongly associated with diabetes incidence . These findings endorse the use of objective measurement of fatty acids for nutritional-epidemiologic studies , and the apparently stronger findings for the plasma fraction should be confirmed in larger studies and in different population OBJECTIVES To evaluate the effect on overall and cardiovascular mortality of diet and physical activity amongst diabetic persons . DESIGN Population -based prospect i ve investigation , from 1993 to mid-2004 , in the Greek arm of the European Prospect i ve Investigation into Cancer and Nutrition . SETTING Volunteers from the general adult Greek population . SUBJECTS From an original sample of 28 572 volunteers , 1013 were taking at enrolment drugs for diabetes mellitus , had no missing information on the study variables and no comorbidity . Diet was assessed at baseline through a vali date d question naire . Proportional hazards regression was used to assess the relation of dietary factors and physical activity with mortality . INTERVENTIONS None . MAIN OUTCOME MEASURES Mortality ratios overall and from cardiovascular causes . RESULTS During 4579 person-years , 80 deaths have occurred , 46 of which from cardiovascular causes . Physical activity was strongly inversely associated with mortality . Two nutritional variables were significantly associated with diabetic mortality , with hazard ratios for increases of daily intake by one st and ard deviation being 1.31 for eggs [ 95 % confidence interval ( 95 % CI ) 1.07 to 1.60 ] and 1.82 for saturated lipids ( 95 % CI , 1.14 to 2.90 ) . These two associations were considerably stronger for cardiovascular mortality . Waist-to-height ratio was positively , whereas hip circumference inversely associated with mortality . No significant interactions with gender for any of the study variables were evident . DISCUSSION Amongst confirmed diabetic persons , increased physical activity is associated with significant reduction of mortality , whereas increased consumption of eggs and saturated fats is associated with significant increase of mortality . Monounsaturated lipids are preferable for diabetic persons OBJECTIVE To examine dietary fat and meat intake in relation to risk of type 2 diabetes . RESEARCH DESIGN AND METHODS We prospect ively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40 - 75 years and free of diagnosed diabetes , cardiovascular disease , and cancer in 1986 . Diet was assessed by a vali date d food frequency question naire and up date d in 1990 and 1994 . During 12 years of follow-up , we ascertained 1,321 incident cases of type 2 diabetes . RESULTS Intakes of total fat ( multivariate RR for extreme quintiles 1.27 , CI 1.04 - 1.55 , P for trend=0.02 ) and saturated fat ( 1.34 , 1.09 - 1.66 , P for trend=0.01 ) were associated with a higher risk of type 2 diabetes . However , these associations disappeared after additional adjustment for BMI ( total fat RR 0.97 , CI 0.79 - 1.18 ; saturated fat 0.97 , 0.79 - 1.20 ) . Intakes of oleic acid , trans-fat , long-chain n-3 fat , and alpha-linolenic acid were not associated with diabetes risk after multivariate adjustment . Linoleic acid was associated with a lower risk of type 2 diabetes in men < 65 years of age ( RR 0.74 , CI 0.60 - 0.92 , P for trend=0.01 ) and in men with a BMI < 25 kg/m(2 ) ( 0.53 , 0.33 - 0.85 , P for trend=0.006 ) but not in older and obese men . Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes ( RR 1.46 , CI 1.14 - 1.86 for > or = 5/week vs. < 1/month , P for trend < 0.0001 ) . CONCLUSIONS Total and saturated fat intake were associated with a higher risk of type 2 diabetes , but these associations were not independent of BMI . Frequent consumption of processed meats may increase risk of type 2 diabetes BACKGROUND Decreased fat intake with weight loss and increased exercise may reduce the risk of diabetes mellitus in persons with impaired glucose tolerance . This study was undertaken to assess the effects of a low-fat dietary pattern on incidence of treated diabetes among generally healthy postmenopausal women . METHODS A r and omized controlled trial was conducted at 40 US clinical centers from 1993 to 2005 , including 48,835 postmenopausal women aged 50 to 79 years . Women were r and omly assigned to a usual-diet comparison group ( n = 29,294 [ 60.0 % ] ) or an intervention group with a 20 % low-fat dietary pattern with increased vegetables , fruits , and grains ( n = 19,541 [ 40.0 % ] ) . Self-reported incident diabetes treated with oral agents or insulin was assessed . RESULTS Incident treated diabetes was reported by 1303 intervention participants ( 7.1 % ) and 2039 comparison participants ( 7.4 % ) ( hazard ratio , 0.96 ; 95 % confidence interval , 0.90 - 1.03 ; P = .25 ) . Weight loss occurred in the intervention group , with a difference between intervention and comparison groups of 1.9 kg after 7.5 years ( P < .001 ) . Subgroup analysis suggested that greater decreases in percentage of energy from total fat reduced diabetes risk ( P for trend = .04 ) , which was not statistically significant after adjusting for weight loss . CONCLUSIONS A low-fat dietary pattern among generally healthy postmenopausal women showed no evidence of reducing diabetes risk after 8.1 years . Trends toward reduced incidence were greater with greater decreases in total fat intake and weight loss . Weight loss , rather than macronutrient composition , may be the dominant predictor of reduced risk of diabetes BACKGROUND A high intake of trans fatty acids decreases HDL cholesterol and is associated with increased LDL cholesterol , inflammation , diabetes , cancer , and mortality from cardiovascular disease . The relation between trans fat intake and all-cause mortality has not been established . OBJECTIVE The aim of this study was to determine the relation between trans fat intake and all-cause mortality . DESIGN We used data from the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) study -a prospect i ve cohort study of white and black men and women residing in the continental United States . Energy-adjusted trans fat intake was categorized into quintiles , and Cox-regression was used to evaluate the association between trans fat intake and all-cause mortality . RESULTS During 7 y of follow-up , there were 1572 deaths in 18,513 participants included in REGARDS . From the first to the fifth quintile of trans fat intake , the mortality rates per 1000 person-years of follow-up ( 95 % CIs ) were 12.8 ( 11.3 , 14.5 ) , 14.3 ( 12.7 , 16.2 ) , 14.6 ( 13.0 , 16.5 ) , 19.0 ( 17.1 , 21.1 ) , and 23.6 ( 21.5 , 25.9 ) , respectively . After adjustment for demographic factors , education , and risk factors for mortality , the HRs ( 95 % CIs ) for all-cause mortality were 1.00 , 1.03 ( 0.86 , 1.23 ) , 0.98 ( 0.82 , 1.17 ) , 1.25 ( 1.05 , 1.48 ) , and 1.24 ( 1.05 , 1.48 ) , respectively ( P-trend = 0.004 ) . The population attributable risk due to trans fat intake was 7 % ( 95 % CI : 5 % , 8 % ) . CONCLUSION Higher trans fat intake is associated with an increased risk of all-cause mortality BACKGROUND Experimental evidence suggests that hepatic de novo lipogenesis ( DNL ) affects insulin homeostasis via synthesis of saturated fatty acids ( SFAs ) and monounsaturated fatty acids ( MUFAs ) . Few prospect i ve studies have used fatty acid biomarkers to assess associations with type 2 diabetes . OBJECTIVES We investigated associations of major circulating SFAs [ palmitic acid ( 16:0 ) and stearic acid ( 18:0 ) ] and MUFA [ oleic acid ( 18:1n-9 ) ] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study . We secondarily assessed other DNL fatty acid biomarkers [ myristic acid ( 14:0 ) , palmitoleic acid ( 16:1n-7 ) , 7-hexadecenoic acid ( 16:1n-9 ) , and vaccenic acid ( 18:1n-7 ) ] and estimated dietary SFAs and MUFAs . DESIGN In 3004 participants free of diabetes , plasma phospholipid fatty acids were measured in 1992 , and incident diabetes was identified by medication use and blood glucose . Usual diets were assessed by using repeated food-frequency question naires . Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes , respectively . RESULTS At baseline , circulating palmitic acid and stearic acid were positively associated with adiposity , triglycerides , inflammation biomarkers , and insulin resistance ( P-trend < 0.01 each ) , whereas oleic acid showed generally beneficial associations ( P-trend < 0.001 each ) . During 30,763 person-years , 297 incident diabetes cases occurred . With adjustment for demographics and lifestyle , palmitic acid ( extreme-quintile HR : 1.89 ; 95 % CI : 1.27 , 2.83 ; P-trend = 0.001 ) and stearic acid ( HR : 1.62 ; 95 % CI : 1.09 , 2.41 ; P-trend = 0.006 ) were associated with higher diabetes risk , whereas oleic acid was not significantly associated . In secondary analyses , vaccenic acid was inversely associated with diabetes ( HR : 0.56 ; 95 % CI : 0.38 , 0.83 ; P-trend = 0.005 ) . Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes . CONCLUSIONS In this large prospect i ve cohort , circulating palmitic acid and stearic acid were associated with higher diabetes risk , and vaccenic acid was associated with lower diabetes risk . These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes To examine the relation between serum fatty acids and coronary heart disease ( CHD ) , the authors conducted a nested case-control study of 94 men with incident CHD and 94 men without incident CHD who were enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial between December 1973 and February 1976 . After confirming the stability of the stored serum sample s , the authors measured serum fatty acid levels by gas-liquid chromatography and examined their association with CHD . In all multivariate models , levels of the cholesterol ester saturated fatty acid palmitic acid ( 16:0 ) were directly associated with CHD risk ( st and ardized odds ratio = 1.68 ; 95 % confidence interval 1.10 - 2.55 in the model that adjusted for total plasma cholesterol level ) . Levels of the phospholipid omega-3 fatty acid docosapentaenoic acid ( 22:5 ) were inversely associated with CHD risk in the two multivariate models that controlled for the effects of total plasma cholesterol level or high density lipoprotein cholesterol to total plasma cholesterol ratio ( st and ardized odds ratio = 0.58 ; 95 % confidence interval 0.38 - 0.89 in the first model that controlled for total plasma cholesterol level ) . In contrast to the first two multivariate models , levels of the docosahexaenoic acid ( 22:6 ) were inversely associated with CHD risk in a third multivariate model that controlled for the effects of high density lipoprotein cholesterol to low density lipoprotein cholesterol ratio ( st and ardized odds ratio = 0.57 ; 95 % confidence interval 0.36 - 0.90 ) . These findings are consistent with other evidence indicating that saturated fatty acids are directly correlated with CHD and that omega-3 polyunsaturated fatty acids are inversely correlated with CHD . Because these associations were present after adjustment for blood lipid levels , other mechanisms , such as a direct effect on blood clotting , may be involved BACKGROUND Although dietary recommendations have focused on restricting saturated fat ( SF ) consumption to reduce cardiovascular disease ( CVD ) risk , evidence from prospect i ve studies has not supported a strong link between total SF intake and CVD events . An underst and ing of whether food sources of SF influence these relations may provide new insights . OBJECTIVE We investigated the association of SF consumption from different food sources and the incidence of CVD events in a multiethnic population . DESIGN Participants who were 45 - 84 y old at baseline ( n = 5209 ) were followed from 2000 to 2010 . Diet was assessed by using a 120-item food-frequency question naire . CVD incidence ( 316 cases ) was assessed during follow-up visits . RESULTS After adjustment for demographics , lifestyle , and dietary confounders , a higher intake of dairy SF was associated with lower CVD risk [ HR ( 95 % CI ) for + 5 g/d and + 5 % of energy from dairy SF : 0.79 ( 0.68 , 0.92 ) and 0.62 ( 0.47 , 0.82 ) , respectively ] . In contrast , a higher intake of meat SF was associated with greater CVD risk [ HR ( 95 % CI ) for + 5 g/d and a + 5 % of energy from meat SF : 1.26 ( 1.02 , 1.54 ) and 1.48 ( 0.98 , 2.23 ) , respectively ] . The substitution of 2 % of energy from meat SF with energy from dairy SF was associated with a 25 % lower CVD risk [ HR ( 95 % CI ) : 0.75 ( 0.63 , 0.91 ) ] . No associations were observed between plant or butter SF and CVD risk , but ranges of intakes were narrow . CONCLUSION Associations of SF with health may depend on food-specific fatty acids or other nutrient constituents in foods that contain SF , in addition to SF BACKGROUND The significance of erythrocyte membrane fatty acids ( EMFAs ) and their ratios to predict hyperglycemia and incident type 2 diabetes is unclear . OBJECTIVE We investigated EMFAs as predictors of the worsening of hyperglycemia and incident type 2 diabetes in a 5-y follow-up of a population -based study . DESIGN We measured EMFAs in 1346 Finnish men aged 45 - 73 y at baseline [ mean ± SD age : 55 ± 6 y ; body mass index ( in kg/m(2 ) ) : 26.5 ± 3.5 ] . Our prospect i ve follow-up study included only men who were nondiabetic at baseline and who had data available at the 5-y follow-up visit ( n = 735 ) . RESULTS Our study showed that , after adjustment for confounding factors , palmitoleic acid ( 16:1n-7 ; P = 2.8 × 10(-7 ) ) , dihomo-γ-linolenic acid ( 20:3n-6 ; P = 2.3 × 10(-4 ) ) , the ratio of 16:1n-7 to 16:0 ( P = 1.6 × 10(-8 ) ) as a marker of stearoyl coenzyme A desaturase 1 activity , and the ratio of 20:3n-6 to 18:2n-6 ( P = 9.4 × 10(-7 ) ) as a marker of Δ(6)-desaturase activity significantly predicted the worsening of hyperglycemia ( glucose area under the curve in an oral-glucose-tolerance test ) . In contrast , linoleic acid ( 18:2n-6 ; P = 0.0015 ) and the ratio of 18:1n-7 to 16:1n-7 ( P = 1.5 × 10(-9 ) ) as a marker of elongase activity had opposite associations . Statistical significance persisted even after adjustment for baseline insulin sensitivity , insulin secretion , and glycemia . Palmitoleic acid ( P = 0.010 ) and the ratio of 16:1n-7 to 16:0 ( P = 0.004 ) nominally predicted incident type 2 diabetes , whereas linoleic acid had an opposite association ( P = 0.004 ) , and n-3 polyunsaturated fatty acids did not show any associations . CONCLUSION EMFAs and their ratios are associated longitudinally with changes in glycemia and the risk type 2 diabetes The Caerphilly Prospect i ve Ischaemic Heart Disease ( IHD ) Study is based on a sample of 2512 men aged 45 - 59 years when first seen . Nutrient intakes , estimated using a self-administered semi-quantitative food frequency question naire , are available for 2423 men ( 96 % ) . Amongst these , 148 major IHD events occurred during the first 5 years of follow-up . Associations were examined between these events and baseline diet . Incident IHD ( new events ) was negatively associated with total energy intake : men who went on to experience an IHD event had consumed 560 kJ ( 134 kcal)/d ( 6 % ) less at baseline than men who experienced no event ( P = 0.01 ) . The relative odds of an IHD event was 1.5 among men in the lowest fifth of energy intake , compared with 1.3 , 1.2 , 0.9 and 1.0 respectively for the other four fifths ( P < 0.05 ) . The difference in energy intake was reflected in lower intakes of every nutrient examined . When expressed as a percentage of total energy , mean intakes of men who experienced an IHD event were virtually identical to those of men who did not . There was some evidence suggesting a positive association between total fat intake and IHD risk , but the trend was not consistent and not statistically significant . There was no association for animal fat . Alcohol consumption was negatively associated with subsequent IHD , but only in men who already had evidence of IHD at baseline ( P < 0.05 ) . Dietary fibre , particularly from fruit and vegetables , was 7 % lower in men who had an incident IHD event ( P < 0.05 ) , but the difference was not independent of total energy . There was a trend of increasing IHD risk with decreasing vitamin C intake , the relative odds of an IHD event being 1.6 among men in the lowest one-fifth of the vitamin C distribution , but this was not statistically significant A controlled intervention trial , with the purpose of testing the hypothesis that the incidence of coronary heart disease ( CHD ) could be decreased by the use of serum-cholesterol-lowering ( SCL ) diet , was carried out in 2 mental hospitals near Helsinki in 1959 - -71 . The subjects were hospitalized middle-aged men . One of the hospitals received the SCL diet , i.e. a diet low in saturated fats and cholesterol and relatively high in polyunsaturated fats , while the other served as the control with a normal hospital diet . Six years later the diets were reversed , and the trial was continued another 6 years . The use of the SCL diet was associated with markedly lowered serum-cholesterol values . The incidence of CHD , as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths , was in both hospitals during the SCL-diet periods about half that during the normal-diet periods . An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the considerable reduction in the incidence of CHD . It is concluded that the use of the serum-cholesterol-lowering diet exerted a substantial preventive effect on CHD BACKGROUND Dairy consumption is linked to a lower risk of type 2 diabetes , but constituents responsible for this relation are not established . Emerging evidence suggests that trans-palmitoleate ( trans 16:1n-7 ) , a fatty acid in dairy and also partially hydrogenated oils , may be associated with a more favorable metabolic profile and less incident diabetes . OBJECTIVE We investigated the association of trans-palmitoleate with metabolic risk and incident diabetes in a multiethnic US cohort . DESIGN Phospholipid fatty acids and metabolic risk factors were measured in 2000 - 2002 among 2617 adults in the Multi-Ethnic Study of Atherosclerosis ( MESA ) , a cohort of white , black , Hispanic , and Chinese Americans . In 2281 participants free of baseline diabetes , we also prospect ively assessed the risk of new-onset diabetes ( 205 cases ) from baseline to 2005 - 2007 . RESULTS trans-Palmitoleate concentrations correlated positively with self-reported consumption of whole-fat dairy , butter , margarine , and baked desserts and with other circulating biomarkers of both dairy fat and partially hydrogenated oil consumption , which suggested mixed dietary sources . After multivariable adjustment , trans-palmitoleate concentrations were associated with higher LDL cholesterol ( quintile 5 compared with quintile 1 : + 6.4 % ; P-trend = 0.005 ) , lower triglycerides ( -19.1 % ; P-trend < 0.001 ) , lower fasting insulin ( -9.1 % ; P-trend = 0.002 ) , and lower systolic blood pressure ( -2.4 mm Hg ; P-trend = 0.01 ) . In prospect i ve analyses , trans-palmitoleate was independently associated with lower incident diabetes ( P-trend = 0.02 ) , including a 48 % lower risk in quintile 5 compared with quintile 1 ( HR : 0.52 ; 95 % CI : 0.32 , 0.85 ) . All findings were similar between men and women and between different race-ethnic subgroups . CONCLUSIONS Circulating trans-palmitoleate is associated with higher LDL cholesterol but also with lower triglycerides , fasting insulin , blood pressure , and incident diabetes in a multiethnic US cohort . Our findings support the need for further experimental and dietary intervention studies that target circulating trans-palmitoleate . The MESA trial was registered at clinical trials.gov as NCT00005487 The trans isomer of oleic acid ( elaidic acid ) increases low density lipoprotein ( LDL ) cholesterol and decreases high density lipoprotein ( HDL ) cholesterol in man . One possible mechanism for this effect is that trans fatty acids increase plasma cholesteryl ester transfer protein ( CETP ) activity . We examined the effect of dietary trans fatty acids on activity of this protein in plasma from 27 men in a double blind crossover comparison . The background diet , containing 15 % energy as fat from dairy products , meat , bread and cereals , was supplemented with oleic or elaidic acid providing a further 20 % energy . The elaidic supplement provided about 6 % energy as trans fatty acid . Activity of CETP in plasma was significantly higher ( P < 0.001 ) after the elaidic acid-rich diet ( 23.95 + /- 1.26 % ) compared with the diet enriched with oleic acid ( 19.61 + /- 0.89 % ) . A significant correlation between the change in plasma trans 18:1 fatty acids and the change in plasma CETP activity ( r = 0.58 , P < 0.002 ) was independent of changes in LDL-cholesterol . The increase in CETP activity was in turn significantly correlated with a fall in HDL-cholesterol among subjects during the elaidic acid-rich period ( r = -0.57 , P < 0.01 ) . We have shown that CETP demonstrates substrate specificity and that the increase in activity with dietary trans fatty acids may contribute to a more atherogenic lipoprotein profile Over twenty years ago , we evaluated diet , serum cholesterol , and other variables in 1900 middle-aged men and repeated the evaluation one year later . No therapeutic suggestions were made . Vital status was determined at the 20th anniversary of the initial examination . Scores summarizing each participant 's dietary intake of cholesterol , saturated fatty acids , and polyunsaturated fatty acids were calculated according to the formulas of Keys and Hegsted and their co-workers . The two scores were highly correlated , and results were similar for both : there was a positive association between diet score and serum cholesterol concentration at the initial examination , a positive association between change in diet score and change in serum cholesterol concentration from the initial to the second examination , and a positive association prospect ively between mean base-line diet score and the 19-year risk of death from coronary heart disease . These associations persisted after adjustment for potentially confounding factors . The results support the conclusion that lipid composition of the diet affects serum cholesterol concentration and risk of coronary death in middle-aged American men BACKGROUND Total intake of trans fat is associated with coronary heart disease ( CHD ) , and recent reports in primarily male population s suggest that blood levels of specific trans isomers may have different effects on risk , particularly risk of sudden cardiac death ( SCD ) . METHODS We prospect ively examined the association between dietary intake of trans fat and SCD among 86,762 women from the Nurses ' Health Study . Coronary heart disease risk factors , including diet and lifestyle factors , were up date d via question naires every 2 to 4 years , beginning in 1980 . RESULTS Over 26 years , we documented 317 SCD events . In the primary analysis , we found no significant association between intake of total trans fat , trans-18:1 , or trans-18:2 isomers and risk of SCD . Compared to the lowest quintile of intake , the relative risk ( 95 % CI ) of SCD in the highest quintile was 1.28 ( 0.82 - 2.00 ) for total trans , 1.08 ( 0.64 - 1.83 ) for trans-18:1 , and 1.19 ( 0.76 - 1.88 ) for trans-18:2 . In a secondary prespecified analysis , total trans fat was significantly related to SCD among women who reported a diagnosis of CHD before SCD ( relative risk 3.24 , 95 % CI 1.42 - 7.40 for the highest vs lowest quintile , P trend = .01 ) ; however , the test for interaction was not significant ( P = .11 ) . CONCLUSIONS In this large prospect i ve cohort of women , neither dietary intake of trans fat nor the individual trans isomers , trans-18:1 and trans-18:2 , were significantly associated with risk of SCD . However , trans fat intake may be associated with SCD risk among women with CHD , suggesting that trans fat intake may play a greater role in SCD risk among those with clinical ly manifest atherosclerosis OBJECTIVE To evaluate the relation between intake and adipose tissue composition of fatty acids and acute myocardial infa rct ion in Portuguese men . DESIGN Case-control study . Diet was assessed using a semiquantitative food frequency question naire . In 49 case and 49 control subjects , adipose tissue composition was assessed by gas-liquid chromatography . SUBJECTS/ SETTING Population -based ; subjects were 297 consecutively admitted cases of first acute myocardial infa rct ion in a tertiary care hospital who were aged > or=40 years . Three hundred ten community controls were selected by r and om-digit dialing . MAIN OUTCOME MEASURE Odds ratio ( OR ) . STATISTICAL ANALYSIS PERFORMED Logistic regression , adjusting for age , education , family history of acute myocardial infa rct ion , smoking , physical activity , body mass index , and energy intake . RESULTS Total fat intake ( OR 0.45 , fourth quartile , P=0.02 ) , lauric acid ( OR 0.44 , fourth quartile , P=0.02 ) , palmitic acid ( OR 0.58 , fourth quartile , P=0.03 ) , and oleic acid ( OR 0.42 , fourth quartile , P=0.03 ) were inversely associated with acute myocardial infa rct ion . No significant effects were found for the remaining fatty acids . In the adipose tissue composition data , the adjusted risk estimates of acute myocardial infa rct ion for the highest vs the lowest tertile were 0.16 , 0.14 , and 0.04 for lauric , oleic , and trans-fatty acids , respectively . A significant direct association was found for palmitic and linoleic acids ( adjusted ORs for the highest tertile were 9.02 and 3.63 , respectively ) . CONCLUSIONS Low intake of total fat and lauric acid from dairy products was associated with acute myocardial infa rct ion . The association of polyunsaturated fatty acids with risk of acute myocardial infa rct ion was nonsignificant after adjustment for energy intake and confounders . Recommendations on fatty acid intake should aim for both an upper and lower limit BACKGROUND The long-term role of fatty acids ( FAs ) in the cause of diabetes remains largely unclear . OBJECTIVE We aim ed to investigate erythrocyte membrane FAs , desaturase activity , and dietary FAs in relation to the incidence of type 2 diabetes . DESIGN We applied a nested case-cohort design ( n = 2724 , including 673 incident diabetes cases ) within the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam Study , which involves 27,548 middle-aged subjects . Thirty erythrocyte membrane FAs ( percentage of total FAs ) and FA intake ( percentage of total fat ) were measured at baseline , and physician-confirmed incident diabetes was assessed during a mean follow-up of 7.0 y. We evaluated Δ⁵ desaturase ( D5D ) and Δ⁶ desaturase ( D6D ) activity by using FA product-to-precursor ratios ( traditional approach ) and by investigating variants in FADS1 and FADS2 genes that encode these desaturases ( Mendelian r and omization approach ) . RESULTS As a main finding , erythrocyte 16:1n-7 and 18:3n-6 and FA ratios , which reflect stearoyl coenzyme A desaturase ( SCD ) and D6D activity , were directly related to diabetes risk in multivariable-adjusted models [ relative risks ( 95 % CIs ) comparing extreme quintiles : 16:1n-7 , 2.11 ( 1.46 , 3.05 ) ; 18:3n-6 , 2.00 ( 1.38 , 2.88 ) ; SCD , 2.61 ( 1.75 , 3.89 ) ; and D6D , 2.46 ( 1.67 , 3.63 ) ] , whereas the FA ratio that reflects D5D activity was inversely associated with risk [ 0.46 ( 0.31 , 0.70 ) ] . The Mendelian r and omization approach corroborated the direct relation for D6D activity and tended to support the inverse relation for D5D activity . Proportions of dietary FAs showed only modest to low correlations with erythrocyte FAs and were not significantly associated with risk . CONCLUSION The FA profile of erythrocyte membrane phospholipids and activity of desaturase enzymes are strongly linked to the incidence of type 2 diabetes Aims /hypothesisThe aim of this study was to investigate the association of dietary macronutrient composition and energy density with the change in body weight and waist circumference and diabetes incidence in the Finnish Diabetes Prevention Study .Subjects and methods Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omised to receive either ‘ st and ard care ’ ( control ) or intensive dietary and exercise counselling . Baseline and annual examinations included assessment of dietary intake with 3-day food records and diabetes status by repeated 75-g OGTTs . For these analyses the treatment groups were combined and only subjects with follow-up data ( n=500 ) were included . Results Individuals with low fat ( < median ) and high fibre ( > median ) intakes lost more weight compared with those consuming a high-fat ( > median ) , low-fibre ( < median ) diet ( 3.1 vs 0.7 kg after 3 years ) . In separate models , hazard ratios for diabetes incidence during a mean follow-up of 4.1 years were ( highest compared with lowest quartile ) 0.38 ( 95 % CI 0.19–0.77 ) for fibre intake , 2.14 ( 95 % CI 1.16–3.92 ) for fat intake , and 1.73 ( 95 % CI 0.89–3.38 ) for saturated-fat intake , after adjustment for sex , intervention assignment , weight and weight change , physical activity , baseline 2-h plasma glucose and intake of the nutrient being investigated . Compared with the low-fat/high-fibre category , hazard ratios were 1.98 ( 95 % CI 0.98–4.02 ) , 2.68 ( 95 % CI 1.40–5.10 ) , and 1.89 ( 95 % CI 1.09–3.30 ) for low-fat/low-fibre , high-fat/high-fibre , and high-fat/low-fibre , respectively . Conclusions /interpretationDietary fat and fibre intake are significant predictors of sustained weight reduction and progression to type 2 diabetes in high-risk subjects , even after adjustment for other risk factors The independent association of serum concentrations of saturated and polyunsaturated fatty acids , apolipoproteins AI and B , selenium and vitamins A and E with the risk of death from coronary artery disease ( CAD ) was studied in 92 persons with no previous myocardial infa rct ion , who died from CAD during a 5-year follow-up , and their 92 1-to-1 matched controls . Case-control pairs came from a r and omly drawn population sample of approximately 12,000 persons aged 30 to 64 years from 2 provinces of eastern Finl and , an area with exceptionally high CAD mortality . Control subjects were matched for sex , age , serum cholesterol , mean arterial pressure , tobacco consumption and history of cardiovascular diseases . The persons who died of CAD had lower serum esterified arachidonic acid concentrations before follow-up than the control subjects ( 41 vs 48 mg/liter , p = 0.05 ) , and this difference was greater for pairs with no chest pain on effort ( 36 vs 50 mg/liter , p less than 0.05 ) . The adjusted risk of CAD death in persons with a serum polyunsaturated to saturated ( P/S ) fatty acid ratio of 0.28 or less ( in the lowest tertile ) was 3.5-fold ( 95 % confidence interval [ CI ] , 1.5 to 8.2 ) compared with those with higher serum P/s ratios in a multivariate logistic model and 5.6-fold ( 95 % CI 1.6 to 19.8 ) for pairs with no chest pain on effort . A low serum apolipoprotein AI concentration ( 1.25 g/liter or less , in the lowest tertile ) was associated with a 2.5-fold ( 95 % CI 1.1 to 5.7 ) adjusted risk of CAD death among the chest pain-free persons . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES Most current dietary guidelines encourage limiting relative fat intake to < 30 % of total daily energy , with saturated and trans fatty acids contributing no more than 10 % . We examined whether total fat intake , saturated fat , monounsaturated , or polyunsaturated fat intake are independent risk factors for prospect i ve all-cause , cardiovascular and cancer mortality . DESIGN Population -based , prospect i ve cohort study . SETTING AND SUBJECTS The Malmö Diet and Cancer Study was set in the city of Malmö , southern Sweden . A total of 28,098 middle-aged individuals participated in the study 1991 - 1996 . MAIN OUTCOME MEASURES Subjects were categorized by quartiles of relative fat intake , with the first quartile used as a reference point in estimating multivariate relative risks ( RR ; 95 % CI , Cox 's regression model ) . Adjustments were made for confounding by age and various lifestyle factors . RESULTS Women in the fourth quartile of total fat intake had a significantly higher RR of cancer mortality ( RR 1.46 ; CI 1.04 - 2.04 ) . A significant downwards trend was observed for cardiovascular mortality amongst men from the first to the fourth quartile ( P=0.028 ) . No deteriorating effects of high saturated fat intake were observed for either sex for any cause of death . Beneficial effects of a relatively high intake of unsaturated fats were not uniform . CONCLUSIONS With the exception of cancer mortality for women , individuals receiving more than 30 % of their total daily energy from fat and more than 10 % from saturated fat , did not have increased mortality . Current dietary guidelines concerning fat intake are thus generally not supported by our observational results It remains unclear what long-term effects of substituting carbohydrates at the expense of protein or fat may have with regard to diabetes risk . Our objective was to evaluate carbohydrate intake in predicting type 2 diabetes using substitution models for fat and protein . We conducted a prospect i ve cohort study of 9,702 men and 15,365 women aged 35 - 65 years and free of diabetes at baseline ( 1994 - 8 ) who were followed for incident type 2 diabetes until 2005 . Dietary intake of macronutrients was estimated with a vali date d FFQ . We estimated the relative risk ( RR ) using Cox proportional hazards analysis . During 176,117 person-years of follow-up we observed 844 incident cases of physician-confirmed type 2 diabetes . After adjustment for age , BMI , waist circumference , potential lifestyle and dietary confounders , substituting 5 % of energy intake from total , saturated , or monounsaturated fat with carbohydrates was not associated with diabetes risk . In contrast , substituting carbohydrates for protein or PUFA was inversely related to diabetes risk ( RR for 5 % energy substitution of protein 0.77 ( 95 % CI 0.64 , 0.91 ) ; RR for PUFA 0.83 ( 95 % CI 0.70 , 0.98 ) ) . These associations appeared to be similar for men and women , but gained statistical significance only among men for protein ( RR 0.78 ( 95 % CI 0.61 , 0.99 ) ) . Restricted cubic spline regression did not indicate non-linearity of these associations ( P for non-linearity in full cohort was 0.353 and 0.349 ) . In conclusion , a higher carbohydrate intake at the expense of protein and PUFA might be associated with decreased diabetes risk CONTEXT Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease ( CVD ) prevention , but long-term intervention data are needed . OBJECTIVE To test the hypothesis that a dietary intervention , intended to be low in fat and high in vegetables , fruits , and grains to reduce cancer , would reduce CVD risk . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 48,835 postmenopausal women aged 50 to 79 years , of diverse background s and ethnicities , who participated in the Women 's Health Initiative Dietary Modification Trial . Women were r and omly assigned to an intervention ( 19,541 [ 40 % ] ) or comparison group ( 29,294 [ 60 % ] ) in a free-living setting . Study enrollment occurred between 1993 and 1998 in 40 US clinical centers ; mean follow-up in this analysis was 8.1 years . INTERVENTION Intensive behavior modification in group and individual sessions design ed to reduce total fat intake to 20 % of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d . The comparison group received diet-related education material s. MAIN OUTCOME MEASURES Fatal and nonfatal coronary heart disease ( CHD ) , fatal and nonfatal stroke , and CVD ( composite of CHD and stroke ) . RESULTS By year 6 , mean fat intake decreased by 8.2 % of energy intake in the intervention vs the comparison group , with small decreases in saturated ( 2.9 % ) , monounsaturated ( 3.3 % ) , and polyunsaturated ( 1.5 % ) fat ; increases occurred in intakes of vegetables/fruits ( 1.1 servings/d ) and grains ( 0.5 serving/d ) . Low-density lipoprotein cholesterol levels , diastolic blood pressure , and factor VIIc levels were significantly reduced by 3.55 mg/dL , 0.31 mm Hg , and 4.29 % , respectively ; levels of high-density lipoprotein cholesterol , triglycerides , glucose , and insulin did not significantly differ in the intervention vs comparison groups . The numbers who developed CHD , stroke , and CVD ( annualized incidence rates ) were 1000 ( 0.63 % ) , 434 ( 0.28 % ) , and 1357 ( 0.86 % ) in the intervention and 1549 ( 0.65 % ) , 642 ( 0.27 % ) , and 2088 ( 0.88 % ) in the comparison group . The diet had no significant effects on incidence of CHD ( hazard ratio [ HR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) , stroke ( HR , 1.02 ; 95 % CI , 0.90 - 1.15 ) , or CVD ( HR , 0.98 ; 95 % CI , 0.92 - 1.05 ) . Excluding participants with baseline CVD ( 3.4 % ) , the HRs ( 95 % CIs ) for CHD and stroke were 0.94 ( 0.86 - 1.02 ) and 1.02 ( 0.90 - 1.17 ) , respectively . Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits . CONCLUSIONS Over a mean of 8.1 years , a dietary intervention that reduced total fat intake and increased intakes of vegetables , fruits , and grains did not significantly reduce the risk of CHD , stroke , or CVD in postmenopausal women and achieved only modest effects on CVD risk factors , suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk . CLINICAL TRIALS REGISTRATION Clinical Trials.gov Identifier : NCT00000611 BACKGROUND Growing evidence suggests that dairy consumption is associated with lower type 2 diabetes risk . However , observational studies have reported inconsistent results , and few have examined dairy 's association with the underlying disorders of insulin resistance and β-cell dysfunction . OBJECTIVE We investigated the association of the dairy fatty acid biomarkers pentadecanoic acid ( 15:0 ) and trans-palmitoleic acid ( trans 16:1n-7 ) with type 2 diabetes traits by evaluating 1 ) prospect i ve associations with incident diabetes after 5 y of follow-up and 2 ) cross-sectional associations with directly measured insulin resistance and β-cell dysfunction . DESIGN The study analyzed 659 adults without diabetes at baseline from the triethnic multicenter Insulin Resistance Atherosclerosis Study ( IRAS ) . Diabetes status was assessed by using oral-glucose-tolerance tests . Frequently sample d intravenous-glucose-tolerance tests measured insulin sensitivity ( SI ) and β-cell function [ disposition index ( DI ) ] . Serum fatty acids were quantified by using gas chromatography . Logistic and linear regression models were adjusted for demographic , lifestyle , and dietary variables . RESULTS Serum 15:0 was a significant biomarker for total dairy intake in the IRAS cohort . It was associated with a decreased incident diabetes risk ( OR : 0.73 , P = 0.02 ) and was positively associated with log SI ( β : 0.84 , P = 0.03 ) and log DI ( β : 2.21 , P = 0.02 ) in fully adjusted models . trans 16:1n-7 was a marker of total partially hydrogenated dietary fat intake and was not associated with outcomes in fully adjusted models . CONCLUSIONS Serum 15:0 , a marker of short-term intake of this fatty acid , was inversely associated with diabetes risk in this multiethnic cohort . This study may contribute to future recommendations regarding the benefits of dairy products on type 2 diabetes risk BACKGROUND Total or red meat intake has been shown to be associated with a higher risk of mortality in Western population s , but little is known of the risks in Asian population s. OBJECTIVE We examined temporal trends in meat consumption and associations between meat intake and all-cause and cause-specific mortality in Asia . DESIGN We used ecological data from the United Nations to compare country-specific meat consumption . Separately , 8 Asian prospect i ve cohort studies in Bangladesh , China , Japan , Korea , and Taiwan consisting of 112,310 men and 184,411 women were followed for 6.6 to 15.6 y with 24,283 all-cause , 9558 cancer , and 6373 cardiovascular disease ( CVD ) deaths . We estimated the study -specific HRs and 95 % CIs by using a Cox regression model and pooled them by using a r and om-effects model . RESULTS Red meat consumption was substantially lower in the Asian countries than in the United States . Fish and seafood consumption was higher in Japan and Korea than in the United States . Our pooled analysis found no association between intake of total meat ( red meat , poultry , and fish/seafood ) and risks of all-cause , CVD , or cancer mortality among men and women ; HRs ( 95 % CIs ) for all-cause mortality from a comparison of the highest with the lowest quartile were 1.02 ( 0.91 , 1.15 ) in men and 0.93 ( 0.86 , 1.01 ) in women . CONCLUSIONS Ecological data indicate an increase in meat intake in Asian countries ; however , our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat , poultry , and fish/seafood . Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries BACKGROUND Studies have suggested that replacing saturated fatty acids ( SFAs ) with carbohydrates is modestly associated with a higher risk of ischemic heart disease , whereas replacing SFAs with polyunsaturated fatty acids is associated with a lower risk of ischemic heart disease . The effect of carbohydrates , however , may depend on the type consumed . OBJECTIVES By using substitution models , we aim ed to investigate the risk of myocardial infa rct ion ( MI ) associated with a higher energy intake from carbohydrates and a concomitant lower energy intake from SFAs . Carbohydrates with different glycemic index ( GI ) values were also investigated . DESIGN Our prospect i ve cohort study included 53,644 women and men free of MI at baseline . RESULTS During a median of 12 y of follow-up , 1943 incident MI cases occurred . There was a nonsignificant inverse association between substitution of carbohydrates with low-GI values for SFAs and risk of MI [ hazard ratio ( HR ) for MI per 5 % increment of energy intake from carbohydrates : 0.88 ; 95 % CI : 0.72 , 1.07 ) . In contrast , there was a statistically significant positive association between substitution of carbohydrates with high-GI values for SFAs and risk of MI ( HR : 1.33 ; 95 % CI : 1.08 , 1.64 ) . There was no association for carbohydrates with medium-GI values ( HR : 0.98 ; 95 % CI : 0.80 , 1.21 ) . No effect modification by sex was observed . CONCLUSION This study suggests that replacing SFAs with carbohydrates with low-GI values is associated with a lower risk of MI , whereas replacing SFAs with carbohydrates with high-GI values is associated with a higher risk of MI |
10,838 | 29,329,778 | No differences were found between two modalities of exercises considering the outcomes HbA1c , systolic and diastolic blood pressure , total cholesterol , HDL and LDL cholesterol , triglycerides , BMI , and waist-to-hip ratio .
CONCLUSION HIIT induces cardiometabolic adaptations similar to those of MICT in prediabetes and T2D , and provides greater benefits to functional capacity in patients with T2D . | AIMS To compare the effects of high-intensity interval training ( HIIT ) versus moderate-intensity continuous training ( MICT ) on functional capacity and cardiometabolic markers in individuals prediabetes and type 2 diabetes ( T2D ) . | Aims /hypothesisCardiac disease remains the leading cause of mortality in type 2 diabetes , yet few strategies to target cardiac dysfunction have been developed . This r and omised controlled trial aim ed to investigate high intensity intermittent training ( HIIT ) as a potential therapy to improve cardiac structure and function in type 2 diabetes . The impact of HIIT on liver fat and metabolic control was also investigated . Methods Using an online r and om allocation sequence , 28 patients with type 2 diabetes ( metformin and diet controlled ) were r and omised to 12 weeks of HIIT ( n = 14 ) or st and ard care ( n = 14 ) . Cardiac structure and function were measured by 3.0 T MRI and tagging . Liver fat was determined by 1H-magnetic resonance spectroscopy and glucose control by an OGTT . MRI analysis was performed by an observer blinded to group allocation . All study procedures took place in Newcastle upon Tyne , UK . Results Five patients did not complete the study and were therefore excluded from analysis : this left 12 HIIT and 11 control patients for the intention-to-treat analysis . Compared with controls , HIIT improved cardiac structure ( left ventricular wall mass 104 ± 17 g to 116 ± 20 g vs 107 ± 25 g to 105 ± 25 g , p < 0.05 ) and systolic function ( stroke volume 76 ± 16 ml to 87 ± 19 ml vs 79 ± 14 ml to 75 ± 15 ml , p < 0.01 ) . Early diastolic filling rates increased ( 241 ± 84 ml/s to 299 ± 89 ml/s vs 250 ± 44 ml/s to 251 ± 47 ml/s , p < 0.05 ) and peak torsion decreased ( 8.1 ± 1.8 ° to 6.9 ± 1.6 ° vs 7.1 ± 2.2 ° to 7.6 ± 1.9 ° , p < 0.05 ) in the treatment group . Following HIIT , there was a 39 % relative reduction in liver fat ( p < 0.05 ) and a reduction in HbA1c ( 7.1 ± 1.0 % [ 54.5 mmol/mol ] to 6.8 ± 0.9 % [ 51.3 mmol/mol ] vs 7.2 ± 0.5 % [ 54.9 mmol/mol ] to 7.4 ± 0.7 % [ 57.0 mmol/mol ] , p < 0.05 ) . Changes in liver fat correlated with changes in HbA1c ( r = 0.70 , p < 0.000 ) and 2 h glucose ( r = 0.57 , p < 0.004 ) . No adverse events were recorded . Conclusions /interpretationThis is the first study to demonstrate improvements in cardiac structure and function , along with the greatest reduction in liver fat , to be recorded following an exercise intervention in type 2 diabetes . HIIT should be considered by clinical care teams as a therapy to improve cardiometabolic risk in patients with type 2 diabetes . Trial registration : www.is rct n.com 78698481 Funding : Medical Research Council OBJECTIVE To evaluate the feasibility of free-living walking training in type 2 diabetic patients and to investigate the effects of interval-walking training versus continuous-walking training upon physical fitness , body composition , and glycemic control . RESEARCH DESIGN AND METHODS Subjects with type 2 diabetes were r and omized to a control ( n = 8) , continuous-walking ( n = 12 ) , or interval-walking group ( n = 12 ) . Training groups were prescribed five sessions per week ( 60 min/session ) and were controlled with an accelerometer and a heart-rate monitor . Continuous walkers performed all training at moderate intensity , whereas interval walkers alternated 3-min repetitions at low and high intensity . Before and after the 4-month intervention , the following variables were measured : VO2max , body composition , and glycemic control ( fasting glucose , HbA1c , oral glucose tolerance test , and continuous glucose monitoring [ CGM ] ) . RESULTS Training adherence was high ( 89 ± 4 % ) , and training energy expenditure and mean intensity were comparable . VO2max increased 16.1 ± 3.7 % in the interval-walking group ( P < 0.05 ) , whereas no changes were observed in the continuous-walking or control group . Body mass and adiposity ( fat mass and visceral fat ) decreased in the interval-walking group only ( P < 0.05 ) . Glycemic control ( elevated mean CGM glucose levels and increased fasting insulin ) worsened in the control group ( P < 0.05 ) , whereas mean ( P = 0.05 ) and maximum ( P < 0.05 ) CGM glucose levels decreased in the interval-walking group . The continuous walkers showed no changes in glycemic control . CONCLUSIONS Free-living walking training is feasible in type 2 diabetic patients . Continuous walking offsets the deterioration in glycemia seen in the control group , and interval walking is superior to energy expenditure – matched continuous walking for improving physical fitness , body composition , and glycemic control Exercise can have anti-inflammatory effects in obesity , but the optimal type and intensity of exercise are not clear . This study compared short-term high-intensity interval training ( HIIT ) with moderate-intensity continuous training ( MICT ) in terms of improvement in cardiorespiratory fitness , markers of inflammation , and glucose control in previously inactive adults at elevated risk of developing type 2 diabetes . Thirty-nine inactive , overweight/obese adults ( 32 women ) were r and omly assigned to 10 sessions over 2 wk of progressive HIIT ( n = 20 , four to ten 1-min sessions at ∼90 % peak heart rate , 1-min rest periods ) or MICT ( n = 19 , 20 - 50 min at ∼65 % peak heart rate ) . Before and 3 days after training , participants performed a peak O2 uptake test , and fasting blood sample s were obtained . Both HIIT ( 1.8 ± 0.4 vs. 1.9 ± 0.4 l/min , pre vs. post ) and MICT ( 1.8 ± 0.5 vs. 1.9 ± 0.5 l/min , pre vs. post ) improved peak O2 uptake ( P < 0.001 ) and lowered plasma fructosamine ( P < 0.05 ) . Toll-like receptor ( TLR ) 4 ( TLR4 ) expression was reduced on lymphocytes and monocytes after both HIIT and MICT ( P < 0.05 ) and on neutrophils after MICT ( P < 0.01 ) . TLR2 on lymphocytes was reduced after HIIT and MICT ( P < 0.05 ) . Plasma inflammatory cytokines were unchanged after training in both groups , but MICT led to a reduction in fasting plasma glucose ( P < 0.05 , 5.9 ± 1.0 vs. 5.6 ± 1.0 mmol/l , pre vs. post ) . Ten days of either HIIT or MICT can improve cardiorespiratory fitness and glucose control and lead to reductions in TLR2 and TLR4 expression . MICT , which involved a longer duration of exercise , may be superior for reducing fasting glucose Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies Low-volume sprint interval training ( SIT ) , or repeated sessions of brief , intense intermittent exercise , elicits metabolic adaptations that resemble traditional high-volume endurance training ( ET ) . The effects of these different forms of exercise training on vascular structure and function remain largely unexplored . To test the hypothesis that SIT and ET would similarly improve peripheral artery distensibility and endothelial function and central artery distensibility , we recruited 20 healthy untrained subjects ( age : 23.3 + /- 2.8 yr ) and had them perform 6 wk of SIT or ET ( n = 5 men and 5 women per group ) . The SIT group completed four to six 30-s " all-out " Wingate tests separated by 4.5 min of recovery 3 days/wk . The ET group completed 40 - 60 min of cycling at 65 % of their peak oxygen uptake ( Vo2peak ) 5 days/wk . Popliteal endothelial function , both relative and normalized to shear stimulus , was improved after training in both groups ( main effect for time , P < 0.05 ) . Carotid artery distensibility was not statistically altered by training ( P = 0.29 ) in either group ; however , popliteal artery distensibility was improved in both groups to the same degree ( main effect , P < 0.05 ) . We conclude that SIT is a time-efficient strategy to elicit improvements in peripheral vascular structure and function that are comparable to ET . However , alterations in central artery distensibility may require a longer training stimuli and /or greater initial vascular stiffness than observed in this group of healthy subjects BACKGROUND The health benefits of leisure-time physical activity are well known , but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear . We assessed the health benefits of a range of volumes of physical activity in a Taiwanese population . METHODS In this prospect i ve cohort study , 416,175 individuals ( 199,265 men and 216,910 women ) participated in a st and ard medical screening programme in Taiwan between 1996 and 2008 , with an average follow-up of 8·05 years ( SD 4·21 ) . On the basis of the amount of weekly exercise indicated in a self-administered question naire , participants were placed into one of five categories of exercise volumes : inactive , or low , medium , high , or very high activity . We calculated hazard ratios ( HR ) for mortality risks for every group compared with the inactive group , and calculated life expectancy for every group . FINDINGS Compared with individuals in the inactive group , those in the low-volume activity group , who exercised for an average of 92 min per week ( 95 % CI 71 - 112 ) or 15 min a day ( SD 1·8 ) , had a 14 % reduced risk of all-cause mortality ( 0·86 , 0·81 - 0·91 ) , and had a 3 year longer life expectancy . Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4 % ( 95 % CI 2·5 - 7·0 ) and all-cancer mortality by 1 % ( 0·3 - 4·5 ) . These benefits were applicable to all age groups and both sexes , and to those with cardiovascular disease risks . Individuals who were inactive had a 17 % ( HR 1·17 , 95 % CI 1·10 - 1·24 ) increased risk of mortality compared with individuals in the low-volume group . INTERPRETATION 15 min a day or 90 min a week of moderate-intensity exercise might be of benefit , even for individuals at risk of cardiovascular disease . FUNDING Taiwan Department of Health Clinical Trial and Research Center of Excellence and National Health Research Institutes To determine the effects of continuous aerobic exercise training ( CON ) vs interval aerobic exercise training ( INT ) on glycemic control and endothelium-dependent vasodilatation , 43 participants with type 2 diabetes were r and omly allocated to the sedentary , CON , and INT groups . The CON and INT exercise training programs were design ed to yield the same energy expenditure/exercise session and included walking on treadmill for 30 and 40 min/day , 3 times/week for 12 weeks . Body fatness and heart rate at rest decreased and leg muscle strength increased ( all P < 0.05 ) in both the CON and INT groups . Fasting blood glucose levels decreased ( P < 0.05 ) in both exercise groups but glycosylated hemoglobin levels decreased ( P < 0.05 ) only in the INT group . Maximal aerobic capacity , flow-mediated dilation , and cutaneous reactive hyperemia increased significantly in both exercise groups ; however , the magnitude of improvements was greater in the INT group . Only the INT group experienced reductions in erythrocyte malondialdehyde and serum von Willebr and factor and increases in plasma glutathione peroxidase and nitric oxide ( all P < 0.05 ) . We concluded that both continuous and interval training were effective in improving glycemic control , aerobic fitness , and endothelium-dependent vasodilation , but the interval training program appears to confer greater improvements than the continuous training program PURPOSE The present study compared the effects of aerobic endurance training at different intensities and with different methods matched for total work and frequency . Responses in maximal oxygen uptake ( VO2max ) , stroke volume of the heart ( SV ) , blood volume , lactate threshold ( LT ) , and running economy ( CR ) were examined . METHODS Forty healthy , nonsmoking , moderately trained male subjects were r and omly assigned to one of four groups:1 ) long slow distance ( 70 % maximal heart rate ; HRmax ) ; 2)lactate threshold ( 85 % HRmax ) ; 3 ) 15/15 interval running ( 15 s of running at 90 - 95 % HRmax followed by 15 s of active resting at 70 % HRmax ) ; and 4 ) 4 x 4 min of interval running ( 4 min of running at 90 - 95 % HRmax followed by 3 min of active resting at 70%HRmax ) . All four training protocol s result ed in similar total oxygen consumption and were performed 3 d.wk for 8 wk . RESULTS High-intensity aerobic interval training result ed in significantly increased VO2max compared with long slow distance and lactate-threshold training intensities ( P<0.01 ) . The percentage increases for the 15/15 and 4 x 4 min groups were 5.5 and 7.2 % , respectively , reflecting increases in V O2max from 60.5 to 64.4 mL x kg(-1 ) x min(-1 ) and 55.5 to 60.4 mL x kg(-1 ) x min(-1 ) . SV increased significantly by approximately 10 % after interval training ( P<0.05 ) . CONCLUSIONS : High-aerobic intensity endurance interval training is significantly more effective than performing the same total work at either lactate threshold or at 70 % HRmax , in improving VO2max . The changes in VO2max correspond with changes in SV , indicating a close link between the two Aims . High-intensity interval training ( HIIT ) leads to improvements in various markers of cardiometabolic health but adherence to HIIT following a supervised laboratory intervention has yet to be tested . We compared self-report and objective measures of physical activity after one month of independent exercise in individuals with prediabetes who were r and omized to HIIT ( n = 15 ) or traditional moderate-intensity continuous training ( MICT , n = 17 ) . Method . After completing 10 sessions of supervised training participants were asked to perform HIIT or MICT three times per week for four weeks . Results . Individuals in HIIT ( 89 ± 11 % ) adhered to their prescribed protocol to a greater extent than individuals in MICT ( 71 ± 31 % ) as determined by training logs completed over one-month follow-up ( P = 0.05 , Cohen 's d = 0.75 ) . Minutes spent in vigorous physical activity per week measured by accelerometer were higher in HIIT ( 24 ± 18 ) as compared to MICT ( 11 ± 10 ) at one-month follow-up ( P = 0.049 , Cohen 's d = 0.92 ) . Cardiorespiratory fitness and systolic blood pressure assessed at one-month follow-up were equally improved ( P 's < 0.05 ) . Conclusions . This study provides preliminary evidence that individuals with prediabetes can adhere to HIIT over the short-term and do so at a level that is greater than MICT Background While current recommendations on exercise type and volume have strong experimental bases , there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes . Objective To compare the effects of moderate-to-high intensity ( HI ) versus low-to-moderate intensity ( LI ) training of equal energy cost , i.e. exercise volume , on modifiable cardiovascular risk factors . Design Pre-specified sub- analysis of the Italian Diabetes and Exercise Study ( IDES ) , a r and omized multicenter prospect i ve trial comparing a supervised exercise intervention with st and ard care for 12 months ( 2005–2006 ) . Setting Twenty-two outpatient diabetes clinics across Italy . Patients Sedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling ( n = 303 ) . Interventions Subjects were r and omized by center to LI ( n = 142 , 136 completed ) or HI ( n = 161 , 152 completed ) progressive aerobic and resistance training , i.e. at 55 % or 70 % of predicted maximal oxygen consumption and at 60 % or 80 % of predicted 1-Repetition Maximum , respectively , of equal volume . Main Outcome Measure(s ) Hemoglobin ( Hb ) A1c and other cardiovascular risk factors ; 10-year coronary heart disease ( CHD ) risk scores . Results Volume of physical activity , both supervised and non-supervised , was similar in LI and HI participants . Compared with LI training , HI training produced only clinical ly marginal , though statistically significant , improvements in HbA1c ( mean difference −0.17 % [ 95 % confidence interval −0.44,0.10 ] , P = 0.03 ) , triglycerides ( −0.12 mmol/l [ −0.34,0.10 ] , P = 0.02 ) and total cholesterol ( −0.24 mmol/l [ −0.46 , −0.01 ] , P = 0.04 ) , but not in other risk factors and CHD risk scores . However , intensity was not an independent predictor of reduction of any of these parameters . Adverse event rate was similar in HI and LI subjects . Conclusions Data from the large IDES cohort indicate that , in low-fitness individuals such as sedentary subjects with type 2 diabetes , increasing exercise intensity is not harmful , but does not provide additional benefits on cardiovascular risk factors . Trial Registration www . IS RCT N.org IS RCT N-04252749 AIMS To compare the feasibility of high intensity interval exercise ( HI-IE ) versus moderate intensity continuous exercise ( MI-CE ) in patients with type 2 diabetes ( T2D ) , and to investigate the preliminary efficacy of HI-IE and MI-CE for improving glycated hemoglobin A1c ( HbA1c ) and body composition . METHODS Individuals with T2D were recruited and r and omly assigned to HI-IE and MI-CE . Exercise training was performed 5 days per week for 12 weeks . Recruitment , retention , adherence , feeling states and self-efficacy were analyzed for feasibility . Changes in HbA1c and percent body fat from baseline were investigated at 12 weeks to determine the preliminary efficacy . RESULTS Of 126 participants showing interest to join the study , 15 individuals were r and omized and completed the program . No participants dropped out from the study after enrollment . Adherence rates were high and did not differ between HI-IE and MI-CE ( p>0.05 ; > 97.2 % of the eligible exercise sessions for both groups ) . Feeling states and self-efficacy did not differ between the groups . Percent trunk fat decreased in both HI-IE and MI-CE ( p=0.007 and 0.085 , respectively ) . Total percent body fat , percent leg fat , and subcutaneous fat width were significantly reduced in both groups ( p<0.05 ) , whereas HbA1c did not change from baseline ( p>0.05 ) . The degree of improvement was similar between the interventions ( p>0.05 ) . CONCLUSION In individuals with T2D , implementing a 12-week structured HI-IE training can be as feasible as MI-CE training . Both interventions are equally effective in lowering total body fat but have little impact on HbA1c in relatively well controlled participants with T2D This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) AIM This study compared the effect of high-intensity interval training ( HIIT ) and moderate-intensity continuous training ( MICT ) for 16 weeks on whole-body and abdominal fat mass ( FM ) in postmenopausal women with type 2 diabetes ( T2D ) . METHODS Seventeen women ( 69±1 years ; BMI : 31±1kg.m-2 ) were r and omly assigned to either a HIIT [ 60 × (8s at 77 - 85 % HRmax , 12s of active recovery ) ] or MICT ( 40min at 55 - 60 % of their individual HRR ) cycling program for 16 weeks , 2 days/week . Dual-energy X-ray absorptiometry was used to measure whole-body and regional FM content , including abdominal adiposity and visceral adipose tissue . Plasma cholesterol , HDL , LDL , triglycerides , glucose and HbA1c levels were measured . Levels of nutritional intake and physical activity were evaluated by 7-day self-reports . RESULTS Dietary energy ( caloric ) intake , physical activity level and total body mass did not vary in either group from the beginning to the end of the training intervention . Overall , total FM decreased and total fat-free mass significantly increased over time ( by around 2 - 3 % ) . Total FM reduction at the end of the intervention was not significantly different between groups . However , significant loss of total abdominal ( -8.3±2.2 % ) and visceral ( -24.2±7.7 % ) FM was observed only with HIIT . Time effects were noted for HbA1c and total cholesterol/HDL ratio . CONCLUSION With no concomitant caloric restriction , an HIIT program in postmenopausal women with T2D ( twice a week for 16 weeks ) appeared to be more effective for reducing central obesity than MICT , and could be proposed as an alternative exercise training program for this population Background —Epidemiological data on the association between body mass index ( BMI ) and heart failure ( HF ) risk among diabetic patients are rare . Methods and Results —We performed a prospect i ve cohort study of risk for HF among 31 155 patients with type 2 diabetes mellitus ( 11 468 men and 19 687 women ) . Cox proportional hazards regression models were used to estimate the association of different levels of BMI with HF risk . During a mean follow-up of 7.8 years , 5834 subjects developed HF ( 2379 men and 3455 women ) . The multivariable-adjusted ( age , race , smoking , income , and type of insurance ) hazard ratios of HF associated with BMI levels ( 18.5–22.9 , 23–24.9 , 25–29.9 [ reference group ] , 30–34.9 , 35–39.9 , and ≥40 kg/m2 ) at baseline were 0.95 , 1.00 , 1.00 , 1.16 , 1.64 , and 2.02 ( Ptrend<0.001 ) for men and 1.16 , 1.16 , 1.00 , 1.23 , 1.55 , and 2.01 ( Pnonlinear<0.001 ) for women , respectively . When we used an up date d mean value of BMI , the association of HF risk with BMI did not change . When stratified by age , race , smoking status , and use of antidiabetic drugs , the positive associations among men and the J-shaped associations among women were still present . Conclusions —Our study suggests a positive association between BMI and HF risk among men and a J-shaped association between BMI and HF risk among women with type 2 diabetes mellitus 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 |
10,839 | 24,183,836 | There is considerable between- study heterogeneity in reports of depressive symptoms in dialysis patients , likely caused by high variability in the way depressive symptoms are measured . | BACKGROUND We aim ed to systematic ally review and analyze the association between depression and mortality risk in adults with kidney failure treated by long-term dialysis . | Depression is an important target of psychological assessment in patients with end-stage renal disease because it predicts their morbidity , mortality , and quality of life . We assessed the effectiveness of cognitive-behavioral therapy in chronic hemodialysis patients diagnosed with major depression by the Mini International Neuropsychiatric Interview ( MINI ) . In a r and omized trial conducted in Brazil , an intervention group of 41 patients was given 12 weekly sessions of cognitive-behavioral group therapy led by a trained psychologist over 3 months while a control group of 44 patients received the usual treatment offered in the dialysis unit . In both groups , the Beck Depression Inventory , the MINI , and the Kidney Disease and Quality of Life-Short Form question naires were administered at baseline , after 3 months of intervention or usual treatment , and after 9 months of follow-up . The intervention group had significant improvements , compared to the control group , in the average scores of the Beck Depression Inventory overall scale , MINI scores , and in quality -of-life dimensions that included the burden of renal disease , sleep , quality of social interaction , overall health , and the mental component summary . We conclude that cognitive-behavioral group therapy is an effective treatment of depression in chronic hemodialysis patients BACKGROUND The medical risk factors associated with increased mortality in hemodialysis ( HD ) patients are well known , but the psychosocial factors that may affect outcome have not been clearly defined . Psychosocial factors could affect mortality through interaction with parents ' nutrition or their compliance with the dialysis prescription . We conducted a prospect i ve , longitudinal , multicenter study of urban HD patients to determine the contribution of compliance and psychosocial factors to patient survival . METHODS Patients were assessed using indices of social support , patient 's assessment s of their well-being , including illness effects ( IEQ ) , and satisfaction with life ( SWLS ) , the Beck Depression Inventory ( BDI ) , serum albumin concentration , Kt/V and protein catabolic rate ( PCR ) . Behavioral compliance was measured three ways : percent time actually dialyzed per treatment compared to prescribed time ( shortening behavior ) ; percent sessions attended ( skipping behavior ) and total integrated time compliance ( % TCOMP ) . A severity index , previously demonstrated to be a mortality marker , was used to grade medical comorbidity . The typed of dialyzer the patient was treated with was noted . A Cox proportional hazards model , controlling for age , medical comorbidity , albumin concentration and dialyzer type was used to assess relative mortality risk of variations in psychosocial factors and behavioral compliance . RESULTS A total of 295 patients ( 60.8 % of those eligible ) agreed to participate . The mean ( + /- SD ) age of our population was 54.6 + /- 14.1 year , mean PCR was 1.06 + /- 0.27 g/kg/day , and mean Kt/V 1.2 + /- 0.4 , suggesting the patients were well nourished and adequately dialyzed . The patients ' mean BDI was 11.4 + /- 8.1 ( in the range of mild depression ) . Patients ' SWLS was similar to that of a group of patients without chronic illness . After a 26 month mean follow-up period , higher levels of perceived social support , improved perception of the effects of illness and increased behavioral compliance were significantly associated with decreased relative mortality risk ( 0.8 , 0.77 , and 0.79 , respectively ) , controlled for variations in patients ' age , severity of illness , serum albumin concentration and dialyzer type . Variations in depression and Kt/V were not predictors of mortality during the observation period . CONCLUSIONS Lower levels of social support , decreased behavioral compliance with the dialysis prescription , and increased negative perception of the effects of illness are independently associated with increased mortality in ESRD patients treated with HD . The effects are of the same order of magnitude as medical risk factors . Such effects may be attributable to a relationship between a patients ' perception of social support and effects of illness and behavior , with other factors such as the provision of better medical care in patients with larger social networks . The mechanism underlying the relationship of psychosocial factors and compliance and survival , and the effect of interventions to improve perception of illness , and increase social support and compliance with the dialysis prescription in HD patients should be studied BACKGROUND The aim of this study was to evaluate the survival of patients initiating haemodialysis ( HD ) , and to analyse whether low health-related quality of life ( HRQoL ) levels are predictors of mortality in the short-term , controlling certain variables that had been shown in other studies to have a bearing on survival , and using scores , st and ardized for age and sex , of the HRQoL measurement tool employed . METHODS This is a multicentric prospect i ve study of all patients on HD in all the dialysis units in Asturias , a region with a little over one million inhabitants , from 1 January 2001 to 30 September 2002 . A total of 199 patients initiated HD in our region and survived the first 3 months . Of these , 137 patients who remained on HD for at least 3 months had complete responses on HRQoL measures . RESULTS It was observed that adjusted relative risk ( RR ) of death increased by 5 % for each year of age increase ( RR=1.05 , 95 % CI 1.01 - 1.09 : P=0.006 ) ; in the same way , for each increase in the Mental Component Summary ( MCS ) score , the adjusted RR of death diminished by 4 % ( RR=0.96 , 95 % CI 0.94 - 0.99 ; P=0.006 ) . CONCLUSION Mental health has been shown to be a factor independently associated with mortality ; as the MCS score worsens the adjusted RR of death of a patient on HD increases The aims of the present study were to determine the prevalence of depression in our dialysis patients , to detect the most powerful variables associated with depression , and to determine the role of depression in prediction of mortality . The prospect i ve follow-up study of 128 patients ( 77 HD and 51 CAPD , 65 male , aged 53.8 + /- 13.5 years , dialysis duration 64.7 + /- 64.8 months ) was carried out over 36 months . Depression by the Beck Depression Inventory-BDI-II score , laboratory parameters ( hemoglobin , serum albumin and creatinine concentration ) , immunological status ( cytokines and hsCRP ) , comorbidity by Index of Physical Impairment ( IPI ) and adequacy of dialysis by Kt/V were monitored . The overall prevalence of depression in the dialysis patients ( BDI score > or = 14 ) was 45.3 % , and 28.2 % , respectively , for moderate and severe depression ( BDI > or = 20 ) . The most powerful variable associated with depression was IL-6 , but associations with albumin , hemoglobin , creatinine and IPI score were also found . During the follow-up period 36 patients died , 7 patients left the cohort and 2 patients were transplanted . If IPI score was not included in the multivariate Cox analysis , the BDI score remained one of the best predictors of mortality along with albumin . In conclusion , because of the close association of depression with inflammation , malnutrition , and cardiovascular mortality , it could be speculated that depression is one branch of the MIA ( malnutrition , inflammation , atherosclerosis ) syndrome This study investigated whether social and /or psychologic factors help to predict older dialysis patients ' continued survival . A stratified ( by race and sex ) r and om sample of patients aged 60 + years was selected from the ESRD Network census of all patients in that age category residing in a single southeastern state ( Georgia ) and receiving chronic dialysis as of November 1987 ; personal interviews with patients were completed in 1988 . This analysis includes 287 patients ( mean age , 69 years ) receiving outpatient hemodialysis for whom primary cause of renal failure and functional status data were complete . Patient tracking and vital statistics data determined that 49 % of the sample survived as of October 31 , 1990 . Study variables included demographic , dialysis , health status , social situation , and psychologic outlook variables reported at the patients ' 1988 interviews . Log rank tests showed univariate associations between patients ' continued survival and race/gender , recovery time following dialysis treatments , cardiovascular co-morbidity , exercise activity score , freedom from health limitation of daily activity , functional status , leisure activity score , self-rated health status , overall life satisfaction , depression , and public religiosity . The Cox proportional hazards model was fit to the data , with continued survival from the time of the 1988 interview as the dependent variable . There was a significantly increased mortality risk for white men relative to the other race/gender groups and for patients reporting severely impaired functional status at the 1988 interview . With functional status in the model , no other social or psychologic variables were significant predictors of mortality . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To assess the effects of intradialytic exercise training on health-related quality of life indices in haemodialysis patients . Subjects/ patients : Thirty-five patients on haemodialysis , with a mean ( SD ) age of 48.8 ( 13.9 ) years , volunteered to participate in the study . They were r and omized either to rehabilitation group ( group A : 19 patients ) , following a 10-month intradialytic exercise training programme or to control group ( group B : 14 patients ) . After the r and omization , two of the patients , one of each group , withdrew from the study for reasons unrelated to exercise training . Method : All patients at the beginning and the end of the study underwent clinical examination , laboratory tests and a treadmill exercise testing with spiroergometric study for the evaluation of their aerobic capacity ( Vo2peak ) . A formal psychosocial assessment , which included affective ( Beck Depression Inventory ) , health-related quality of life ( Quality of Life Index , Living Question naire of Minnesota , Life Satisfaction Index and Short Form-36 question naire ) and personality ( Eysenck Personality Question naire ) parameters , was evaluated at beginning and end of the study . The dose of erythropoietin was changed as needed , according to the level of the haemoglobin , aim ing to keep it at 11 ( 2 ) g/dL during the study . Results : Baseline values were similar between the two groups . After training in group A , Vo2peak was increased by 21.1 % ( P<0.05 ) and exercise time by 23.6 % ( P<0.05 ) . Moreover , group A showed a decrease in self-reported depression ( Beck Depression Index ) of 39.4 % ( P<0.001 ) . In addition , trained patients demonstrated a significant improvement in Quality of Life Index ( from 6.5 ( 1.8 ) to 9.0 ( 1.3 ) , P<0.001 ) and Life Satisfaction Index ( from 44.8 ( 8.6 ) to 53.0 ( 5.6 ) , P<0.001 ) , and an increase in the Physical Component Scale of the SF-36 ( from 40.5 ( 5.6 ) to 44.5 ( 5.5 ) , P<0.05 ) , while the Mental Component Scale remained unchanged . Multiple regression analysis indicated that the improvement in quality of life depended on the participation in exercise programmes , the effects of training and the reduction in the level of depression . No changes were observed in Eysenck Personality Question naire by the end of the study , while all the above parameters remained almost unchanged in the controls . Conclusion : The results demonstrated that intradialytic exercise training improves both physical functioning and psychological status in haemodialysis patients , leading to an improvement of patients ' quality of life AIM To evaluate the prevalence and the influence on survival of depressive symptoms in a European cohort of end-stage renal disease ( ESRD ) patients on renal replacement therapy ( RRT ) . METHODS In a prospect i ve fashion , symptoms of depression were evaluated in ESRD patients on RRT using the depression subscore of the Hospital Anxiety and Depression Scale ( HADS ) . Fatal and non-fatal clinical events were determined during a 1-year follow-up . RESULTS Of 101 patients with ESRD , 42 % showed manifest depressive symptoms , defined as a HADS-D score > or = 7 . No association was found between depressive symptoms and severity of somatic disease . During follow-up , all-cause mortality was significantly higher in patients with depressive symptoms above threshold ( n = 42 , mortality : 26 % ) compared to patients with depressive symptoms below threshold ( n = 59 , mortality 8 % ) , ( crude HR 3.3 , CI 1.2 - 9.6 , P = 0.02 ) . The excess in mortality was mainly caused by a higher incidence of septicaemia ( 0 versus 12 % , P = 0.01 ) . After adjustment for clinical parameters , this association between depressive symptoms and mortality became even stronger . There was no significant difference observed in the incidence of cardiovascular events . CONCLUSIONS Patients with ESRD treated with dialysis show a high level of depressive symptoms that is independently associated with poor survival . Future research should address appropriate therapeutic regimens BACKGROUND The relationship between severity of depressive symptoms reported by incident dialysis patients and first-year outcomes is not known . METHODS We evaluated the association between self-report of depressive symptoms in incident hemodialysis patients admitted at Fresenius Medical Care North America facilities between 1 January and 31 December 2006 and mortality or withdrawal from dialysis for up to 1 year after the initial survey . The impact of depression scores calculated from two Short Form-36 ( SF-36 ) question naires was determined independently of the mental and physical component scores , case-mix and laboratory variables using stepwise Cox models . RESULTS We received 6415 SF-36 responses within 46±24 days of first dialysis from a cohort with a mean age of 62.3±15.2 years ; 58 % were diabetic , 45 % were female and 69 % were Caucasian . A 1-point increase in depression score was associated with unadjusted hazard ratio ( HR ) of 1.09 ( 1.03 , 1.15 ) for mortality and 1.15 ( 1.05 , 1.26 ) for withdrawal from dialysis . After adjustment , a 1-point increase in depression score had a mortality HR of 1.08 ( 1.01 , 1.14 ) and for withdrawal 1.19 ( 1.08 , 1.31 ) . CONCLUSIONS Depressive symptoms reported within the first 90 days of dialysis were associated with greater dialysis withdrawal and mortality risk over the succeeding year . Whether further evaluation for and treatment of depression during this early vulnerable period may improve symptoms , increase survival and decrease premature withdrawal from dialysis requires confirmation in prospect i ve clinical trials BACKGROUND Although dementia has predicted mortality in large dialysis cohorts , little is known about the relationship between less pronounced cognitive deficits and mortality in patients with end-stage renal disease . This study assessed whether cognitive impairment without dementia was an independent predictor of 7-year survival in dialysis patients after controlling for other risk factors . STUDY DESIGN Prospect i ve single-cohort study . SETTING & PARTICIPANTS 145 prevalent dialysis patients from 2 units in London , UK , were followed up for 64.3 ± 27.4 months and censored at the time of change to a different treatment . PREDICTORS Cognitive impairment , defined as performance 1 st and ard deviation less than normative values on 2 or more cognitive tests within a neurocognitive battery assessing attention/concentration , memory , and psychomotor function domains . Depression , quality -of-life , and clinical measures also were obtained . OUTCOMES & MEASUREMENTS All-cause mortality was the primary outcome . Cox proportional hazard models were used to assess the contribution of demographics and clinical and psychological measures and cognitive impairment to mortality . RESULTS 98 ( 67.6 % ) patients were cognitively impaired at baseline . At follow-up , 56 ( 38.6 % ) patients had died , 29 of cardiac causes . Unadjusted Kaplan-Meier analysis showed higher mortality in cognitively impaired patients , in whom 7-year survival was 49 % versus 83.2 % in those with no cognitive impairment ( P < 0.001 ) . Mortality risk associated with cognitive impairment remained significant in adjusted analysis controlling for sociodemographic , clinical , and psychological factors ( adjusted HR , 2.53 ; 95 % CI , 1.03 - 6.22 ; P = 0.04 ) . LIMITATIONS Small sample size and number of events . CONCLUSIONS Cognitive impairment is an independent predictor of mortality in dialysis patients . Although the implication s of early recognition and treatment of cognitive impairment for clinical outcomes are unclear , these results suggest that patient management protocol s should attempt to ensure prevention of cognitive decline in addition to managing coexisting medical conditions CONTEXT Depression is associated with an increased mortality risk . It is not known to what extent depression characteristics such as severity and length of exposure to depression contribute to the association with excess mortality . OBJECTIVES To investigate the association between depression severity and duration with mortality in community-living elderly . DESIGN Two-wave prospect i ve cohort study with 10-year follow-up of vital status . Assessment of depression at baseline and at three year follow-up ( GMS-AGECAT ) . Cox proportional hazards analyses of mortality with depression according to severity and length of exposure , adjusted for demographic variables , physical illnesses , cognitive decline and functional disabilities . SETTING AND PARTICIPANTS R and omly selected cohort of 3 746 non-demented older community-living persons in the city of Amsterdam . MAIN OUTCOME MEASURES Excess mortality of both the baseline cohort , and of non-demented subjects participating in both assessment s ( n = 1989 ) . RESULTS Both moderate ( MHR 1.29 , 95 % CI 1.03 - 1.61 ) and severe depression ( MHR 1.34 , 95 % CI 1.07 - 1.68 ) predicted 10-year mortality after multivariate adjustment . Chronic depression was associated with a 41 % higher mortality risk in 6-year follow-up compared to subjects without depression . CONCLUSIONS Severity and chronicity of depression are associated with a higher mortality risk . In combination with other findings this is suggestive of a causal relationship and may have implication s for both preventive and treatment strategies of late-life depression OBJECTIVES Depression is the most common psychiatric disorder in patients with chronic kidney disease ( CKD ) . We sought to determine the association of major depression with mortality among diabetic patients with late stage CKD . METHOD The Pathways Study is a longitudinal , prospect i ve cohort study initiated to determine the impact of depression on outcomes among primary care diabetic patients . Subjects were followed from 2001 until 2007 for a mean duration of 4.4 years . Major depression , identified by the Patient Health Question naire-9 , was the primary exposure of interest . Stage 5 CKD was determined by dialysis codes and estimated glomerular filtration rate ( < 15 ml/min ) . An adjusted Cox proportional hazards multivariable model was used to determine the association of baseline major depression with mortality . RESULTS Of the 4128 enrolled subjects , 110 were identified with stage 5 CKD at baseline . Of those , 34 ( 22.1 % ) had major depression . Over a period of 5 years , major depression was associated with 2.95-fold greater risk of death ( 95 % CI=1.24 - 7.02 ) compared to those with no or few depressive symptoms . CONCLUSION Major depression at baseline was associated with a 2.95-fold greater risk of mortality among stage 5 CKD diabetic patients . Given the high mortality risk , further testing of targeted depression interventions should be considered in this population A role of depression in affecting outcome in patients with end stage renal disease ( ESRD ) has been suggested but few have assessed psychological parameters and medical factors thought to influence survival simultaneously and prospect ively . To assess whether depression or perception of illness influences survival in patients treated for ESRD , we prospect ively evaluated fifty-seven patients with ESRD treated with hemodialysis ( HD , n = 43 ) or continuous ambulatory peritoneal dialysis ( CAPD , n = 14 ) . Patients were interviewed and completed the Beck Depression Inventory ( BDI ) and the Illness Effects Question naire ( IEQ ) . An ESRD severity coefficient was used to measure chronic illness severity . A cognitive item subset of the BDI ( CDI ) was used as an additional measure of depression . One and two years later , records were examined to determine survival . When initial results of the assessment of survivors and non-survivors were compared , at one year follow-up , there were no differences in mean age , duration of dialysis , severity scores , BDI or IEQ scores . The initial mean CDI scores in the group of non-survivors , however , were significantly greater than the scores in the survivor group . At two year follow-up , CDI scores were significantly different between groups , and were significant in a hazards regression . Disease severity , age and duration of dialysis were also significantly related to mortality at two year follow-up . We conclude cognitive depression is an important , early , indicator of grave prognosis in patients treated for ESRD . Early recognition of and therapeutic efforts directed toward the treatment of depression might modify outcome in ESRD patients Abstract . Objective : To study the effects of severe renal failure and haemodialysis on the pharmacokinetics of citalopram . Methods : Four patients with renal failure undergoing haemodialysis and eight healthy controls were given a single dose of citalopram . The concentrations of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were measured in serum and urine . On a different day , the four patients undergoing haemodialysis were given another single dose of citalopram , and the drug concentrations were measured in serum from the artery leading to the dialyser and in the dialysate . In addition , one anuric patient treated with citalopram on a regular basis was included in the study . Results : There were no significant differences between the two groups in any of the pharmacokinetic parameters with the exception of the renal clearance of citalopram , which was significantly lower in the renal failure group than in the control group ( 1.70 ml/min versus 66.2 ml/min , P<0.001 ) . Oral clearance of citalopram was almost identical in the two groups ( 452 ml/min versus 456 ml/min ) . The process of haemodialysis cleared about 1 % of the dose as citalopram and 1 % as desmethylcitalopram only . Conclusion : Severe renal failure does not affect the pharmacokinetics of citalopram and modification of the usual citalopram dose does thus not seem to be necessary . The contribution of haemodialysis to the total elimination of citalopram is negligible BACKGROUND Depression is related to morbidity and mortality in patients with kidney failure treated by dialysis , but its influence on patients with earlier stages of chronic kidney disease ( CKD ) is uncertain . This study investigates the association of depressive symptoms with clinical outcomes in patients with CKD not requiring dialysis . STUDY DESIGN Prospect i ve observational cohort study . SETTING & PARTICIPANTS 568 participants with CKD not requiring maintenance dialysis were recruited consecutively at a tertiary hospital in Southern Taiwan and followed up for 4 years . PREDICTORS Baseline status of depressive symptoms . OUTCOMES The primary outcome is a composite of progression to end-stage renal disease ( ESRD ) , defined as requiring maintenance dialysis treatment , or all-cause mortality ; and secondary outcome was first hospitalization . MEASUREMENTS Depressive symptoms were assessed by Beck Depression Inventory . Estimated glomerular filtration rate ( eGFR ) was computed using the 4-variable MDRD ( Modification of Diet in Renal Disease ) Study equation . RESULTS 428 participants completed the question naires and 160 ( 37 % ) had depressive symptoms . During a mean follow-up of 25.2 ± 11.9 months , 136 participants ( 32 % ) reached the primary outcome ( 119 reached ESRD and 17 died ) and 110 participants ( 26 % ) were hospitalized . High depressive symptoms increased the risk of progression to ESRD or death ( HR , 1.66 ; 95 % CI , 1.14 - 2.44 ) and first hospitalization ( HR , 1.59 ; 95 % CI , 1.03 - 2.47 ) . Participants with high depressive symptoms had more rapid GFR decrease ( eGFR slopes of -2.3 [ 25th-75th percentile , -5.3 to -0.4 ] vs -1.2 [ 25th-75th percentile , -3.5 to 0.3 ] mL/min/1.73 m(2 ) per year ; P = 0.001 ) and initial dialysis treatment at a higher eGFR ( OR for initiation of dialysis at eGFR > 5 mL/min/1.73 m(2 ) , 4.45 ; 95 % CI , 1.44 - 13.78 ) . LIMITATIONS A single-center study of Taiwanese , Beck Depression Inventory evaluates only depressive symptom burden . CONCLUSIONS Depressive symptoms in CKD are independent predictors of adverse clinical outcomes , including faster eGFR decrease , dialysis therapy initiation , death , or hospitalization . Depression should be evaluated early and treated in patients with CKD BACKGROUND The medical risk factors associated with increased mortality in hemodialysis ( HD ) patients are well known , but the psychosocial factors that may affect outcome have not been clearly defined . One key psychosocial factor , depression , has been considered a predictor of mortality , but previous studies have provided equivocal results regarding the association . We sought to determine whether depressive affect is associated with mortality in a longitudinal study of end-stage renal disease ( ESRD ) patients treated with HD , using multiple assessment s over time . METHODS Two hundred ninety-five out patients with ESRD treated with HD were recruited from three outpatient dialysis units in Washington D.C. to participate in a prospect i ve cohort study with longitudinal follow-up . Patients were assessed every six months for up to two years using the Beck Depression Inventory ( BDI ) , age , serum albumin concentration , Kt/V , and protein catabolic rate ( PCR ) . A severity index , previously demonstrated to be a mortality marker , was used to grade medical comorbidity . The type of dialyzer with which the patient was treated was noted . Patient mortality status was tracked for a minimum of 20 and a maximum of 60 months after the first interview . Cox proportional hazards models , treating depression scores as time-varying covariates in a univariable analysis , and controlling for age , medical comorbidity , albumin concentration , and dialyzer type and site in multivariable models , were used to assess the relative mortality risk . RESULTS The mean ( + /- SD ) age of our population at initial interview was 54.6 + /- 14.1 years . The mean PCR was 1.06 + /- 0.27 g/kg/day , and the mean Kt/V was 1.2 + /- 0.4 at baseline , suggesting that the patients were well nourished and dialyzed comparably to contemporary U.S. patients . The patients ' mean BDI at enrollment was 11.4 + /- 8.1 , in the range of mild depression . Patients ' baseline level of depression was not a significant predictor of mortality at 38.6 months of follow-up . In contrast , when depression was treated as a time-varying covariate based on periodic follow-up assessment s , the level of depressive affect was significantly associated with mortality in both single variable and multivariable analyses . CONCLUSIONS Higher levels of depressive affect in ESRD patients treated with HD are associated with increased mortality . The effects of depression on patient survival are of the same order of magnitude as medical risk factors . Our findings using both controls for factors possibly confounded with depressive affect in patients with ESRD and time-varying covariate analyses may explain the inconsistent results of previous studies of depression and mortality in ESRD patients . Time-varying analyses in longitudinal studies may add power to defining and sensitivity to establishing the association of psychosocial factors and survival in ESRD patients . The mechanism underlying the relationship of depression and survival and the effect of interventions to improve depression in HD out patients and general medical in patients should be studied OBJECTIVE Previous examinations of depression as a predictor of mortality in end-stage renal disease have yielded inconsistent findings . We sought to clarify the possible link with mortality by assessing depression at an earlier stage of renal impairment before the uremic disease state and depressive symptoms become highly confounded , and then following patients during the period of disease progression . DESIGN Prospect i ve design using an assessment of depression before initiation of renal replacement therapy to predict mortality status an average of 81 months later in patients in the early stages of chronic kidney disease . MAIN OUTCOME MEASURES Mortality status . RESULTS After controlling for relevant mortality risk factors ( i.e. , age , gender , presence of diabetes and cardiovascular disease , and potassium level ) , results of Cox regression analyses indicated that higher levels of nonsomatic depression symptoms were predictive of an increased mortality risk , χ²(1 , N = 359 ) = 8.02 , p = .005 . Patients with nonsomatic depression scores 1 SD above the mean had an estimated mortality rate 21.4 % higher than average scorers in this sample . CONCLUSION Clinical implication s of these findings point to the importance of assessment and treatment of depressive symptoms in patients with chronic kidney disease Objective There is little information on the relationship between depressive symptoms and survival in peritoneal dialysis ( PD ) patients . We examined whether a single measurement of depressive symptoms using a simple self-administered tool predicts survival . Design Screening test of depressive symptoms as a predictor of outcome . Setting Three dialysis centers in Southwestern Pennsylvania . Participants 66 adult PD subjects were screened in 1997–1998 for depression using the Zung scale . Main Outcome Measures Baseline data collection included assessment s of comorbidity , residual renal function , total Kt/V , nPNA , previous renal transplant , and serum albumin . Outcomes were collected prospect ively after completion of the depression survey to 12/01 . Cox regression analysis of patient survival was performed using all cofactors with p < 0.05 on univariate analysis . Results One third of patients had depressive symptoms . Compared to nondepressed patients , depressive symptom patients were older ( 62.5 vs 52.5 years , p = 0.012 ) , had borderline lower serum albumin levels ( 3.47 vs 3.70 g/dL , p = 0.058 ) , and were more disabled ( Karnofsky score 70 vs 90 , p < 0.001 ) , but had similar Kt/V , residual renal function , and previous time on PD at the point of the testing . Using multivariate analysis and controlling for comorbidity ( using a measurement that includes diabetes mellitus and age ) and serum albumin , the survival of patients with depressive symptoms was significantly reduced compared to nondepressed patients . Conclusion A single measurement of depressive symptoms using a simple self-administered test was an independent predictor of death in a cohort of PD patients , which extends observations in hemodialysis patients . Screening for depressive symptoms should be routine for dialysis patients , and those depressed should have thorough assessment and treatment . Whether treating depression will have an impact on survival is unclear and needs to be studied Background : Depression increases the risk of mortality in hemodialysis patients . Alexithymia , a disorder of affect regulation , has also been reported to be associated with mortality risk in the general population . We conducted a prospect i ve study to estimate the independent impact of depression and alexithymia on long-term mortality . Methods : A total of 230 hemodialysis out patients , with a mean age of 56.3 ± 9.6 years , completed a batch of self-report measures including the Beck Depression Inventory-II ( BDI-II ) , the 20-item Toronto Alexithymia Scale ( TAS-20 ) and the 36-item Short Form Health Survey ( SF-36 ) . Survival status was confirmed every 6 months for up to 5 years . The presence of depression and alexithymia was defined by a BDI-II score of ≧14 and a TAS-20 score of ≧61 , respectively . Results : During the follow-up period , 27 deaths were confirmed . Both depression and alexithymia were associated with an increased risk for all-cause mortality ; the age- and sex-adjusted hazard ratio for depression was 2.36 ( 95 % CI : 1.08–5.15 ; p = 0.03 ) and that for alexithymia was 4.29 ( 95 % CI : 1.95–9.42 ; p < 0.001 ) . Depression lost its statistical significance after controlling for alexithymia , whereas alexithymia remained significant even after adjusting for the baseline depression , health status ( the summary scores of the SF-36 ) , marital status and clinical covariates ( multivariate adjusted hazard ratio = 3.62 ; 95 % CI : 1.32–9.93 ; p = 0.01 ) . Conclusions : Alexithymia is a strong independent risk factor for all-cause mortality in hemodialysis patients BACKGROUND Depressive symptoms and depression are the most frequent psychologic problems reported by hemodialysis patients . We assessed the prevalence of depressive symptoms and physician-diagnosed depression , their variations by country , and associations with treatment by antidepressants among hemodialysis patients . We also assessed whether depressive symptoms were independently associated with mortality , hospitalization , and dialysis withdrawal . METHODS The sample was represented by 9382 hemodialysis patients r and omly selected from dialysis centers of 12 countries enrolled in the Dialysis Outcomes and Practice Patterns Study ( DOPPS II ) . Depressive symptoms were assessed by the short version of the Center for Epidemiological Studies Depression Screening Index ( CES-D ) , using > or = 10 CES-D score as the cut-off value . RESULTS Overall prevalence of physician-diagnosed depression was 13.9 % , and percentage of CES-D score > or = 10 43.0 % . While the smallest prevalence of physician-diagnosed depression was observed in Japan ( 2.0 % ) and France ( 10.6 % ) , the percentage of CES-D score > or = 10 in these counties was similar to the whole sample . Patients on antidepressants also varied by country , 34.9 % and 17.3 % among those with physician-diagnosed depression and CES-D scores > or = 10 , respectively . In Cox models adjusted for several comorbidities , CES-D scores > or = 10 were associated with significantly higher relative risks ( RR ) of death ( RR = 1.42 ; 95 % CI = 1.29 to 1.57 ) , hospitalization ( RR = 1.12 ; 95 % CI = 1.03 to 1.22 ) , and dialysis withdrawal ( RR = 1.55 ; 95 % CI = 1.29 to 1.85 ) . CONCLUSION The data suggest that depression is underdiagnosed and undertreated among hemodialysis patients . CES-D can help identify hemodialysis patients who are at higher risk of death and hospitalization . Interventions should target these patients with the goal to improve survival and reduce hospitalizations We prospect ively studied the influence of 29 demographic , social , psychological , and somatic factors on survival of 78 patients over age 70 years receiving long-term dialysis . Three years after the prospect i ve evaluation , 54 % of the patients had died . Only four factors , all psychosocial , were prognostically important . The patients who survived rated higher on the Karnofsky scale ( 85 vs 78 points ) , gained less weight between dialyses ( 1.5 vs 1.9 kg ) , more often underwent home dialysis ( 44 % vs 21 % ) , and less often wished for transplantation ( 28 % vs 57 % ) . In stepwise and multiple regression analysis , home dialysis and Karnofsky scale result ed in best fit . No somatic variable predicted outcome . Thirty-one patients were reinterviewed three years later . At that time , more patients were depressed and had a lower income , fewer wanted a transplant , and five had lost their living companion . There was a decrease in the number of patients who cooked their own meals , spent time outdoors , went to church , or had hobbies . Activity on the Karnofsky scale decreased from 87 to 84 points . The home dialysis patients ' perceived health decreased from 3.9 to 3.4 points . Our study shows that psychosocial , but not somatic variables , are prognostically important in survival of older patients undergoing dialysis , and there is a measurable decline in these variables during a three-year follow-up period BACKGROUND Hospital admissions consume a large proportion of costs for the end-stage renal disease ( ESRD ) program in the United States . We investigated whether a physician diagnosis of depression increases the risk for hospitalization or death in patients with ESRD receiving long-term hemodialysis ( HD ) , independent of medical comorbidities . METHODS Central ized Veterans Affairs ( VA ) data bases were used to identify a population -based prevalence cohort of 1,588 male patients with ESRD receiving long-term HD in VA facilities between September 1 , 2000 , and September 30 , 2000 . International Classification of Diseases , Ninth Revision , codes were used to identify comorbidities and depression diagnosis . Negative binomial regression models were used to examine the association between depression diagnosis and number of hospitalizations and cumulative hospital days in a 2-year observation period . Logistic regression models were used to investigate the association between depression diagnosis and hospitalization , death , and death or hospitalization . RESULTS The prevalence of physician-diagnosed depression was 14.7 % . Patients with a depression diagnosis were more likely to be white and have more comorbidities . Depression diagnosis was associated with increased hospital days ( rate ratio for adjusted model , 1.31 ; 95 % confidence interval , 1.04 to 1.66 ) and increased number of hospitalizations ( rate ratio for adjusted model , 1.30 ; 95 % confidence interval , 1.11 to 1.52 ) . Depression diagnosis was not statistically associated with death or the composite of death or hospitalization in adjusted models . CONCLUSION Physician-diagnosed depression was associated significantly with both increased hospitalization rate and length of stay in patients with ESRD receiving outpatient HD in VA facilities , independent of demographics and comorbidities . Prospect i ve studies should be conducted to assess whether treatment of depression will decrease hospitalization in these patients BACKGROUND Depression is not uncommon among patients with end-stage renal disease ( ESRD ) being treated by hemodialysis . We investigated whether risk of mortality and rate of hospitalization may be predicted from physician-diagnosed depression and patients ' self-reports of depressive symptoms . METHODS Data were analyzed from the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) for r and omly selected ESRD patients being treated by hemodialysis in the United States ( 142 facilities , 2855 patients ) and five European countries ( 101 facilities , 2401 patients ) . The diagnosis of depression during the past year was abstract ed from the medical records . In addition , the patients were asked to indicate how much of their time over the previous four weeks they had felt ( 1 ) " so down in the dumps that nothing could cheer you up " and ( 2 ) " downhearted and blue . " A response of " a good bit,""most , " or " all " of the time were classified as depressed . RESULTS The prevalence of depression was nearly 20 % . The relative risks of mortality and hospitalization among depressed ( vs. non-depressed ) , adjusted for time on dialysis , age , race , socioeconomic status , comorbid indicators and country were , respectively : 1.23 and 1.11 for physician-diagnosed depression , 1.48 and 1.15 for the " so down in the dumps " question , and 1.35 and 1.11 for the " downhearted and blue " question ( P < 0.05 for all six relative risks ) . These associations were not significantly different between US and European patients . CONCLUSIONS Self-reported depression by two simple questions was associated with increased risks of mortality and hospitalization for hemodialysis patients . Future research needs to assess whether early identification and treatment of depression may help to improve quality of life and survival in hemodialysis patients Background : Illness perceptions have been shown to be important determinants of functional and psychosocial outcomes , including quality of life and treatment adherence in end-stage renal disease patients . The aim of this prospect i ve study was to determine whether haemodialysis patients ’ illness perceptions impact upon survival . Methods : Haemodialysis patients from a UK renal service completed the Revised Illness Perception Question naire . Over the study period ( May 2007 to December 2010 ) , all-cause mortality was recorded as the endpoint . Results : 223 patients were followed up for a median of 15.9 months ( min . 10 days , max . 42.7 months ) . The median dialysis vintage was 17.6 months ( min . 4 days , max . 391.3 months ) . Treatment control perceptions demonstrated a significant association with mortality ( HR = 0.91 , 95 % CI : 0.83–0.99 , p = 0.03 ) . After controlling for covariates , including age , albumin , extra renal comorbidity and depression scores , perception of treatment control remained a significant predictor of mortality ( HR = 0.89 , 95 % CI : 0.80–0.99 , p = 0.03 ) . Conclusions : Patients ’ perceptions of treatment control ( dialysis therapy ) predict survival independently of survival risk factors , including comorbidity . Studies are required to test whether psychological interventions design ed to modify maladaptive illness perceptions influence clinical outcomes in this patient setting Objective : To test the safety and efficacy of fluoxetine in patients with renal failure on dialysis . Method : Fourteen patients with major depression and end stage renal disease on hemodialysis were r and omized into two groups for an eight-week study . Subjects as well as investigators were blinded as to which subject received fluoxetine and which placebo . Patients were carefully monitored concerning adverse events , serum fluoxetine and norfluoxetine levels , and psychological measurements of degree of depression . Results : No patients discontinued treatment because of adverse events , all of which were minor . All psychological tests showed improvement in depression at the four-week and eight-weeks point , although statistical significance could only be demonstrated at the fourth week of this study . All patients in the active group had serum plasma concentrations of fluoxetine and norfluoxetine less than 250 ng/ml at eight weeks , similar to levels in patients with normal renal function in a previous open label study . Conclusions : This study confirms the relative safety of fluoxetine in depressed patients in renal failure on hemodialysis . It also suggests that fluoxetine may be efficacious in depressed patients on dialysis Many hemodialysis patients in Japan have symptoms of depression , but whether those patients are treated appropriately is unknown . As part of the Dialysis Outcomes and Practice Patterns Study , data on symptoms of depression , physician-diagnosed depression , prescribed medications , and death were collected prospect ively in cohorts in Japan ( n=1603 ) and 11 other countries ( n=5872 ) . Symptoms of depression were as prevalent in Japan as elsewhere , but in Japan a much smaller percentage of patients had physician-diagnosed depression : only 2 % in Japan vs 17 % elsewhere . Antidepressants were much less commonly prescribed in Japan : only 1 % in Japan vs 17 % elsewhere for patients with many and frequent symptoms of depression , and 16 % in Japan vs 34 % elsewhere for patients with physician-diagnosed depression . In Japan , symptoms of depression were associated with prescription of benzodiazepines ( without antidepressants ) , and patients with physician-diagnosed depression were twice as likely to be given benzodiazepines : 32 % in Japan vs 16 % elsewhere . Benzodiazepine monotherapy was associated with death ( relative risk 1.56 , 95 % confidence interval ( CI ) , 1.25 - 1.94 ) , even after adjustments for 13 likely confounders ( relative risk 1.27 , 95 % CI , 1.01 - 1.59 ) . Hemodialysis patients in Japan with symptoms of depression are given not antidepressants but benzodiazepines , a practice associated with higher mortality CONTEXT Patients with chronic kidney disease ( CKD ) experience increased rates of hospitalization and death . Depressive disorders are associated with morbidity and mortality . Whether depression contributes to poor outcomes in patients with CKD not receiving dialysis is unknown . OBJECTIVE To determine whether the presence of a current major depressive episode ( MDE ) is associated with poorer outcomes in patients with CKD . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 267 consecutively recruited out patients with CKD ( stages 2 - 5 and who were not receiving dialysis ) at a VA medical center between May 2005 and November 2006 and followed up for 1 year . An MDE was diagnosed by blinded personnel using the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) criteria . MAIN OUTCOME MEASURES The primary outcome was event-free survival defined as the composite of death , dialysis initiation , or hospitalization . Secondary outcomes included each of these events assessed separately . RESULTS Among 267 patients , 56 had a current MDE ( 21 % ) and 211 did not ( 79 % ) . There were 127 composite events , 116 hospitalizations , 38 dialysis initiations , and 18 deaths . Events occurred more often in patients with an MDE compared with those without an MDE ( 61 % vs 44 % , respectively , P = .03 ) . Four patients with missing date s of hospitalization were excluded from survival analyses . The mean ( SD ) time to the composite event was 206.5 ( 19.8 ) days ( 95 % CI , 167.7 - 245.3 days ) for those with an MDE compared with 273.3 ( 8.5 ) days ( 95 % CI , 256.6 - 290.0 days ) for those without an MDE ( P = .003 ) . The adjusted hazard ratio ( HR ) for the composite event for patients with an MDE was 1.86 ( 95 % CI , 1.23 - 2.84 ) . An MDE at baseline independently predicted progression to dialysis ( HR , 3.51 ; 95 % CI , 1.77 - 6.97 ) and hospitalization ( HR , 1.90 ; 95 % CI , 1.23 - 2.95 ) . CONCLUSION The presence of an MDE was associated with an increased risk of poor outcomes in CKD patients who were not receiving dialysis , independent of comorbidities and kidney disease severity BACKGROUND AND OBJECTIVES When patients start dialysis , their employment rate declines and disability benefits are an option . With patient sociodemographic and clinical characteristics including disability income status controlled , we investigated the significance of depressed mood and usual activity level as predictors of patients ' continued employment after dialysis start . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Incident patients from 296 r and omly selected dialysis clinics were surveyed in the Comprehensive Dialysis Study ( CDS ) . Participants provided information about employment status , disability income status , education , depressive symptoms measured by the Patient Health Question naire-2 ( PHQ-2 ) , and usual activity level/energy expenditure measured by the Human Activity Profile . Age , gender , race , insurance , diabetes , inability to ambulate or transfer , chronic obstructive pulmonary disease , cardiovascular conditions , and hemoglobin and serum albumin values at treatment start were obtained from US Renal Data System files . Dialysis modality was defined at time of interview . RESULTS Among 585 CDS participants who worked in the previous year , 191 ( 32.6 % ) continued working after dialysis start . On the basis of the PHQ-2 cutoff score ≥3 , 12.1 % of patients who remained employed had possible or probable depression , compared with 32.8 % of patients who were no longer employed . In adjusted analyses , higher Human Activity Profile scores were associated with increased likelihood of continued employment , and there was a borderline association between lower PHQ-2 scores and continued employment . CONCLUSIONS Screening and management of depressive symptoms and support for increased activity level may facilitate patients ' opportunity for continued employment after dialysis start , along with generally improving their overall quality of life |
10,840 | 29,740,786 | Patients did not experience improvements in quality of life , blood pressure , or weight , regardless of app used or type of diabetes .
Discussion Limited evidence suggests that use of some commercially available apps , when combined with additional support from a healthcare provider or study staff , may improve some short-term diabetes-related outcomes .
The impact of these apps on longer-term outcomes is unclear . | Background Patients with diabetes lack information on which commercially available applications ( apps ) improve diabetes-related outcomes .
We conducted a rapid evidence review to examine features , clinical efficacy , and usability of apps for self-management of type 1 and type 2 diabetes in adults . | 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 Introduction The role of mobile technology in patient-reported outcomes ( PRO ) and glycemic control in adults with type 1 diabetes ( T1D ) needs further evaluation . Methods The single-center , prospect i ve , 6-month , open-label , investigator-initiated study r and omized 100 subjects with T1D in a 1:1 fashion to a control group using self-monitoring of blood glucose ( SMBG ) with Accu-Chek Nano ® and an intervention group using SMBG with iPhone plus glucose meter ( iBGStar ® ) . The primary endpoint was the change in PRO ( hypoglycemia fear score , behavior and worry subscores ) . Secondary outcomes were the improvement in glycemic variability indices and the reduction in A1c values . Results Baseline demographics and glycosylated hemoglobin ( A1c ) values were similar in the two groups . There was a significant decrease in A1c value at 6 months in iBGStar ® group compared to the control group ( −0.16 vs. −0.51 , p = 0.04 ) . The total insulin dose increased significantly in the iBGStar ® group at 3 months but did not change at 6 months . The hypoglycemia fear scale ( PRO ) improved in both groups at 6 months ( −1.4 ± 10.0 vs. −3.9 ± 12.5 , p = 0.32 ) . Conclusion The use of iBGStar ® result ed in better glycemic control and improvement in some PRO ( hypoglycemia fear and behavior scores ) compared to the control group at 6 months with no increased risk of hypoglycemia . Clinical trial registration Clinical Trials.gov : NCT01825382 . Funding Sanofi Background Mobile health apps for diabetes self-management have different functions . However , the efficacy and safety of each function are not well studied , and no classification is available for these functions . Objective The aims of this study were to ( 1 ) develop and vali date a taxonomy of apps for diabetes self-management , ( 2 ) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of r and omized controlled trials ( RCTs ) , and ( 3 ) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy . Methods We developed a 3-axis taxonomy with columns of clinical modules , rows of functional modules and cells of functions with risk assessment s. This taxonomy was vali date d by review ing and classifying commercially available diabetes apps . We search ed MEDLINE , EMBASE , the Cochrane Central Register of Controlled Trials , the Chinese Biomedical Literature Data base , and Clinical Trials.gov from January 2007 to May 2016 . We included RCTs of adult out patients with diabetes that compared using mobile app-based interventions with usual care alone . The mean differences ( MDs ) in hemoglobin A1c ( HbA1c ) concentrations and risk ratios of adverse events were pooled using a r and om-effects meta- analysis . After taxonomic classification , we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions . Results Across 12 included trials involving 974 participants , using app-based interventions was associated with a clinical ly significant reduction of HbA1c ( MD 0.48 % , 95 % CI 0.19%-0.78 % ) without excess adverse events . Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes ( MD 0.67 % , 95 % CI 0.30%-1.03 % vs MD 0.37 % , 95 % CI –0.12%-0.86 % ) . Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction ( with complication prevention : MD 1.31 % , 95 % CI 0.66%-1.96 % vs without : MD 0.38 % , 95 % CI 0.09%-0.67 % ; intersubgroup P=.01 ) , as was having a structured display ( with structured display : MD 0.69 % , 95 % CI 0.32%-1.06 % vs without : MD 0.69 % , 95 % CI –0.18%-0.53 % ; intersubgroup P=.03 ) . However , having a clinical decision-making function was not associated with a larger HbA1c reduction ( with clinical decision making : MD 0.19 % , 95 % CI –0.24%-0.63 % vs without : MD 0.61 % , 95 % CI 0.27%-0.95 % ; intersubgroup P=.14 ) . Conclusions The use of mobile app-based interventions yields a clinical ly significant HbA1c reduction among adult out patients with diabetes , especially among those with type 2 diabetes . Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps OBJECTIVE Widespread use of carbohydrate counting is limited by its complex education . In this study we compared a Diabetes Interactive Diary ( DID ) with st and ard carbohydrate counting in terms of metabolic and weight control , time required for education , quality of life , and treatment satisfaction . RESEARCH DESIGN AND METHODS Adults with type 1 diabetes were r and omly assigned to DID ( group A , n = 67 ) or st and ard education ( group B , n = 63 ) and followed for 6 months . A subgroup also completed the SF-36 Health Survey ( SF-36 ) and World Health Organization-Diabetes Treatment Satisfaction Question naire ( WHO-DTSQ ) at each visit . RESULTS Of 130 patients ( aged 35.7 ± 9.4 years ; diabetes duration 16.5 ± 10.5 years ) , 11 dropped out . Time for education was 6 h ( range 2–15 h ) in group A and 12 h ( 2.5–25 h ) in group B ( P = 0.07 ) . A1C reduction was similar in both groups ( group A from 8.2 ± 0.8 to 7.8 ± 0.8 % and group B from 8.4 ± 0.7 to 7.9 ± 1.1 % ; P = 0.68 ) . Nonsignificant differences in favor of group A were documented for fasting blood glucose and body weight . No severe hypoglycemic episode occurred . WHO-DTSQ scores increased significantly more in group A ( from 26.7 ± 4.4 to 30.3 ± 4.5 ) than in group B ( from 27.5 ± 4.8 to 28.6 ± 5.1 ) ( P = 0.04 ) . Role Physical , General Health , Vitality , and Role Emotional SF-36 scores improved significantly more in group A than in group B. CONCLUSIONS DID is at least as effective as traditional carbohydrate counting education , allowing dietary freedom for a larger proportion of type 1 diabetic patients . DID is safe , requires less time for education , and is associated with lower weight gain . DID significantly improved treatment satisfaction and several quality -of-life dimensions The dem and for new healthcare services is growing rapidly . Improving accessibility of the African population to diabetes care seems to be a big challenge in most countries where the number of care centers and medical staff is reduced . Information and communication technologies ( ICT ) have great potential to address some of these challenges faced by several countries in providing accessible , cost-effective , and high- quality health care services . This paper presents the Mobil Diab system which is a telemedical approach proposed for the management of long-term diseases . The system applies modern mobile and web technologies which overcome geographical barriers , and increase access to health care services . The idea of the system is to involve patients in the therapy process and motivate them for an active participation . For validation of the system in African context , a trial was conducted in the Democratic Republic of Congo . 40 Subjects with diabetes divided r and omly into control and intervention groups were included in the test . Results show that Mobil Diab is suitable for African countries and presents a number of benefits for the population and public health care system . It improves clinical management and delivery of diabetes care services by enhancing access , quality , motivation , reassurance , efficiency , and cost-effectiveness Background Adoptions of health behaviors are crucial for maintaining good health after type 2 diabetes mellitus ( T2DM ) diagnoses . However , adherence to glucoregulating behaviors like regular exercise and balanced diet can be challenging , especially for people living in lower-socioeconomic status ( SES ) communities . Providing cost-effective interventions that improve self-management is important for improving quality of life and the sustainability of health care systems . Objective To evaluate a health coach intervention with and without the use of mobile phones to support health behavior change in patients with type 2 diabetes . Methods In this noninferiority , pragmatic r and omized controlled trial ( RCT ) , patients from two primary care health centers in Toronto , Canada , with type 2 diabetes and a glycated hemoglobin/hemoglobin A1c ( HbA1c ) level of ≥7.3 % ( 56.3 mmol/mol ) were r and omized to receive 6 months of health coaching with or without mobile phone monitoring support . We hypothesized that both approaches would result in significant HbA1c reductions , although health coaching with mobile phone monitoring would result in significantly larger effects . Participants were evaluated at baseline , 3 months , and 6 months . The primary outcome was the change in HbA1c from baseline to 6 months ( difference between and within groups ) . Other outcomes included weight , waist circumference , body mass index ( BMI ) , satisfaction with life , depression and anxiety ( Hospital Anxiety and Depression Scale [ HADS ] ) , positive and negative affect ( Positive and Negative Affect Schedule [ PANAS ] ) , and quality of life ( Short Form Health Survey-12 [ SF-12 ] ) . Results A total of 138 patients were r and omized and 7 were excluded for a sub study ; of the remaining 131 , 67 were allocated to the intervention group and 64 to the control group . Primary outcome data were available for 97 participants ( 74.0 % ) . While both groups reduced their HbA1c levels , there were no significant between-group differences in change of HbA1c at 6 months using intention-to-treat ( last observation carried forward [ LOCF ] ) ( P=.48 ) or per- protocol ( P=.83 ) principles . However , the intervention group did achieve an accelerated HbA1c reduction , leading to a significant between-group difference at 3 months ( P=.03 ) . This difference was reduced at the 6-month follow-up as the control group continued to improve , achieving a reduction of 0.81 % ( 8.9 mmol/mol ) ( P=.001 ) compared with a reduction of 0.84 % ( 9.2 mmol/mol)(P=.001 ) in the intervention group . Intervention group participants also had significant decreases in weight ( P=.006 ) and waist circumference ( P=.01 ) while controls did not . Both groups reported improvements in mood , satisfaction with life , and quality of life . Conclusions Health coaching with and without access to mobile technology appeared to improve glucoregulation and mental health in a lower-SES , T2DM population . The accelerated improvement in the mobile phone group suggests the connectivity provided may more quickly improve adoption and adherence to health behaviors within a clinical diabetes management program . Overall , health coaching in primary care appears to lead to significant benefits for patients from lower-SES communities with poorly controlled type 2 diabetes . Trial Registration Clinical Trials.gov NCT02036892 ; http:// clinical trials.gov/ct2/show/NCT02036892 ( Archived by WebCite at http://www.webcitation.org/6b3cJYJOD AIMS The primary objective was to evaluate the impact of the smart phone-based diabetes management application , Welltang , on glycated hemoglobin ( HbA1c ) . The second objective was to measure whether Welltang improves blood glucose , low-density lipoprotein cholesterol , weight , blood pressure , hypoglycemic events , satisfaction of patients to use Welltang , diabetes knowledge of patients , and self-care behaviors . METHODS One hundred evenly r and omized subjects with diabetes , aged 18 - 74years , were recruited from the outpatient Department of Endocrinology for a 3-month study . The Welltang intervention group received training for the use of Welltang , while the control group received their usual st and ard of care . HbA1c , blood glucose , low-density lipoprotein cholesterol , weight , blood pressure , hypoglycemic events , satisfaction of patients to use Welltang , diabetes knowledge of patients , and self-care behaviors were measured . Patient data were analyzed using independent t test and paired sample test using SPSS version 12 . RESULTS The average decrease in HbA1c was 1.95 % ( 21mmol/mol ) in the intervention group and 0.79 % ( 8mmol/mol ) in the control group ( P<0.001 ) . Measures of self-monitored blood glucose , diabetes knowledge , and self-care behaviors improved in patients in the intervention group . Eighty four percent of patients in the intervention group were satisfied with the use of Welltang . Differences in hypoglycemic events , low-density lipoprotein cholesterol , weight , and blood pressure were not statistically significant . CONCLUSION Diabetes patients using the Welltang application achieved statistically significant improvements in HbA1c , blood glucose , satisfaction of patients to use of Welltang , diabetes knowledge , and self-care behaviors Quinn CC , Shardell MD , Terrin ML , Barr EA , Ballew SH , Gruber-Baldini AL . Cluster-r and omized trial of a mobile phone personalized behavioral intervention for blood glucose control . Diabetes Care 2011;34:1934–1942 In the article listed above , the values for the 9-month glycated hemoglobins are incorrect due to a programming error . The significance of the results and the discussion remained unchanged . The changes to Table 1 and to the text are detailed below 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 OBJECTIVE To demonstrate that Diabeo software enabling individualized insulin dose adjustments combined with telemedicine support significantly improves HbA1c in poorly controlled type 1 diabetic patients . RESEARCH DESIGN AND METHODS In a six-month open-label parallel-group , multicenter study , adult patients ( n = 180 ) with type 1 diabetes ( > 1 year ) , on a basal-bolus insulin regimen ( > 6 months ) , with HbA1c ≥8 % , were r and omized to usual quarterly follow-up ( G1 ) , home use of a smartphone recommending insulin doses with quarterly visits ( G2 ) , or use of the smartphone with short teleconsultations every 2 weeks but no visit until point end ( G3 ) . RESULTS Six-month mean HbA1c in G3 ( 8.41 ± 1.04 % ) was lower than in G1 ( 9.10 ± 1.16 % ; P = 0.0019 ) . G2 displayed intermediate results ( 8.63 ± 1.07 % ) . The Diabeo system gave a 0.91 % ( 0.60 ; 1.21 ) improvement in HbA1c over controls and a 0.67 % ( 0.35 ; 0.99 ) reduction when used without teleconsultation . There was no difference in the frequency of hypoglycemic episodes or in medical time spent for hospital or telephone consultations . However , patients in G1 and G2 spent nearly 5 h more than G3 patients attending hospital visits . CONCLUSIONS The Diabeo system gives a substantial improvement to metabolic control in chronic , poorly controlled type 1 diabetic patients without requiring more medical time and at a lower overall cost for the patient than usual care |
10,841 | 24,341,605 | The most frequently reported facilitator was strong management support .
Conclusions Process evaluations are not systematic ally performed alongside effectiveness studies for WHPPs .
The quality of the process evaluations is mostly poor to average , result ing in a lack of systematic ally measured barriers/facilitators .
The narrow focus on implementation makes it difficult to explore the relationship between effectiveness and implementation . | Background Numerous worksite health promotion program ( WHPPs ) have been implemented the past years to improve employees ’ health and lifestyle ( i.e. , physical activity , nutrition , smoking , alcohol use and relaxation ) .
Research primarily focused on the effectiveness of these WHPPs .
Whereas process evaluations provide essential information necessary to improve large scale implementation across other setting s. Therefore , this review aims to : ( 1 ) further our underst and ing of the quality of process evaluations alongside effect evaluations for WHPPs , ( 2 ) identify barriers/facilitators affecting implementation , and ( 3 ) explore the relationship between effectiveness and the implementation process . | Background Both low back pain ( LBP ) and neck pain ( NP ) are major occupational health problems . In the workplace , participatory ergonomics ( PE ) is frequently used on musculoskeletal disorders . However , evidence on the effectiveness of PE to prevent LBP and NP obtained from r and omised controlled trials ( RCTs ) is scarce . This study evaluates the process of the Stay@Work participatory ergonomics programme , including the perceived implementation of the prioritised ergonomic measures . Methods This cluster- RCT was conducted at the departments of four Dutch companies ( a railway transportation company , an airline company , a steel company , and a university including its university medical hospital ) . Directly after the r and omisation outcome , intervention departments formed a working group that followed the steps of PE during a six-hour working group meeting . Guided by an ergonomist , working groups identified and prioritised risk factors for LBP and NP , and composed and prioritised ergonomic measures . Within three months after the meeting , working groups had to implement the prioritised ergonomic measures at their department . Data on various process components ( recruitment , reach , fidelity , satisfaction , and implementation components , i.e. , dose delivered and dose received ) were collected and analysed on two levels : department ( i.e. , working group members from intervention departments ) and participant ( i.e. , workers from intervention departments ) . Results A total of 19 intervention departments ( n = 10 with mental workloads , n = 1 with a light physical workload , n = 4 departments with physical and mental workloads , and n = 4 with heavy physical workloads ) were recruited for participation , and the reach among working group members who participated was high ( 87 % ) . Fidelity and satisfaction towards the PE programme rated by the working group members was good ( 7.3 or higher ) . The same was found for the Stay@Work ergocoach training ( 7.5 or higher ) . In total , 66 ergonomic measures were prioritised by the working groups . Altogether , 34 % of all prioritised ergonomic measures were perceived as implemented ( dose delivered ) , while the workers at the intervention departments perceived 26 % as implemented ( dose received ) . Conclusions PE can be a successful method to develop and to prioritise ergonomic measures to prevent LBP and NP . Despite the positive rating of the PE programme the implementation of the prioritised ergonomic measures was lower than expected . Trial registration Current Controlled Trials IS RCT In web-based health promotion programs , large variations in participant engagement are common . The aim was to investigate determinants of high use of a worksite self-help web-based program for stress management . Two versions of the program were offered to r and omly selected departments in IT and media companies . A static version of the program including health screening tool , diary and information about stress was offered to the control group . Additional material s , i.e. interactive , cognitive-based and classical stress management exercises and a chat room , were offered to the intervention group . Baseline data regarding participants ' demographics , health ( self-ratings and biological measures ) , lifestyle , work-related factors and group membership were analyzed to study determinants of employees ' participation in the program during a period of 12 months . Multiple logistic regression analysis was used and found intervention group membership , being a woman , having at most a secondary education , regular physical exercise habits and having positive expectations of the program were significant predictors of high use . The findings demonstrate that the interactivity of a web-based program is an important factor for determining participation in a web-based worksite stress management program . Implication s for those developing and implementing future web-based health promotion activities are discussed OBJECTIVE To evaluate the effectiveness of a lifestyle intervention for male workers in the construction industry at risk of cardiovascular disease ( CVD ) . METHODS In a r and omized controlled trial performed in the Netherl and s between 2007 and 2009 , usual care was compared to 6 months of individual counseling using motivational interviewing techniques , delivered face to face and by telephone . Participants aim ed at improving energy balance-related behavior or smoking cessation . Linear regression analyses were performed to determine the effects . RESULTS Body weight had significantly decreased at 6 ( β=-1.9 , 95 % CI -2.6 ; -1.2 ) and 12 months ( β=-1.8 , 95%CI -2.8 ; -1.1 ) . The intervention effects were also significant for diastolic blood pressure at 6 months ( β=-1.7 , 95 % CI -3.3 ; -0.1 ) . Among participants who had aim ed at energy balance , the intervention had a significant favorable effect on body weight at 6 ( β=-2.1 , 95 % CI -2.9 ; -1.3 ) and 12 months ( β=-2.2 , 95 % CI -3.1 ; -1.3 ) and at HDL cholesterol ( β=0.05 , 95 % CI 0.01 ; 0.10 ) and HbA1c ( β=-0.06 , 95%CI -0.12 ; -0.001 ) at 12 months , although there was no intervention effect on these variables over time . CONCLUSION Individual-based counseling result ed in significant beneficial long-term effects on body weight . This is an important finding for occupational health , considering the rising prevalence of obesity and CVD BACKGROUND This study explored the experiences of university employees recruited to a 10-week r and omized controlled trial ( n = 64 ) . The trial compared " walking routes " with " walking-while-working " on daily step totals , showing that , compared with controls , interventions result ed in around 1000 extra steps per day . METHODS A sub sample of 15 academic and administrative employees from intervention groups completed interviews at the end of intervention . Interviews were transcribed verbatim and subject to inductive coding within the major themes of benefits /positives and problems/barriers . FINDINGS Both interventions benefited employee health and work productivity but were difficult to implement in the workplace . Involvement in walking routes was challenged by the difficulties of managing time pressures , and individuals assigned to walking-while-working had to deal with local management subcultures favoring physical presence and inactivity . CONCLUSIONS Findings highlight the need for further research , advocate the value of walking at work , and provide insights into the challenges that face staff in workplace interventions Background Only a few workplace initiatives among cleaners have been reported , even though they constitute a job group in great need of health promotion . The purpose of this trial was to evaluate the effect of either physical coordination training or cognitive behavioural training on musculoskeletal pain , work ability and sickness absence among cleaners . Methods A cluster-r and omised controlled trial was conducted among 294 female cleaners allocated to either physical coordination training ( PCT ) , cognitive behavioural training ( CBTr ) or a reference group ( REF ) . Question naires about musculoskeletal pain and work ability were completed at baseline and after one year 's intervention . Sickness absence data were obtained from the managers ' records . Analyses were performed according to the intention-to-treat-principle ( ITT ) . Results No overall reduction in musculoskeletal pain , work ability or sickness absence from either PCT or CBTr compared with REF was found in conservative ITT analyses . However , explorative analyses revealed a treatment effect for musculoskeletal pain of the PCT . People with chronic neck/shoulder pain at baseline were more frequently non-chronic at follow-up after PCT compared with REF ( p = 0.05 ) . Conclusions The PCT intervention appeared effective for reducing chronic neck/shoulder pain among the female cleaners . It is recommended that future interventions among similar high-risk job groups focus on the implementation aspects of the interventions to maximise outcomes more distal from the intervention such as work ability and sickness absence . Trial registration IS RCT N : IS RCT Background Low back pain ( LBP ) and neck pain ( NP ) are common among workers . Participatory Ergonomics ( PE ) is used as an implementation strategy to prevent these symptoms . By following the steps of PE , working groups composed and prioritised ergonomic measures , and developed an implementation plan . Working group members were responsible to implement the ergonomic measures in their departments . Little is known about factors that hamper ( barriers ) or enhance ( facilitators ) the implementation of ergonomic measures . This study aim ed to identify and underst and the possible barriers and facilitators that were perceived during implementation . Methods This study is embedded in a cluster r and omised controlled trial that investigated the effectiveness of PE to prevent LBP and NP among workers . For the purpose of the current study , question naires were sent to 81 working group members . Their answers were used to make a first inventory of possible barriers and facilitators to implementation . Based on the question naire information , 15 semi-structured interviews were held to explore the barriers and facilitators in more detail . All interviews were audio taped , transcribed verbatim , and analysed according to a systematic approach . Results All possible barriers and facilitators were obtained from question naire data , indicating that the semi-structured interviews did not yield information about new factors . Various barriers and facilitators were experienced . The presence of implementation plans for ergonomic measures that were already approved by the management facilitated implementation before the working group meeting . In these cases , PE served as a strategy to improve the implementation of the approved measures . Furthermore , the findings showed that the composition of a working group ( i.e. , including decision makers and a worker who led the implementation process ) was important . Moreover , stakeholder involvement and collaboration were reported to considerably improve implementation . Conclusions This study showed that the working group as well as stakeholder involvement and collaboration were important facilitating factors . Moreover , PE was used as a strategy to improve the implementation of existing ergonomic measures . The results can be used to improve PE programmes , and thereby may contribute to the prevention of LBP and NP.Trial registration numberIS RCT Background : Environmental interventions directed at portion size might help consumers to reduce their food intake . Objective : To assess whether offering a smaller hot meal , in addition to the existing size , stimulates people to replace their large meal with a smaller meal . Design : Longitudinal r and omized controlled trial assessing the impact of introducing small portion sizes and pricing strategies on consumer choices . Setting / participants : In all , 25 worksite cafeterias and a panel consisting of 308 consumers ( mean age=39.18 years , 50 % women).Intervention : A small portion size of hot meals was offered in addition to the existing size . The meals were either proportionally priced ( that is , the price per gram was comparable regardless of the size ) or value size pricing was employed . Main outcome measures : Daily sales of small and the total number of meals , consumers ’ self-reported compensation behavior and frequency of purchasing small meals . Results : The ratio of small meals sales in relation to large meals sales was 10.2 % . No effect of proportional pricing was found B=−0.11 ( 0.33 ) , P=0.74 , confidence interval ( CI ) : −0.76 to 0.54 ) . The consumer data indicated that 19.5 % of the participants who had selected a small meal often-to-always purchased more products than usual in the worksite cafeteria . Small meal purchases were negatively related to being male ( B=−0.85 ( 0.20 ) , P=0.00 , CI : −1.24 to −0.46 , n=178 ) . Conclusion : When offering a small meal in addition to the existing size , a percentage of consumers that is considered reasonable were inclined to replace the large meal with the small meal . Proportional prices did not have an additional effect . The possible occurrence of compensation behavior is an issue that merits further attention Objectives To study the effect of a participatory ergonomics intervention on psychosocial factors among kitchen workers . Design A cluster r and omised controlled trial . Setting Four cities in Finl and , 2002–2005 . Participants 504 workers in 119 municipal kitchens . Intervention Kitchens were r and omised to intervention ( n=59 ) and control ( n=60 ) groups . The intervention lasted 11–14 months and was based on the workers ' active participation in work analysis , planning and implementing the ergonomic changes aim ed at decreasing the physical and mental workload . Main outcome measures Mental stress , mental strenuousness of work , hurry , job satisfaction , job control , skill discretion , co-worker relationships and supervisor support . Data were collected by question naire at baseline , at the end of the intervention , and at a 12-month follow-up ( PI12 ) . Results At the end of the intervention , the OR of job dissatisfaction for the intervention group as compared with the control group was 3.0 ( 95 % CI 1.1 to 8.5 ) , of mental stress 2.3 ( 1.2 to 4.7 ) and of poor co-worker relationships 2.3 ( 1.0 to 5.2 ) . At the PI12 , the OR of job dissatisfaction was 3.0 ( 1.2 to 7.8 ) . Analysis of the independent and joint effects of the intervention and unconnected organisational reforms showed that adverse changes were accentuated among those with exposure to both . Conclusions No favourable effects on psychosocial factors at work were found . The adverse changes were due to a joint effect of the intervention and the unconnected organisational reforms . The findings do not support the usefulness of this kind of intervention in changing unsatisfactory psychosocial working conditions BACKGROUND Smoking is the leading preventable cause of premature death in the United States . Previous studies of financial incentives for smoking cessation in work setting s have not shown that such incentives have significant effects on cessation rates , but these studies have had limited power , and the incentives used may have been insufficient . METHODS We r and omly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs ( 442 employees ) or to receive information about programs plus financial incentives ( 436 employees ) . The financial incentives were $ 100 for completion of a smoking-cessation program , $ 250 for cessation of smoking within 6 months after study enrollment , as confirmed by a biochemical test , and $ 400 for abstinence for an additional 6 months after the initial cessation , as confirmed by a biochemical test . Individual participants were stratified according to work site , heavy or nonheavy smoking , and income . The primary end point was smoking cessation 9 or 12 months after enrollment , depending on whether initial cessation was reported at 3 or 6 months . Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs . RESULTS The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment ( 14.7 % vs. 5.0 % , P<0.001 ) and 15 or 18 months after enrollment ( 9.4 % vs. 3.6 % , P<0.001 ) . Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program ( 15.4 % vs. 5.4 % , P<0.001 ) , completion of a smoking-cessation program ( 10.8 % vs. 2.5 % , P<0.001 ) , and smoking cessation within the first 6 months after enrollment ( 20.9 % vs. 11.8 % , P<0.001 ) . CONCLUSIONS In this study of employees of one large company , financial incentives for smoking cessation significantly increased the rates of smoking cessation . ( Clinical Trials.gov number , NCT00128375 . Objectives This study investigated the effectiveness of the Stay@Work participatory ergonomics programme to reduce workers′ exposure to psychosocial and physical risk factors . Methods 37 departments ( n=3047 workers ) from four Dutch companies participated in this cluster r and omised controlled trial ; 19 ( n=1472 workers ) were r and omised to an intervention group ( participatory ergonomics ) and 18 ( n=1575 workers ) to a control group ( no participatory ergonomics ) . During a 6 h meeting guided by an ergonomist , working groups devised ergonomic measures to reduce psychosocial and physical workload and implemented them within 3 months in their departments . Data on psychosocial and physical risk factors for low back pain and neck pain were collected at baseline and after 6 months . Psychosocial risk factors were measured using the Job Content Question naire and physical risk factors using the Dutch Musculoskeletal Question naire . Intervention effects were studied using multilevel analysis . Results Intervention group workers significantly increased on decision latitude ( 0.29 points ; 95 % CI 0.07 to 0.52 ) and decision authority ( 0.16 points ; 95 % CI 0.04 to 0.28 ) compared to control workers . However , exposure to awkward trunk working postures significantly increased in the intervention group ( OR 1.86 ; 95 % CI 1.15 to 3.01 ) compared to the control group . No significant differences between the intervention and control group were found for the remaining risk factors . After 6 months , loss to follow-up was 35 % in the intervention group and 29 % in the control group . Conclusion Participatory ergonomics was not effective in reducing exposure to psychosocial and physical risk factors for low back pain and neck pain among a large group of workers . Trial registration IS RCT N27472278 OBJECTIVES We examined the efficacy of a cancer prevention intervention design ed to improve health behaviors among working-class , multiethnic population s employed in small manufacturing businesses . METHODS Worksites were r and omly assigned to an intervention or minimal-intervention control condition . The intervention targeted fruit and vegetable consumption , red meat consumption , multivitamin use , and physical activity . RESULTS Employees in the intervention group showed greater improvements for every outcome compared with employees in the control group . Differences in improvement were statistically significant for multivitamin use and physical activity . Intervention effects were larger among workers than among managers for fruit and vegetable consumption and for physical activity . CONCLUSIONS The social- context model holds promise for reducing disparities in health behaviors . Further research is needed to improve the effectiveness of the intervention Objective To evaluate the effectiveness of a worksite vitality intervention on vigorous physical activity ( VPA ) , fruit intake , aerobic capacity , mental health and need for recovery after work among older hospital workers ( ie , 45 years and older ) . Methods The 6-month intervention was evaluated using a r and omised controlled trial design . Workers who were r and omised to the intervention group ( n=367 ; control : n=363 ) received the Vital@Work intervention containing ( 1 ) a Vitality Exercise Program ( VEP ) combined with ( 2 ) three visits to Personal Vitality Coach . The VEP consisted of a weekly yoga session , a weekly workout session and weekly unsupervised aerobic exercising . Free fruit was provided at the VEP . Data on the outcome measures were collected ( ie , year 2009–2010 ) at baseline ( n=730 ) and 6 months of follow-up after baseline ( n=575 ) using question naires , accelerometers and 2 km walk tests . Effects were analysed according to the intention-to-treat principle with complete cases ( n=575 ) and imputed data ( n=730 ) using linear regression analyses . Additional analyses were performed for high yoga and workout compliance ( ie , > mean number of sessions ) . Results Effects were found for sports activities ( β=40.4 min/week , 95 % CI 13.0 to 67.7 ) and fruit intake ( β=2.7 pieces/week , 95 % CI 0.07 to 4.7 ) and were stronger for workers with high compliance to yoga ( sport : β=49.6 min/week , 95 % CI 13.9 to 85.2 ; fruit : β=3.8 pieces/week , 95 % CI 1.1 to 6.4 ) and workout sessions ( sport : β=72.9 min/week , 95 % CI 36.1 to 109.8 ; fruit : β=4.0 pieces/week , 95 % CI 1.1 to 6.4 ) . The intervention group lowered their need for recovery , when compared to controls ( β=−3.5 , 95 % CI −6.4 to −0.54 ) , with stronger effects for high workout compliance ( β=−5.3 , 95 % CI −9.3 to −1.3 ) . No effects were found on VPA , aerobic capacity or mental health . Conclusions Implementation of worksite yoga and workout facilities and minimal fruit interventions should be considered by employers to promote transitions into healthier lifestyles and thereby health Objectives Novel approaches to worksite health promotion are needed for high-risk workers who change job sites frequently , and thus may have limited access to worksite health promotion efforts . The objective of this study was to test a behavioral intervention among construction laborers . Methods Using a r and omized-controlled design , we tested the efficacy of a tailored telephone-delivered and mailed intervention to promote smoking cessation and increased fruit and vegetable consumption ( n = 582 ) . Results At baseline , 40 % of control group participants and 45 % of intervention group participants reported using any tobacco in the last seven days . At final , 8 % of baseline cigarette smokers in the control group had quit , compared to 19 % in the intervention group ( p = 0.03 ) . In both groups , the mean consumption of fruits and vegetables at baseline was over five servings per day . At final , the intervention group had increased consumption by approximately one and one-half servings , compared to a slight decrease in consumption in the control group ( p < 0.001 ) . Conclusions A tailored intervention can be efficacious in promoting tobacco use cessation and increased fruit and vegetable consumption among construction laborers , a high-risk , mobile workforce Background The process evaluation of the Vital@Work intervention was primary aim ed at gaining insight into the context , dose delivered , fidelity , reach , dose received , and participants ' attitude . Further , the differences between intervention locations were evaluated . Methods Eligible for this study were 730 workers , aged ≥ 45 years , from two academic hospitals . Workers r and omised to the intervention group ( n = 367 ) received a 6-months intervention consisting a Vitality Exercise Programme ( VEP ) combined with three visits to a Personal Vitality Coach ( PVC ) , aim ed at goal setting , feedback , and problem solving . The VEP consisted of a guided yoga session , a guided workout session , and aerobic exercising without direct face-to-face instruction , all once a week . Data were collected by means of a question naire after the intervention , attendance registration forms ( i.e. attendance at guided VEP group sessions ) , and coaching registration forms ( filled in by the PVCs ) . Results The dose delivered of the yoga and workout sessions were 72.3 % and 96.3 % . All PVC visits ( 100 % ) were offered . The reach for the yoga sessions , workout sessions and PVC visits was 70.6 % , 63.8 % , and 89.6 % , respectively . When taken these three intervention components together , the reach was 52 % . This differed between the two locations ( 59.2 % versus 36.8 % ) . The dose received was for the yoga 10.4 sessions/24 weeks and for the workout 11.1 sessions/24 weeks . The attendance rate , defined as the mean percentage of attended group sessions in relation to the total provided group sessions , for the yoga and workout sessions was 51.7 % and 44.8 % , respectively . For the yoga sessions this rate was different between the two locations ( 63.2 % versus 46.5 % ) . No differences were found between the locations regarding the workout sessions and PVC visits . Workers attended on average 2.7 PVC visits . Overall , workers were satisfied with the intervention components : 7.5 for yoga sessions , 7.8 for workout sessions , and 6.9 for PVC visits . Conclusions The implementation of the intervention was accomplished as planned with respect to the dose delivered . Based on the reach , most workers were willing to attend the guided group sessions and the PVC visits , although there were differences between the locations and between intervention components . Overall , workers were positive about the intervention . Trial registration Trial registration Objective : To present feasibility data on SMART , the first teen worksite behavioural tobacco control intervention . Design : This phase II study was design ed to estimate the efficacy and feasibility of a small scale , r and omised , controlled intervention . Setting and subjects : This study , addressing youths aged 15–18 years , was implemented in four intervention and five control grocery stores that had an average of 44 eligible teens . Interventions : The tobacco use cessation and prevention interventions were based on social influences and peer leader models . Employee break rooms served as centres both for interactive activities including open houses , teen advisory boards , peer leader interviews , games and contests ; and non-interactive interventions including bulletin boards and table tents with health messages and home mailings . Main process measures : Project staff collected process data on the extent of implementation of intervention activities , participation rates in activities , and contacts with peer leaders . On the final survey , teens reported on awareness of , participation in , and motivation for participating in project activities . Results : Indicators of feasibility were identified and discussed , including the number of activities implemented , teen participation , management support , cost , and barriers to and facilitators of implementation . During the 12 month intervention , a mean of 24.1 interactive activities and 55.3 non-interactive activities were implemented , and a mean 14.2 % participation rate per activity per site was achieved . Eighty four per cent of teens reported being aware of SMART , and 39 % reported participating in interactive and 67 % in non-interactive activities . Conclusions : Teen smoking cessation rates in worksite programmes might be improved if they are conducted in companies where there is job stability and if teen programmes are part of worksite-wide tobacco control programmes that include both teens and adults Background The aim of the present study was to assess possible effects on mental and physical well-being and stress-related biological markers of a web-based health promotion tool . Methods A r and omized , prospect ively controlled study was conducted with before and after measurements , involving 303 employees ( 187 men and 116 women , age 23–64 ) from four information technology and two media companies . Half of the participants were offered web-based health promotion and stress management training ( intervention ) lasting for six months . All other participants constituted the reference group . Different biological markers were measured to detect possible physiological changes . Results After six months the intervention group had improved statistically significantly compared to the reference group on ratings of ability to manage stress , sleep quality , mental energy , concentration ability and social support . The anabolic hormone dehydroepi and osterone sulphate ( DHEA-S ) decreased significantly in the reference group as compared to unchanged levels in the intervention group . Neuropeptide Y ( NPY ) increased significantly in the intervention group compared to the reference group . Chromogranin A ( CgA ) decreased significantly in the intervention group as compared to the reference group . Tumour necrosis factor α ( TNFα ) decreased significantly in the reference group compared to the intervention group . Logistic regression analysis revealed that group ( intervention vs. reference ) remained a significant factor in five out of nine predictive models . Conclusion The results indicate that an automatic web-based system might have short-term beneficial physiological and psychological effects and thus might be an opportunity in counteracting some clinical ly relevant and common stress and health issues of today Objective : The SMART Teens Against the Risks of Tobacco Study was design ed to test the feasibility and efficacy of tobacco control intervention methods for employed teens . Methods : A r and omized controlled pilot study tested the efficacy of a behavioral intervention delivered between September , 1999 , and August , 2000 . Baseline and final survey data were collected on 560 teens in four intervention and five control stores . Results : Although smoking prevalence decreased and intention to quit increased more among teens in the intervention stores compared to those in the control stores , the differences were not statistically significant . Conclusions : The worksite holds promise as a possible venue for tobacco prevention and cessation interventions for youth although further research is needed to increase the efficacy of interventions for this setting Environmental interventions such as labeling and an increased availability of healthy foods may help consumers to meet guidelines for a healthy diet . This article describes a study into the effectiveness of two environmental programs to be used in worksite cafeterias along with an educational program . The aim of the interventions was to reduce fat intake , and to increase fruit and vegetable intake . In the labeling program , low-fat products were labeled . The food supply program comprised an increased availability of low-fat products and fruits and vegetables in worksite cafeterias . The educational program consisted of information about healthy nutrition through brochures , table tents , a self-help manual and posters . The design consisted of a pre-test-post-test experimental control group design , with four conditions : the educational program ; the food supply program plus educational program ; the labeling program plus educational program ; and a control group . Seventeen worksites were r and omly assigned to one of the four research conditions . Total fat , fruit and vegetable intake was measured with a quantitative , self-administered food frequency question naire ( 35 questions ) . Intake during lunch was measured by asking respondents to write down which food items they had purchased during their last lunch in the cafeteria . Furthermore , sales data for some targeted product categories were collected ( milk , butter , cheese , meat products , desserts ) . For the whole study population , no significant effects on consumption data were found for any of the programs . The data showed a beneficial and significant treatment effect of the labeling program on total fat intake for respondents who believed they ate a high-fat diet . Sales data revealed a significant effect of the labeling program on desserts , but not for the other products & NA ; Regular physical exercise is a cornerstone in rehabilitation programs , but adherence to comprehensive exercise remains low . This study determined the effectiveness of small daily amounts of progressive resistance training for relieving neck/shoulder pain in healthy adults with frequent symptoms ; 174 women and 24 men working at least 30 h per week and with frequent neck/shoulder pain were r and omly assigned to resistance training with elastic tubing for 2 or 12 minutes per day 5 times per week , or weekly information on general health ( control group ) . Primary outcomes were changes in intensity of neck/shoulder pain ( scale 0 to 10 ) , examiner‐verified tenderness of the neck/shoulder muscles ( total tenderness score of 0 to 32 ) , and isometric muscle strength at 10 weeks . Compared with the control group , neck/shoulder pain and tenderness , respectively , decreased 1.4 points ( 95 % confidence interval −2.0 to −0.7 , p < 0.0001 ) and 4.2 points ( 95 % confidence interval −5.7 to −2.7 , p < 0.0001 ) in the 2‐minute group and 1.9 points ( 95 % confidence interval −2.5 to −1.2 , p < 0.0001 ) and 4.4 points ( 95 % confidence interval −5.9 to −2.9 , p < 0.0001 ) in the 12‐minute group . Compared with the control group , muscle strength increased 2.0 Nm ( 95 % confidence interval 0.5 to 3.5 Nm , p = 0.01 ) in the 2‐minute group and 1.7 Nm ( 95 % confidence interval 0.2 to 3.3 Nm , p = 0.02 ) in the 12‐minute group . In conclusion , as little as 2 minutes of daily progressive resistance training for 10 weeks results in clinical ly relevant reductions of pain and tenderness in healthy adults with frequent neck/shoulder symptoms . Trial registration : www.is rct n.org/IS RCT N60264809 . In generally healthy adults with frequent neck/shoulder muscle pain , as little as 2 minutes of daily progressive resistance training reduces pain and tenderness Deficiencies in the quality and safety of health care remain a significant concern in the United States and abroad as evidence documenting gaps between actual and recommended clinical practice s continues to accumulate ( 1 , 2 ) . The significance of the well-recognized health care quality chasm has been acknowledged by a broad array of stakeholders , who have responded with efforts to identify , underst and , and correct specific shortcomings in health care delivery . The quality improvement collaborative ( QIC ) examined by L and on and colleagues in this issue ( 3 ) is arguably the health care delivery industry 's most important response to quality and safety gaps ; it represents substantial investments of time , effort , and funding . Largely developed and popularized by the Boston-based Institute for Healthcare Improvement ( IHI ) and best exemplified by IHI 's Breakthrough Series collaborative program , the QIC method has been adopted on a large scale by the U.S. Health Re sources and Services Administration ( HRSA ) ( 4 ) and the United Kingdom 's National Health Service ( NHS ) ( 5 ) . The Veterans Health Administration ( 6 ) and numerous smaller health care systems and individual hospitals and clinics worldwide have adopted the method on a smaller scale ( 7 ) . The QIC method brings together a group of participating ( collaborating ) health care delivery organizations ( typically between 20 and 40 ) and guides them in study ing a specific health care quality problem , design ing and implementing specific solutions , evaluating and refining these solutions , and disseminating findings to other organizations . Each participating organization is represented by a 3- or 4-person team ; all teams meet together with a small faculty of experts in a series of 2 or 3 multiday collaborative learning session meetings , which take place over several months . During the meetings , the team members learn improvement techniques , exchange insights and advice , and generate enthusiasm and a shared sense of commitment to achieving common improvement goals and outcomes . Teams return to their organizations between learning sessions to apply their new knowledge and ideas in a Pl anD o Study Act framework ( 8) . They conduct repeated cycles of quality problem diagnosis , development and implementation of small-scale improvement efforts , assessment of effects , and refinement and expansion of effective actions until desired outcomes are achieved . The QIC method is described in detail elsewhere ( 7 , 9 , 10 ) . Although estimates of total investment and applications of the QIC method are not available , IHI reports that Since 1995 , IHI has sponsored over 50 [ Breakthrough Collaborative ] projects on several dozen topics involving over 2,000 teams from 1,000 healthcare organizations ( 11 ) . The IHI tally includes a large series of collaboratives conducted under HRSA sponsorship but excludes NHS-sponsored collaboratives and numerous other collaborative efforts conducted without IHI 's direct involvement . The widespread acceptance and application of the QIC method are often question ed by observers citing the modest quantity and quality of published evidence that supports its effectiveness ( 12 , 13 ) . Although numerous reports of collaboratives have been published , they consist primarily of subjective or self-report assessment s of QIC effects and qualitative summaries of key lessons learned by collaborative leaders and participants . Such first-h and reports offer important insights into the black box of improvement methods and processes ( information generally absent from published evaluations of other quality improvement methods ) . However , they are incomplete without complementary , objective impact evaluations and are probably biased in favor of positive findings . This bias results from dem and and supply factors . Dem and -induced bias occurs because much of the published information is concentrated in management- and practitioner-oriented journals , such as The Joint Commission Journal on Quality and Safety and Quality Management in Health Care , whose mission and readership attract articles offering practical guidance and insights from only the successful quality improvement efforts . Supply-induced bias occurs when authors pursue quality improvement rather than research goals and document only successful collaboratives . Method ologic weaknesses in the individual studies exacerbate distortion in the published QIC evidence base caused by publication bias . Published assessment s of collaboratives generally use uncontrolled pretestpost-test design s that can not rule out plausible alternative explanations for observed improvements , such as secular trends . ( A detailed table listing published assessment s of collaboratives and describing key features of the evaluation design , methods , and measures in each published article is available from the author upon request . ) Although QIC authors routinely acknowledge design limitations and suggest cautious interpretation of positive findings ( 14 ) , such caution s are easily overlooked . Probable errors in measurement are also pervasive . They include outcome measures that rely on participants ' unvali date d self-reports or collaborative leaders ' subjective ratings of readily observed phenomena ( such as team enthusiasm , commitment , and adherence to the collaborative process ) rather than objective measures of clinical practice or outcome change . Participants ' self-reported outcome measures are typically derived from nonrigorous , highly variable measurement efforts , which often focus on short-term effects measured during or immediately following the intensive collaborative period . This results in the capture of positive effects that may be temporary and driven by Hawthorne effects rather than fundamental , lasting change . Furthermore , subjective ratings provided by collaborative participants and leaders are subject to unintentional and unrecognized biases generated by common human decision and judgment heuristics . For example , expectation biases and the phenomenon of belief perseverance combine to produce systematic overweighting of evidence and observations that confirm a priori expectations and beliefs and underweighting or discounting of evidence that does not support the effectiveness of the QIC method ( 15 ) . These phenomena reinforce faith and belief in the effectiveness of the QIC method , which contributes to further accumulation of published positive findings and an escalating cycle of belief and confirmatory evidence ( 12 , 16 ) . The apparent inconsistency between widespread belief in and use of the QIC method and the available supporting evidence heightens the importance of the study by L and on and colleagues . The authors reported on a large HRSA-sponsored collaborative that addresses the care of patients with HIV infection or AIDS . The HRSA has embraced the QIC method and has recently encouraged or m and ated the participation of grantee clinics in a series of QIC projects ( 4 ) . L and on and colleagues studied 44 HRSA-contracted clinics participating in the collaborative ( some on a voluntary basis and some to meet contract requirements ) and 25 comparison clinics . Although clinics were not r and omly assigned , the authors selected comparison clinics through a careful matching process , which provided a basis for ruling out secular trends and other possible explanations of the positive effects often observed in uncontrolled pretestpost-test evaluations of collaboratives . Outcome measures were defined consistently across all sites , and comparable measures were obtained through chart review for representative patient sample s from all sites . Although medical record review ers were selected from the participating sites and the authors provide no information about chart review er training ( or about reliability , validity checks , or other efforts to minimize measurement error ) , the level of rigor in the study by L and on and colleagues exceeds that of earlier evaluations of collaboratives . Any remaining bias seems more likely to produce false-positive rather than false-negative findings . L and on and colleagues ' study demonstrates small and generally insignificant prepost improvements among both intervention and control sites in most of the 8 quality indicators measured . For the 2 indicators showing the greatest improvement ( 11 % and 7.3 % ) among intervention clinics , comparable improvements were seen among control clinics as well . The small differences between the intervention and control clinics did not reach statistical significance and therefore did not preclude the attribution of observed improvement to secular trends . Several supplementary analyses compared subgroups of clinics ( for example , newly funded vs. more established HRSA-funded clinics and clinics with low quality -of-care indicator scores at baseline vs. those with higher baseline scores ) and subgroups of patients ( for example , patients already receiving highly active antiretroviral therapy ) . The authors consider and rule out numerous potential explanations for their null findings , including the possibility that control clinics conducted their own improvement initiatives . They summarize many of the key design shortcomings in the existing evidence base and note that their own study would have reported ( and attributed to the intervention ) statistically significant improvements in 2 key measures in the absence of comparison group data . L and on and colleagues thoroughly discuss the limitations of their study but note that most seem unlikely to have produced their null results . Unfortunately , the data collected do not provide the information needed to underst and and explain their findings . For example , the intervention sites may not have correctly diagnosed and understood the causes of targeted quality problems and may not have developed or fully implemented appropriate corrective actions . In addition , corrections may not have been sufficient to overcome the full spectrum of barriers to improvement . Thus , although the study by L and on and Step Ahead was a r and omized controlled trial testing ecologically based weight gain prevention interventions in the hospital workplace . The RE- AIM framework is used to assess the intervention ’s Reach , Effectiveness , Adoption , Implementation , and Maintenance . Some intervention components reached a large percentage of the workforce . Although the intervention was not effective in changing BMI on a population level , a dose response was observed , in which persons who used more of the intervention components and material s were more likely to prevent weight gain . Adoption of the intervention by sites invited was 100 % . Implementation of healthy eating interventions in the hospital setting was especially challenging because close collaboration was necessary with hospital employees and contractors , and their mission and priorities often were at odds with the intervention goals . There are some notable instances of intervention maintenance at the institutional level : Farmers markets have been exp and ed at both sites since the end of the intervention period , and new wellness programs are being adopted and implemented . Implication s for practice include the translation of this research into other workplace setting Objective : Process evaluation of a worksite intervention in which employees were offered $ 750 to complete a cessation program and to quit smoking . Methods : Awareness and attitudes about financial incentives were assessed following a r and omized controlled trial of 878 smokers at a US-based company . Results : Cessation program attendance was higher in incentive group versus control ( 20.2 % vs 7.1 % , P < 0.01 ) . Most quitters ( 69.8 % ) in the incentive group who were already motivated to quit and reported that they would have quit for less money , said incentives were “ not at all ” or only “ somewhat ” important . Most nonquitters in the incentive group reported that even $ 1500 would not have motivated them to quit . Conclusions : Financial incentives are ineffective at motivating some smokers to quit . Internal motivation and readiness to quit need to be sufficiently high for relatively modest incentives to be effective BACKGROUND 5 a Day for Better Health is a simple message encouraging people to eat more fruits and vegetables . The Seattle 5 a Day worksite investigators design ed and evaluated an intervention , organized on stages of behavioral change , to increase worksitewide fruit and vegetable consumption . METHODS We recruited 28 worksites with cafeterias and r and omized 14 to intervention and 14 to control . The intervention addressed both changes in the work environment and individual level behavior change . In each worksite , an employee advisory board , with study interventionist assistance , implemented the program . By surveying cross-sectional sample s of 125 employees per worksite , we compared worksite mean fruit and vegetable consumption at 2-year follow-up with that at baseline . Unobtrusive site-level indicators including plate observation and cafeteria checklist were also used . RESULTS The difference at 2 years was 0.5 for the intervention worksites and 0.2 for the control worksites , with an intervention effect of 0.3 daily serving ( P < 0.05 ) . Other measures of fruit and vegetable consumption , including unobtrusive indicators , supported the effectiveness of the intervention . CONCLUSIONS This simple 5 a Day intervention is feasible and acceptable for use in worksites with cafeterias . There was a significant differential increase in fruit and vegetable consumption in the intervention worksites . This kind of worksite intervention can achieve important health benefits on a population basis , because of its potential to reach large numbers of people OBJECTIVE Using a r and omised control trial design , this study assessed the impact of two walking interventions , on the work day step counts and health of UK academic and administrative , university employees . METHOD A convenience sample of 58 women ( age 42+/-10 years ) and 6 men ( age 40+/-11 years ) completed baseline and intervention measures for step counts , % body fat , waist circumference and systolic/diastolic blood pressure , during a ten-week period ( October to December , 2005 ) . Before intervention , baseline step counts ( five working days ) were used to r and omly allocate participants to a control ( maintain normal behaviour , n=22 ) and two treatment groups ( " walking routes " , n=21 ; " walking in tasks " , n=21 ) . Intervention effects were evaluated by calculating differences between pre-intervention and intervention data . A one-way ANOVA analysed significant differences between groups . RESULTS A significant intervention effect ( p<0.002 ) was found for step counts , with mean differences indicating a decrease in steps for the control group ( -767 steps/day ) and increases in the " walking routes " ( + 926 steps/day ) and " walking in tasks " ( + 997 steps/day ) groups . Small , non-significant changes were found in % body fat , waist circumference and blood pressure . CONCLUSIONS Findings have implication s for work-based physical activity promotion and the development of walking interventions within the completion of work-based tasks The purpose of this study was to evaluate the impact tailored e-mail messages , based on participants ' identified needs , have on intentional physical activity . A quasi-experimental design ( two groups , repeated measures ) in a population of manufacturing workers ( 73 employees from two distribution plants of a multi-national manufacturer ) was used . Significant differences were found between contemplation-staged participants in the intervention and the comparison groups . In the intervention group , 53.3 % of the workers moved forward , as opposed to 19.2 % in the comparison group ( medium effect size = 0.353 ) . Although both the intervention group and the comparison group increased their number of steps , the comparison group 's improvement was most likely attributed to a Hawthorne effect . These results are highly promising given the small sample size and limited " dose " . The intervention is one most industries could feasibly implement . Such efforts have the potential to significantly impact public health Objective : To determine the relation between body mass index ( BMI ) and absenteeism . Methods : Data were collected in a prospect i ve cohort study ( n = 1284 ) . Multilevel analyses ( linear mixed model with r and om intercept ) with two levels ( employee and company ) were used to test whether BMI was related to duration and frequency of absenteeism and whether this relation was influenced by sports participation . Results : Obese employees were absent 14 days a year more than normal-weight employees . Also the frequency of absenteeism of more than 7 days was significantly higher . The differences in absenteeism between obese and normal-weight employees were larger for employees who did not practice sport regularly . Conclusions : Obese employees are more often absent and are absent longer , especially when they do not practice sport regularly . An active company policy to prevent obesity is needed , both from a health and a business efficiency perspective We evaluated a participatory ergonomic intervention process applied in 59 municipal kitchens . In groups of three to five kitchens , the workers participated in eight workshops , and generated and evaluated solutions to optimize musculoskeletal load in their work . An ergonomist initiated and supported the process . By the end , 402 changes were implemented . Evaluative data were collected using research diaries , question naires , and focus group interviews . The intervention model proved feasible and the participatory approach was mostly experienced as motivating . The workers ' knowledge and awareness of ergonomics increased , which improved their ability to tackle ergonomic problems by themselves . The changes in ergonomics were perceived to decrease physical load and improve musculoskeletal health . As hindering factors for implementation , lack of time and motivation , and insufficient financial re sources were mentioned . In addition , the workers expressed a wish for more support from the management , technical staff , and ergonomists OBJECTIVE The results of an 18-month worksite intervention to prevent obesity among metropolitan transit workers are reported . METHODS Four garages in a major metropolitan area were r and omized to intervention or control groups . Data were collected during the fall of 2005 prior to the start of the intervention and during the fall of 2007 , after the intervention ended . Intervention program components at the garage included enhancement of the physical activity facilities , increased availability of and lower prices on healthy vending machine choices , and group behavioral programs . Mixed model estimates from cross-sectional and cohort sample s were pooled with weights inverse to the variance of their respective estimates of the intervention effects . RESULTS Measurement participation rates were 78 % at baseline and 74 % at follow-up . The intervention effect on garage mean BMI change was not significant ( -0.14 kg/m(2 ) ) . Energy intake decreased significantly , and fruit and vegetable intake increased significantly in intervention garages compared to control garages . Physical activity change was not significant . CONCLUSION Worksite environmental interventions for nutrition and physical activity behavior change may have limited impact on BMI among transit workers who spend most of their workday outside the worksite Objectives To present the results of a study of a worksite-based intervention to promote tobacco use cessation and improve weight management among motor freight workers . Methods This study used a pre-test/post-test , non-r and omized design to assess the effectiveness of a four-month intervention that addressed the social context of the work setting . We evaluated 7-day tobacco quit prevalence among baseline tobacco users , and successful weight management , defined as no weight gain in workers with BMI < 25 at baseline and any weight loss among overweight and obese workers . Results At baseline , 40 % were current tobacco users , and 88 % had a BMI of 25 or greater . Of 542 workers invited to participate , 227 agreed to participate and received at least the first telephone call ( 42 % ) . Ten-month post-baseline , baseline tobacco users who participated in the intervention were more likely to have quit using tobacco than non- participants : 23.8 % vs. 9.1 % ( p = 0.02 ) . There was no significant improvement in weight management . Conclusions Incorporating work experiences and job conditions into messages of health behavior change result ed in significant tobacco use cessation among participating motor freight workers The Healthy Directions – Small Business r and omized , controlled study aim ed to reduce cancer risk among multiethnic workers in small manufacturing businesses by increasing fruit and vegetable consumption , physical activity , and daily multivitamin in take and decreasing consumption of red meat . The intervention incorporated participatory strategies and was built on a social- context ual framework that addressed people with varying cultural background s and literacy levels . In addition , the intervention aim ed to reduce worker exposure to occupational hazards . Process evaluation was conductedusing quantitative and qualitative research methods . Quantitative results showed high levels of worker awareness of and participation in programs . Qualitative findings suggested that management support , worker input , and a history of social interaction between workers and management may have contributed to high participation rates . Future studies need to examine characteristics associated with participation and nonparticipation of both managers and nonmanagers to increase the likelihood of participation and ultimately improve health behavior The Seattle 5-a-Day Work-Site Project developed a community-based intervention to increase fruit and vegetable intake , using both environmental ( including cafeteria and work-site-wide events ) and individual strategies . The Employee Advisory Board developed its own protocol from a common skeleton and a minimum set of activities . Small work sites and work sites with fewer female employees delivered more displays , posters , and table tents per employee ( p < .01 and p < .05 , respectively ) . Dose was neither related to use of the intervention nor to change in fruit and vegetable intake . Use of informational material s increased fruit and vegetable intake in the cohort of employees with both baseline and follow-up data ( p≅ .05 ) . The intervention was associated both with increased employee use of the intervention ( activities and material s ) and with increased intake of fruit and vegetables . Work sites with medium average baseline intake were the most responsive . These findings can guide the development of more efficient community-based dietary interventions Objective To evaluate the effectiveness of a draft occupational health practice guideline aim ed at preventing weight gain on employees ' physical activity , sedentary behaviour and dietary behaviour and on body weight-related outcomes . Methods A r and omised controlled trial was performed comparing guideline -based care to usual care among 16 occupational physicians and 523 employees in the Netherl and s between 2009 and 2011 . Occupational physicians in the intervention group followed the draft guideline by providing advice to employers on how to assess and intervene on the obesogenic work environment and conducted five face-to-face behavioural change counselling sessions with employees to improve their lifestyle . Data of employees were collected by question naire and physical measurements at baseline and 6-months follow-up . Linear and logistic regression analyses were performed to determine effects . Results The intervention showed significant effects on sedentary behaviour at work ( β −28 min/day , 95 % CI −2 to −54 ) and on fruit intake ( β 2.1 pieces/week ; 95 % CI 0.6 to 3.6 ) . No significant intervention effects were found for physical activity , sedentary behaviour in leisure time or during weekend days , snack intake and body weight-related outcomes . Conclusion Guideline -based care result ed in a more favourable sedentary behaviour at work and increased fruit intake but did not improve employees ' physical activity , snack intake or body weight-related outcomes . Trial registration number IS RCT N/73545254 and NTR/1190 BACKGROUND Workplaces are important setting s for interventions to increase physical activity , but effects have been modest . PURPOSE To evaluate the efficacy of Move to Improve , a social-ecologic intervention delivered at the workplace to increase leisure-time physical activity . METHODS A group-r and omized 12-week intervention consisting of organizational action and personal and team goal - setting was implemented in Fall 2005 , with a multi-racial/ethnic sample of 1442 employees at 16 worksites of The Home Depot , Inc. Change in physical activity was analyzed in Fall 2007 using latent growth modeling and latent transition analysis . RESULTS Participants in the intervention had greater increases in moderate and vigorous physical activity and walking compared to participants in a health education control condition . The proportion of participants that met the Healthy People 2010 recommendation for regular participation in either moderate or vigorous physical activity remained near 25 % at control sites during the study but increased to 51 % at intervention sites . During the last 6 weeks of the study , intervention participants exceeded 300 weekly minutes of self-reported moderate-to-vigorous physical activity and 9000 daily pedometer steps . CONCLUSIONS The results support the feasibility and efficacy of the Move to Improve intervention and the role of goal - setting for attaining increased physical activity levels Objective : Physical exercise can reduce the prevalence of musculoskeletal disorders , but adherence to exercise is challenging for many employees . This study determines prognostic factors for adherence to workplace exercise . Methods : In Copenhagen , 132 office workers with neck/shoulder pain were r and omized to 2 or 12 minutes of exercise five days a week . Low , medium , and high adherence was defined as performing less than 10 , 10–30 , or more than 30 exercise sessions during the subsequent 10 weeks . Odds ratios ( OR ) for adherence were modeled by logistic regression . Results : Lower adherence to the 10-week exercise program was predicted by poorer psychosocial work environment and lower exercise self-efficacy . A longer exercise program was not associated with lower adherence . Conclusions : Concurrent strategies to improve psychosocial work environment and individual exercise beliefs should be considered when implementing exercise at the workplace Purpose . Evaluate counselors ' adherence to an intervention protocol , counselors ' competence , and the associations between three process indicators and body weight at follow-up in a 6-month individually based lifestyle intervention for construction workers . Design . Process evaluation with qualitative and quantitative data . Setting . Occupational health service . Subjects . A total of 408 male construction workers with an elevated risk of cardiovascular disease received the intervention , and 27 occupational health professionals delivered the intervention . Intervention . Seven counseling sessions , the first during which four prescribed items had to be discussed . Motivational interviewing ( MI ) was used as a counseling technique . Measures and Analysis . The number of sessions and the items discussed were registered by the counselors . Adherence to MI was determined by expert scoring of transcripts of r and om segments of 19 counseling sessions . Counselors ' competence was rated by participants and counselors separately . Associations between three process indicators and body weight at follow-up were determined by linear and logistic regression analyses . Results . Two-thirds of all participants attended five or more sessions , and 38.5 % attended all seven sessions . In 90.2 % of all cases , the counselor discussed all obligatory items in the first session . MI adherence was reached in one audiotaped fragment . Most ( 86.3 % ) of all participants agreed with the counselor being competent . Neither counselors ' competence nor number of sessions or items discussed was significantly associated with body weight loss . Conclusions . Performing five sessions and discussing four prescribed items was feasible for the counselors , whereas performing MI was not . Still , participants were positive about the counselors ' competence and willing to attend the intervention sessions . Investigators are encouraged to report the evaluation of their intervention process to improve future lifestyle interventions in research or in practice This study evaluates the implementation of physical coordination training ( PCT ) and cognitive behavioural training ( CBTr ) interventions in a r and omised controlled trial at nine cleaners ’ workplaces . Female cleaners ( n = 294 ) were r and omised into a PCT , a CBTr or a reference ( REF ) group . Both 12-week interventions were performed in groups guided by an instructor . Records were kept on intervention dose ( adherence ) unanticipated events at the work place ( context ) and quality of intervention delivery ( fidelity ) . Participant adherence was 37 % in the PCT and 49 % in the CBTr interventions . Optimal implementation was reached by only 6 % in PCT and 42 % in the CBTr . Analysis of the barriers to successful implementation indicated that the intervention process is sensitive to unanticipated events . In order to succeed in improving the health of high-risk population s such as cleaners and to correctly interpret intervention effects , more research on implementation is needed . Trial registration : IS RCT N96241850 . Practitioner Summary : Both physical coordination training and cognitive behavioural training are potential effective workplace interventions among low educated job groups with high physical work dem and s. However , thorough consideration should be given to feasibility in the design of interventions . The optimal intervention should be tailored to closely match the implementation context and be robust and flexible to minimise susceptibility to changes in work organisation BACKGROUND The worksite represents a promising venue in which to address the issue of obesity . DESIGN Pair-matched , cluster- RCT . Data were collected from 2005 to 2008 and analyzed in 2008 . SETTING / PARTICIPANTS A r and om sample of 806 employees was selected to represent the workforce of six hospitals in central Massachusetts . INTERVENTION The 2-year ecologic intervention sought to prevent weight gain through changes in worksite weight-related norms using strategies targeted at the organization , interpersonal environment , and employees . MAIN OUTCOME MEASURES The primary outcome was change in BMI at the 12- and 24-month follow-ups . Change in perceptions of organizational commitment to employee health and normative coworker behaviors were secondary outcomes . RESULTS There was no impact of the intervention on change in BMI from baseline to 12 ( beta=0.272 ; 95 % CI=-0.271 , 0.782 ) or 24 months ( beta=0.276 ; 95 % CI=-0.338 , 0.890 ) in intention-to-treat analysis . When intervention exposure ( scale=0 to 100 ) was used as the independent variable , there was a decrease of 0.012 BMI units ( 95 % CI=-0.025 , 0.001 ) for each unit increase in intervention participation at the 24-month follow-up . Employees in intervention sites reported significantly greater improvements in perceptions of organizational commitment to employee health at 12 and 24 months compared to control sites , but there was no impact on perceptions of normative coworker behaviors . CONCLUSIONS The intervention had a dose-response relationship with BMI , with positive effects proportional to extent of participation . Although the intervention was able to change organizational perceptions , successfully improving changes in actual and perceived social norms may be needed to achieve population -level impact in complex worksite organizations |
10,842 | 17,915,541 | Studies using high-rated approaches represent a growing proportion of the job-stress intervention evaluation literature .
Individual-focused , low-rated approaches are effective at the individual level , favorably affecting individual-level outcomes , but tend not to have favorable impacts at the organizational level .
Organizationally focused high- and moderate-rated approaches are beneficial at both individual and organizational levels . | null | null |
10,843 | 19,560,946 | We found that plasma fibrinogen and D-dimer concentrations are likely to be higher in cases with AAA than control subjects .
Higher plasma fibrinogen and D-dimer concentrations may be associated with the presence of AAA | OBJECTIVES To summarise the present evidence for an association between circulating fibrinogen or D-dimer and presence of abdominal aortic aneurysm ( AAA ) presence . | Background Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature . In explant culture , aneurysm biopsies secrete large amounts of interleukin-6 ( IL-6 ) , and among aneurysm patients , the circulating concentration of IL-6 appears to be increased . Methods and Results We investigated , in 19 patients , whether aneurysm wall was an important source of circulating IL-6 . We also tested the hypotheses , in 466 patients with a small aneurysm , that ( 1 ) high concentrations of circulating IL-6 signaled rapid aneurysm growth and ( 2 ) the −174 G→C polymorphism in the IL-6 promoter predicted survival . For 19 patients with large or inflammatory aneurysms , the concentration of IL-6 was higher in the iliac arteries than the brachial arteries ( median difference 26.5 pg/mL , this difference increasing with aneurysm diameter , P = 0.01 ) . In 466 patients with small aneurysms , the frequency of the −174 C allele ( 0.40 ) was similar to that in a normal healthy population . Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes ( medians 1.9 , 4.8 , and 15.6 pg/mL , respectively , Kruskal-Wallis P = 0.047 ) . Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype : hazard ratios 0.32 ( 95 % CI 0.12 to 0.93 ) , P = 0.036 , and 0.51 ( 95 % CI 0.25 to 1.00 ) , P = 0.05 , respectively . There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth . Conclusions Aortic aneurysms appear to be an important source of circulating IL-6 , the concentration being influenced by genotype . For patients with small aneurysms , the −174 G→C IL-6 genotype predicts future cardiovascular mortality The native fibrin gel structure formed in vitro from plasma sample s was examined by liquid permeation of hydrated fibrin gel networks in 38 unselected men who had suffered a myocardial infa rct ion before the age of 45 years and in 88 age-matched population -based control men . Both the fibrin gel porosity ( permeability coefficient , Ks ) and the calculated fiber mass-length ratio varied considerably within the two groups , but were generally lower in the patients . Ks was 8.3 + /- 5.2 cm2 x 10(9 ) ( mean + /- SD ) in the patient group and 12.5 + /- 5.7 cm2 x 10(9 ) among controls ( p < 0.001 ) . The corresponding figures for fiber mass-length ratio were 13.1 + /- 7.7 and 16.5 + /- 7.5 Dalton/ cm x 10(-13 ) , respectively ( p < 0.01 ) . Around 50 % of the patients had Ks values below the 10th percentile of the control group . A strong inverse correlation was seen between plasma plasminogen activator inhibitor-1 ( PAI-1 ) activity and Ks ( r = -0.603 , p < 0.001 ) or fiber mass-length ratio ( r = -0.565 , p < 0.001 ) in the patient group . Corresponding weaker associations of PAI-1 with fibrin gel properties were also present in the control group . In addition , inverse relationships of very low density lipoprotein ( VLDL ) triglyceride concentrations to Ks ( r = -0.362 , p < 0.001 ) and fiber mass-length ratio ( r = -0.283 , p < 0.01 ) were found among the controls . Proneness to formation of tight and rigid fibrin gel networks with abnormal architecture in vitro is in vivo associated with myocardial infa rct ion at a young age . Impaired fibrinolytic function secondary to a raised plasma PAI-1 activity level is associated with abnormal fibrin gel structure Abdominal aortic aneurysms have traditionally been thought to be a consequence of severe atherosclerosis of the arterial wall . To date , the role of haemostatic factors in aneurysmal disease has not been extensively research ed . The aim of this study was to see if such factors were independently related to the occurrence of aortic aneurysm . Furthermore , were the associations maintained after taking into account the presence of underlying atherosclerotic disease ? Using data from the Edinburgh Artery Study , a nested case-control design was used involving 40 cases of aortic aneurysm , each being matched to five controls by sex and within a 5-year age b and . After adjustment for age and sex , both fibrinogen ( P × 0.01 ) and fibrin D-dimer ( P × 0.001 ) were each associated with a significant increased risk of aneurysm . Further adjustment for packyears , history of cardiovascular disease and the ankle brachial pressure index result ed in odds ratios of 1.51 ( 95 % CI 1.05 to 2.16 , P × 0.05 ) for fibrinogen and 3.75 ( 95 % CI 1.80 to 7.82 , P × 0.001 ) for fibrin D-dimer . These associations probably arise as a consequence of fibrin deposition and turnover within the aneurysmal sac , although further prospect i ve studies are needed before thrombotic factors can be used in the identification of a group who are at high risk of developing an abdominal aortic aneurysm OBJECTIVE To assess the incidence of lupus anticoagulant ( LAC ) in patients with peripheral vascular disease . DESIGN Prospect i ve clinical study . SETTING University Hospital . MATERIAL S 20 patients with claudication ( group 2 ) , 20 patients with critical ischaemia ( group 3 ) and 20 patients prior to elective abdominal aortic aneurysm surgery ( group 4 ) were compared to 20 general surgical controls ( group 1 ) . CHIEF OUTCOME MEASURES Venous blood sample s for coagulation assay . MAIN RESULTS Positive results for LAC by the Dilute Russell 's viper venom time ( DRVVT ) with the platelet neutralisation procedure were present in 26 out of 60 vascular patients compared with none of the 20 general surgical controls . The three vascular groups showed a similar prevalence of LAC and this differed significantly from that in the control group ( chi 2 = 10.94 , p = 0.0009 ) . Of the 26 positive results only three were associated with an abnormal activated partial thromboplastin time ( APTT ) , which has previously been used as a marker for the presence of LAC activity . Fibrinogen levels were raised in seven of 20 patients in group 2 but were normal in the remaining vascular groups ( p = 0.001 ) . The mean factor VII level ( 124.1 units dl-1 ) in group 2 was higher than the mean of the remaining vascular patients ( 109.3 units dl-1 , p < 0.05 ) . CONCLUSIONS The high prevalence of LAC in patients with peripheral vascular disease and the associated increased risk of early graft thrombosis may justify routine testing by DRVVT prior to reconstructive vascular surgery . Treatment of these patients with antiplatelet agents or formal anticoagulation perioperatively should be considered BACKGROUND A ruptured abdominal aortic aneurysm ( AAA ) is associated with high mortality . Postoperative complications such as hemorrhage , multiple organ failure , myocardial infa rct ion , and thromboembolism are common . An active and balanced hemostatic system is essential to avoid bleeding as well as thrombosis . When these activities are not properly regulated the patient is at risk of developing either excessive bleeding or thrombosis-related complications . Previous studies have shown a state of activated coagulation in patients with ruptured AAA . However , there are conflicting results regarding the fibrinolytic response . OBJECTIVES The aim of the present study was to investigate the fibrinolytic state pre-operatively in patients with ruptured and non-ruptured AAA in relation to the clinical outcome with special regard to the influence of shock . METHODS A prospect i ve study was performed on 95 patients who underwent surgery for a ruptured AAA with shock ( n = 43 ) , a ruptured AAA without shock ( n = 12 ) , and a non-ruptured AAA ( n = 40 ) . Forty-one controls without an aneurysm were matched to the AAA patients according to age , gender and smoking habits . Plasma levels of tissue plasminogen activator antigen ( tPAag ) , and plasminogen activator inhibitor type-1 ( PAI-1 ) were measured as markers of fibrinolytic activity . D-dimer , a marker of fibrin turnover , was also measured . RESULTS D-dimer was significantly higher in patients with a non-ruptured AAA compared with controls without AAA . There were significantly higher levels of D-dimer , tPAag , and PAI-1 in patients operated for ruptured compared with non-ruptured AAA . tPAag was also significantly higher in ruptured AAA patients with shock compared with without shock . No deaths occurred in patients operated on for a non-ruptured AAA or ruptured AAA without shock . There were 12 deaths after repair of a ruptured AAA with shock , of which two patients died from bleeding and the remaining 10 from multiple organ failure and cardiac failure . CONCLUSION Our results indicate a state of activated coagulation in patients with a non-ruptured AAA , the state being intensified by rupture . The present data show normal fibrinolytic activities in patients with a non-ruptured AAA , but increased systemic fibrinolysis , as demonstrated by elevated tPAag level , in patients with a ruptured AAA . The elevated PAI-1 level indicates a simultaneous inhibition of the systemic fibrinolysis . Furthermore , the hyperfibrinolytic state was reinforced by shock in this study . However , the clinical outcome , with a relatively high incidence of thrombosis-related deaths , indicate a prothrombotic state instead of a hyperfibrinolytic state as a major point of attention in patients with shock as a result of a ruptured AAA OBJECTIVES the aim of the study was to determine the effects of infrarenal asymptomatic abdominal aortic aneurysm ( AAA ) on platelet count and activation . DESIGN prospect i ve clinical study in a University Department of Vascular Surgery . PATIENTS one hundred and five patients with AAA . Thirty-two control patients with symptomatic carotid artery stenoses . METHODS platelet count ( PC ) , plasma glycocalicin levels , prothrombin ratio ( PTR ) , activated partial thromboplastin time ( APPT ) , fibrinogen and D-dimer were measured in 23 patients with AAA and 16 control patients with symptomatic carotid artery stenoses . PC alone was measured in a further 84 patients with AAA and 16 with carotid artery stenoses . RESULTS PC was below the normal range in 8/105 patients and mean PC ( 215x10(9)/l , S.D. 47.5 ) was significantly lower than that of a control population ( 242x10(9)/l , S.D. 16.8 ) and patients with carotid disease ( 269x10(9)/l , S.D. 57 ) . Glycocalicin level was above the normal range in 7/23 patients and the median level ( 28 fg/plt ) was significantly higher than that of a normal population ( 21.6 fg/plt ) and patients with carotid disease ( 12.3 fg/plt ) . Fibrinogen levels , PTR and APPT were all within the normal range . One patient had a minimally elevated level of D-dimer . CONCLUSIONS the combination of low PC and high glycocalicin levels suggests that there is increased platelet destruction , most likely due to activation within the aneurysm sac |
10,844 | 28,127,931 | We found that professional help for mental disorders generally enjoys high esteem .
If respondents have to rank sources of help , they tend to favor mental health professionals , while open questions yield results more favorable to general practitioners .
Psychiatrists and psychologists/psychotherapists are equally recommended for the treatment of schizophrenia , while for depression psychologists/psychotherapists are more recommended , at least in Europe and America .
Psychotherapy is consistently preferred over medication .
Attitudes towards seeking help from psychiatrists or psychologists/psychotherapists as well as towards medication and psychotherapy have markedly improved over the last twenty-five years .
Biological concepts of mental illness are associated with stronger approval of psychiatric help , particularly medication .
Self-stigma and negative attitudes towards persons with mental illness decrease the likelihood of personally considering psychiatric help .
In conclusion , the public readily recommends psychiatric help for the treatment of mental disorders .
Psychotherapy is the most popular method of psychiatric treatment . | Public attitudes towards psychiatry are crucial determinants of help-seeking for mental illness .
It has been argued that psychiatry as a discipline enjoys low esteem among the public , and a " crisis " of psychiatry has been noted .
We conducted a systematic review and meta- analysis of population studies examining public attitudes towards various aspects of psychiatric care .
While general practitioners are the preferred source of help for depression , mental health professionals are the most trusted helpers for schizophrenia . | AIMS The aim of the study was to investigate preferences in the general population regarding type of treatment for alcohol problems and the preferred setting for delivery of treatment and reasons for not seeking treatment for alcohol problems . METHOD Data were from a r and om , cross-sectional , interview survey of 9005 of the Swedish general population . Proportions of respondents preferring a certain treatment and source of treatment , and reasons suggested for why people do not seek treatment , were analysed in relation to number of st and ard drinks , employment status , education and income . RESULTS Most frequently endorsed forms of treatment were alcoholics anonymous or similar support groups and psychotherapy . More than 50 % preferred psychiatric or addiction specialist treatment . Around 10 % preferred primary health care and around 20 % the occupational health services . About 5 % preferred the social services . Respondents rated ' feeling ashamed ' as the most important reason why people would not seek help for alcohol problems . CONCLUSION Large majorities of the respondents preferred treatment in the health care services and few in the social services . Internet-based treatment and pharmacological treatment attracted few respondents , the majority preferring more traditional forms of treatment . Alcohol treatment remains a stigmatized field , evidence d by shame being the most commonly reported reason for not seeking treatment Background : Public attitudes towards a given medical procedure can have a significant influence on the employment of that method . Electroconvulsive therapy ( ECT ) is a medical procedure that has received an exceptionally ambiguous public reception since its inception . Aim : To survey the level of information about and attitudes towards ECT in a general population sample of the Chuvash Republic of the Russian Federation . Methods : A r and omly selected cohort of 5,373 people was contacted by telephone . The respondents were asked three closed and three open questions . Results : The response rate was 74.7 % . Only 35.2 % of those interviewed said they knew anything about ECT . Health professionals and younger respondents were better informed . The two main sources of information about ECT were foreign films and the mass media . The main indication of ECT was thought to be schizophrenia . The majority ( 63.3 % ) of the respondents had negative opinions and emotions about ECT . Conclusion : Limited information about and generally negative attitudes towards ECT were found in the general population of the Chuvash Republic . Gender , age , education level , employment in the health industry , and information source were found to be the determining factors in the knowledge of and attitudes towards ECT Objective It is often assumed that individual stigmatizing attitudes toward the mentally ill are linked to stigmatizing attitudes in the social milieu and that both , individual and social stigmatizing attitudes are major barriers to mental health treatment seeking . This study aims to examine these assumptions . Method Data from the 2005–2006 Eurobarometer general population survey ( N = 29,248 ) are used to examine the association of social stigmatizing attitudes assessed in a r and om half of the sample with individual stigmatizing attitudes assessed in the other half of the sample , and to examine the association of both individual and social stigmatizing attitudes with willingness to seek professional help . Results Social stigmatizing attitudes are specifically and strongly associated with individual stigmatizing attitudes . Both social and individual stigmatizing attitudes are associated with willingness to seek professional help . Believing the mentally ill to be dangerous or not likely to recover , or living in a community with such beliefs , are associated with increased willingness to seek help ; whereas , believing the mentally ill to be unpredictable or blameworthy for their illness , or living in a community with strong beliefs in blameworthiness of the mentally ill , are associated with decreased willingness to seek professional help . Conclusion The view that all stigmatizing attitudes toward mental illness are associated with reluctance to seek professional help may be naive as some stigmatizing attitudes may be associated with increased willingness to seek help . The complex association of different stigmatizing attitudes with professional help seeking should be carefully considered in planning anti-stigma campaigns Objective : We investigated the lay public 's attitudes toward help seeking and preferences for treatment of Alzheimer 's disease ( AD ) in the city of São Paulo , Brazil . Method : Cross-sectional population -based r and om sample of 500 household residents over 18 years old participated in face-to-face interviews in São Paulo , which included a case vignette depicting AD and a structured question naire . Results : Public opinion rests firmly in the lay support system . Psychologists and self-help groups and close relatives were often rated as helpful . Many alternative treatments ( such as vitamins , physical exercise , vacation ) were often rated as helpful . Limited education , younger age and experience with psychiatric problems are associated with the ‘ medical ’ intervention model . Female sex and middle age are associated with ‘ alternative ’ interventions . Conclusion : Our results suggest that attitudes and belief systems have an important impact on help-seeking and treatment recommendations Objective . Public social policies in New Zeal and assume that there are fundamental differences between Maori views of health phenomena and non‐Maori perceptions . The biomedical model and a Maori model known as Te Whare Tapa Wha are commonly employed to characterise these differences . Using the categorical ethnicity demarcation ‘ Maori/non‐Maori ’ we investigate this cl aim with respect to mental health literacy about depression . Design . Participants were r and omly selected from the General and Maori Electoral Rolls and recruited by post ( N=205 ) . A vignette methodology was employed and involved the development of a fictional character as a target stimulus who exhibited the minimum DSM‐IV‐R criteria for a major depressive disorder . Participants responded to items regarding problem recognition , well‐being , causal attributions , treatment preferences , and likely prognosis . Results . The majority of Maori and non‐Maori participants correctly identified the problem the vignette character was experiencing and nominated congruent attributions for the causes of the problem . In relation to treatment strategies and likely prognosis , independent of self‐assigned ethnicity , participants rated professional treatments above alternative options . Overall the categorical ethnicity distinction ‘ Maori and non‐Maori ’ produced no systematic variation with regards to individual evaluative responses about a major depressive disorder . Conclusions . Contrary to the embedded assumption within New Zeal and 's public health strategies that there are essential differences between the way Maori and non‐Maori view health problems , and that the categorical ethnicity demarcation reliably reflects these differences , we found no evidence for the veracity of this cl aim using a major depressive disorder as a target for judgements . Alternative explanations are canvassed as to why this assumption about fundamental differences based on categorical ethnicity has gained ascendancy and prominence within the sphere of New Zeal and health OBJECTIVE Stigma associated with mental illness continues to be a significant barrier to help seeking , leading to negative attitudes about mental health treatment and deterring individuals who need services from seeking care . This study examined the impact of public stigma ( negative attitudes held by the public ) and internalized stigma ( negative attitudes held by stigmatized individuals about themselves ) on racial differences in treatment-seeking attitudes and behaviors among older adults with depression . METHOD R and om digit dialing was utilized to identify a representative sample of 248 African American and white older adults ( older than 60 years ) with depression ( symptoms assessed by the Patient Health Question naire-9 ) . Telephone-based surveys were conducted to assess their treatment-seeking attitudes and behaviors and the factors that impacted these behaviors . RESULTS Depressed older adult participants endorsed a high level of public stigma and were not likely to be currently engaged in or did they intend to seek mental health treatment . Results also suggested that African American older adults were more likely to internalize stigma and endorsed less positive attitudes toward seeking mental health treatment than their white counterparts . Multiple regression analysis indicated that internalized stigma partially mediated the relationship between race and attitudes toward treatment . CONCLUSION Stigma associated with having a mental illness has a negative influence on attitudes and intentions toward seeking mental health services among older adults with depression , particularly African American elders . Interventions to target internalized stigma are needed to help engage this population in psychosocial mental health treatments OBJECTIVE To identify changes in mental health literacy in regard to depression between 1998 and 2004 . DESIGN AND SETTING Face-to-face interviews with a r and om and representative sample of the South Australian population in 2004 , compared with a similarly conducted survey in 1998 that used the same vignette , questions and methodology . PARTICIPANTS 3015 r and omly selected participants , aged 15 years and over . MAIN OUTCOME MEASURES Responses to both open-ended and direct questions about symptoms and treatment options for depression . RESULTS The 3015 interviews conducted represented a response rate of 65.9 % . Compared with 1998 , in 2004 there was a significant increase in the proportion of people recognising depression in the vignette , acknowledging personal experience of depression , and perceiving professional assistance to be more helpful and less harmful . However , although more people nominated psychiatrists or psychologists as therapists of choice , the difference between 1998 and 2004 was not significant . CONCLUSIONS There has been a significant increase in mental health literacy , at least as regards depression , in the South Australian community between 1998 and 2004 . The lack of significant change in psychiatrists and /or psychologists being perceived as therapists of choice is of concern and suggests that community education about their expertise may be appropriate Background Mental ill health is a common condition in the general population , yet only about half of those with a mental disorder have treatment contact . Personal experience may affect attitudes , which in turn influence the help-seeking process . This study investigated differences in mental health literacy and attitudes among mentally healthy persons and in persons with symptoms of mental illness with and without treatment contact . Method A postal screening question naire was sent to a r and om sample of the general population aged 20–64 in the county of Skaraborg , Sweden in order to ascertain mental health status and history of treatment contact ; 3538 responded ( 49 % ) . Face-to-face interviews were carried out in r and om sub sample s of mentally healthy persons ( n = 128 ) and in mentally ill persons with ( n = 125 ) and without ( n = 105 ) mental health care contact . Mental health literacy and attitudes to treatment were assessed using questions based on a vignette depicting a person with depression . Past month mental disorder was diagnosed according to the Schedule for Clinical Assessment in Neuropsychiatry ( SCAN ) . Results Two thirds failed to recognize depression in a vignette ; recognition was equally poor in mentally healthy persons and in persons with symptoms of mental illness with and without treatment contact . In response to an open-ended question concerning appropriate interventions , one third suggested counselling and only one percent proposed antidepressant treatment . Again , proportions were similar in all groups . Persons with a history of mental health contact more often suggested that a GP would provide the best form of help . When presented with a list of possible interventions , those with a history of mental health contact were more positive to medical interventions such as antidepressants , hypnotics , and inpatient psychiatric treatment . When asked about the prognosis for the condition described in the vignette , persons with treatment contact were less likely to believe in full recovery without intervention ; mentally ill without treatment contact were more optimistic . Conclusion Mental health literacy , specially concerning attitudes towards interventions is associated with personal history of mental health care Objective A community survey evaluated whether the development of a shared mental health care intervention had an impact on health care perceptions and mental health status of subjects with common mental health problems ( MHP ) . Methods Adults < 70 years old with common MHP ( DSM-IV/CIDI-SF major depressive disorder , generalized anxiety or MHI-SF 36 psychic distress diagnoses ) , were r and omly drawn from the general population in the intervention area ( IA , n = 349 ) and in a control area ( CA , n = 360 ) , and evaluated twice at an interval of 18 months ( percentage of follow-up : IA = 69.3 % , CA = 71.9 % , P = .44 ) . CA and IA groups did not differ for the criteria of interest at baseline . Results At 18 months , compared to CA , IA reported significantly different help-seeking attitudes or behaviours ( P = .02 for all subjects and .006 for subjects with current MHP ) and greater general satisfaction with care ( P = .03 for both ) . Remission rates and daily life functioning did not differ . Conclusions After 4 years of development of a mental health network based on a consultation-liaison model , Shared Mental Health Care was associated with greater satisfaction and access with care among subjects with common MHP . The association was not found with mental health status , but the study lacked power to adequately address the issues BACKGROUND Most studies showed that patients would first go to their primary care physicians ( PCPs ) when depressed . This choice is probably due to PCP being the entry point into the health care system . We studied the general population 's initial choice of mental care in Hong Kong , where patients were unclear about family medicine and free to choose doctors of any specialty . METHODS A combined qualitative and quantitative approach was adopted . We held focus groups with participants recruited from community centers and a telephone survey with adults ages 18 or above r and omly selected from the domestic telephone directory . RESULTS Of 1,647 adults successfully interviewed , 49.0 % would seek help from their regular PCP , 19.3 % from psychiatrists , 4.8 % from any doctors , 16.5 % from non-medical re sources ; 6.9 % would not seek any help , and 3.5 % were uncertain of what to do . Those who did not seek any help were more likely to be male or without regular doctors . The focus group participants highlighted the stigmatizing effect of consulting psychiatrists and expressed strong expectation of empathic relationship , time , and communication skills from their care providers . Some participants were not aware that PCP could manage mental illness . CONCLUSIONS Given free choice of health care service , most people would first consult their regular doctors for treatment of depression specifically because of better relationship and no stigmatization . To draw depressed patients to seek help , especially from primary care , public education of the PCPs role in mental health should be promoted , and the PCPs could demonstrate their empathy and listening skills to patients Background : Studies have shown that many drugs have a lower effectiveness in clinical practice than would be expected from results reported in r and omised controlled clinical trials . Many factors influence the use of drugs . Personal factors such as knowledge , attitudes , motivation , expectations are considered to be of particular consequence . The aim of the study was to analyse attitudes towards drugs from an epidemiological perspective . Design : Cross-sectional survey Setting : The county of Uppsala , Sweden , 1995 . Results : 5,404 completed the question naire ( response rate=68 % ) . A majority either considered drugs as something positive , a help ( 60 % ) , or as something necessary but evil ( 38 % ) . A small proportion — around 2 % — considered drugs as a danger . There were differences in attitudes according to education and income , self-care orientation , medication knowledge , and state of health . We also found differences in attitudes between users and non-users of certain types of drugs . Users of hypertensive drugs more often considered drugs as necessary but evil than did non-users of these drugs , while users of psychotropic drugs more often viewed drugs as something positive than did patients who did not use psychotropic drugs . Conclusion : A better underst and ing of the general attitudes towards drugs is important when giving both written and oral information to patients and to the public at large . It is also important to be aware of differences in attitudes between various patient groups and that certain patients , e.g. , patients prescribed hypertensive drugs , could require more attention from health care professionals Objective : To assess the public 's knowledge about depression , attitudes toward treatments for depression , perceived causal factors for depression , and reported prognoses of depression , overall and by sex . Methods : We conducted a cross-sectional telephone survey in Alberta between February and June 2006 . We used a r and om phone number selection procedure to identify a sample of adults in the community ( n = 3047 ) . Participants were presented with a vignette describing an individual with depression and then asked questions to assess recognition of depression , attitudes toward mental health treatments , possible causal factors for depression , and prognosis of depression . Results : The response rate was 75.2 % . Among the final participants , 75.6 % could correctly recognize depression described in a case vignette . General practitioners or family doctors were considered as being the best help for depression . Of the participants , 35 % were in complete agreement with health professionals about appropriate interventions for depression , 28 % believed in dealing with depression alone , and 43 % thought that “ weakness of character ” was a likely cause of depression . Men had poorer mental health literacy than women and were more likely to endorse the use of alcohol to cope . Conclusions : Mental health promotion and education efforts are needed to improve the general public 's mental health literacy and to clarify misunderst and ing about depression . Men need to be a particular target of these efforts OBJECTIVES To determine the degree of recognition and underst and ing of depression and its treatments in Australia in 2001 , and detail factors and personal experiences that influence awareness of and attitudes to depression . DESIGN AND SETTING Cross-sectional survey of a representative community sample ( 900 r and omly selected respondents ) , via telephone interview , conducted 5 - 7 October 2001 . MAIN OUTCOME MEASURES Reports of community awareness , knowledge and attitudes to depression and its treatments in Australia . RESULTS The Australian community does not view mental health as a major general health issue . When asked specifically , depression was recognised as the most common mental health problem . Recognition of depression was greater among women and younger people . Most people ( 58 % ; 508/879 ) reported that they or a family member had experienced depression . People younger than 55 years and people with personal or family experiences of depression viewed depression as more disabling than other chronic medical conditions . Half the respondents differentiated depression from normal sadness . Awareness of common risk versus protective factors was limited . Most people endorsed a preference for self-help and non-pharmacological treatments , but community views of antidepressant drugs were less negative than expected . General practitioners were identified as the preferred point of first contact among healthcare professionals . CONCLUSIONS Although mental health is still not highlighted as a major health issue , Australians do recognise depression as the major mental health problem . Women and younger people have more substantial knowledge about key aspects of depression and its treatments In Icel and , antidepressant sales figures rose from 8 Defined Daily Doses ( DDD ) per 1000 subjects in 1975 to 95 DDD/1000 in 2005 . The aim of the study was to examine the views of adult Icel and ers on antidepressant treatment and to identify the factors most influential in shaping their views , using cross-sectional national survey of views on antidepressant treatment in a r and omly drawn sample of 2000 Icel and ers aged 18–80 years old . Nine in 10 responders believed that regular exercise is an efficacious treatment for depression ( 92.6 % ) but supportive interviews came second ( 82.3 % ) . Seven out of 10 believed that antidepressants are efficacious and the same proportion was willing to use antidepressants as a treatment for depression . The strongest predictor of this inclination was previous use of antidepressants ( odds ratio , OR=6.9 , 95 % CI 3.4–13.8 ) , followed by knowing someone well who had been treated with antidepressants ( OR=2.3 , 95 % CI 1.6 to 3.3 ) . Eight out of every 100 responders were taking antidepressants and further 8.3 % had previously been on antidepressants for at least 6 weeks . Among past users of antidepressants , 77 % felt that the benefits of therapy had outweighed the disadvantages . More knowledge on antidepressants was associated ( chi-squared test=9.96 , df=2 , P=0.007 ) with willingness to use them . The majority of adult Icel and ers are willing to use antidepressants for depression . The factors influencing their views most strongly are subjects ’ own experience and the experience of close friends or relatives as users OBJECTIVE Research has shown that people are reluctant to seek professional help for depression , especially from mental health professionals . This may be because of the impact of stigma which can involve people 's own responses to depression and help-seeking ( self stigma ) as well as their perceptions of others ' negative responses ( perceived stigma ) . The aim of this article was to examine community help-seeking intentions and stigmatizing beliefs associated with depression . METHOD A total of 1,312 adults r and omly sample d from the Australian community completed a question naire providing a depression vignette and measures of self- and perceived-stigmatizing responses , source -specific help-seeking intentions , current depressive symptoms and depression experience , and demographics . RESULTS Many people reported they would feel embarrassed about seeking help from professionals , and believed that other people would have a negative reaction to them if they sought such help . Some expected professionals to respond negatively to them . Responses varied according to the sources of professional help . Self-embarrassment and expectations that others would respond negatively predicted the likelihood of help-seeking from professional sources . CONCLUSION Self- and perceived-stigmatizing responses to help-seeking for depression are prevalent in the community and are associated with reluctance to seek professional help . Interventions should focus on minimizing expectations of negative responses from others and negative self-responses to help-seeking , and should target younger people BACKGROUND Depression has been traditionally considered to increase with age , although that may be due to sampling of those who have presented with depressive conditions . It is now recognised that patients ' underst and ing of depression and beliefs about its appropriate treatment , mental health literacy , influences treatment-seeking behaviour . OBJECTIVES This study delineates depression , recent use of health services and mental health literacy in a r and om and representative community sample of younger and older South Australians . METHODS Depression , health service utilisation and mental health literacy were assessed in a r and om and representative sample of 2010 South Australians . Results for those aged between 65 and 74 years ( n=300 ) and those aged 15 to 24 years ( n=521 ) were compared . RESULTS Compared with the younger group , older subjects did not report greater levels of current depression although they were more likely to have seen a medical practitioner in the last 12 months and be taking antidepressants . However , their mental health literacy in terms of recognition of a mental health problem in a vignette was somewhat poorer and fewer recommended treatment from a counsellor , telephone service or psychologist and more considered that a psychiatrist would be harmful . They also more often perceived the clergy as helpful . CONCLUSIONS Depression was not more common among older than younger members of the community . Despite recognising depression in a vignette less often and perceiving less likelihood of help from several different mental health professionals , those in the older group were more likely to receive antidepressant medication and to have recently consulted a medical practitioner The underutilization of professional care is a perennial problem among Chinese population s. To examine the social-cognitive factors that may affect help-seeking intentions , the present study applied and extended Ajzen ’s theory of planned behavior ( TPB ) to underst and the intention to seek help from mental health professionals among Chinese . The effect of mental health and perceived barriers to help-seeking were also examined . Nine hundred and forty-one Chinese were recruited using a r and omized household design in Hong Kong . Results from structural equation modeling showed that attitude , subjective norm , perceived behavioral control , and perceived barriers significantly predicted help-seeking intention . Mental health showed no significant effect on help-seeking intention . In addition , subjective norm indirectly predicted intention to seek help from mental health professionals through influencing attitude and perceived behavioral control . Results from multi-group analyses revealed that all path coefficients were invariant across gender . Results supported the utilization of TPB in underst and ing help-seeking intentions and highlighted the importance of subjective norm among Chinese . Implication s on the enhancement of mental health awareness and the promotion of mental health services through a social-cognitive approach were highlighted OBJECTIVES The aim of this study was to assess the awareness of , and attitudes to , mental health issues in rural dwelling Queensl and residents . A secondary objective was to provide baseline data of mental health literacy prior to the implementation of Australian Integrated Mental Health Initiative -- a health promotion strategy aim ed at improving the health outcomes of people with chronic or recurring mental disorders . METHOD In 2004 a r and om sample of 2 % ( 2132 ) of the estimated adult population in each of eight towns in rural Queensl and was sent a postal survey and invited to participate in the project . A series of questions were asked based on a vignette describing a person suffering major depression . In addition , questions assessed respondents ' awareness and perceptions of community mental health agencies . RESULTS Approximately one-third ( 36 % ) of those surveyed completed and returned the question naire . While a higher proportion of respondents ( 81 % ) correctly identified and labelled the problem in the vignette as depression than previously reported in Australian community surveys , the majority of respondents ( 66 % ) underestimated the prevalence of mental health problems in the community . Furthermore , a substantial number of respondents ( 37 % ) were unaware of agencies in their community to assist people with mental health issues while a majority of respondents ( 57.6 % ) considered that the services offered by those agencies were poor . CONCLUSION While mental health literacy in rural Queensl and appears to be comparable to other Australian regions , several gaps in knowledge were identified . This is in spite of recent widespread coverage of depression in the media and thus , there is a continuing need for mental health education in rural Queensl and OBJECTIVE To determine whether the prevalence of depression , its associated quality of life , treatment and mental health literacy about depression varied according to accessibility to health services . DESIGN Face-to-face interviews with a r and om and representative sample of the South Australian population ( aged > or= 15 years ) were conducted between March and June 2004 , with the respondents stratified using the Accessibility and Remoteness Index of Australia into categories of ' highly accessible ' , ' accessible ' , and ' moderately accessible and remote ' . RESULTS From 4700 households selected , 3015 participants were interviewed ( 65.9 % response rate ) . The prevalence of major depression and other depressions was not significantly different between each of the categories , although there was a trend for those from moderately accessible and remote areas to be less depressed overall . A significantly lower proportion of respondents from moderately accessible and remote locations reported that they had family or close friends who had suffered from symptoms consistent with depression , or that they had ever had treatment for those symptoms . However , there was no significant difference between the groups in those who had ever had or who were currently taking antidepressant medication . For those who were depressed , a significantly higher proportion from the accessible , and moderately accessible and remote regions had seen a community or district health service , social worker or other counsellor as compared with those from the highly accessible area . CONCLUSIONS These findings indicate that depression is no more prevalent in less accessible regions of South Australia , and that when it is present , its treatment , in terms of antidepressants , which can be considered as a proxy marker for the overall management of depression , is similar to treatment in more accessible areas Over the years a lot of research of attitudes towards mental disorders , towards people with mental illness and towards psychiatric services and treatment have shown a persistent negative attitude . There are , however , few studies on changes over time . The aim of this study was to compare responses to a question naire on attitudes towards mental disorders and psychiatric patients and the perception of psychiatric treatment in a community in northern Sweden in 1976 and 2003 . In 1976 a r and om sample of 391 persons 18–70 years of age were asked and in 2003 a new sample of 500 persons from the same community were approached with the same questions . There are considerable changes over time . In 2003 , almost 90 % agree to the statement that mental illness harms the reputation more than physical illness , compared with 50 % in 1976 . In 2003 , 51 % agreed to the statement “ Most people with mental disorders commit violent acts more than others ” compared with 24 % in 1976 . There is an apparent ambivalence towards psychiatric treatment . Whilst 88 % would advice a person with mental problems to contact a psychiatrist , still 26 % would not like themselves to be referred to a psychiatrist . We argue that improving treatment methods is as important as changing attitudes through accurate information Mental health literacy is the knowledge and beliefs about mental disorders that aid in their recognition , management , or prevention ; it is also a determinant of help seeking . As such , it is presumed to be important in community suicide prevention programs . In Australia there have been a number of government , professional , and charitable organizations as well as pharmaceutical company suicide prevention initiatives which have been design ed to enhance public and professional knowledge about mental disorders , particularly depression . This naturalistic study conducted between 1998 and 2004 in a r and om and representative population sample examined the changes in mental health literacy and treatment seeking of those with major depression , both with and without suicidal ideation , and those who were neither depressed nor suicidal . Results indicated that there was marked improvement in mental health literacy for all three groups , although there was less change for those most in need of intervention ( i.e. , those with major depression and suicidal ideation ) . Furthermore , there were fewer changes in appropriate treatment seeking in those with major depression and suicidal ideation . These findings are consistent with literature reporting limited problem solving and decision making in those who are suicidal , and indicate that there are limits to broadbased community education programs . More focused suicide prevention initiatives are required , specifically for those who are depressed and suicidal |
10,845 | 12,214,838 | In conclusion , there is weak and unreliable evidence that ice chips prevent mucositis .
There is evidence that prophylactic use of antifungal agents , which are absorbed or partially absorbed from the gastrointestinal tract , reduce the clinical signs of oral c and idiasis | The objectives of this study were to determine whether oral prophylactic agents are superior to placebo or no treatment on the incidence of oral mucositis and oral c and idiasis for patients with cancer . | Painful oral mucositis is a common complication after bone marrow transplantation ( BMT ) . Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium . This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT . Glutamine or a placebo ( glycine ) were administered from admission until day + 28 in 193 BMT patients in a r and omized , double-blind , placebo-controlled study at a dose of 1.0 g amino acid/m2/dose swish and swallow four times a day . In autologous BMT patients ( n = 87 ) glutamine was associated with significantly less mouth pain by self report and by opiate use ( 5.0 ± 6.2 days of morphine for glutamine vs 10.3 ± 9.8 days for placebo ; P = 0.005 ) . Matched sibling BMT patients had no effect by self report and an increased duration of opiate use ( 23.2 ± 5.7 days for glutamine vs 16.3 ± 8.3 days for placebo ) ( P = 0.002 ) . However , day 28 survival of allogeneic patients was improved by glutamine . No significant differences in TPN use , rate of relapse or progression of malignancy , parenteral antibiotic use , acute or chronic GVHD , or days of hospitalization were observed in either autologous or allogeneic recipients . No toxicity of glutamine was observed . We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients , possibly due to interaction with methotrexate The impact of prophylaxis with 400 mg/day fluconazole on fungal colonization at different body sites was assessed in a r and omized , double-blind , placebo controlled study among patients with leukaemia and those undergoing bone marrow transplantation . The study drug was given throughout the period of neutropenia and sample s were obtained at weekly intervals . Of the 23 patients in each group , 11 of those given fluconazole and 12 placebo recipients were colonized at entry . The commonest sites were the oropharynx and rectum and C and ida albicans was the most frequent isolate . Fluconazole led to a marked reduction in colonization by the second week of treatment to 29 % compared with 68 % for those given the placebo . Two-weeks after stopping the study regimen there was little change with yeast being isolated from 33 % and 81 % respectively . Fluconazole was particularly effective in reducing the carriage of C. albicans in the oropharynx from 46 % to 0 - 10 % and in maintaining this throughout prophylaxis . Recovery of C and ida ( Torulopsis ) glabrata from the perianal region steadily increased to around 30 % in both patient groups and while C and ida krusei species were found exclusively in patients given fluconazole , other c and ida were more common in the placebo group . These results demonstrate that by rapidly reducing the colonization of the alimentary tract , fluconazole eliminates the major reservoir for infection with yeasts other than C. glabrata and C. krusei during the critical period of neutropenia Fungal infections are a major problem in patients with hematologic malignancy . Attempts to reduce their frequency with antifungal agents have not been successful . A double-blind , controlled , single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy . Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions . End points were amphotericin B use , fungal infection , stable neutrophil count > 0.5 x 10(9)/L , toxicity precluding further fluconazole use , and death . By Kaplan-Meier estimation , the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole ( P = .003 ) . Also , fluconazole reduced the number of febrile days by 20 % ( P = .002 ) and prevented oropharyngeal c and idiasis ( 1/75 vs. 9/76 , P = .018 ) . The frequency of deep mycoses ( 8/76 vs. 8/75 ) and outcome were unaffected . Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia ( P = .01 ) Oropharyngeal c and idiasis is frequently a complication of patients with altered immune states . Clotrimazole troches are effective in the treatment of C and ida and were evaluated in this study in a prophylaxis regimen . Patients with malignant neoplasms who were receiving chemotherapy and renal transplant recipients who were receiving immunosuppressives were r and omized to receive either clotrimazole ( 10 mg ) or placebo troches three times a day in a prospect i ve , double-blinded study . Eighty-four patients were r and omized into the study , 18 patients with leukemia , 19 patients with malignant neoplasms , and 47 patients with renal transplants . Among all patients , thrush developed in 57 % while receiving placebo compared with 13 % while receiving clotrimazole prophylaxis . Prophylaxis showed significant benefit for the renal transplant recipients and for patients with solid malignant neoplasms , but not for the leukemic patients . Clotrimazole troches are effective in preventing oral c and idiasis in a select group of patients We determined whether ketoconazole prophylaxis might reduce C and ida colonization and infections in adult patients with acute leukaemia . During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily , while 57 patients received placebo in a double-blind , r and omized trial . The duration of severe neutropenia ( granulocytes less than 0.1 x 10(9 ) l-1 ) represented 36 % of the study period in the ketoconazole group and 26 % in the placebo group ( P = 0.043 ) . Although fewer patients presented with positive C and ida surveillance cultures and serological evidence of C and ida infection in the ketoconazole group compared to the placebo group , two c and idaemias and one Trichosporum fungaemia were observed in the ketoconazole group . Moreover , significantly more bacteraemias were noted in the ketoconazole group ( n = 37 ) than in the placebo group ( n = 21 ) ( P = 0.004 ) . Thus , although oral ketoconazole prophylaxis might be associated with less C and ida colonization and fewer seroconversions , it also result ed in more bacteraemias and longer duration of severe neutropenia , suggesting that caution should be exercised when ketoconazole ( or related drugs ) is given to this group of immunocompromised hosts Oral mucositis is a dose-limiting toxicity of intensive chemotherapy . It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia . Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia . It also reduces quality of life . At present , no effective causal prophylaxis or treatment against oral mucositis is established . We performed a prospect i ve r and omised placebo-controlled trial using topical oral r-metHuG-CSF ( filgrastim ) in high- grade lymphoma patients treated according to the B-NHL protocol , which contains high-dose methotrexate and causes severe oral mucositis ( WHO grade s I – IV ) in > 50 % of patients . Between August 1996 and July 1997 , a total of 32 chemotherapy cycles were documented in eight patients ( four male , four female ) . Mucosal erythema and ulceration were recorded . All patients assessed their oral pain and impact on swallowing daily , using a subjective scale from no to maximal discomfort ( 1–10 ) . In addition , oral mucositis was assessed according to the WHO score . Filgrastim was administered in 16 cycles as a viscous mouthrinse ( carboxymethyl- cellulose 2 % , oleum citrii ) 4 × 120 μg/day from days 10 to 16 . Sixteen cycles were given to control patients , of these 14 with placebo , and another two cycles with no treatment . Severe mucositis ( WHO grade III/IV ) was documented in 21 of 32 cycles ( 65.5 % ) . A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo ( P = 0.058 ) , with a reduction of WHO grade IV of 50 % ( four G-CSF vs eight control ) . The number of days in hospital was reduced significantly in the G-CSF group ( P = 0.02 ) . In conclusion , topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis In some clinical situations the endogenous production of glutamine may be insufficient to maintain optimal tissue structure and function such that glutamine becomes a conditionally essential amino acid . Studies in laboratory animals have demonstrated that glutamine supplementation can reduce the incidence and severity of cytotoxic-induced mucositis . This study examined the role of oral glutamine supplementation in the management of mucositis caused by 5-fluorouracil ( 5-FU ) and folinic acid . Twenty-eight patients with gastrointestinal cancers were r and omised to receive 16 g of glutamine per day for 8 days , or placebo , in a r and omised double-blind trial before crossing over to the alternative supplement during the second treatment cycle . The supplement was well tolerated with no apparent adverse effects , but failed to have any significant effect on oral mucositis assessed by the patients or investigator . The possible reasons for this apparent lack of benefit are discussed Disruption of the oral mucosal lining and the lack of normal defense mechanisms predispose bone marrow transplant ( BMT ) patients to life-threatening infections , often caused by oral flora . Chlorhexidine , used as an oral antiseptic , appears promising in limiting oral bacteria and fungi , and therefore , may decrease oral complications associated with BMT . The purpose of this study was to determine in pediatric BMT recipients if a 0.12 % chlorhexidine mouthrinse , used as an adjunct to normal in-hospital oral care regimens , would decrease the severity of oral mucositis as measured by oral ulcerations , bacteremia , and length of hospital stay . Forty-seven pediatric BMT subjects were included in this double-blind study . Subjects were instructed to use 15 ml of a mouthrinse 3 times daily to be swished and gargled for 30 sec. Each subject had 7 oral sites scored for the percentage of ulcerated mucosa twice weekly until day + 35 or hospital discharge or death . Blood was cultured daily during neutropenia . Additionally , the number of days from onset of cytoreduction to hospital discharge or death was recorded for each subject . Alpha was set at .05 . There was no significant difference in the severity of oral ulceration between the chlorhexidine and placebo groups ( P = .18 ) . Chlorhexidine did not reduce the development of bacteremia ( P greater than .5 ) , nor did it significantly decrease the length of hospital stay ( P = .68 ) . ( ABSTRACT TRUNCATED AT 250 WORDS From April 1993 to September 1993 , 15 patients with lymphoid or solid neoplasms underwent 16 non-cryopreserved peripheral stem cell transplantation courses using the ICE ( ifosfamide , carboplatin , etoposide ) program . They were r and omized in a double-blind clinical trial to received oral misoprostol or placebo for mucositis prophylaxis . The active drug or placebo administration began jointly with chemotherapy at day -4 and was continued until day 16 . The mucositis incidence and severity was significantly higher in patients who received misoprostol . We found no differences regarding myelosuppression , infections or other chemotherapy complications . Our results do not support the use of oral misoprostol as administered in this study , for high-dose chemotherapy-induced mucositis prophylaxis Fifty-six untreated patients with acute leukemia ( 38 acute myelogenous leukemia , 16 acute lymphoblastic leukemia , and 2 blast crisis of chronic granulocytic leukemia ) were r and omized on admission to one of three groups -- one to receive oral antic and idal prophylaxis through the period of remission induction chemotherapy with nystatin , another to receive natamycin , and the third to receive no antic and idal prophylaxis . Neither of the first two groups show any advantage over the last and it is concluded that provided gut sterilization regimes are not employed , prophylactic oral antic and idal treatment is of no value in these patients and should be reserved until there is clinical evidence of infection Patients receiving cytotoxic antineoplastic therapy often have treatment-associated stomatitis . A 0.12 % chlorhexidine digluconate mouthrinse was evaluated ( 15 ml , three times a day ) in a prospect i ve , double-blind r and omized trial as prophylaxis against cytotoxic therapy-induced damage to oral soft tissues . Seventy subjects , forty in patients receiving high-dose chemotherapy and thirty out patients receiving high-dose head and neck radiation therapy , were evaluated . Chlorhexidine mouthrinse significantly reduced the incidence of oral mucositis in the chemotherapy group on day 14 ( p less than 0.02 ) and at 1 week follow-up on day 28 ( p less than 0.002 ) . Mucositis in the patients undergoing chemotherapy who received chlorhexidine also resolved more rapidly . Mucositis severity was significantly less compared to the control chemotherapy group on day 14 ( p less than 0.03 ) , day 21 ( p less than 0.04 ) , and on 1 week follow-up ( p less than 0.02 ) . Concomitant trends in the reduction in oral streptococci and yeast were noted in the chemotherapy group receiving chlorhexidine mouthrinse . Although no differences were observed in oral mucositis between the control and chlorhexidine groups of patients undergoing high-dose radiotherapy , similar reductions of oral microflora to those seen in the chemotherapy population were also noted for patients undergoing radiation therapy who received chlorhexidine . Although generally not significant , some increase in gram-negative bacilli was noted in the chlorhexidine-treated patients in both the chemotherapy and radiotherapy groups , but there was no correlation with increased systemic infection . Prophylactic chlorhexidine mouthrinse reduces oral mucositis and microbial burden in patients with cancer undergoing intensive chemotherapy Recently , a r and omised study demonstrated the utility of oral cooling ( cryotherapy ) in the prevention of 5-fluorouracil (5FU)-induced stomatitis . In order to verify these results a confirmatory study , using identical treatment regimen , was initiated . 84 patients treated with a 5-FU-containing regimen were r and omised to a control arm or to receive oral cryotherapy . End point evaluation was obtained by a global assessment of the physician 's judgement and patients ' description of mucositis severity grade d 0 - 4 . Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy ( the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group , P < or = 0.05 ) and all the chemotherapeutic courses ( the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group , P < or = 0.05 ) . In conclusion , the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens Oral mucosal ulceration complicating bone marrow transplantation interferes with patients ' comfort , nutrition and may lead to systemic infection derived from the mouth . The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection . Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis , we performed a r and omized , placebo controlled , double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications . One hundred patients were r and omly assigned to receive either chlorhexidine gluconate 0.12 % mouth rinse or placebo three times daily from the initiation ( day -8 ) of chemoradiotherapy conditioning until day + 35 post-BMT . Chlorhexidine use result ed in a trend toward improved oral hygiene index ( reduced dental plaque ) ( p = 0.06 ) but did not modify the oral mucositis . Patients using chlorhexidine developed a maximum ulceration of 18 + /- 22 % of their oral mucosa , while placebo patients ulcerated 25 + /- 31 % of the mouth . Ulcerative mucositis was significantly worse in adults compared with children , in individuals who received methotrexate for graft-versus-host disease prophylaxis , and was most prominent on non-keratinized epithelium . Overall , there was no clinical ly demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis , controlling oral pain , facilitating oral nutrition , shortening hospital stay , or reducing oral infection with herpes simplex virus . There was a trend toward diminished oral c and idiasis in chlorhexidine users ( p = 0.06 ) . ( ABSTRACT TRUNCATED AT 250 WORDS A total of 202 evaluable cancer patients were r and omly assigned to receive or not receive oral clotrimazole as antifungal prophylaxis during hospitalization . Oropharyngeal c and idiasis occurred in 1 % of the former patients and 27 % of the latter patients ( P less than .00001 ) . C and ida sp were cultured from the initial throat specimens of 53 control patients and 55 patients who received prophylaxis . Oropharyngeal c and idiasis subsequently developed in 2 % of the former patients and 38 % of the latter patients ( P = less than .00001 ) . Oral clotrimazole is an effective agent for prophylaxis of oropharyngeal c and idiasis in susceptible cancer patients Mucositis is a significant dose-limiting toxicity associated with fluorouracil ( 5FU ) , particularly when it is combined with leucovorin . We hypothesized that oral cryotherapy would cause local vasoconstriction and would temporarily decrease blood flow to the oral mucous membranes . If cryotherapy were used during the time of peak serum 5FU levels , then the oral mucous membranes would have less exposure to 5FU and thus develop less mucositis . To test this hypothesis , 95 patients scheduled to receive their first cycle of 5FU plus leucovorin were r and omized to have oral cryotherapy at the time of chemotherapy administration or to serve as a control group . Subsequent mucositis was significantly reduced in the group assigned to receive cryotherapy as judged by the attending physicians ( P = .0002 ) and by the patients themselves ( P = .0001 ) . We now routinely recommend this cryotherapy procedure for our patients receiving daily bolus 5FU plus leucovorin We report a prospect i ve , r and omized , controlled study of antifungal chemoprophylaxis in forty immunocompromised children with hematologic malignancies , receiving respectively itraconazole , ketoconazole , amphotericin-B and no prophylaxis . Fungal isolates from patients ' saliva or stools were obtained from 19/40 patients ( C and ida albicans from 15 patients ) . Disseminated infection was never observed . Fungal isolates were significantly less frequent in the ketoconazole group of patients vs any other group . Systemic antifungal chemoprophylaxis with ketoconazole appears more effective even than the recently introduced itraconazole PURPOSE / OBJECTIVES To test the effectiveness of a nurse-initiated systematic oral hygiene teaching program-PRO-SELF : Mouth Aware (PSMA)-in conjunction with two mouthwashes ( 0.12 % chlorhexidine or sterile water ) in preventing chemotherapy-induced oral mucositis . DESIGN R and omized , double-blind , placebo-controlled , clinical trial . SETTING S 23 outpatient clinics and office practice s in California . SAMPLE 222 patients who were starting a cycle of mucositis-inducing chemotherapy . METHOD Participants were followed over three chemotherapy cycles . All patients were provided the PSMA program . R and om assignment to a mouthwash occurred prior to the development of oral mucositis . Research ers used the Oral Assessment Guide to assess the patients oral cavities monthly ( with the patients cycles of chemotherapy ) and when patients reported any oral changes between cycles . MAIN RESEARCH VARIABLES Type of mouthwash , incidence , days to onset , and severity of chemotherapy-induced oral mucositis . FINDINGS No significant differences existed between the two mouthwashes in regard to incidence , days to onset , and severity of mucositis . CONCLUSIONS Because chlorhexidine ( S20 per pint ) was no more effective than water , a substantial cost savings can be realized by rinsing with water . Interestingly , the PSMA program appeared to reduce the incidence of mucositis from on a prior estimate of 44 % to less than 26 % . IMPLICATION S FOR NURSING PRACTICE A nursing prescription of a systematic oral hygiene program using water as a mouth rinse is cost efficient and may be effective in preventing oral mucositis Nystatin , one million units every four hours , was prospect ively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi : 104 received nystatin and 60 served as controls . Fungal colonization occurred in 68/104 ( 65 % ) nystatin recipients and in 43/60 ( 71 % ) controls . However , nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization . Despite these alterations in colonization profile , 16/104 ( 15 % ) nystatin recipients developed disseminated fungal infections , as compared to 5/60 ( 8 % ) control patients ( 0.5 greater than p greater than 0.1 , N.S ) . Differences in the clinical course of colonized and non-colonized patients were observed . Eighteen of 111 ( 16 % ) colonized patients had afebrile clinical courses as compared to 16/53 ( 30 % ) non-colonized patients ( p less than 0.05 ) . Twenty-nine of 93 ( 31 % ) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 ( 8 % ) episodes in non-colonized patients ( p less than 0.01 ) . Disseminated fungal infections were diagnosed in 19/111 ( 17 % ) of colonized patients , as compared to 1/53 ( 2 % ) non-colonized patients ( p less than 0.02 ) . We conclude that colonized patients are more likely to develop febrile clinical courses , to fail to respond to empiric antibiotic therapy , and to develop disseminated fungal infection . Nystatin altered colonization patterns but did not prevent disseminated fungal infection The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers . The current r and omized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine , nystatin , and saline solution rinses to reduce the findings of oral mucositis , gingivitis , and oral infection . The results of this study did not show a reduction in mucositis with the use of these rinses . However , potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse The effects of chlorhexidine mouthrinses , used as a supplement to mechanical oral hygiene measures , were studied in patients receiving treatment for acute leukemia . Twenty-eight patients were r and omly divided into two groups . During two periods , when the patients were taking medication for the leukemia , one group rinsed with a 0.2 % chlorhexidine solution twice daily and the other group did not . Chlorhexidine had no effects of any clinical significance on parameters such as number of days with fever , number of oral lesions , plaque score , gingival bleeding score , or occurrence of c and idiasis . There was , however , an increased number of patients who had a burning sensation in the mouth , and a tendency toward increased numbers of salivary enterococci , enterobacteria , and /or Pseudomonas in patients who rinsed with chlorhexidine . The results of the present study do not support the use of chlorhexidine mouthrinses in patients who are able to maintain good oral hygiene by mechanical means during their illness A total of 112 cancer patients who could ultimately be evaluated were r and omly assigned in a double-blind study to receive either fluconazole or placebo as antifungal prophylaxis during hospitalization . Thrush , defined by appropriate lesions in the oropharynx and confirmed by scrapings and cultures positive for C and ida species , occurred in 2 % of the 58 patients given fluconazole and in 28 % of the 54 patients given placebo ( P = .0003 ) . C and ida species were cultured from initial throat specimens from 29 patients given fluconazole and from 26 patients given placebo . Oropharyngeal c and idiasis was detected subsequently in 3 % of the former patients and 54 % of the latter patients ( P = .0001 ) . Adverse reactions that were probably due to or aggravated by fluconazole occurred in only four patients and consisted of transient liver function abnormalities in three instances and nausea and vomiting in one . Oral fluconazole is an effective agent for prophylaxis of oropharyngeal c and idiasis in susceptible cancer patients Patients undergoing therapy for metastatic malignancies were r and omly assigned to receive fluconazole or placebo as antifungal prophylaxis . Oropharyngeal c and idiasis developed in 28 % of 54 evaluable patients receiving placebo but in only 2 % of 58 evaluable patients receiving fluconazole ( P = .0003 ) . Among patients receiving placebo , oropharyngeal c and idiasis ( thrush ) occurred in 30 % of those receiving antibiotic therapy and in 44 % of those receiving adrenal corticosteroid therapy . Oropharyngeal c and idiasis developed in 54 % of the placebo patients who were colonized by C and ida sp at the onset of prophylaxis . Fluconazole proved to be effective for prophylaxis of oropharyngeal c and idiasis in susceptible patients and was well tolerated Pursuant to a promising report suggesting that an allopurinol mouthwash could have a protective effect against 5‐fluorouracil (5‐FU)‐induced stomatitis , the authors performed a r and omized , placebo‐controlled , double‐blind , crossover study . Seventy‐seven patients , receiving their first 5‐day course of chemotherapy with 5‐FU ± leucovorin , were assigned to use a mouthwash containing 20 mg of allopurinol or a placebo . The mouthwash was administered every hour for four doses commencing with each chemotherapy dose . The severity of subsequent mucositis was grade d ( on a 0‐4 scale ) by the attending physician and also by a patient‐completed question naire . There was trend toward less mucositis in the placebo group with mean physician‐judged mucositis scores of 1.3 for placebo and 1.8 for allopurinol ( P = 0.07 ) and mean patient‐judged mucositis scores of 1.5 for placebo and 1.9 for allopurinol ( P = 0.15 ) . There were no substantial differences in mucositis attributable to the two mouthwashes in the patients who crossed‐over on their second cycle of chemotherapy . These data demonstrate that the tested allopurinol mouthwash regimen does not offer any protective effect against 5‐FU‐induced mucositis A prospect i ve , r and omized , controlled , double-blind study was performed between 1982 and 1985 to assess the ability of ketoconazole to prevent fungal infections in selected patients with cancer . Fifty-six patients receiving induction chemotherapy for acute leukemia , autologous bone marrow transplant for refractory nonhematopoietic malignant neoplasms , multidrug chemotherapy for malignant lymphoma , or corticosteroids for brain metastases were r and omized to receive either oral ketoconazole , 400 mg/d , or placebo and observed until leukopenia resolved or corticosteroid therapy was stopped . Oral c and idiasis developed in eight ( 28 % ) of 29 patients receiving placebo compared with none of 27 receiving ketoconazole . However , ketoconazole failed to prevent C and ida esophagitis and vulvovaginitis in two patients and one patient , respectively . Furthermore , prophylactic use of ketoconazole did not significantly alter the total number of hospital days , febrile days , or antibiotic days or the requirement for amphotericin B in patients with acute leukemia and autologous bone marrow transplant . Since oral c and idiasis can be successfully managed by several different treatment modalities when it does occur , we do not think that the routine prophylactic use of ketoconazole is justified Stomatitis has been found to be a major dose‐limiting toxicity from bolus 5‐fluorouracil‐based ( 5‐FU ) chemotherapy regimens , despite the use of oral cryotherapy . Pursuant to preliminary data which suggested that a chamomile mouthwash might ameliorate this toxicity , a prospect i ve trial was developed to test chamomile in this situation Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection . In a prospect i ve , double-blind , r and omized study , we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients . Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis . Mucositis also resolved more quickly in patients receiving chlorhexidine . Concomitant reductions in total oral streptococci ( p less than 0.02-p less than 0.001 ) and oral c and ida ( p less than 0.004 ) were seen in patients using chlorhexidine . Persistent clinical oral c and idiasis ( thrush ) was observed in 15 to 27 control group patients ( 56 % ) , but only transiently in two ( 8 % ) of 24 patients who used chlorhexidine rinse ( p less than 0.001 ) . Five of 27 control group patients ( 19 % ) had c and idemia , while no c and idemia was observed in the chlorhexidine group ( p less than 0.03 ) . Three deaths from disseminated c and idiasis occurred in the placebo group ; none occurred in patients who received chlorhexidine . Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation . The reductions in mucositis and in oral c and ida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation The efficacy of orally administered sucralfate suspension in preventing and treating chemotherapy-induced mucositis was evaluated in a double-blind trial . Forty-eight children and adolescents with newly diagnosed acute nonlymphocytic leukemia were r and omized to receive suspensions of either sucralfate or placebo orally every 6 hours during the first 10 weeks of intensive remission-induction chemotherapy . Patients given sucralfate suspension were less likely than subjects receiving placebo to acquire colonization with potentially pathogenic microorganisms : 14 ( 58 % ) of 24 versus 22 ( 92 % ) of 24 , respectively ( p = 0.008 ) . However , no effect on preexisting colonization was noted . Subjective reporting of discomfort , objective scoring of the severity of mucositis , and the maximal percent of body weight lost during therapy were similar ; 58 % of patients receiving sucralfate reported no oral pain compared with 25 % receiving placebo ( p = 0.06 ) . Ten episodes of gastrointestinal bleeding , 25 documented infections , and 886 days with fever were also equally distributed between sucralfate and placebo groups . We conclude that sucralfate suspension is of limited , if any efficacy , in the prevention and treatment of chemotherapy-induced mucositis . Sucralfate administration can , however , reduce acquisition of alimentary colonization with potential pathogens , perhaps by interfering with adherence to mucosal membranes In a placebo-controlled double-blind study the prophylactic value of oral systemic treatment with the antimycotic agent miconazole was assessed in 30 highly predisposed patients receiving intensive cytostatic chemotherapy because of haematological malignancies . Patients colonized with C and ida before treatment were not freed from this micro-organism by miconazole treatment . However , only 3 out of 6 initially non-colonized miconazole-treated patients became colonized during the study , against 10 out of 10 placebo-treated patients ( p = 0.036 ) . Seven out of 15 patients in the placebo group developed clinical mycosis , against only two out of 15 in the miconazole group . The miconazole-treated patients remained clinical ly free of mycosis for 252 out of 264 treatment days , while the placebo-treated patients remained free of mycosis for only 263 out or 338 treatment days ( p = 0.0001 ) . The results indicate that systemic miconazole treatment protects highly predisposed patients from colonization with C and ida and prevents or postpones clinical ly established c and idosis Uncontrolled clinical trials have shown that parenteral administration of GM-CSF reduces the frequency of chemotherapy-induced mucositis . The mechanism of this effect could be related to acceleration of haematopoiesis and /or increase in functional activation of WBC . We conducted a double-blind , placebo-controlled , dose ranging study of GM-CSF ( mol-gramostim ) mouthwash in patients with breast cancer during the first treatment cycle of a combination chemotherapy regimen which has historically produced dose-limiting ( grade > or = 3 ) mucositis in approximately 39 % of patients . Subjects were r and omized to receive either placebo mouthwash ( 0.1 percent albumin ) or one of four concentrations of GM-CSF mouthwash ( 0.01 , 0.1 , 1.0 or 10 mcg/ml ) . The primary endpoint was to evaluate the relationship between dose of GM-CSF mouthwash received and probability of grade > or = 3 mucositis using a logistic model . Solutions were administered four times daily starting within 24 hours of chemotherapy initiation and continuing until the end of the cycle ( day 21 ) . Mucositis was assessed on days 1 - 6 , 10 , 15 and 21 . Day 6 plasma sample s were assayed for GM-CSF . Forty-five patients were evaluable for response ( nine per dosing group ) . A 42 % risk ( 15/36 ) of mucositis grade > or = 3 was evident on day 15 in patients receiving GM-CSF compared to 2 of 9 patients on the placebo arm . No evidence of dose response was found by logistic regression . Five patients had a detectable plasma concentration of GM-CSF ( 56 - 209 pg/ml ) . A positive correlation between GM-CSF dose and leukocyte recovery was noted ( P = 0.04 ) The prophylactic value of twice-daily mouth rinses with a solution of 0.1 % chlorhexidine gluconate in minimizing oral complications during remission-induction chemotherapy was tested in sixteen patients with acute myeloblastic leukemia . The study design was double blind with a placebo control . St and ardized measurement indices were employed to assess the dental plaque levels and the degree of gingivitis and mucositis during remission-induction . The treatment group demonstrated superior oral health on the basis of each of these measurement parameters . A moderate increase in tooth staining was observed in the treatment group . The results also suggested the potential value of chlorhexidine mouth rinses in the prophylaxis of oral c and idiasis in the myelosuppressed patient Fungal infections have become an increasing cause of morbidity in patients with acute leukemia undergoing chemotherapy . Oral c and idiasis is prone to develop in these patients , and there is also a risk of the development of esophageal C and ida infection . Clotrimazole troches have been previously reported to be effective in the treatment of documented oral C and ida infection . This report documents a double-blind controlled study in 30 patients with acute leukemia in which the effectiveness of clotrimazole troches in preventing oropharyngeal c and idiasis was assessed . Patients were r and omly assigned to receive 10 mg troches of clotrimazole or a placebo three times per day . Mucosal scrapings were obtained weekly and examined directly by smear and culture . There were 28 evaluable patients . Of 12 patients with oral C and ida infection , 11 were taking placebo and one received clotrimazole ( p = 0.0002 ) . Clotrimazole is effective in preventing oropharyngeal c and idiasis Infections continue to be common causes of morbidity and mortality in neutropenic patients undergoing chemotherapy for acute leukemia [ 1 , 2 ] . Although bacteria are usually the primary pathogens in neutropenic patients , most bacterial infections can now be treated successfully with currently available antibacterial drugs [ 3 , 4 ] . In contrast , fungal infections , often documented only at autopsy , are increasing in frequency in patients with acute leukemia and are now responsible for most fatal infections [ 5 - 7 ] . C and ida species are the predominant fungal pathogens , followed by Aspergillus species , the zygomycetes , and several newly recognized opportunistic fungi . Survival from invasive fungal infections has generally been poor in neutropenic patients with acute leukemia . In many cases , this poor survival can be linked to delays in diagnosis . Obstacles to the rapid diagnosis of invasive fungal infection include difficulty in isolation of fungi in cultures , inability to perform biopsies or other invasive diagnostic procedures in patients with disorders of coagulation , and the nonavailability of reliable serologic tests [ 8 ] . Because of these difficulties , amphotericin B is frequently administered empirically to patients with neutropenia and persistent fever refractory to antibacterial therapy [ 3 , 9 , 10 ] . This approach , however , is limited by the toxicity of amphotericin B , especially in patients receiving other nephrotoxic drugs . The problems associated with effective therapy of serious fungal infections in neutropenic patients with acute leukemia have been the stimulus for using antifungal drugs for prophylaxis . Unfortunately , prophylaxis with oral agents such as nystatin , clotrimazole , and ketoconazole has produced inconsistent results either due to lack of efficacy or poor patient compliance [ 11 ] . Similarly , prophylaxis with parenteral drugs like intravenous miconazole or amphotericin B has been used only on a limited basis because of concerns about toxicity and overall effectiveness [ 12 , 13 ] . Thus , there is currently no uniformly accepted or proven approach for prevention of fungal infections in neutropenic patients with acute leukemia . Fluconazole is a new triazole antifungal agent with activity against many common fungal pathogens causing infection in patients with acute leukemia [ 14 ] . Fluconazole has a favorable pharmacokinetic profile that includes a long serum half-life , making once-daily administration possible , more consistent absorption from the gastrointestinal tract than that of ketoconazole , excellent penetration into the cerebrospinal fluid , and elimination predominantly by renal mechanisms . Significant side effects related to fluconazole have been uncommon and occur less frequently than those associated with amphotericin B. Fluconazole is currently approved for treatment of C and ida and cryptococcal infections [ 15 , 16 ] . Studies in neutropenic animal models also suggest that fluconazole may be effective for prevention of C and ida infection and for treatment of invasive aspergillosis when given at high doses [ 17 , 18 ] . Similar studies in neutropenic bone marrow transplants found that prophylactic fluconazole prevents both systemic and superficial fungal infections [ 19 ] . For these reasons , we did a double-blind , placebo-controlled trial of prophylactic fluconazole in neutropenic patients undergoing chemotherapy for acute leukemia . Methods Patients Patients were eligible for the study if they satisfied the following criteria : 1 ) undergoing chemotherapy for acute leukemia or the blast crisis of chronic myelogenous leukemia ; 2 ) 13 years of age or older ; 3 ) anticipated neutropenia of less than 500 neutrophils per mm3 for 7 or more days ; 4 ) no clinical evidence of fungal infection at time of study entry ; 5 ) no systemic antifungal therapy within the 2 weeks before r and omization ; and 6 ) no allergy to the imidazoles or azoles . Patients with moderate or severe liver disease ( aspartate aminotransferase [ AST ] , alanine aminotransferase [ ALT ] , or alkaline phosphatase greater than five times the upper limit of normal or a total bilirubin greater than 43 mol/L ) and patients with renal insufficiency ( creatinine clearance of less than 0.83 mL/s ) were excluded from the study . Our trial involved 18 oncology centers . Informed consent approved by the institutional review board at each center was obtained from each patient . Study Drugs Eligible patients were r and omly assigned to receive either prophylactic fluconazole or placebo in a double-blind fashion . The fluconazole or placebo was begun at the time of initiation of chemotherapy and administered in identically appearing capsules . A capsule contained 100 mg of fluconazole , and each patient received four capsules ( 400 mg ) as a single daily dose . For patients unable to tolerate oral capsules , the fluconazole or placebo was administered intravenously . The intravenous dose of fluconazole was 200 mg every 12 hours and was infused over 1 hour . The daily dose of fluconazole was reduced in patients who developed renal failure [ 20 ] . Prophylaxis with the study drug was continued through the course of chemotherapy and neutropenia and until 7 days after the neutrophil count reached 1000 cells per mm3 or greater . The maximum duration of prophylaxis was 10 weeks . Prophylaxis was discontinued if one of the following events occurred : 1 ) development of a documented invasive fungal infection ; 2 ) initiation of empiric systemic antifungal therapy ( amphotericin B ) for clinical ly suspected invasive fungal infection ; 3 ) adverse side effects related to the study drug ; or 4 ) patient 's inability to continue in the study due to noncompliance or death . Patients who developed a documented superficial fungal infection could be treated with topical clotrimazole while continuing to receive the study drug . Laboratory Procedures Complete blood counts , prothrombin times , blood urea nitrogen levels , serum creatinine and electrolyte determinations , urinalyses , and liver function studies ( AST , ALT , alkaline phosphatase , and total bilirubin ) were obtained at the time of study entry , once or twice weekly during the study , and at the end of prophylaxis to assess patients for drug-related side effects . Patients were also examined at least twice weekly for clinical symptoms and signs of adverse effects related to the study drugs . A serum pregnancy test was done on all women of child-bearing potential before the study began . Surveillance cultures of the nasopharynx , oropharynx , axillae , urine , perirectal area , and stool were done at the time of study entry , once weekly during the study , and at the end of prophylaxis to determine the presence of fungal colonization . Cultures of blood and other suspected sites of fungal infection were obtained during the study whenever a patient 's clinical condition suggested the possibility of fungal infection . Amphotericin B therapy was initiated in accordance with previously established guidelines when a reasonable clinical suspicion of systemic fungal infection existed [ 3 , 9 , 10 ] . Definition of Fungal Colonization and Infection Fungal colonization was defined as the presence of a fungus in one or more surveillance cultures in the absence of any clinical symptoms or signs of infection . Superficial fungal infections were diagnosed by the isolation of a fungus from the skin , oropharynx , or gastrointestinal tract in association with signs of inflammation , ulcerations , plaques , or exu date s not explainable by other pathogens . Invasive fungal infections were diagnosed by the presence of fungus in the blood , pulmonary tissue or secretions , sinuses , soft tissues , or other organ structures in association with symptoms and signs of infection not explainable by other pathogens . Data Collection and Statistical Analysis Data required by the study protocol were collected and recorded in case report forms by the investigators at each oncology center . Barton and Polansky Associates independently review ed all case report forms for accuracy and compliance with the protocol by comparing the case report forms with patients ' medical and pharmacy records . The case report forms were then su bmi tted to clinical research personnel at Pfizer Central Research for review and entry of data into computer programs . All review s , classifications of infections , and data entry were done blindly before the statistical analyses were performed . Proven fungal infections were required to meet the definitions of infection established by the protocol and approved by the Federal Drug Administration before the study . There was no interim analysis . All statistical tests were performed as two-tailed tests . The Fisher exact test was used to compare differences in proportions , whereas the e quality of two distributions was compared by the Wilcoxon rank-sum test . Univariate comparisons of times to specific events were performed by using Kaplan-Meier estimates of survival distributions and the Gehan generalized Wilcoxon test [ 21 ] . The SAS procedure LIFETEST was used for these comparisons [ 22 ] . The Cochran-Mantel-Haenszel chi-square test was used to check the e quality of mean scores of ordinal response variables adjusted for center effect . Except for one placebo patient who did not receive the study drug and one fluconazole patient with invasive fungal infection at baseline , all patients were included in the efficacy analysis ( intent-to-treat analysis ) . Center by treatment interactions were tested by using the Breslow-Day test of homogeneity of odds ratio [ 23 ] . Results Patient Characteristics Two hundred fifty-seven patients were enrolled into the study . One patient r and omized to the placebo group did not receive the study drug and was excluded from all analyses . The characteristics of the other 256 patients are summarized in Table 1 . One hundred thirty-two patients received placebo , and 124 patients were given fluconazole . The two groups of patients were similar in terms of age , sex , underlying disease , and baseline fungal Immunosuppressive chemotherapy and bone marrow transplantation are increasingly used to treat and , in some cases , cure numerous malignant conditions . The systemic sequelae as a result of these immunosuppressive techniques lead to a host of oral and dental complications . The direct and indirect stomatotoxic effects lead to development of ulcerative , hemorrhagic , or infectious complications that potentially can lead to increased mortality and morbidity . Chlorhexidine was studied to evaluate its broad spectrum antimicrobial properties and to evaluate its effect on immunosuppression-induced mucositis . Our double-blind r and omized study revealed that chlorhexidine versus controls had considerable effect in the bone marrow transplant cohort . Patients who received chlorhexidine while undergoing bone marrow transplantation were found to exhibit fewer and less painful mucositis lesions . This study supports prophylactic use of chlorhexidine in patients who undergo bone marrow transplantation Between October 1988 and December 1990 , 60 patients with leukaemia ( 25 with AML , 19 ALL and 16 CML ) undergoing BMT were r and omised in a double-blind clinical trial to receive prostagl and in E2 ( PGE ) ( Prostin E2 , 0.5 mg per tablet ) or placebo for prophylaxis of oral mucositis . Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT . The incidence of severe oral mucositis was similar for both groups , 55 % in patients receiving PGE and 52 % in patients receiving placebo . The duration of severe mucositis did not differ between PGE and placebo groups ( chi-square 0.95 , p = NS ) . The incidence of HSV infection was significantly higher in patients receiving PGE . Patients with HSV infection receiving PGE also had a higher incidence of severe oral mucositis . The results presented indicate that PGE is not effective for prophylaxis of oral mucositis in BMT recipients |
10,846 | 23,153,955 | RESULTS Patients with schizophrenia have a poor diet , mainly characterized by a high intake of saturated fat and a low consumption of fibre and fruit .
Such diet is more likely to increase the risk to develop metabolic abnormalities .
Subjects with schizophrenia show a poor diet that partly accounts for their higher incidence of metabolic abnormalities . | OBJECTIVE People with schizophrenia show a high incidence of metabolic syndrome , which is associated with a high mortality from cardiovascular disease .
The aetiology of the metabolic syndrome in schizophrenia is multi-factorial and may involve antipsychotic treatment , high levels of stress and unhealthy lifestyle , such as poor diet .
As a poor diet can predispose to the development of metabolic abnormalities , the aims of this review are to clarify : 1 ) the dietary patterns of patients with schizophrenia , 2 ) the association of these dietary patterns with a worse metabolic profile , and 3 ) the possible factors influencing these dietary patterns . | OBJECTIVE The authors studied weight gain mechanisms and energy balance in patients treated with olanzapine . METHOD The body mass index of male schizophrenic adolescent in patients treated with olanzapine ( N=10 ) and of 10 matched patients treated with haloperidol ( N=10 ) were measured at baseline and after 4 weeks of treatment . For the patients treated with olanzapine , caloric intake , resting energy expenditure , and physical activity ( determined through accelerometry and heart rate monitoring ) were assessed at baseline and after 4 weeks of treatment . RESULTS Body mass index significantly increased in those treated with olanzapine but not in those given haloperidol . The increase in body mass index was due to an increase in caloric intake without change in diet composition . Olanzapine had no significant effect on resting energy expenditure . Daily energy expenditure was very low before and after treatment . CONCLUSIONS Olanzapine-induced weight gain is associated with a general increase in caloric intake OBJECTIVE Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine , risperidone , and haloperidol were sought through retrospective analyses . METHOD Six-week body-weight data from 2 trials , study 1 comparing olanzapine and haloperidol ( N = 1,369 ) and study 2 olanzapine and risperidone ( N = 268 ) , were analyzed . Effects of 8 clinical ly relevant covariates -- therapy , clinical outcome ( Brief Psychiatric Rating Scale ) , baseline body mass index ( B BMI ) , increased appetite , age , gender , race , and dose -- on weight were compared . RESULTS In study 1 , olanzapine ( vs. haloperidol ) therapy , better clinical outcome , lower B BMI , and nonwhite race significantly affected weight gain . Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol . In study 2 , better clinical outcome , lower B BMI , and younger age significantly affected weight gain . Increased appetite was more frequent during olanzapine treatment than during haloperidol , but not significantly different from risperidone . Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone . No evidence was found that lower antipsychotic drug doses were associated with lower weight gain . CONCLUSION This report identifies predictive factors of acute weight change in patients with schizophrenia . Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome , low B BMI , and nonwhite race . Factors differing between conventional ( haloperidol ) and atypical ( olanzapine ) agents included increased appetite and gender . Choice of atypical antipsychotic drug ( olanzapine vs. risperidone ) was of minor importance with regard to influence on acute weight gain The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic – pituitary – adrenal ( HPA ) axis to the stimulatory influence of cytokines and stress-related mediators . Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia . We determined the relationship between cortisol , cytokines interleukin-2 ( IL-2 ) and interleukin-6 ( IL-6 ) , and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs . Subjects included 30 healthy controls ( HC ) and 78 schizophrenic ( SCH ) in- patients . SCH were r and omly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design . Clinical efficacy was determined using the Positive and Negative Syndrome Scale ( PANSS ) . Serum cortisol and IL-2 levels were assayed by radioimmunometric assay , and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay . Following a 2-week washout period , serum levels of cortisol , IL-2 , and IL-6 were increased in patients with schizophrenia compared to HC . Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH . Moreover , elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms . In all , 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms , but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol . The improvement of negative symptoms was related to the change in cortisol . Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms , and is improved with atypical antipsychotic treatment The aim of this study was to determine the location of antipsychotic-induced weight gain in drug naïve , first episode patients with schizophrenia . Various fatness and fat distribution parameters ( by Computerized Tomography scanning and anthropometry ) and 1600 hr plasma cortisol were measured in 19 ( 15 men and 4 women ) subjects with schizophrenia ( mean age = 31.0 years ; mean body mass index [ BMI ] = 24.6 kg/m2 ) and an equal number of age- and sex- matched controls ( mean age = 32.6 yr ; mean BMI = 23.0 kg/m2 ) . Patients were then given either olanzapine or risperidone . Sixteen patients were re-tested following a treatment period lasting approximately 6 months . Patients with schizophrenia , had significantly more intra-abdominal fat [ IAF ] ( 116.8 + /- 20.2 cm2 vs. 38.0 + /- 4.8 cm2 , respectively ; t = 3.80 , df = 18 , p < 0.0001 ) and had higher levels of plasma cortisol ( 360.2 + /- 49.6 nmol/L vs. 192.7 + /- 19.7 nmol/L , respectively ; t = 3.13 , df = 18 , p < 0.003 ) than appropriately matched control subjects . Treatment with atypical antipsychotics did not result in a significant increase in IAF ( 116.8 + /- 20.2 cm2 vs. 131.7 + /- 20.9 cm2 ; p = NS ) though visceral fat stores still remained significantly higher than those seen in controls ( 38.0 + /- 4.8 cm2 ) ( F = 9.34 ; df = 2 , 51 ; p < 0.0003 ) . However , plasma levels of cortisol did significantly decrease ( 360.2 + /- 49.6 nmol/L + /- vs. 316.2 + /- 48.4 nmol/L ; p < 0.05 ) . Pre-treatment levels of IAF did not differ between those who received risperidone and those who were given olanzapine ( 123.0 + /- 35.9 cm2 vs. 113.1 + /- 15.7 cm2 , respectively ; t = 0.20 , df = 16 , p < 0.84 ) . The increase in IAF did not differ between those given risperidone and those who received olanzapine ( 26.9 + /- 12.1 cm2 vs. 18.24 + /- 11.44 cm2 , respectively ; t = 0.50 , df = 16 , p < 0.63 ) . Patients with drug naïve , first episode , schizophrenia have higher levels of visceral fats stores as compared to matched control subjects . Treatment with atypical antipsychotics does not result in a significant increase in IAF distribution Obesity results from chronic deregulation of energy balance , which may in part be caused by stress . Our objective was to investigate the effect of acute and psychological stress on food intake , using the eating in the absence of hunger paradigm , in normal and overweight men and women ( while taking dietary restraint and disinhibition into account ) . In 129 subjects ( BMI = 24.5 + /- 3.4 kg/m(2 ) and age = 27.6 + /- 8.8 years ) , scores were determined on the Three Factor Eating Question naire ( dietary restraint = 7.2 + /- 4.4 ; disinhibition = 4.5 + /- 2.6 ; feeling of hunger = 3.9 + /- 2.6 ) and State-Trait Anxiety Inventory ( trait score = 31.7 + /- 24.2 ) . In a r and omized crossover design , the " eating in absence of hunger " protocol was measured as a function of acute stress vs. a control task and of state anxiety scores . Energy intake from sweet foods ( 708.1 kJ vs. 599.4 kJ , P < 0.03 ) and total energy intake ( 965.2 kJ vs. 793.8 kJ , P < 0.01 ) were significantly higher in the stress condition compared to the control condition . Differences in energy intake between the stress and control condition were a function of increase in state anxiety scores during the stress task ( Delta state anxiety scores ) ( R(2 ) = 0.05 , P < 0.01 ) . This positive relationship was stronger in subjects with high disinhibition scores ( R(2 ) = 0.12 , P < 0.05 ) . Differences in state anxiety scores were a function of trait anxiety scores ( R(2 ) = 0.07 , P < 0.05 ) . We conclude that acute psychological stress is associated with eating in the absence of hunger , especially in vulnerable individuals characterized by disinhibited eating behavior and sensitivity to chronic stress |
10,847 | 24,825,770 | On the basis of very low quality evidence we are unable to determine the effects of pericyazine in comparison with typical or atypical antipsychotics for the treatment of schizophrenia . | BACKGROUND Pericyazine is a 3-cyano-10 ( 3 - 4'-hydroxypiperidinopropyl ) phenothiazine .
It is overall pharmacologically similar with chlorpromazine , though particularly sedating .
Dopamine receptor subtype analysis has not been performed for pericyazine , but the drug appears to induce greater noradrenergic than dopaminergic blockade .
Compared to chlorpromazine , pericyazine reportedly has more potent antiemetic , antiserotonin , and anticholinergic activity .
OBJECTIVES To evaluate the clinical effects and safety of pericyazine in comparison with placebo , typical and atypical antipsychotic agents and st and ard care for people with schizophrenia . | OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate 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 Remitted schizophrenic out patients were treated in order to prevent relapse with three doses of haloperidol or propericiazine for 1 year in a double-blind controlled study employing a r and omized design . The drug 's ability to prevent relapse was evaluated by counting the number of symptom-free days for each patient before any sign of relapse or over-dose appeared . Patients were r and omly assinged to the following drugs orally administered once per day at night : placebo ; haloperidol 1 mg , 3 mg , and 6 mg ; propericiazine 10 mg , 30 mg , and 60 mg . Serum prolactin levels in each patient were estimated by radioimmunoassay . All patients treated with placebo relapsed within 1 year and the relapse rate with placebo was significantly higher than with any dose of the two neuroleptics . Haloperidol increased the number of symptom-free days in a dose-dependent manner . Propericiazine at 10 mg and 30 mg also increased the number of symptom-free days dose-dependently but at 60 mg , the number decreased . It appears that propericiazine shows an inverted U-shaped dose-response curve . Prolactin levels were elevated dose-dependently by both drugs but failed to show a significant correlation with the number of symptom-free days . The present results indicate that haloperidol is superior to propericiazine from the viewpoint of the wider “ therapeutic window ” in maintenance treatment and antidopaminergic properties of neuroleptics , wherein it is important to prevent relapse even in remitted schizophrenics Remitted schizophrenic out patients were prophylactically treated to prevent relapse with three different doses of timiperone or sulpiride for a year in a double-blind controlled study employing a r and omized design . Each drug 's ability to prevent relapse was by counting the number of subjects with different outcomes ( remission , relapse , adverse reactions ) during the trial and /or the number of symptom-free days for each patient before any sign of relapse or adverse reactions appeared . Patients were r and omly assigned to the following drugs , which were orally administered once every night : placebo ; timiperone 1 mg , 3 mg , 6 mg ; sulpiride 100 mg , 300 mg , 600 mg . Data from previous studies involving haloperidol and propericiazine were utilized as a retrospective placebo group to compare the characteristics of the four drugs for maintenance treatment of remitted schizophrenic out patients . Both timiperone and sulpiride increased the number of patients in remission and decreased the number of patients who relapsed , compared with the placebo group . With timiperone , there was an especially marked increase in the number of patients who showed signs of adverse reactions compared with sulpiride . Sulpiride was the only drug that increased the number of dose-dependent symptom-free days . However , both of these drugs significantly increased the number of symptom-free days compared with placebo . By comparing the dose-response curves of four drugs tested in the same fashion , haloperidol and sulpiride were superior to propericiazine and timiperone because they displayed a wider dose range for the maintenance treatment of remitted schizophrenic out patients Forty-seven chronic hospitalized schizophrenics were treated in turn with placebos , pericyazine , and thioridazine for 12-week periods in a double blind cross-over trial lasting one year in all . The Wing rating scale was used for assessment . Both drugs were more effective than placebo , but neither was better in general than the pre-trial treatment . Pericyazine seemed less effective against the individual symptom of coherent delusions , and thioridazine scored significantly better against the symptom group socially embarrassing behaviour Its pharmacological action in animals is similar to that of the major tranquillizers . It has a five times more potent cataleptic action than prochlorperazine , seventeen times more potent antiemetic activity and four times more potent antiserotonin activity than chlorpromazine . In clinical studies propericiazine has been found to be an effective antipsychotic medication ( 1,3,4,6,7 ) . Furthermore , it was noted that the drug had particular usefulness in the treatment of character disorders ( 6 ) and in patients manifesting aggressive behaviour ( 2,5 ) . In a previous study propericiazine was tested for its calming effect when given as PRN ( prorenata ) medication to agitated hospitalized psychiatric patients under treatment with various other psychiatric drugs . The drug had a calming effect in forty-four of the fifty cases ( 7 ) . To further substantiate these findings in this study the efficacy and side effects of propericiazine were compared with 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 |
10,848 | 30,012,142 | There was no significant difference in outcomes between groups of patients with diagnosed anxiety disorders and patients who had raised anxiety on a rating scale .
Conclusions were limited by the small number of studies and wide variation in the delivery of exercise interventions .
Conclusion Exercise programmes are a viable treatment option for the treatment of anxiety .
High intensity exercise regimens were found to be more effective than low intensity regimens . | Background Anxiety disorders are common , yet treatment options in general practice are often limited to medication or CBT .
There is a lack of evidence for the effectiveness of exercise in the treatment of anxiety in patients who present to general practice and also about the intensity of exercise required to lead to improvement .
The aim of this systematic review was to assess the use of exercise versus waiting list control groups in the treatment of anxiety and also to assess the benefit of high intensity exercise vs low intensity exercise . | Background : Exercise training may be especially helpful for patients with generalized anxiety disorder ( GAD ) . We conducted a r and omized controlled trial to quantify the effects of 6 weeks of resistance ( RET ) or aerobic exercise training ( AET ) on remission and worry symptoms among sedentary patients with GAD . Methods : Thirty sedentary women aged 18–37 years , diagnosed by clinicians blinded to treatment allocation with a primary DSM-IV diagnosis of GAD and not engaged in any treatment other than pharmacotherapy , were r and omly allocated to RET , AET , or a wait list ( WL ) . RET involved 2 weekly sessions of lower-body weightlifting . AET involved 2 weekly sessions of leg cycling matched with RET for body region , positive work , time actively engaged in exercise , and load progression . Remission was measured by the number needed to treat ( NNT ) . Worry symptoms were measured by the Penn State Worry Question naire . Results : There were no adverse events . Remission rates were 60 % , 40 % , and 30 % for RET , AET , and WL , respectively . The NNT was 3 ( 95 % CI 2 to 56 ) for RET and 10 ( 95 % CI –7 to 3 ) for AET . A significant condition-by-time interaction was found for worry symptoms . A follow-up contrast showed significant reductions in worry symptoms for combined exercise conditions versus the WL . Conclusions : Exercise training , including RET , is a feasible , low-risk treatment that can potentially reduce worry symptoms among GAD patients and may be an effective adjuvant , short-term treatment or augmentation for GAD . Preliminary findings warrant further investigation The prevalence of mental health disorders among college students is rising and the increasing rates of anxiety and depression have important societal implication s. Physical activity has been proposed as an adjuvant to traditional treatment approaches ( i.e. psychotherapy or pharmacotherapy ) , and the internet is a potentially useful means of delivering physical activity information to the college-aged population . This r and omized pilot trial examined the effects of an internet-based physical activity intervention on physical activity , self-efficacy , depression , and anxiety in college students ( n = 47 ) receiving mental health counseling . Physical activity , depression , anxiety , exercise self-efficacy , and barriers self-efficacy were assessed at baseline and post-intervention . There was a significant time effect for physical activity , with both groups increasing their physical activity levels across the 10-week intervention but with a larger increase in the intervention condition ( d = 0.68 ) than the control condition ( d = 0.05 ) . Exercise and barriers self-efficacy declined across the intervention , but more so in the control than intervention condition . Effects on depression and anxiety were nonsignificant . Finally , correlation analyses showed increases in physical activity were associated with increases in exercise self-efficacy ( r = 0.62 ) and barriers self-efficacy ( r = 0.63 ) and decreases in depression ( r = −0.44 ) in the intervention condition , but not in the control condition . These results suggest that an internet-delivered physical activity intervention may be a promising approach to promoting physical activity among college students undergoing mental health counseling Background : Previous studies have suggested that physical exercise can reduce symptoms for subjects suffering from panic disorder ( PD ) . The efficacy of this intervention has so far not been compared to an established psychotherapy , such as cognitive behaviour therapy ( CBT ) . Assessment of controlled long-term effects and the clinical significance of the treatment are also lacking . Aim : To compare physical exercise to CBT as treatment for PD , and assess controlled long-term and clinical ly significant effects . Method : PD- patients were r and omized to either three weekly sessions of physical exercise ( n = 17 ) , or one weekly session of CBT ( n = 19 ) . Both treatments ran for 12 weeks , were manualized and administered in groups . Patients were assessed twice before the start of treatment , at post-treatment and at 6 and 12 months thereafter . Primary outcome - measures consisted of the Mobility Inventory ( MI ) , the Agoraphobia Cognitions Question naire ( ACQ ) and the Body Sensations Question naire ( BSQ ) . Results : A two-way repeated measures MANOVA of these measures demonstrated a significant effect of time , F(16 , 544 ) = 7.28 , p < .01 , as well as a significant interaction effect , F(16 , 544 ) = 1.71 , p < .05 , in favour of CBT . This finding was supported by the assessment of clinical ly significant changes of avoidant behaviour and of treatment-seeking one year later . Conclusion : Group CBT is more effective than group physical exercise as treatment of panic disorder , both immediately following treatment and at follow-up assessment A moderate to vigorous intensity exercise program is emerging as a promising strategy for reducing anxiety sensitivity ( AS ) . Initial evidence suggests that the effects of exercise on mental health outcomes may vary as a function of gender , with men benefitting more than women . Building upon this evidence , the present study tested the hypothesis that the effect of exercise on AS would vary as a function of gender , such that the effect would be stronger for men than for women . We tested this hypothesis using the data from a published study ( Smits , Berry , Rosenfield , et al. , 2008 ) . In this study , participants ( N = 60 ) with elevated levels of AS were r and omly assigned to a two-week exercise intervention [ EX ] or a waitlist control condition [ WL ] . Results revealed that males showed significantly greater initial AS reductions relative to females ( following 1 week of exercise ) . However , these gender differences were no longer evident at the end of the intervention . Possible mechanisms for the observed findings and directions for future research are discussed Background It is generally believed that exhaustive search es of bibliographic data bases are needed for systematic review s of health care interventions . The CENTRAL data base of controlled trials ( RCTs ) has been built up by exhaustive search ing . The CONSORT statement aims to encourage better reporting , and hence indexing , of RCTs . Our aim was to assess whether developments in the CENTRAL data base , and the CONSORT statement , mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic review s of health care interventions . Methods RCTs used in the Cochrane review s were identified . A brief RCT search strategy ( BRSS ) , consisting of a search of CENTRAL , and then for variants of the word r and om across all fields ( r and om$.af . ) in MEDLINE and EMBASE , was devised and run . Any trials included in the meta-analyses , but missed by the BRSS , were identified . The meta-analyses were then re-run , with and without the missed RCTs , and the differences quantified . The proportion of trials with variants of the word r and om in the title or abstract was calculated for each year . The number of RCTs retrieved by search ing with " r and om$.af . " was compared to the highly sensitive search strategy ( HSSS ) . Results The BRSS had a sensitivity of 94 % . It found all journal RCTs in 47 of the 57 review s. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five review s , but no important differences in conclusions result ed . In the post-CONSORT years , 1997–2003 , the percentage of RCTs with r and om in the title or abstract was 85 % , a mean increase of 17 % compared to the seven years pre-CONSORT ( 95 % CI , 8.3 % to 25.9 % ) . The search using r and om$.af . reduced the MEDLINE retrieval by 84 % , compared to the HSSS , thereby reducing the workload of checking retrievals . Conclusion A brief RCT search strategy is now sufficient to locate RCTs for systematic review s in most cases . Exhaustive search ing is no longer cost-effective , because in effect it has already been done for CENTRAL Abstract Anxiety sensitivity , or the belief that anxiety-related sensations can have negative consequences , has been shown to play an important role in the etiology and maintenance of panic disorder and other anxiety-related pathology . Aerobic exercise involves exposure to physiological cues similar to those experienced during anxiety reactions . The present study sought to investigate the efficacy of a brief aerobic exercise intervention for high anxiety sensitivity . Accordingly , 24 participants with high anxiety sensitivity scores ( Anxiety Sensitivity Index-Revised scores > 28 ) were r and omly assigned to complete either six 20-minute sessions of aerobic exercise or a no-exercise control condition . The results indicated that individuals assigned to the aerobic exercise condition reported significantly less anxiety sensitivity subsequent to exercise , whereas anxiety sensitivity scores among non-exercisers did not significantly change . The clinical research and public health implication s of these findings are discussed , and several potential directions for additional research are recommended Anxiety disorders are the most common mental illness , but are not uniform , many clinical diagnoses include the symptoms of anxiety . That is the reason why there are relatively small numbers of population surveys and r and omized-controlled trials which have examined the relationship between exercise and the various anxiety symptoms/ disorders . In our review we summarize meta-analytic studies , epidemiological surveys and r and omized controlled studies which examine the role of regular physical activity in the prevention and treatment of sub clinical anxiety/anxiety symptoms and anxiety disorders . The meta-analytic studies and r and omized-controlled trials examining the relationship between sub clinical anxiety disorders and anxiety symptoms demonstrated small to moderate effect of exercise in the decrease of anxiety symptoms , especially for moderate-intensity exercise . This relationship was confirmed for both acute and chronic exercise , for state and trait anxiety in different sex , age and state of health groups . In the case of the anxiety disorders based on review ed studies , we can conclude that there is a potential association between decreased symptoms of anxiety and exercise . The regular , moderate-intensity exercise can reduce and alleviate the symptoms of anxiety - at least in panic , agoraphobia and generalized anxiety disorders . The review ed studies have been highlighted the fact , that exercise can be effective in psychiatric practice as an alternative or adjuvant therapy . Physically healthy people with anxiety symptoms , or patients with anxiety disorders can perform exercise , there are no contraindications . Although based on previous studies , we can not assume that the relationship is causal , but we can not ignore the evidence s that are already available OBJECTIVE Effective treatments for social anxiety disorder ( SAD ) exist , but additional treatment options are needed for nonresponders as well as those who are either unable or unwilling to engage in traditional treatments . Mindfulness-based stress reduction ( MBSR ) is one nontraditional treatment that has demonstrated efficacy in treating other mood and anxiety disorders , and preliminary data suggest its efficacy in SAD as well . METHOD Fifty-six adults ( 52 % female ; 41 % Caucasian ; age mean [ M ] ± st and ard deviation [ SD ] : 32.8 ± 8.4 ) with SAD were r and omized to MBSR or an active comparison condition , aerobic exercise ( AE ) . At baseline and post-intervention , participants completed measures of clinical symptoms ( Liebowitz Social Anxiety Scale , Social Interaction Anxiety Scale , Beck Depression Inventory-II , and Perceived Stress Scale ) and subjective well-being ( Rosenberg Self-Esteem Scale , Satisfaction with Life Scale , Self-Compassion Scale , and UCLA-8 Loneliness Scale ) . At 3 months post-intervention , a subset of these measures was readministered . For clinical significance analyses , 48 healthy adults ( 52.1 % female ; 56.3 % Caucasian ; age [ M ± SD ] : 33.9 ± 9.8 ) were recruited . MBSR and AE participants were also compared with a separate untreated group of 29 adults ( 44.8 % female ; 48.3 % Caucasian ; age [ M ± SD ] : 32.3 ± 9.4 ) with generalized SAD who completed assessment s over a comparable time period with no intervening treatment . RESULTS A 2 ( Group ) x 2 ( Time ) repeated measures analyses of variance ( ANOVAs ) on measures of clinical symptoms and well-being were conducted to examine pre-intervention to post-intervention and pre-intervention to 3-month follow-up . Both MBSR and AE were associated with reductions in social anxiety and depression and increases in subjective well-being , both immediately post-intervention and at 3 months post-intervention . When participants in the r and omized controlled trial were compared with the untreated SAD group , participants in both interventions exhibited improvements on measures of clinical symptoms and well-being . CONCLUSION Nontraditional interventions such as MBSR and AE merit further exploration as alternative or complementary treatments for SAD A group r and omized trial of adding a home-based walking program to a st and ard group cognitive behavioral therapy ( GCBT+EX ) was compared with groups receiving GCBT and educational sessions ( GCBT+ED ) . The study was implemented in an outpatient clinic providing GCBT for clients diagnosed with panic disorder , generalized anxiety disorder or social phobia . Pre- and post-treatment measures included the self-report depression , anxiety , and stress scale ( DASS-21 ) and measures of physical activity . From January 2004 to May 2005 , six groups were allocated to GCBT+EX ( n=38 ) and five to GCBT+ED ( n=36 ) . Analysis of covariance for completed cases ( GCBT+EX , n=21 ; GCBT+ED , n=20 ) , adjusting for the group design , baseline DASS-21 scores , and anxiety diagnosis showed significant effect for GCBT+EX on depression , anxiety , and stress ( regression coefficients=-6.21 , -3.41 , and -5.14 , respectively , p<0.05 ) compared to the GCBT+ED . The potential of exercise interventions as adjunct to GCBT for anxiety disorder needs to be further explored Anxiety sensitivity is a known precursor to panic attacks and panic disorder , and involves the misinterpretation of anxiety-related sensations . Aerobic exercise has been shown to reduce generalized anxiety , and may also reduce anxiety sensitivity through exposure to feared physiological sensations . Accordingly , 54 participants with elevated anxiety sensitivity scores completed six 20-min treadmill exercise sessions at either a high-intensity aerobic ( n = 29 ) or low-intensity ( n = 25 ) level . Self-ratings of anxiety sensitivity , fear of physiological sensations associated with anxiety , and generalized anxiety were obtained at pre-treatment , post-treatment , and one-week follow-up . Results indicated that both high- and low-intensity exercise reduced anxiety sensitivity . However , high-intensity exercise caused more rapid reductions in a global measure of anxiety sensitivity and produced more treatment responders than low-intensity exercise . Only high-intensity exercise reduced fear of anxiety-related bodily sensations . The implication s of these findings are discussed Objective To investigate the effectiveness of facilitated physical activity as an adjunctive treatment for adults with depression presenting in primary care . Design Pragmatic , multicentre , two arm parallel r and omised controlled trial . Setting General practice s in Bristol and Exeter . Participants 361 adults aged 18 - 69 who had recently consulted their general practitioner with symptoms of depression . All those r and omised had a diagnosis of an episode of depression as assessed by the clinical interview schedule-revised and a Beck depression inventory score of 14 or more . Interventions In addition to usual care , intervention participants were offered up to three face to face sessions and 10 telephone calls with a trained physical activity facilitator over eight months . The intervention was based on theory and aim ed to provide individually tailored support and encouragement to engage in physical activity . Main outcome measures The primary outcome was self reported symptoms of depression , assessed with the Beck depression inventory at four months post-r and omisation . Secondary outcomes included use of antidepressants and physical activity at the four , eight , and 12 month follow-up points , and symptoms of depression at eight and 12 month follow-up . Results There was no evidence that participants offered the physical activity intervention reported improvement in mood by the four month follow-up point compared with those in the usual care group ; adjusted between group difference in mean Beck depression inventory score −0.54 ( 95 % confidence interval −3.06 to 1.99 ; P=0.68 ) . Similarly , there was no evidence that the intervention group reported a change in mood by the eight and 12 month follow-up points . Nor was there evidence that the intervention reduced antidepressant use compared with usual care ( adjusted odds ratio 0.63 , 95 % confidence interval 0.19 to 2.06 ; P=0.44 ) over the duration of the trial . However , participants allocated to the intervention group reported more physical activity during the follow-up period than those allocated to the usual care group ( adjusted odds ratio 2.27 , 95 % confidence interval 1.32 to 3.89 ; P=0.003 ) . Conclusions The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone . Trial registration Current Controlled Trials IS RCT N16900744 OBJECTIVE The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo . METHOD Forty-six out patients suffering from moderate to severe panic disorder with or without agoraphobia ( DSM-III-R criteria ) were r and omly assigned to a 10-week treatment protocol of regular aerobic exercise ( running ) , clomipramine ( 112.5 mg/day ) , or placebo pills . RESULTS The dropout rate was 31 % for the exercise group , 27 % for the placebo group , and 0 % for the clomipramine group . In comparison with placebo , both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures ( analysis of variance , last-observation-carried-forward method and completer analysis ) . A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively . Depressive symptoms were also significantly improved by exercise and clomipramine treatment . CONCLUSIONS These results suggest that regular aerobic exercise alone , in comparison with placebo , is associated with significant clinical improvement in patients suffering from panic disorder , but that it is less effective than treatment with clomipramine BACKGROUND Chronic exercise has been shown to have therapeutic effects in panic disorder ( PD ) . The mechanism of these effects is unknown . Acute exercise reduces the effect of a panic challenge in healthy volunteers . Such an effect has not yet been demonstrated in PD patients . The present study aim ed at exploring the antipanic effects of acute exercise on a 35 % CO2 panic provocation in treatment-naïve PD patients to further eluci date the mechanisms of the beneficial effects of exercise on panic . METHODS Eighteen PD patients performed either moderate/hard exercise or very-light exercise before a 35 % CO2 challenge in a r and omized , between-group design . The reactivity to CO2 was assessed with the Visual Analogue Anxiety Scale and the DSM-IV Panic Symptom List . RESULTS Panic reactions to CO2 were smaller in patients that performed moderate/hard exercise in contrast to those that performed very-light exercise . Increments in both measurements and panic rates were consistently reduced by intense exercise . LIMITATIONS Since this study focuses on the acute effects of exercise on CO2 sensitivity in patients with PD , the results of repetitive exercise sessions on the rate of spontaneous panic attacks and overall symptoms are warranted . The small sample size and other limitations are addressed . CONCLUSIONS Exercise reduced the panicogenic effects of a CO2 challenge . In addition to its therapeutic potential , exercise may also be useful as a laboratory maneuver with heuristic value in experimental research into the mechanisms of antipanic treatment AIM AND OBJECTIVE To evaluate the influence of an exercise programme on postmenopausal women with symptoms of anxiety and depression . BACKGROUND The menopause is a period of hormonal changes when mood variations are probably more severe than at any other period of women 's lives . DESIGN Prospect i ve study with control group and pre- and post-treatment measures , after six months treatment . Conducted at two healthcare clinics , in the province of Granada ( Spain ) . METHODS A convenience sample of 60 postmenopausal women aged 60 - 70 years , with symptoms of depression and anxiety , was recruited . The women were r and omly divided into two groups : ( 1 ) control group , no treatment ( n = 30 ) ; ( 2 ) exercise group , which carried out a programme of mixed physical exercises with musical support ( n = 30 ) . All subjects answered question naires for the Hamilton Anxiety Scale and the Brink and Yesavage Geriatric Depression Scale before and after treatment . RESULTS In the exercise group , statistically significant improvements were observed in subjects with moderate and severe depression ( 18 and 22 % , respectively ) and in those with symptoms of anxiety . No such changes were observed in the control group . CONCLUSIONS A controlled programme of physical exercise for postmenopausal women alleviates symptoms of anxiety and depression , and its inclusion in primary healthcare programmes should be considered . RELEVANCE TO CLINICAL PRACTICE Menopausal women may benefit from physical exercise , which attenuates the effects of the physiological and psychological changes associated with the menopause and prevents pathologic changes A comparison was carried out of the psychological effects of a moderate aerobic training programme ( n = 24 ) and an attention-placebo strength and flexibility training programme ( n = 23 ) in previously inactive anxious adults from the general population . Training consisted of one supervised and three unsupervised sessions per week for 10 weeks . Effects were assessed with the Profile of Mood States , the State-Trait Anxiety Inventory and question naires indexing perceived coping ability . Seven participants dropped out of each condition during the training period . Expectations of benefit assessed pre-training , and satisfaction assessed post-training , did not differ between conditions . The moderate exercise programme led to significant improvements in aerobic fitness , and was associated with significantly greater reductions in tension-anxiety , depression and other moods than the attention-placebo condition , together with increases in perceived ability to cope with stress . Psychological responses were not correlated with changes in fitness assessed with bicycle ergometry or the 12 min walk/run test . These effects were maintained on 3 month follow up Abstract Objectives . Regular aerobic exercise ( running ) has been shown to be superior to a pill placebo in the treatment of panic disorder . Combined drug and exercise treatment has not been investigated in r and omized controlled studies to date . Methods . This is a r and omized , 10-week , controlled , parallel group , pilot study . A total of 75 out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 ) received either ( 1 ) exercise plus paroxetine 40 mg/day ( n=21 ) , ( 2 ) relaxation plus paroxetine ( n=17 ) , ( 3 ) exercise plus pill placebo ( n=20 ) , or ( 4 ) relaxation plus pill placebo ( n=17 ) . Changes in the Panic and Agoraphobia Scale ( P&A ) , and the Clinical Global Impression Scale ( CGI ) underwent repeated measure analysis . Results . Effects sizes were large for all groups ( d=1.53–3.87 ) , however not significantly different . Paroxetine-treated patients were significantly more improved than placebo-treated patients . On the CGI , patients in the exercise groups ( plus paroxetine or placebo ) had a trend toward better improvement compared to relaxation ( P=0.06 ) . Response and remission rates were higher in the paroxetine compared to pill placebo groups . Conclusions . While paroxetine was superior to placebo , aerobic exercise did not differ from relaxation training in most efficacy measures Background : The first objective of this study was to compare the changes in physical self-concept , global self-esteem , depression and anxiety after participation in one of two 16-week psychomotor therapy programs for nonpsychotic psychiatric in patients . The second objective was to study the relationship between changes in these variables . Methods : One hundred and ninety-nine in patients were r and omly assigned to either a personalized psychomotor fitness program , consisting of aerobic exercise and weight training , or a general program of psychomotor therapy , consisting of different forms of physical exercises and relaxation training . Physical self-con cept was evaluated using the Dutch version of the Physical Self-Perception Profile at baseline , after 8 weeks , and after completion of the 16-week interventions . At the same time points , additional variables of global self-esteem , depression and anxiety were assessed by means of the Rosenberg Self-Esteem Inventory , the Beck Depression Inventory and the Trait Anxiety Inventory , respectively . Results : After 16 weeks , both groups showed significant improvements in all outcome measures ( p values ranged from 0.01 to < 0.0001 ) , with no between-group differences . In both groups , the improvement in physical self-concept was correlated with increased global self-esteem and decreased depression and anxiety levels ( p < 0.01 ) . Conclusions : The results suggest that both psychomotor therapy programs are equally effective in enhancing physical self-concept . The relationship between improvements in physical self-concept and enhancements in global self-esteem , depression and anxiety supports the potential role of the physical self-concept in the recovery process of depressed and anxious psychiatric in patients BACKGROUND Exercise interventions repeatedly have been shown to be efficacious for the treatment of depression , and initial studies indicate similar efficacy for the treatment of anxiety conditions . To further study the potential beneficial role of prescriptive exercise for anxiety-related conditions , we examined the role of exercise in reducing fears of anxiety-related sensations ( anxiety sensitivity ) . METHODS We r and omly assigned 60 participants with elevated levels of anxiety sensitivity to a 2-week exercise intervention , a 2-week exercise plus cognitive restructuring intervention , or a waitlist control condition . Assessment of outcome was completed at pretreatment , midtreatment , 1-week posttreatment , and 3-week follow-up . RESULTS We found that both exercise conditions led to clinical ly significant changes in anxiety sensitivity that were superior to the waitlist condition , representing a large controlled effect size ( d=2.15 ) . Adding a cognitive component did not facilitate the effects of the exercise intervention . Consistent with hypotheses , changes in anxiety sensitivity mediated the beneficial effects of exercise on anxious and depressed mood . CONCLUSIONS We discuss these findings in terms of the potential role of exercise as an additional psychosocial intervention for conditions such as panic disorder , where anxiety sensitivity is a prominent component of pathology Endurance capacity was determined by bicycle spiroergometry in patients with panic disorder before ( n = 38 ) and after ( n = 10 ) a 10 week running program and compared to untrained healthy control subjects carrying out the same training ( n = 11 ) and patients receiving clomipramine drug therapy ( n = 7 ) or placebo ( n = 7 ) . Before the running program maximal oxygen uptake ( VO2peak ) and the workload corresponding to a lactate concentration of 4 mmol/l ( PLAC4 ) were significantly reduced in panic patients compared to controls . Patients in the running program and healthy controls improved PLaC4 significantly by running . No significant differences in endurance gains were found between these groups , showing that patients and controls improved equally . At study termination ( week 10 ) running was more efficient than placebo in improving panic symptoms ( B and elow PanicAgoraphobia Scale , Hamilton Anxiety Scale , Clinical Global Impression Scale ) . Clomipramine treatment was better than placebo ( all scales ) and running ( only Clinical Global Impression ) . Endurance capacity did not correlate with anxiety scores at baseline , nor did improvement in fitness substantially correlate with changes in psychopathology measures during the study . Panic patients were shown to have a decreased endurance capacity which can be raised by training . Endurance training based on spiroergometric results gives rise to clinical improvement Background The Wales National Exercise Referral Scheme ( NERS ) is a 16-week programme including motivational interviewing , goal setting and relapse prevention . Method A pragmatic r and omised controlled trial with nested economic evaluation of 2160 inactive participants with coronary heart disease risk ( CHD , 1559 , 72 % ) , mild to moderate depression , anxiety or stress ( 79 , 4 % ) or both ( 522 , 24 % ) r and omised to receive ( 1 ) NERS or ( 2 ) normal care and brief written information . Outcome measures at 12 months included the 7-day physical activity recall , the hospital anxiety and depression scale . Results Ordinal regression identified increased physical activity among those r and omised to NERS compared with those receiving normal care in all participants ( OR 1.19 , 95 % CI 0.99 to 1.43 ) , and among those referred for CHD only ( OR 1.29 , 95 % CI 1.04 to 1.60 ) . For those referred for mental health reason alone , or in combination with CHD , there were significantly lower levels of anxiety ( OR −1.56 , 95 % CI −2.75 to −0.38 ) and depression ( OR −1.39 , 95 % CI −2.60 to −0.18 ) , but no effect on physical activity . The base-case incremental cost-effectiveness ratio was £ 12 111 per quality adjusted life year , falling to £ 9741 if participants were to contribute £ 2 per session . Conclusions NERS was effective in increasing physical activity among those referred for CHD risk only . Among mental health referrals , NERS did not influence physical activity but was associated with reduced anxiety and depression . Effects were dependent on adherence . NERS is likely to be cost effective with respect to prevailing payer thresholds . Trial registration Current Controlled Trials IS RCT N47680448 |
10,849 | 31,237,921 | Insulin and sulfonylureas were associated with an increased risk of severe hypoglycemia .
CONCLUSIONS SGLT-2 inhibitors and GLP-1 agonists have the most beneficial effects , especially in T2D patients with previous CV diseases . | BACKGROUND The last international consensus on the management of type 2 diabetes ( T2D ) recommends SGLT-2 inhibitors or GLP-1 agonists for patients with clinical cardiovascular ( CV ) disease ; metformin remains the first-line glucose lowering medication .
Last studies suggested beneficial effects of SGLT-2 inhibitors or GLP-1 agonists compared to DPP-4 inhibitors , in secondary CV prevention .
Recently , a potential benefit of SGLT-2 inhibitors in primary CV prevention also has been suggested .
However , no comparison of all the new and the old hypoglycemic drugs is available on CV outcomes .
We aim ed to compare the effects of old and new hypoglycemic drugs in T2D , on major adverse cardiovascular events ( MACE ) and mortality . | Abstract Objective : To evaluate the efficacy of pioglitazone for the prevention of macrovascular outcomes in Japanese patients with type 2 diabetes , without a recent history of macrovascular morbidity . Research design and methods : This 2.5–4 year , prospect i ve , r and omized , open-label , blinded-endpoint study was conducted in 20 Japanese centers . Patients received pioglitazone ± other oral glucose-lowering drugs ( excluding another thiazolidinedione ) [ n = 293 ] or oral glucose-lowering drugs excluding thiazolidinediones ( n = 294 ) . Treatment was adjusted to achieve HbA1c < 6.5 % . The primary endpoint was the time to onset of a macrovascular event . Results : Pioglitazone delayed the time to onset of macrovascular events and was associated with a lower cumulative incidence of such events ( 3.56 % vs. 4.49 % for controls ) . Neither finding achieved statistical significance . This was likely because of the type of patient included in the study ( i.e. no recent history of cardiovascular events ) and the high use of concomitant anti-diabetic agents . Reductions in HbA1c , fasting blood glucose and fasting blood insulin levels , and an increase in HDL-C were significantly greater with pioglitazone throughout most of the study ( p < 0.05 ) . Fewer patients in the pioglitazone group commenced permanent treatment with insulin ( 3.3 % vs. 13.7 % in the control group ) . Adverse events were reported by 97.6 % of the pioglitazone group and 96.9 % of the control group ( serious adverse events , including deaths , were 20.1 vs. 22.2 % , respectively ) . The only notable difference between the two groups was a higher incidence of edema in the pioglitazone group . The main limitation of this study was that too few patients were included to identify statistically significant differences in the primary endpoint . Conclusions : Pioglitazone produced good glycemic control in Japanese patients with type 2 diabetes , and significantly fewer patients treated with pioglitazone needed long-term insulin therapy . These changes were associated with a trend towards delayed onset of macrovascular events . Clinical trial registration : UMIN000001363 CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes ( NCT01243424 ) is an ongoing , r and omized trial in subjects with early type 2 diabetes and increased cardiovascular risk or established complications that will determine the long-term cardiovascular impact of linagliptin versus the sulphonylurea glimepiride . Eligible patients were sulphonylurea-naïve with HbA1c 6.5%–8.5 % or previously exposed to sulphonylurea ( in monotherapy or in a combination regimen < 5 years ) with HbA1c 6.5%–7.5 % . Primary outcome is time to first occurrence of cardiovascular death , non-fatal myocardial infa rct ion , non-fatal stroke or hospitalization for unstable angina . A total of 631 patients with primary outcome events will be required to provide 91 % power to demonstrate non-inferiority in cardiovascular safety by comparing the upper limit of the two-sided 95 % confidence interval as being below 1.3 for a given hazard ratio . Hierarchical testing for superiority will follow , and the trial has 80 % power to demonstrate a 20 % relative cardiovascular risk reduction . A total of 6041 patients were treated with median type 2 diabetes duration 6.2 years , 40.0 % female , mean HbA1c 7.2 % , 66 % on 1 and 24 % on 2 glucose-lowering agents and 34.5 % had previous cardiovascular complications . The results of CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes may influence the decision-making process for selecting a second glucose-lowering agent after metformin in type 2 diabetes BACKGROUND The cardiovascular effects of adding once‐weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown . METHODS We r and omly assigned patients with type 2 diabetes , with or without previous cardiovascular disease , to receive subcutaneous injections of extended‐release exenatide at a dose of 2 mg or matching placebo once weekly . The primary composite outcome was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The co primary hypotheses were that exenatide , administered once weekly , would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy . RESULTS In all , 14,752 patients ( of whom 10,782 [ 73.1 % ] had previous cardiovascular disease ) were followed for a median of 3.2 years ( interquartile range , 2.2 to 4.4 ) . A primary composite outcome event occurred in 839 of 7356 patients ( 11.4 % ; 3.7 events per 100 person‐years ) in the exenatide group and in 905 of 7396 patients ( 12.2 % ; 4.0 events per 100 person‐years ) in the placebo group ( hazard ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.83 to 1.00 ) , with the intention‐to‐treat analysis indicating that exenatide , administered once weekly , was noninferior to placebo with respect to safety ( P<0.001 for noninferiority ) but was not superior to placebo with respect to efficacy ( P=0.06 for superiority ) . The rates of death from cardiovascular causes , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , hospitalization for heart failure , and hospitalization for acute coronary syndrome , and the incidence of acute pancreatitis , pancreatic cancer , medullary thyroid carcinoma , and serious adverse events did not differ significantly between the two groups . CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease , the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo . ( Funded by Amylin Pharmaceuticals ; EXSCEL Clinical Trials.gov number , NCT01144338 . Inhibitors of the sodium-glucose co-transporter-2 ( SGLT-2 ) are a novel class of glucose-lowering agents that show promising results . However , the use of canagliflozin has been associated with an increased risk of lower-limb amputation . Whether this risk concerns other SGLT-2 inhibitors is unclear , and our objective was to address this issue . We performed a disproportionality analysis using the WHO global data base of individual case safety reports ( VigiBase ) . Among the 8 293 886 reports available between January 2013 and December 2017 , we identified 79 reports of lower-limb amputation that were associated with SGLT-2 inhibitors . Among all blood glucose lowering drugs , the proportional reporting ratio ( PRR ) was increased only for SGLT-2 inhibitors ( 5.55 [ 4.23 , 7.29 ] ) . While we observed an expected signal for canagliflozin ( 7.09 [ 5.25 , 9.57 ] ) , the PRR was also high for empagliflozin ( 4.96 [ 2.89 , 8.50 ] ) and , for toe amputations only , for dapagliflozin ( 2.62 [ 1.33 , 5.14 ] ) . In conclusion , our results reveal a positive disproportionality signal for canagliflozin , and also for empagliflozin , and , for toe amputations only , for dapagliflozin . However , our analysis relies on a limited number of cases and is exposed to the biases inherent to pharmacovigilance studies . Further prospect i ve data are therefore needed to better characterize the risk of amputations with different SGLT-2 inhibitors ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glycated hemoglobin of > or equal to 7.0 % and < or equal to 10.5 % . Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease , and to have an estimated glomerular filtration rate ( eGFR ) of > 30 ml/min . Patients were r and omized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS , and to canagliflozin 100 mg with a possible increase to 300 mg , or placebo , in CANVAS-Renal . Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practice s in their community . There was a significant 14 % reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke in the canagliflozin treated patients . There was also a pattern of improvement in markers of renal disease , including the change in the level and nature of albuminuria , a 40 % decrease in the glomerular filtration rate , the need for renal replacement therapy , or death from renal causes . This study exp and s the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study , raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most , if not all , type 2 diabetes patients , not only to control hyperglycemia but also to reduce cardiovascular and renal events BACKGROUND The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events , but such a possibility has not been formally tested . METHODS We r and omly assigned 12,537 people ( mean age , 63.5 years ) with cardiovascular risk factors plus impaired fasting glucose , impaired glucose tolerance , or type 2 diabetes to receive insulin glargine ( with a target fasting blood glucose level of ≤95 mg per deciliter [ 5.3 mmol per liter ] ) or st and ard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design . The results of the comparison between insulin glargine and st and ard care are reported here . The co primary outcomes were nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure . Microvascular outcomes , incident diabetes , hypoglycemia , weight , and cancers were also compared between groups . RESULTS The median follow-up was 6.2 years ( interquartile range , 5.8 to 6.7 ) . Rates of incident cardiovascular outcomes were similar in the insulin-glargine and st and ard-care groups : 2.94 and 2.85 per 100 person-years , respectively , for the first co primary outcome ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.94 to 1.11 ; P=0.63 ) and 5.52 and 5.28 per 100 person-years , respectively , for the second co primary outcome ( hazard ratio , 1.04 ; 95 % CI , 0.97 to 1.11 ; P=0.27 ) . New diabetes was diagnosed approximately 3 months after therapy was stopped among 30 % versus 35 % of 1456 participants without baseline diabetes ( odds ratio , 0.80 ; 95 % CI , 0.64 to 1.00 ; P=0.05 ) . Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years . Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the st and ard-care group . There was no significant difference in cancers ( hazard ratio , 1.00 ; 95 % CI , 0.88 to 1.13 ; P=0.97 ) . CONCLUSIONS When used to target normal fasting plasma glucose levels for more than 6 years , insulin glargine had a neutral effect on cardiovascular outcomes and cancers . Although it reduced new-onset diabetes , insulin glargine also increased hypoglycemia and modestly increased weight . ( Funded by Sanofi ; ORIGIN Clinical Trials.gov number , NCT00069784 . ) BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) Background — Rosiglitazone has several properties that may affect progression of atherosclerosis . The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients With Cardiovascular History ( APPROACH ) study was undertaken to determine the effect of the thiazolidinedione rosiglitazone on coronary atherosclerosis as assessed by intravascular ultrasound compared with the sulfonylurea glipizide . Methods and Results — This was a r and omized , double-blind , controlled 18-month study in 672 patients aged 30 to 80 years with established type 2 diabetes mellitus treated by lifestyle , 1 oral agent , or submaximal doses of 2 oral agents who had at least 1 atherosclerotic plaque with 10 % to 50 % luminal narrowing in a coronary artery that had not undergone intervention during a clinical ly indicated coronary angiography or percutaneous coronary intervention . The primary outcome was change in percent atheroma volume in the longest and least angulated epicardial coronary artery that had not undergone intervention . Secondary outcomes included change in normalized total atheroma volume and change in total atheroma volume in the most diseased baseline 10-mm segment . Rosiglitazone did not significantly reduce the primary outcome of percent atheroma volume compared with glipizide ( −0.64 % ; 95 % confidence interval , −1.46 to 0.17 ; P=0.12 ) . The secondary outcome of normalized total atheroma volume was significantly reduced by rosiglitazone compared with glipizide ( −5.1 mm3 ; 95 % confidence interval , −10.0 to −0.3 ; P=0.04 ) ; however , no significant difference between groups was observed for the change in total atheroma volume within the most diseased baseline 10-mm segment ( −1.7 mm3 ; 95 % confidence interval , −3.9 to 0.5 ; P=0.13 ) . Conclusions — Rosiglitazone did not significantly decrease the primary end point of progression of coronary atherosclerosis more than glipizide in patients with type 2 diabetes mellitus and coronary atherosclerosis . Clinical Trial Registration — http://www . clinical trials.gov . Unique Identifier : NCT00116831 Conflicting data regarding cardiovascular effects of thiazolidinediones ( TZDs ) and extra-skeletal effects of vitamin D supported the need for a definitive trial . The Thiazolidinedione Intervention with vitamin D Evaluation ( TIDE ) trial aim ed to assess the effects of TZDs ( rosiglitazone and pioglitazone ) on cardiovascular outcomes and the effects of vitamin D ( cholecalciferol ) on cancers and mortality . A large multicentre 3 × 2 factorial double-blind placebo-controlled r and omised trial recruited from outpatient primary care and specialty clinics in 33 countries . From June 2009 to July 2010 , 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥50 years whose HbA1c was 6.5–9.5 % ( 48–80 mmol/mol ) when using two or fewer glucose-lowering drugs were r and omised by a central computer system to placebo ( n = 541 ) , rosiglitazone 4–8 mg/day ( n = 399 ) or pioglitazone 30–45 mg/day ( n = 392 ) ; 1,221 participants were r and omised to placebo ( n = 614 ) or vitamin D 1,000 IU/day ( n = 607 ) . Participants and all study personnel were blind to treatment allocation . The primary outcome for the TZD arm was the composite of myocardial infa rct ion , stroke or cardiovascular death , and for the vitamin D arm it was cancer or all-cause death . All r and omised participants were included in the primary analysis . From the study design , 16,000 people were to be followed for approximately 5.5 years . However , the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data . In the TZD arm , the cardiovascular outcome occurred in five participants ( 0.9 % ) in the placebo groups and three participants ( 0.4 % ) in the TZD groups ( two allocated to pioglitazone , one to rosiglitazone ) . In the vitamin D arm , the primary outcome occurred in three participants ( 0.5 % ) in the placebo group and in two participants ( 0.3 % ) receiving vitamin D. Adverse events were comparable in all groups . Uncertainty persists regarding the clinical ly relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial . Clinical Trials.gov NCT00879970 The study was funded by GlaxoSmithKline BACKGROUND Thiazolidinediones are associated with fluid retention , often interpreted as worsening cardiac function , limiting their use in patients with heart failure ( HF ) . We compared the effects of pioglitazone and glyburide on cardiac function in patients with type 2 diabetes , systolic dysfunction , and New York Heart Association ( NYHA ) functional Class II/III HF . METHODS AND RESULTS Participants received pioglitazone or glyburide ( + /-insulin ) for 6 months in this double-blind , r and omized , multicenter study . The primary end point was time to HF , a composite of cardiovascular mortality and hospitalization or emergency room ( ER ) visit for HF . Secondary endpoints included echocardiographic and functional classification assessment s. An earlier time to onset and higher incidence of the primary endpoint was noted with pioglitazone ( 13 % ) versus glyburide ( 8 % ) ( P = .024 ) . Hospitalization or ER visit occurred in 30 pioglitazone and 15 glyburide participants , 19 and 12 of whom , respectively , continued treatment . Cardiac mortality ( 5 versus 6 participants , respectively ) and cardiac function , as measured by change in ventricular mass index ( P = .959 ) , ejection fraction ( P = .413 ) , or fractional shortening ( P = .280 ) , were similar between treatments . CONCLUSIONS Pioglitazone was associated with a higher incidence of hospitalization for HF without an increase in cardiovascular mortality or worsening cardiac function ( by echocardiography ) Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more CONTEXT No antidiabetic regimen has demonstrated the ability to reduce progression of coronary atherosclerosis . Commonly used oral glucose-lowering agents include sulfonylureas , which are insulin secretagogues , and thiazolidinediones , which are insulin sensitizers . OBJECTIVE To compare the effects of an insulin sensitizer , pioglitazone , with an insulin secretagogue , glimepiride , on the progression of coronary atherosclerosis in patients with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , multicenter trial at 97 academic and community hospitals in North and South America ( enrollment August 2003-March 2006 ) in 543 patients with coronary disease and type 2 diabetes . INTERVENTIONS A total of 543 patients underwent coronary intravascular ultrasonography and were r and omized to receive glimepiride , 1 to 4 mg , or pioglitazone , 15 to 45 mg , for 18 months with titration to maximum dosage , if tolerated . Atherosclerosis progression was measured by repeat intravascular ultrasonography examination in 360 patients at study completion . MAIN OUTCOME MEASURE Change in percent atheroma volume ( PAV ) from baseline to study completion . RESULTS Least squares mean PAV increased 0.73 % ( 95 % CI , 0.33 % to 1.12 % ) with glimepiride and decreased 0.16 % ( 95 % CI , -0.57 % to 0.25 % ) with pioglitazone(P = .002 ) . An alternative analysis imputing values for noncompleters based on baseline characteristics showed an increase in PAV of 0.64 % ( 95 % CI , 0.23 % to 1.05 % ) for glimepiride and a decrease of 0.06 % ( -0.47 % to 0.35 % ) for pioglitazone ( between-group P = .02 ) . Mean ( SD ) baseline HbA(1c ) levels were 7.4 % ( 1.0 % ) in both groups and declined during treatment an average 0.55 % ( 95 % CI , -0.68 % to -0.42 % ) with pioglitazone and 0.36 % ( 95 % CI , -0.48 % to -0.24 % ) with glimepiride ( between-group P = .03 ) . In the pioglitazone group , compared with glimepiride , high-density lipoprotein levels increased 5.7 mg/dL ( 95 % CI , 4.4 to 7.0 mg/dL ; 16.0 % ) vs 0.9 mg/dL ( 95 % CI , -0.3 to 2.1 mg/dL ; 4.1 % ) , and median triglyceride levels decreased 16.3 mg/dL ( 95 % CI , -27.7 to -11.0 mg/dL ; 15.3 % ) vs an increase of 3.3 mg/dL ( 95 % CI , -10.7 to 11.7 mg/dL ; 0.6 % ) ( P < .001 for both comparisons ) . Median fasting insulin levels decreased with pioglitazone and increased with glimepiride ( P < .001 ) . Hypoglycemia was more common in the glimepiride group and edema , fractures , and decreased hemoglobin levels occurred more frequently in the pioglitazone group . CONCLUSION In patients with type 2 diabetes and coronary artery disease , treatment with pioglitazone result ed in a significantly lower rate of progression of coronary atherosclerosis compared with glimepiride . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00225277 BACKGROUND Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infa rct ion and stroke . There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma ( PPAR gamma ) could reduce macrovascular complications . Our aim , therefore , was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes . METHODS We did a prospect i ve , r and omised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease . We recruited patients from primary -care practice s and hospitals . We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg ( n=2605 ) or matching placebo ( n=2633 ) , to be taken in addition to their glucose-lowering drugs and other medications . Our primary endpoint was the composite of all-cause mortality , non fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) , stroke , acute coronary syndrome , endovascular or surgical intervention in the coronary or leg arteries , and amputation above the ankle . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N NCT00174993 . FINDINGS Two patients were lost to follow-up , but were included in analyses . The average time of observation was 34.5 months . 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint ( HR 0.90 , 95 % CI 0.80 - 1.02 , p=0.095 ) . The main secondary endpoint was the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke . 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint ( 0.84 , 0.72 - 0.98 , p=0.027 ) . Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified . 6 % ( 149 of 2065 ) and 4 % ( 108 of 2633 ) of those in the pioglitazone and placebo groups , respectively , were admitted to hospital with heart failure ; mortality rates from heart failure did not differ between groups . INTERPRETATION Pioglitazone reduces the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke in patients with type 2 diabetes who have a high risk of macrovascular events AIM The present study evaluated the effects of pioglitazone treatment on the incidence of primary cardiovascular events in Japanese subjects with type 2 diabetes mellitus at high risk of stroke . METHODS A prospect i ve , multicenter , r and omized , open label , comparative study was conducted among diabetic patients recruited from 50 medical institutions nationwide . A total of 522 patients with hypertension and /or dyslipidemia who had one or more silent cerebral infa rcts , advanced carotid atherosclerosis or microalbuminuria at baseline were r and omly treated with ( n=254 ) or without pioglitazone ( n=268 ) and observed for a medium of 672 days . The hypertension and dyslipidemia were concurrently treated according to the respective treatment guidelines . The primary outcome was the time to the first occurrence of a composite of all-cause death , nonfatal cerebral infa rct ion and nonfatal myocardial infa rct ion . RESULTS Treatment with pioglitazone result ed in significant reductions in the levels of HbA1c , diastolic blood pressure and LDL-cholesterol and a significant increase in the levels of HDL-cholesterol . The pioglitazone non-users exhibited a significant reduction in the LDL-cholesterol levels alone . Primary events were registered during the study period in nine patients in the pioglitazone group and 10 patients in the non-pioglitazone group . The difference in the cumulative incidence of the primary outcome was not significant between the two groups(1.8 % per year ) . CONCLUSIONS Pioglitazone therapy produces immediate and effective improvements in glycemic control , diastolic blood pressure and lipid profiles . While this study was too underpowered to determine the effects of pioglitazone on the incidence of cardiovascular events , the results indicated that two years of pioglitazone treatment did not produce any statistically significant reductions in the rate of primary cardiovascular events Purpose Thiazolidinediones are insulin-sensitizing agents that reduce neointimal proliferation and the adverse clinical outcomes associated with percutaneous coronary intervention ( PCI ) in patients with diabetes mellitus ( DM ) . There is little data on whether or not low dose pioglitazone reduces adverse clinical outcomes . Material s and Methods The study population included 121 DM patients with coronary artery disease and they were r and omly assigned to 60 patients taking 15 mg of pioglitazone daily in addition to their diabetic medications and 61 patients with placebo after the index procedure with drug-eluting stents ( DESs ) . The primary end points were rate of in-stent restenosis ( ISR ) and change in atheroma volume and in-stent neointimal volume . The secondary end points were all-cause death , myocardial infa rct ion ( MI ) , stent thrombosis and re-PCI . Results There were no statistical differences in the clinical outcomes and the rate of ISR between the two groups [ all-cause death ; n=0 ( 0 % ) in the pioglitazone group vs. n=1 ( 1.6 % ) in the control group , p=0.504 , MI ; n=2 ( 3.3 % ) vs. n=1 ( 1.6 % ) , p=0.465 , re-PCI ; n=6 ( 10.0 % ) vs. n=6 ( 9.8 % ) , p=0.652 , ISR ; n=4 ( 9.3 % ) vs. n=4 ( 7.5 % ) , p=1.000 , respectively ] . There were no differences in changes in neointimal volume , percent neointimal volume , total plaque volume and percent plaque volume between the two groups on intravascular ultrasonography ( IVUS ) study . Conclusion Our study demonstrated that low dose pioglitazone does not reduce rate of ISR , neointimal volume nor atheroma volume in DM patients who have undergone PCI with DESs , despite the limitations of the study OBJECTIVE Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a r and omized trial to evaluate the risk of lactic acidosis or other serious adverse events ( SAEs ) with this agent , under usual care conditions . RESEARCH DESIGN AND METHODS The Comparative Outcomes Study of Metformin Intervention versus Conventional ( COSMIC ) Approach Study was a r and omized , open-label , active-comparator , parallel-group , 1-year trial in type 2 diabetic patients suboptimally controlled on diet or sulfonylurea . Patients received metformin ( n = 7,227 ) or other usual care treatments ( n = 1,505 ) . The primary end point was the incidence of SAEs , death , and hospitalization . RESULTS SAEs occurred in 10.3 % ( 95 % CI 9.6 - 11.1 % ) of the metformin group and in 11.0 % ( 9.5 - 12.7 % ) of the usual care group ( P = 0.431 ) . Lactic acidosis did not occur . All-cause mortality ( 1.1 % [ 0.9 - 1.4 % ] vs. 1.3 % [ 0.8 - 2.0 % ] , P = 0.596 ) and hospitalization ( 9.4 % [ 8.8 - 10.1 % ] vs. 10.4 % [ 8.9 - 12.1 % ] , P = 0.229 ) were similar between groups . CONCLUSIONS The incidence of SAEs was similar between groups . Lactic acidosis was not observed . Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected . This study demonstrates the utility of large , simple trials for risk evaluation of treatments for common diseases OBJECTIVE The two major classes of antidiabetic drugs , sulfonylureas and metformin , may differentially affect macrovascular complications and mortality in diabetic patients . We compared the long-term effects of glipizide and metformin on the major cardiovascular events in type 2 diabetic patients who had a history of coronary artery disease ( CAD ) . RESEARCH DESIGN AND METHODS This study is a multicenter , r and omized , double-blind , placebo-controlled clinical trial . A total of 304 type 2 diabetic patients with CAD , mean age = 63.3 years ( range , 36–80 years ) , were enrolled . Participants were r and omly assigned to receive either glipizide ( 30 mg daily ) or metformin ( 1.5 g daily ) for 3 years . The primary end points were times to the composite of recurrent cardiovascular events , including death from a cardiovascular cause , death from any cause , nonfatal myocardial infa rct ion , nonfatal stroke , or arterial revascularization . RESULTS At the end of study drug administration , both groups achieved a significant decrease in the level of glycated hemoglobin ( 7.1 % in the glipizide group and 7.0 % in the metformin group ) . At a median follow-up of 5.0 years , 91 participants had developed 103 primary end points . Intention-to-treat analysis showed an adjusted hazard ratio ( HR ) of 0.54 ( 95 % CI 0.30–0.90 ; P = 0.026 ) for the composites of cardiovascular events among the patients that received metformin , compared with glipizide . The secondary end points and adverse events were not significantly different between the two groups . CONCLUSIONS Treatment with metformin for 3 years substantially reduced major cardiovascular events in a median follow-up of 5.0 years compared with glipizide . Our results indicated a potential benefit of metformin therapy on cardiovascular outcomes in high-risk patients AIM Prediabetes is an independent risk factor for future stroke . However , no effective treatment has yet been established for the recurrence of stroke in patients with prediabetes . Here we investigated the effects of pioglitazone , a potent peroxisome proliferator-activated receptor-gamma agonist , for the reduction of recurrent stroke in patients with prediabetes . METHODS Participants were patients who had a symptomatic ischemic stroke or transient ischemic attack ( TIA ) without a history of type 2 diabetes mellitus and who were diagnosed to have IGT or newly diagnosed diabetes by a 75-g oral glucose tolerance test . These patients were r and omized to either receive or not receive pioglitazone . The primary endpoint was a recurrence of ischemic stroke . RESULTS A total of 120 patients were enrolled in the study . Sixty-three patients received pioglitazone and 57 were enrolled in the control group that did not receive pioglitazone . The majority of patients ( 68.3 % ) were prescribed 15 mg of pioglitazone , while the remaining patients ( 31.7 % ) were treated with 30 mg of pioglitazone . Over a median follow-up period of 2.8 years , treatment with pioglitazone was found to be associated with a lower rate of the primary endpoint ( recurrence of stroke ) than that observed in the control group [ event rate=4.8 % pioglitazone vs 10.5 % control , hazard ratio=0.62 , 95 % confidence interval 0.13 - 2.35 , p=0.49 ] . However , differences were not statistically significant . CONCLUSIONS While this study was too underpowered to determine the effect of pioglitazone , the result failed to show beneficial effects in patients of ischemic stroke or TIA with impaired glucose tolerance and newly diagnosed diabetes BACKGROUND Rosiglitazone is an insulin sensitiser used in combination with metformin , a sulfonylurea , or both , for lowering blood glucose in people with type 2 diabetes . We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the combination of the two over 5 - 7 years of follow-up . We also assessed comparative safety . METHODS In a multicentre , open-label trial , 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A(1c ) ( HbA(1c ) ) of 7.9 % were r and omly assigned to addition of rosiglitazone ( n=2220 ) or to a combination of metformin and sulfonylurea ( active control group , n=2227 ) . The primary endpoint was cardiovascular hospitalisation or cardiovascular death , with a hazard ratio ( HR ) non-inferiority margin of 1.20 . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00379769 . FINDINGS 321 people in the rosiglitazone group and 323 in the active control group experienced the primary outcome during a mean 5.5-year follow-up , meeting the criterion of non-inferiority ( HR 0.99 , 95 % CI 0.85 - 1.16 ) . HR was 0.84 ( 0.59 - 1.18 ) for cardiovascular death , 1.14 ( 0.80 - 1.63 ) for myocardial infa rct ion , and 0.72 ( 0.49 - 1.06 ) for stroke . Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group ( HR 2.10 , 1.35 - 3.27 , risk difference per 1000 person-years 2.6 , 1.1 - 4.1 ) . Upper and distal lower limb fracture rates were increased mainly in women r and omly assigned to rosiglitazone . Mean HbA(1c ) was lower in the rosiglitazone group than in the control group at 5 years . INTERPRETATION Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart failure and of some fractures , mainly in women . Although the data are inconclusive about any possible effect on myocardial infa rct ion , rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with st and ard glucose-lowering drugs . FUNDING GlaxoSmithKline plc , UK BACKGROUND The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated . We aim ed to compare the long-term effects of pioglitazone versus sulfonylureas , given in addition to metformin , on cardiovascular events in patients with type 2 diabetes . METHODS TOSCA.IT was a multicentre , r and omised , pragmatic clinical trial , in which patients aged 50 - 75 years with type 2 diabetes inadequately controlled with metformin monotherapy ( 2 - 3 g per day ) were recruited from 57 diabetes clinics in Italy . Patients were r and omly assigned ( 1:1 ) , by permuted blocks r and omisation ( block size 10 ) , stratified by site and previous cardiovascular events , to add-on pioglitazone ( 15 - 45 mg ) or a sulfonylurea ( 5 - 15 mg glibenclamide , 2 - 6 mg glimepiride , or 30 - 120 mg gliclazide , in accordance with local practice ) . The trial was unblinded , but event adjudicators were unaware of treatment assignment . The primary outcome , assessed with a Cox proportional-hazards model , was a composite of first occurrence of all-cause death , non-fatal myocardial infa rct ion , non-fatal stroke , or urgent coronary revascularisation , assessed in the modified intention-to-treat population ( all r and omly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria ) . This study is registered with Clinical Trials.gov , number NCT00700856 . FINDINGS Between Sept 18 , 2008 , and Jan 15 , 2014 , 3028 patients were r and omly assigned and included in the analyses . 1535 were assigned to pioglitazone and 1493 to sulfonylureas ( glibenclamide 24 [ 2 % ] , glimepiride 723 [ 48 % ] , gliclazide 745 [ 50 % ] ) . At baseline , 335 ( 11 % ) participants had a previous cardiovascular event . The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months . The primary outcome occurred in 105 patients ( 1·5 per 100 person-years ) who were given pioglitazone and 108 ( 1·5 per 100 person-years ) who were given sulfonylureas ( hazard ratio 0·96 , 95 % CI 0·74 - 1·26 , p=0·79 ) . Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group ( 148 [ 10 % ] vs 508 [ 34 % ] , p<0·0001 ) . Moderate weight gain ( less than 2 kg , on average ) occurred in both groups . Rates of heart failure , bladder cancer , and fractures were not significantly different between treatment groups . INTERPRETATION In this long-term , pragmatic trial , incidence of cardiovascular events was similar with sulfonylureas ( mostly glimepiride and gliclazide ) and pioglitazone as add-on treatments to metformin . Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events , although pioglitazone was associated with fewer hypoglycaemia events . FUNDING Italian Medicines Agency , Diabete Ricerca , and Italian Diabetes Society " Field ( clinical ) trials are indispensable . They will continue to be an ordeal . They lack glamour , they strain our re sources and our patience , and they protract the moment of truth to excruciating limits . Still , they are among the most challenging tests of our skills .... If , in major medical dilemmas the alternative is to pay the cost of perpetual uncertainty , have we really any choice ? " 1 The clinical trial of the effect of hypoglycemic agents on the vascular complications of diabetes mellitus conducted by the University Group Program ( UGDP ) for the past ten years bears witness to the truthfulness of the above quotation . The hypothesis that control of the blood glucose level prevents or delays the vascular complications of diabetes has been supported so far only by evidence which is largely conjectural . 2 Such a relationship can be documented only with prospect i ve study of patients r and omly assigned to treatment regimens that BACKGROUND Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin , a dipeptidyl peptidase 4 inhibitor , to usual care in patients with type 2 diabetes and cardiovascular disease . METHODS In this r and omized , double-blind study , we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy . Open-label use of antihyperglycemic therapy was encouraged as required , aim ed at reaching individually appropriate glycemic targets in all patients . To determine whether sitagliptin was noninferior to placebo , we used a relative risk of 1.3 as the marginal upper boundary . The primary cardiovascular outcome was a composite of cardiovascular death , nonfatal myocardial infa rct ion , nonfatal stroke , or hospitalization for unstable angina . RESULTS During a median follow-up of 3.0 years , there was a small difference in glycated hemoglobin levels ( least-squares mean difference for sitagliptin vs. placebo , -0.29 percentage points ; 95 % confidence interval [ CI ] , -0.32 to -0.27 ) . Overall , the primary outcome occurred in 839 patients in the sitagliptin group ( 11.4 % ; 4.06 per 100 person-years ) and 851 patients in the placebo group ( 11.6 % ; 4.17 per 100 person-years ) . Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome ( hazard ratio , 0.98 ; 95 % CI , 0.88 to 1.09 ; P<0.001 ) . Rates of hospitalization for heart failure did not differ between the two groups ( hazard ratio , 1.00 ; 95 % CI , 0.83 to 1.20 ; P=0.98 ) . There were no significant between-group differences in rates of acute pancreatitis ( P=0.07 ) or pancreatic cancer ( P=0.32 ) . CONCLUSIONS Among patients with type 2 diabetes and established cardiovascular disease , adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events , hospitalization for heart failure , or other adverse events . ( Funded by Merck Sharp & Dohme ; TECOS Clinical Trials.gov number , NCT00790205 . ) BACKGROUND Glucagon-like peptide 1 receptor agonists differ in chemical structure , duration of action , and in their effects on clinical outcomes . The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown . We aim ed to determine the safety and efficacy of albiglutide in preventing cardiovascular death , myocardial infa rct ion , or stroke . METHODS We did a double-blind , r and omised , placebo-controlled trial in 610 sites across 28 countries . We r and omly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease ( at a 1:1 ratio ) to groups that either received a subcutaneous injection of albiglutide ( 30 - 50 mg , based on glycaemic response and tolerability ) or of a matched volume of placebo once a week , in addition to their st and ard care . Investigators used an interactive voice or web response system to obtain treatment assignment , and patients and all study investigators were masked to their treatment allocation . We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death , myocardial infa rct ion , or stroke , which was assessed in the intention-to-treat population . If non-inferiority was confirmed by an upper limit of the 95 % CI for a hazard ratio of less than 1·30 , closed testing for superiority was prespecified . This study is registered with Clinical Trials.gov , number NCT02465515 . FINDINGS Patients were screened between July 1 , 2015 , and Nov 24 , 2016 . 10 793 patients were screened and 9463 participants were enrolled and r and omly assigned to groups : 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo . On Nov 8 , 2017 , it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued , and participants returned for a final visit and discontinuation from study treatment ; the last patient visit was on March 12 , 2018 . These 9463 patients , the intention-to-treat population , were evaluated for a median duration of 1·6 years and were assessed for the primary outcome . The primary composite outcome occurred in 338 ( 7 % ) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 ( 9 % ) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group ( hazard ratio 0·78 , 95 % CI 0·68 - 0·90 ) , which indicated that albiglutide was superior to placebo ( p<0·0001 for non-inferiority ; p=0·0006 for superiority ) . The incidence of acute pancreatitis ( ten patients in the albiglutide group and seven patients in the placebo group ) , pancreatic cancer ( six patients in the albiglutide group and five patients in the placebo group ) , medullary thyroid carcinoma ( zero patients in both groups ) , and other serious adverse events did not differ between the two groups . There were three ( < 1 % ) deaths in the placebo group that were assessed by investigators , who were masked to study drug assignment , to be treatment-related and two ( < 1 % ) deaths in the albiglutide group . INTERPRETATION In patients with type 2 diabetes and cardiovascular disease , albiglutide was superior to placebo with respect to major adverse cardiovascular events . Evidence -based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes . FUNDING GlaxoSmithKline BACKGROUND The cardiovascular safety profile of dapagliflozin , a selective inhibitor of sodium – glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes , is undefined . METHODS We r and omly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo . The primary safety outcome was a composite of major adverse cardiovascular events ( MACE ) , defined as cardiovascular death , myocardial infa rct ion , or ischemic stroke . The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure . Secondary efficacy outcomes were a renal composite ( ≥40 % decrease in estimated glomerular filtration rate to < 60 ml per minute per 1.73 m2 of body‐surface area , new end‐stage renal disease , or death from renal or cardiovascular causes ) and death from any cause . RESULTS We evaluated 17,160 patients , including 10,186 without atherosclerotic cardiovascular disease , who were followed for a median of 4.2 years . In the primary safety outcome analysis , dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE ( upper boundary of the 95 % confidence interval [ CI ] , < 1.3 ; P<0.001 for noninferiority ) . In the two primary efficacy analyses , dapagliflozin did not result in a lower rate of MACE ( 8.8 % in the dapagliflozin group and 9.4 % in the placebo group ; hazard ratio , 0.93 ; 95 % CI , 0.84 to 1.03 ; P=0.17 ) but did result in a lower rate of cardiovascular death or hospitalization for heart failure ( 4.9 % vs. 5.8 % ; hazard ratio , 0.83 ; 95 % CI , 0.73 to 0.95 ; P=0.005 ) , which reflected a lower rate of hospitalization for heart failure ( hazard ratio , 0.73 ; 95 % CI , 0.61 to 0.88 ) ; there was no between‐group difference in cardiovascular death ( hazard ratio , 0.98 ; 95 % CI , 0.82 to 1.17 ) . A renal event occurred in 4.3 % in the dapagliflozin group and in 5.6 % in the placebo group ( hazard ratio , 0.76 ; 95 % CI , 0.67 to 0.87 ) , and death from any cause occurred in 6.2 % and 6.6 % , respectively ( hazard ratio , 0.93 ; 95 % CI , 0.82 to 1.04 ) . Diabetic ketoacidosis was more common with dapagliflozin than with placebo ( 0.3 % vs. 0.1 % , P=0.02 ) , as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events ( 0.9 % vs. 0.1 % , P<0.001 ) . CONCLUSIONS In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease , treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure , a finding that reflects a lower rate of hospitalization for heart failure . ( Funded by AstraZeneca ; DECLARE – TIMI 58 Clinical Trials.gov number , NCT01730534 . BACKGROUND Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes , particularly those with concomitant cardiovascular diseases , than in most other population s. We assessed the effects of lixisenatide , a glucagon-like peptide 1-receptor agonist , on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event . METHODS We r and omly assigned patients with type 2 diabetes who had had a myocardial infa rct ion or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined st and ards of care . The trial was design ed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo , as defined by an upper boundary of the 95 % confidence interval for the hazard ratio of less than 1.3 and 1.0 , respectively , for the primary composite end point of cardiovascular death , myocardial infa rct ion , stroke , or hospitalization for unstable angina . RESULTS The 6068 patients who underwent r and omization were followed for a median of 25 months . A primary end-point event occurred in 406 patients ( 13.4 % ) in the lixisenatide group and in 399 ( 13.2 % ) in the placebo group ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.89 to 1.17 ) , which showed the noninferiority of lixisenatide to placebo ( P<0.001 ) but did not show superiority ( P=0.81 ) . There were no significant between-group differences in the rate of hospitalization for heart failure ( hazard ratio in the lixisenatide group , 0.96 ; 95 % CI , 0.75 to 1.23 ) or the rate of death ( hazard ratio , 0.94 ; 95 % CI , 0.78 to 1.13 ) . Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia , pancreatitis , pancreatic neoplasms , or allergic reactions than was placebo . CONCLUSIONS In patients with type 2 diabetes and a recent acute coronary syndrome , the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events . ( Funded by Sanofi ; ELIXA Clinical Trials.gov number , NCT01147250 . ) |
10,850 | 31,494,601 | No concerns relating to long-term adverse events were reported .
For a range of treatments there was no evidence linking them with unfavourable pain outcomes .
Conclusions To prevent chronic pain after TKR , several perioperative interventions show benefits and merit further research .
Good- quality studies assessing long-term pain after perioperative interventions are feasible and necessary to ensure that patients with osteoarthritis achieve good long-term outcomes after TKR | Objectives For many people with advanced osteoarthritis , total knee replacement ( TKR ) is an effective treatment for relieving pain and improving function .
Features of perioperative care may be associated with the adverse event of chronic pain 6 months or longer after surgery ; effects may be direct , for example , through nerve damage or surgical complications , or indirect through adverse events .
This systematic review aims to evaluate whether non-surgical perioperative interventions prevent long-term pain after TKR . | Background Recently , a number of studies using intra-articular application of tranexamic acid ( IA-TXA ) , with different dosage and techniques , successfully reduced postoperative blood loss in total knee replacement ( TKR ) . However , best of our knowledge , the very low dose of IA-TXA with drain clamping technique in conventional TKR has not been yet studied . This study aim ed to evaluate the effectiveness and dose-response effect of two low-dose IA-TXA regimens in conventional TKR on blood loss and blood transfusion reduction . Methods Between 2010 and 2011 , a triple-blinded r and omized controlled study was conducted in 135 patients undergoing conventional TKR . The patients were allocated into three groups according to intra-articular solution received : Control group ( physiologic saline ) , TXA-250 group ( TXA 250 mg ) , and TXA-500 group ( TXA 500 mg ) . The solution was injected after wound closure followed by drain clamping for 2 hours . Blood loss and transfusion were recorded . Duplex ultrasound was performed . Functional outcome and complication were followed for one year . Results There were forty-five patients per groups . The mean total hemoglobin loss was 2.9 g/dL in control group compared with 2.2 g/dL in both TXA groups ( p > 0.001 ) . Ten patients ( 22 % , control ) , six patients ( 13 % , TXA-250 ) and none ( TXA-500 ) required transfusion ( p = 0.005 ) . Thromboembolic events were detected in 7 patients ( 4 controls , 1 TXA-250 , and 2 TXA-500 ) . Functional outcome was non-significant difference between groups . Conclusions Combined low-dose IA-TXA , as 500 mg , with 2-hour clamp drain is effective for reducing postoperative blood loss and transfusion in conventional TKR without significant difference in postoperative knee function or complication . Trial registration Clinical Trials.gov NCT01850394 Background Total knee arthroplasty ( TKA ) is often associated with a severe local inflammatory reaction which , unless controlled , leads to persistent pain up to one year after surgery . St and ard and accelerated rehabilitation protocol s are currently being implemented after TKA , but no consensus exists regarding the long-term effects . Biophysical stimulation with pulsed electromagnetic fields ( PEMFs ) has been demonstrated to exert an anti-inflammatory effect , to promote early functional recovery and to maintain a positive long-term effect in patients undergoing joint arthroscopy . The aim of this study was to evaluate whether PEMFs can be used to limit the pain and enhance patient recovery after TKA . Methods A prospect i ve , r and omized , controlled study in 30 patients undergoing TKA was conducted . Patients were r and omized into experimental PEMFs or a control group . Patients in the experimental group were instructed to use I-ONE stimulator 4hours/day for 60days . Postoperatively , all patients received the same rehabilitation program . Treatment outcome was assessed using the Knee Society Score , SF-36 Health-Survey and VAS . Patients were evaluated pre-operatively and one , two , six and 12 months after TKA . Joint swelling and Non Steroidal Anti Inflammatory Drug ( NSAID ) consumption were recorded . Comparisons between the two groups were carried out using a two-tail heteroschedastic Student ’s t-test . Analysis of variance for each individual subject during the study was performed using ANOVA for multiple comparisons , applied on each group , and a Dunnet post hoc test . A p value < 0.05 was considered statistically significant . Results Pre-operatively , no differences were observed between groups in terms of age , sex , weight , height , Knee-Score , VAS , SF-36 and joint swelling , with the exception of the Functional Score . The Knee-Score , SF-36 and VAS demonstrated significantly positive outcomes in the I-ONE stimulated group compared with the controls at follow-ups . In the I-ONE group , NSAID use was reduced and joint swelling resolution was more rapid than in controls . The effect of I-ONE therapy was maintained after use of the device was discontinued . Conclusions The results of the study show early functional recovery in the I-ONE group . I-ONE therapy should be considered after TKA to prevent the inflammatory reaction elicited by surgery , for pain relief and to speed functional recovery . Trial registration Current Controlled Trials IS RCT OBJECTIVE Continuous femoral nerve block ( CFNB ) , guided by ultrasound combined nerve stimulations , offers advantages for both sides and provides effective postoperative analgesia after total knee arthroplasty ( TKA ) . The objective of this study was to evaluate the medium-term impact of continuous femoral nerve block on knee function and quality of life in patients following TKA . METHODS This was a follow-up study . Total 168 adult patients scheduled for elective TKA were r and omly allocated to receive postoperative continuous femoral nerve block guided by ultrasound combined nerve stimulator ( group CFNB , n = 82 ) or patient-controlled epidural analgesia ( group PCEA , n = 86 ) . Quality of life , knee function , patient satisfaction , pain medication and associated adverse effects were compared at 1 , 3 , 6 , and 12 months postoperatively . Quality of life was assessed using the Medical Outcomes Study Short Form-36 Health Survey ( MOS SF-36 ) , and clinical results were assessed using the Hospital for Special Surgery ( HSS ) Knee Scoring System . Patient satisfaction scores were divided into four categories . RESULTS A total of 162 patients completed the 12-month follow-up . The CFNB group patients had significantly improved SF-36 scores and physical function at 1 month postoperatively ( P < 0.05 ) ; the remaining seven dimensions were similar between the two groups . No differences were observed at 3 , 6 or 12 months . HSS scores for the four observational time points were comparable . The CFNB group patients reported less pain ; improved knee function , maximum flexion and strength ; less celecoxib consumption and fewer side effects at 1 month than the PCEA group patients . The satisfaction score at 12 months decreased significantly , compared with that at 1 month in both groups ( 3.6 to 2.95 and 3.4 to 2.45 , respectively ) . No difference in satisfaction score was observed between the two groups . CONCLUSIONS Continuous femoral nerve block not only could provide effective postoperative analgesia but also could improve joint function and quality of life in patients at one month postoperatively . Continuous femoral nerve block is a good choice for postoperative analgesia after TKA Purpose Despite the documented blood-saving effects of tranexamic acid ( TNA ) in total knee arthroplasty ( TKA ) , the question whether clinical values of TNA are identical in unilateral and bilateral TKAs remains unclear . This study was undertaken to determine the clinical values of TNA in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol in terms of efficacy ( total blood loss and transfusion rate ) and safety ( the incidences of symptomatic deep vein thrombosis and pulmonary embolism ) . Methods One hundred and eighty unilateral and 146 bilateral TKA patients were r and omized into TNA group or control group . In unilateral TKA patients , TNA ( 10 mg/kg ) was administered intravenously 20 min before tourniquet deflation and repeated 3 h after surgery . In bilateral TKA patients , one more dose ( 10 mg/kg ) was given before tourniquet deflation in the second TKA . A contemporary blood-saving protocol was applied to all patients . The TNA and control groups were compared separately in unilateral and bilateral TKA patients for the efficacy and safety variables . Results In unilateral TKA patients , the TNA group had less total blood loss ( 905 vs. 1,018 mL , p = 0.018 ) than the control group , but there was no difference in the allogenic transfusion rate ( 1 vs. 7 % , n.s . ) . In bilateral TKA patients , the TNA group showed no differences in total blood loss ( 1,282 vs. 1,379 mL , n.s . ) , but a significant reduction in the allogenic transfusion rate ( 7 vs. 27 % , p = 0.002 ) . No symptomatic deep vein thrombosis or pulmonary embolism was found in all patients . Conclusion This study demonstrates that the use of TNA reduces total blood loss , but the effects on the transfusion rate can differ depending on the type of TKAs ( unilateral vs. bilateral ) and the blood-saving protocol s . Level of evidence Therapeutic study , Level I ( double blind r and omized controlled trial ) Introduction The surgical wound of total knee arthroplasty ( TKA ) needs continuous flexion and extension movement . Silicone gel treatment is widely used to treat hypertrophic scars and keloids since it is easily applied and prevents scar pain and itching . The aim of this study was to evaluate the clinical efficacy and safety of silicone gel applied to surgical scars of TKA on postoperative scar pain and pruritus . Material s and methods One hundred TKAs were r and omized into a silicone gel group ( silicone gel was applied to the wound after stitch-out for 1 month ) or a placebo group . The postoperative scar pain and pruritus were evaluated with the use of a visual analog scale ( VAS ) at postoperative 3 months , 6 months and 1 year . Scar assessment was done using the Vancouver scar scale by evaluating scar pigmentation , vascularity , pliability , and height . Results Although silicone gel group showed better pigmentation and height scales than placebo group ( P < 0.05 ) , there were no significant differences in the postoperative scar pain and pruritus VAS scores between the groups ( P > 0.05 ) . Conclusions Application of silicone gel had no beneficial effects on scar pain and itching relief during the early postoperative period of TKA.Level of evidence I-R and omized Controlled Background Postoperative knee swelling is common and impairs early postoperative function following total knee arthroplasty . It was hypothesised that the use of a short-stretch , inelastic compression b and age would reduce knee swelling and improve pain and early function . The aim of this study was to provide preliminary data and test feasibility with a view to informing a larger , future trial . Methods Fifty consecutive patients selected for primary total knee arthroplasty underwent distance r and omisation to receive a short-stretch , inelastic compression b and age or a st and ard wool and crepe b and age for the first 24 h postoperatively . Study feasibility including recruitment rates , retention rates and complications were analysed . The Oxford Knee Score , the EQ-5D-3L index score , knee swelling , knee range of motion , visual analogue pain score and length of stay were compared between groups . Analysis of covariance ( ANCOVA ) was performed adjusting for the preoperative measurement . Results Sixty-eight percent of eligible patients were recruited into the trial . The retention rate was 88 % . There were no complications regarding compression b and age use . There was a greater mean but non-significant improvement in Oxford Knee Score ( p = 0.580 ; point estimate = 2.1 ; 95 % CI −3.288 to 7.449 ) and EQ-5D-3L index score ( p = 0.057 ; point estimate = 0.147 ; 95 % CI −0.328 to 0.005 ) in the compression b and age group at 6 months . There was no significant difference between groups regarding knee swelling , knee range of motion , visual analogue pain score , complications and length of stay . Conclusion Preliminary data suggests that the use of an inelastic , short-stretch compression b and age following total knee arthroplasty is a safe technique that is acceptable to patients . A larger , multicentre trial is required to determine its effect postoperatively . Trial registration The study was registered with Current Controlled Trials , identifier : IS RCT N86903140 . Registered on 30 May 2013 OBJECTIVES . To evaluate the effectiveness of our new multidisciplinary pathway for total knee replacement patients and compare outcomes after continuous femoral nerve blockade versus conventional patient-controlled analgesia for postoperative pain . DESIGN . R and omised controlled trial in a routine clinical setting . SETTING . Acute orthopaedic wards and operating theatres , Yan Chai Hospital , Hong Kong . PATIENTS . Sixty patients underwent elective unilateral total knee replacement under spinal anaesthesia from May 2009 to September 2011 and were r and omly assigned to continuous femoral nerve blockade or conventional patient-controlled analgesia ( 30 patients in each group ) . MAIN OUTCOME MEASURES . Quality of pain control was evaluated by pain scores at rest and during mobilisation , opioid consumption , frequency of side-effects , and patient satisfaction score . Rehabilitation progress was assessed according to the day of first starting weight-bearing exercise , day of independent walking in the ward with aid , Timed Up and Go test , and time elapsing till discharge . Surgical outcome was assessed by the Knee Society score 6 months after discharge , re-admissions , and occurrence of complications . RESULTS . Patients having continuous femoral nerve blockade tended to have less pain on movement and achieved earlier mobilisation than those having patient-controlled analgesia . The former group consumed less opioids , had fewer side-effects , and were more satisfied with their postoperative analgesia . Both groups showed an equally high degree of satisfaction with the new management pathway . Hospital stays , surgical outcomes , and frequency of complications were similar in the two groups . CONCLUSION . Continuous femoral nerve blockade proved to be a feasible and better alternative mode of postoperative analgesia than our conventional patient-controlled analgesia . Our new multidisciplinary management pathway and multimodal analgesic regimen featuring the continuous femoral nerve blockade appeared beneficial to patients and effective in our clinical setting BACKGROUND / AIM Total knee replacement ( TKR ) surgery is one of the most frequent and the most extensive procedures in orthopedic surgery , accompanied with some serious complications . Perioperative blood loss is one of the most serious losses , so it is vital to recognize and treat such losses properly . Autologous blood transfusion is the only true alternative for the allogeneic blood . The aim of this study was to to examine if autologous blood transfusion reduces usage of allogenic blood in total knee replacement surgery , as well as to examine possible effect of autologous blood transfusion on postoperative complications , recovery and hospital stay of patients after total knee replacement surgery . METHODS During the controlled , prospect i ve , r and omised study we compared two groups of patients ( n = 112 ) with total prosthesis implanted in their knee . The group I consisted of the patients who received the transfusion of other people 's ( allogeneic ) blood ( n = 57 ) and the group II of the patients whose blood was collected postoperatively and then given them [ their own ( autologous ) blood ] ( n = 55 ) . The transfusion trigger for both groups was hemoglobin level of 85 g/L. RESULTS In the group of patients whose blood was collected perioperatively only 9 ( 0.9 % ) of the patients received transfusion of allogeneic blood , as opposed to the control group in which 98.24 % of the patients received the transfusion of allogeneic blood ( p < or = 0.01 ) . The patients whose blood was collected stayed in hospital for 6.18 days , while the patients of the control group stayed 7.67 days ( p < 0.01 ) . CONCLUSION Autologous blood transfusion is a very effective method for reducing consumption of allogenic blood and thus , indirectly for reducing all complications related to allogenic blood transfusion . There is also a positive influence on postoperative recovery after total knee replacement surgery due to the reduction of hospital stay , and indirectly on the reduction of hospital costs OBJECTIVES To study responsiveness and establish the minimal clinical ly important differences ( MCIDs ) and minimal detectable change ( MDC ) in patients undergoing total knee replacement ( TKR ) using the Short Form 36 ( SF-36 ) and Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . METHODS Prospect i ve observational study in three public hospitals of all consecutive patients on waiting lists to undergo TKR intervention with diagnosis of knee osteoarthritis ( OA ) . Patients were asked to complete before the intervention and at 6 months and 2 years afterward the SF-36 and the WOMAC health-related quality of life question naires ( HRQoL ) , and additional transition questions which measured the changes in their joint at 6 months . In both question naires the possible range of values is from 0 to 100 points . RESULTS In WOMAC improvement at 6 months after a TKR was between 27 ( stiffness ) and 31 points ( pain ) . The SF-36 showed improvements between the 28.3 points of role physical and 2.79 of general health . From 6 months to 2 years , WOMAC improvements were between 2 and 6 points . The MCID ranged from 14.52 ( stiffness ) to 22.87 ( pain ) on the WOMAC and in the physical domains of SF-36 from 11.56 ( physical function ) to 16.86 ( bodily pain ) . On the WOMAC , the MDC ranged from 13.11 ( function ) to 29.12 ( stiffness ) , and on SF-36 from 19.50 ( physical function ) to 41.23 ( social functioning ) . CONCLUSIONS The MCID for TKR is around 15 on WOMAC , while with the SF-36 of at least 10 points . These values should not be considered as absolute thresholds Purpose It has been reported that even one year after total knee arthroplasty ( TKA ) , a relevant percentage of patients does not attain complete recovery and indicate unfavourable long-term pain outcome . We compared the clinical outcome of 33 patients undergoing TKA r and omly assigned to the control or the pulsed electromagnetic field group ( I-ONE therapy ) . Methods I-ONE therapy was administered postoperatively four hours per day for 60 days . Patients were assessed before surgery and then at one , two and six months postoperatively using international scores . Results One month after TKA , pain , knee swelling and functional score were significantly better in the treated compared with the control group . Pain was still significantly lower in the treated group at the six month follow-up . Three years after surgery , severe pain and occasional walking limitations were reported in a significantly lower number of patients in the treated group . Conclusions Advantages deriving from early control of joint inflammation may explain the maintenance of results at follow-up . I-ONE therapy should be considered an effective completion of the TKA procedure Background Pain management after TKA remains challenging and the efficacy of continuously infused intraarticular anesthetics remains a controversial topic . Questions / purpose sWe compared the side effect profile , analgesic efficacy , and functional recovery between patients receiving a continuous intraarticular infusion of ropivacaine and patients receiving an epidural plus femoral nerve block ( FNB ) after TKA . Methods Ninety-four patients undergoing unilateral TKA were prospect ively r and omized to receive a spinal-epidural analgesic infusion plus a single-injection FNB or a spinal anesthetic plus a continuous postoperative intraarticular infusion of 0.2 % ropivacaine . All patients were blinded to their treatment with placebo saline catheters . Blinded coinvestigators collected data concerning side effect profiles ( nausea , hypotension ) , analgesic efficacy ( VAS pain scores , narcotic usage ) , and functional recovery ( timed up and go test , quadriceps strength , WOMAC scores , Knee Society scores , early postoperative ambulatory ability , in-hospital falls ) . All complications and adverse events were recorded . Results The frequency of nausea and hypertension was not different between the study groups . During the first 12 and 24 postoperative hours , the mean maximum VAS pain scores were higher in the ropivacaine group than in the epidural group ( first 12 hours : 3.93 versus 1.14 , respectively , p < 0.0001 ; 12–24 hours : 3.52 versus 1.93 , respectively , p = 0.008 ) . After 24 hours , pain scores were similar between groups . Narcotic consumption was significantly higher in the ropivacaine group on the day of surgery , but overall in-hospital narcotic usage was similar between groups . There were no clinical ly important differences in functional recovery between groups at any time point , but patients in the epidural group were more likely to have knee buckling ( 32.7 % versus 6.7 % , p = 0.002 ) and delayed ambulation ( 16.3 % versus 0.0 % , p = 0.006 ) than patients in the ropivacaine group , though not in-hospital falls . No infections occurred in either group , and the frequency of complications was not different between groups . Conclusions A continuous intraarticular infusion of ropivacaine can be recommended as a safe , effective alternative to epidural analgesia plus single-injection FNB after TKA . Improved analgesic efficacy in the group that received epidural analgesia plus single-injection FNB must be weighed against the disadvantage of a higher likelihood of knee buckling and delayed ambulation with that treatment approach . Level of Evidence Level I , therapeutic study . See Instructions for Authors for a complete description of levels of evidence A high-dose local tranexamic acid has been introduced in total knee arthroplasty for bleeding control . We are not sure about the systemic absorption and side effects . The aim of this study was to evaluate the effect of low dosage of intra-articular tranexamic acid injection combined with 2-hour clamp drain in minimally bleeding computer-assisted surgery total knee replacement ( CAS-TKR ) . A prospect i ve r and omized controlled trial was conducted in a total of 48 patients underwent CAS-TKR . The patients were r and omly assigned to receive either of a mixed intra-articular solution of tranexamic acid 250 mg with physiologic saline ( TXA group ) , or physiologic saline ( control group ) and then followed by clamp drain for 2 hours . Postoperative blood loss was measured by three different methods as drainage volume , total hemoglobin loss and calculated total blood loss . Transfusion requirement and postoperative complications were recorded . All patients were screened for deep vein thrombosis and the functional outcomes were evaluated at 6 months after surgery . The mean postoperative drainage volume , total hemoglobin loss and calculated total blood loss in TXA group were 308.8 mL , 2.1 g/dL and 206.3 mL compared to 529.0 mL , 3.0 g/dL and 385.1 mL in the control group ( P=0.0003 , 0.0005 and < 0.0001 respectively ) . Allogenic blood transfusion was needed for one patient ( 4.2 % ) in TXA group and for eight patients ( 33.3 % ) in the control group . Postoperative knee scores were not significantly different between groups . No deep vein thrombosis , infection or wound complication was detected in both groups . In this study , low dose intra-articular tranexamic acid injection combined with 2-hour clamping drain was effective for reducing postoperative blood loss and transfusion requirement in CAS-TKR without significant difference in postoperative complications or functional outcomes Background The ideal local anesthetic regime for femoral nerve block that balances analgesia with mobility after total knee arthroplasty ( TKA ) remains undefined . Questions / purpose sWe compared two volumes and concentrations of a fixed dose of ropivacaine for continuous femoral nerve block after TKA to a single injection femoral nerve block with ropivacaine to determine ( 1 ) time to discharge readiness ; ( 2 ) early pain scores and analgesic consumption ; and ( 3 ) functional outcomes , including range of motion and WOMAC scores at the time of recovery . Methods Ninety-nine patients were allocated to one of three continuous femoral nerve block groups for this r and omized , placebo-controlled , double-blind trial : a high concentration group ( ropivacaine 0.2 % infusion ) , a low concentration group ( ropivacaine 0.1 % infusion ) , or a placebo infusion group ( saline 0.9 % infusion ) . Infusions were discontinued on postoperative Day ( POD ) 2 . The primary outcome was time to discharge readiness . Secondary outcomes included opioid consumption , pain , and functional outcomes . Ninety-three patients completed the study protocol ; the study was halted early because of unanticipated changes to pain protocol s at the host institution , by which time only 61 % of the required number of patients had been enrolled . Results With the numbers available , the mean time to discharge readiness was not different between groups ( high concentration group , 62 hours [ 95 % confidence interval [ CI ] , 51–72 hours ] ; low concentration group , 73 hours [ 95 % CI , 63–83 hours ] ; placebo infusion group 65 hours [ 95 % CI , 56–75 hours ] ; p = 0.27 ) . Patients in the low concentration group consumed significantly less morphine during the period of infusion ( POD 1 , high concentration group , 56 mg [ 95 % CI , 42–70 mg ] ; low concentration group , 35 mg [ 95 % CI , 27–43 mg ] ; placebo infusion group , 48 mg [ 95 % CI , 38–59 mg ] , p = 0.02 ; POD 2 , high concentration group , 50 mg [ 95 % CI , 41–60 mg ] ; low concentration group , 33 mg [ 95 % CI , 24–42 mg ] ; placebo infusion group , 39 mg [ 95 % CI , 30–48 mg ] , p = 0.04 ) ; however , there were no important differences in pain scores or opioid-related side effects with the numbers available . Likewise , there were no important differences in functional outcomes between groups . Conclusions Based on this study , which was terminated prematurely before the desired sample size could be achieved , we were unable to demonstrate that varying the concentration and volume of a fixed-dose ropivacaine infusion for continuous femoral nerve block influences time to discharge readiness when compared with a conventional single-injection femoral nerve block after TKA . A low concentration of ropivacaine infusion can reduce postoperative opioid consumption but without any important differences in pain scores , side effects , or functional outcomes . These pilot data may be used to inform the statistical power of future r and omized trials . Level of Evidence Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence This study was conducted to compare postoperative total knee arthroplasty rehabilitation protocol s. The hypothesis of this study was that patients undergoing total knee arthroplasty could achieve range of motion and hospital discharge in the same period using a postoperative rehabilitation protocol that did not use a continuous passive motion machine . This r and omized prospect i ve study compared 46 total knee arthroplasties in which a continuous passive motion machine was used with 37 total knees that were rehabilitated with early passive flexion of the knee ( named drop and dangle protocol ) . Postoperative physical therapy regimens were otherwise the same for both groups . Surgical technique was the same for both groups except for closure which was performed in the drop and dangle group with the knee at 90 ° to 95 ° flexion . Only patients with osteoarthritis were included in the study , and in both groups of patients received the same prosthetic components . Patients in the drop and dangle group were discharged from the hospital 1 day earlier ( p = 0.01 ) and had a statistically better extension range of 2.8 ° at 6 months ( p = 0.03 ) . Knees in the drop and dangle group had less drainage ( p = 0.06 ) . Range of motion and hospital discharge can be achieved in a similar time interval with the drop and dangle technique as with using a continuous passive motion device , and that such a device is not required for postoperative knee rehabilitation Reducing blood loss during primary total knee arthroplasty ( TKA ) can improve outcomes by reducing transfusion requirements and wound complications . We examined the use of bovine thrombin to augment hemostasis during primary TKA . A double-blinded r and omized trial was performed with 80 primary TKA patients . Half received intraarticular bovine thrombin at the time of wound closure , and half did not . Hemoglobin levels in the study group did decline less than the control group , but no statistically significant difference was found in rates of transfusion , drain outputs , length of stay , or Knee Society scores . This agent does appear to slightly reduce blood loss , but routine use is not cost effective . Thrombin may be considered for patients who would benefit more from greater blood conservation BACKGROUND Home-based rehabilitation is increasingly utilized to reduce health-care costs ; however , with a shorter hospital stay , the possibility arises for an increase in adverse clinical outcomes . We evaluated the effectiveness and cost of care of home-based compared with inpatient rehabilitation following primary total hip or knee joint replacement . METHODS We r and omized 234 patients , using block r and omization techniques , to either home-based or inpatient rehabilitation following total joint replacement . All patients followed st and ardized care pathways and were evaluated , with use of vali date d outcome measures ( Western Ontario and McMaster Universities Osteoarthritis Index [ WOMAC ] , Short Form-36 , and patient satisfaction ) , prior to surgery and at three and twelve months following surgery . The primary outcome was the WOMAC function score at three months after surgery . RESULTS The mean length of stay ( and st and ard deviation ) in the acute care hospital was 6.3 + /- 2.5 days for the group design ated for inpatient rehabilitation prior to transfer to that facility compared with 7.0 + /- 3.0 days for the home-based rehabilitation group prior to discharge home ( p = 0.06 ) . The mean length of stay in inpatient rehabilitation was 17.7 + /- 8.6 days . The mean number of postoperative home-based rehabilitation visits was eight . The prevalence of postoperative complications up to twelve months postoperatively was similar in both groups , which each had a 2 % rate of dislocation and a 3 % rate of clinical ly important deep venous thrombosis . The prevalence of infection was 0 % in the home-based group and 2 % in the inpatient group . None of these differences was clinical ly important . Both groups showed substantial improvements at three and twelve months , with no significant differences between the groups with respect to WOMAC , Short Form-36 , or patient satisfaction scores ( p > 0.05 ) . The total episode-of-care costs ( in Canadian dollars ) for the inpatient rehabilitation and home-based rehabilitation arms were $ 14,532 and $ 11,082 , respectively ( p < 0.01 ) . CONCLUSIONS Despite concerns about early hospital discharge , there was no difference in pain , functional outcomes , or patient satisfaction between the group that received home-based rehabilitation and the group that had inpatient rehabilitation . On the basis of our findings , we recommend the use of a home-based rehabilitation protocol following elective primary total hip or knee replacement as it is the more cost-effective strategy Effect of continuous passive motion ( CPM ) protocol s on outcomes after total knee arthroplasty . In this prospect i ve r and omized controlled study , 147 patients were assigned to 1 of 3 treatment groups : CPM from 0 degrees to 40 degrees and increased by 10 degrees per day , CPM from 90 degrees to 50 degrees ( early flexion ) and gradually progressed into full extension over a 3-day period , and a no-CPM group . The CPM was administered twice a day for 3 hours over a 5-day period . All patients participated in the same postoperative physiotherapy program . Patients were assessed preoperatively , day 5 , 3 months , and 1 year postoperatively . The early flexion group had significantly more range of flexion than both the st and ard and control groups at day 5 . There was no significant difference between the groups for any other variable tested at any time frame . Key words : total knee arthroplasty , CPM , rehabilitation , outcomes The effects of using a tourniquet during total knee arthroplasty were studied in 80 patients r and omly allocated to two groups , either with or without a tourniquet . The groups were similar in mean age , gender , preoperative knee score and radiographic grading and the patients were all operated on by the same surgeon using one type of prosthesis . There was no significant difference between the two groups in operating time or total blood loss but postoperative pain was less in the patients in whom a tourniquet had not been used . They achieved straight-leg raising and knee flexion earlier and had fewer superficial wound infections and deep-vein thromboses . Total knee arthroplasty can be safely performed without the use of the tourniquet with the benefit that several adverse effects associated with its use can be avoided OBJECTIVE To determine the minimal perceptible clinical improvement ( MPCI ) in patients with osteoarthritis ( OA ) with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) question naire , and patient and investigator global assessment of disease status in r and omized clinical trials for treatment of OA . METHODS Subjects with OA of the knee or hip were r and omized to receive either rofecoxib 12.5 or 25 mg once daily , ibuprofen 800 mg 3 times daily , or placebo for 6 weeks . The WOMAC and global assessment s were completed at baseline and Weeks 2 , 4 , and 6 . A patient global assessment of response to therapy ( 0 to 4 scale ) was used to " anchor " the WOMAC scores . MPCI was defined as the difference in mean change from baseline in WOMAC ( 100 mm normalized visual analog scale , VAS ) between patients with 0 = " None " global response to therapy and patients with 1 = " Poor " global response to therapy . RESULTS MPCI was determined to be 9.7 , 9.3 , and 10.0 mm for the WOMAC pain , physical function and stiffness subscales , respectively , and 11.1 mm for WOMAC question 1 : Pain walking on a flat surface . The MPCI for the investigator was 0.4 with investigator assessment of disease status reported on a 0 to 4 Likert scale . Of note , the estimated MPCI for the WOMAC and investigator globals were similar irrespective of treatment , sex , age , or geographic region . CONCLUSION In this analysis , mean changes of roughly 9 to 12 mm ( 100 mm normalized VAS ) on WOMAC scales were perceptible changes to patients with hip and knee OA . A mean decrease of 0.4 in global disease status ( 0 to 4 Likert scale ) as assessed by the investigator corresponded to the patients ' MPCI . Underst and ing the minimal perceptible differences may permit a better assessment of the clinical relevance of therapeutic interventions in OA BACKGROUND : Despite the enormous success of total knee arthroplasty ( TKA ) , chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established . We hypothesized that perioperative treatment with pregabalin , a chronic pain medication , would reduce the incidence of postsurgical neuropathic pain . METHODS : We performed a r and omized , placebo-controlled , double-blind trial of pregabalin ( 300 mg ) administered before TKA and for 14 days after TKA ( 150–50 mg twice daily ) . Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale . Secondary outcomes included postsurgical recovery and rehabilitation measures , including knee range of motion , opioid consumption , postoperative pain scores , sleep disturbance , and time to discharge as well as the occurrence of postoperative systemic complications . RESULTS : Of the 240 patients r and omly assigned to the 2 treatment groups ( 120 in each ) , data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients . At both 3 and 6 mo postoperatively , the incidence of neuropathic pain was less frequent in the pregabalin group ( 0 % ) compared with the placebo group ( 8.7 % and 5.2 % at 3 and 6 mo , respectively ; P = 0.001 and P = 0.014 ) . Patients receiving pregabalin also consumed less epidural opioids ( P = 0.003 ) , required less oral opioid pain medication while hospitalized ( P = 0.005 ) , and had greater active flexion over the first 30 postoperative days ( P = 0.013 ) . There were no differences in the actual recorded duration of hospitalization between the 2 groups , although time to achieve hospital discharge criteria was longer for placebo patients , 69.0 ± 16.0 h ( mean ± sd ) , than that of pregabalin patients , 60.2 ± 15.8 h ( P = 0.001 ) . Sedation ( P = 0.005 ) and confusion ( P = 0.013 ) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin . CONCLUSION : Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA , with less opioid consumption and better range of motion during the first 30 days of rehabilitation . However , in the doses tested , it is associated with a higher risk of early postoperative sedation and confusion Background and purpose — Tourniquet application is still a common practice in total knee arthroplasty ( TKA ) surgery despite being associated with several adverse effects . We evaluated the effects of tourniquet use on functional and clinical outcome and on knee range of motion ( ROM ) . Patients and methods — 70 patients who underwent TKA were r and omized into a tourniquet group ( n = 35 ) and a non-tourniquet group ( n = 35 ) . All operations were performed by the same surgeon and follow-up was for 1 year . Primary outcomes were functional and clinical outcomes , as evaluated by KOOS and knee ROM . Secondary outcomes were intraoperative blood loss , surgical time and visibility , postoperative pain , analgesic consumption , and transfusion requirements . Results — Patients in the non-tourniquet group showed a better outcome in all KOOS subscores and better early knee ROM from surgery to week 8 . No difference was detected at the 6- and 12-month follow-ups . Postoperative pain and analgesic consumption were less when a tourniquet was not used . Surgical time and visibility were similar between groups . Intraoperative blood loss was greater when not using a tourniquet , but no postoperative transfusions were required . Interpretation— This study shows that TKA without the use of a tourniquet results in faster recovery in terms of better functional outcome and improved knee ROM . Furthermore , reduced pain and analgesic use were registered and no intraoperative difficulties were encountered Background Total knee arthroplasty is reported to improve the patient 's quality of life and mobility . However loss of mobility and pain prior to surgery often results in disuse atrophy of muscle . As a consequence the baseline functional state prior to surgery may result in poorer outcome " post surgery " and extended rehabilitation may be required . The use of anabolic steroids for performance enhancement and to influence muscle mass is well established . The positive effects of such treatment on bone and muscle could therefore be beneficial in the rehabilitation of elderly patients . The purpose of this study was to investigate the effects of small doses of N and rolone decanoate on recovery and muscle strength after total knee replacement and to establish the safety of this drug in multimorbid patients . Methods This study was design ed as a prospect i ve double blind r and omized investigation . Five patients ( treatment group ) with a mean age of 66.2 ( 58 - 72 ) , average BMI of 30.76 ( 24.3 - 35.3 ) received 50 mg n and rolone decanoate intramuscular bi-weekly for 6 months . The control group ( five patients ; mean age 65.2 , range 59 - 72 ; average BMI 31.7 , range 21.2 - 35.2 ) was injected with saline solution . " Pre-operatively " and " post-operatively " ( 6 weeks , 3,6,9 and 12 months ) all patients were assessed using the knee society score ( KSS ) , isokinetic strength testing and functional tests ( a sit-to-st and and timed walking tests ) . In addition , a bone density scan was used preoperatively and 6 month postoperatively to assess bone mineral density . Results Whilst the steroid group generally performed better than the placebo group for all of the functional tests , ANOVA failed to reveal any significant differences . The steroid group demonstrated higher levels of quadriceps muscle strength across the postoperative period which reached significance at 3 ( p = 0.02 ) , 6 ( p = 0.01 ) , and 12 months ( p = 0.02 ) . There was a significant difference for the KSS at 6 weeks ( p = 0.02 ) , 6 ( p = 0.02 ) and 12 month ( p = 0.01 ) . The steroid group demonstrated a reduction in the amount of bone mineral density at both the femur and lumbar spine from " pre- " to " post-surgery " , however , these results did not reach significance ( p < 0.05 ) using one-way ANOVA . Conclusions This project strongly suggests that the use of anabolic steroids result in an improved outcome as assessed by the KSS and significantly increases extensor strength . No side effects were seen in either the study or control group . Trial Registration NumberRegional Health District : Register No. 03.05Human Research Ethics Committee University : Clearance Number : 04/03 - Background — R and omized trials evaluating efficacy of local infiltration analgesia ( LIA ) have been published but many of these lack st and ardized analgesics . There is a paucity of reports on the effects of LIA on functional capability and quality of life . Methods — 56 patients undergoing unilateral total knee arthroplasty ( TKA ) were r and omized into 2 groups in this placebo-controlled study with 12-month follow-up . In the LIA group , a mixture of levobupivacaine ( 150 mg ) , ketorolac ( 30 mg ) , and adrenaline ( 0.5 mg ) was infiltrated periarticularly . In the placebo group , infiltration contained saline . 4 different patient-reported outcome measures ( PROMs ) were used for evaluation of functional outcome and quality of life . Results — During the first 48 hours postoperatively , patients in the LIA group used less oxycodone than patients in the placebo group in both cumulative and time-interval follow-up . The effect was most significant during the first 6 postoperative hours . The PROMs were similar between the groups during the 1-year follow-up . Interpretation — Single periarticular infiltration reduced the amount of oxycodone used and enabled adequate pain management in conjunction with st and ardized peroral medication without adverse effects . No clinical ly marked effects on the functional outcome after TKA were detected BACKGROUND Recently , high-volume local infiltration analgesia ( LIA ) in total knee arthroplasty ( TKA ) has been introduced , but dosage , timing , and effects of adjuvants are still debated . METHODS We r and omized 102 patients undergoing TKA to receive either epidural analgesia ( EDA group ) or LIA ( ropivacaine 150 mg and epinephrine 0.5 mg ) combined with ketorolac 30 mg and morphine 5 mg given either locally ( LIA group ) or i.v . ( LIAiv group ) . Epidural analgesia was maintained for 48 h. Intra-articular re-injection via a catheter with ropivacaine 142.5 mg and either intra-articular or i.v . ketorolac 30 mg was given 24 h after surgery . Pain scores , morphine consumption , side-effects , and readiness for hospital discharge were studied . RESULTS At discharge from the postoperative anaesthetic care unit , verbal pain scores were lower in the EDA group ( P=0.004 ) , but discharge was delayed [ difference 101 min , 95 % CI : ( 23 , 178 ) , P=0.007 ] . Group LIA reported lower pain scores at rest beyond 24 h after surgery [ mean VAS ( sd ) at 24/48/72 h : LIA group 16/12/10 (14)/(13)/(11 ) ; LIAiv group 22/18/15 (17)/(15)/(12 ) ; EDA group 27/30/21 (21)/(29)/(19 ) ] . Both the LIA and the LIAiv groups were mobilized faster and were earlier ready for hospital discharge [ 3.5 days ( LIA group ) vs 4 days ( LIAiv group ) vs 5.5 days ( EDA group ) ; P<0.001 ] . Cumulated morphine consumption ( 72 h ) was lowest for the LIA group [ 80 vs 101 mg ( EDA group ) vs 118 mg ( LIAiv group ) , P=0.007 ] . CONCLUSIONS LIA with local adjuvants compared with epidural analgesia results in reduced opioid consumption , faster mobilization , and earlier readiness for hospital discharge . Ketorolac and morphine are more efficient when given locally than systemically . The study has been registered at clinical trials.gov ( NCT00562627 ) before onset of participant enrolment : http:// clinical trials.gov/ct2/show/NCT00562627?term=spreng&rank=2 ( April 21 , 2010 ) Objective This study investigated the effect of the knee position during wound closure on early knee function recovery after total knee arthroplasty ( TKA ) . Methods This study included 80 primary total knee arthroplasties due to osteoarthritis . The patients were r and omized according to the type of wound closure : extension group for full extension and flexion group for 90 ° flexion . The incision of articular capsule was marked for precise wound alignment . In the flexion group , the knee was kept in high flexion for 1 to 2 min after wound closure . The two groups were treated with the same postoperative rehabilitation exercises . The range of motion ( ROM ) , visual analogue scale ( VAS ) score of anterior knee pain , Knee Society Score ( KSS ) and postoperative complications were assessed at 6 weeks , 3 months and 6 months , postoperatively . Results At 6 weeks and 3 months postoperatively , the ROM in flexion group was 98.95 ± 10.33 ° and 110.05 ± 4.93 ° respectively , with 87.62 ± 8.92 ° and 95.62 ± 6.51 ° in extension group , respectively ; The VAS score of anterior knee pain in flexion group was 2.02 ± 1.38 and 2.21 ± 0.87 , respectively , with 2.57 ± 1.07 and 2.87 ± 0.83 in extension group , respectively . The ROM and VAS pain score of the two groups were significantly different at these two time points , with no significant difference at 6 months postoperatively . The two groups were not significantly different in KSS , and no apparent complication was observed at three time points . Conclusion Marking the articular capsule incision , wound closure in flexion and high flexion after wound closure can effectively decrease anterior knee pain after TKA and promote the early recovery of ROM Abstract Total hip replacement ( THR ) and total knee replacement ( TKR ) are usually effective at relieving pain ; however , 7 % to 23 % of patients experience chronic postsurgical pain . These trials aim ed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis . Between November 2009 and February 2012 , 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind r and omised controlled trial . Participants were r and omly assigned ( 1:1 ) to receive local anaesthetic infiltration and st and ard care or st and ard care alone . Participants and outcomes assessors were masked to group allocation . The primary outcome was pain severity on the WOMAC Pain Scale at 12 months after surgery . Analyses were conducted using intention-to-treat and per- protocol approaches . In the hip trial , patients in the intervention group had significantly less pain at 12 months postoperative than patients in the st and ard care group ( differences in means : 4.74 ; 95 % confidence interval [ CI ] : 0.95 - 8.54 ; P = 0.015 ) , although the difference was not clinical ly significant . Post hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the st and ard care group ( odds ratio : 10.19 ; 95 % CI : 2.10 - 49.55 ; P = 0.004 ) . In the knee trial , there was no strong evidence that the intervention influenced pain severity at 12 months postoperative ( difference in means : 3.83 ; 95 % CI : −0.83 to 8.49 ; P = 0.107 ) . In conclusion , routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR The aim of this study was to determine whether the dry needling of myofascial trigger points ( MTrPs ) is superior to placebo in the prevention of pain after total knee arthroplasty . Forty subjects were r and omised to a true dry needling group ( T ) or to a sham group ( S ) . All were examined for MTrPs by an experienced physical therapist 4–5 hours before surgery . Immediately following anesthesiology and before surgery started , subjects in the T group were dry needled in all previously diagnosed MTrPs , while the S group received no treatment in their MTrPs . Subjects were blinded to group allocation as well as the examiner in presurgical and follow-up examinations performed 1 , 3 , and 6 months after arthroplasty . Subjects in the T group had less pain after intervention , with statistically significant differences in the variation rate of the visual analogue scale ( VAS ) measurements 1 month after intervention and in the need for immediate postsurgery analgesics . Differences were not significant at 3- and 6-month follow-up examinations . In conclusion , a single dry needling treatment of MTrP under anaesthesia reduced pain in the first month after knee arthroplasty , when pain was the most severe . Results show a superiority of dry needling versus placebo . An interesting novel placebo methodology for dry needling , with a real blinding procedure , is presented Objectives . To evaluate the comparative analgesia effectiveness and safety of postoperative continuous femoral nerve block ( CFNB ) with patient controlled intravenous analgesia ( PCIA ) and their impact on knee function and chronic postoperative pain . Methods . Participants were r and omly allocated to receive postoperative continuous femoral nerve block ( group CFNB ) or intravenous patient controlled analgesia ( group PCIA ) . Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores for knee and incidence of chronic postoperative pain at 3 , 6 , and 12 months postoperatively were compared . postoperative pain and salvage medication at rest or during mobilization 24 hours , 48 hours , and 7 days postoperatively were also recorded . Results . After discharge from the hospital and rehabilitation of joint function , patients in group CFNB reported significantly improved knee flexion and less incidence of chronic postoperative pain at 3 months and 6 months postoperatively ( P < 0.05 ) . Analgesic rescue medications were significantly reduced in patients receiving CFNB ( P < 0.001 and P = 0.031 , resp . ) . Conclusion . With st and ardized rehabilitation therapy , continuous femoral nerve block analgesia reduced the incidence of chronic postoperative pain , improved motility of replaced joints , and reduced the dosages of rescue analgesic medications , suggesting a recovery-enhancing effect of peripheral nerve block analgesia Purpose A pneumatic tourniquet is commonly used in total knee arthroplasty ( TKA ) to improve surgical field visualisation but may result in quadriceps muscle ischaemia . We performed this study to analyse the effect of the tourniquet on recovery following TKA . Material s and Methods A prospect i ve r and omised single-blinded trial was undertaken to examine the effect of the tourniquet on post-operative pain , swelling , blood loss , quadriceps function and outcome following TKA . Twenty patients with osteoarthritis of the knee were r and omised to tourniquet or no tourniquet groups . Quadriceps function was assessed using surface electromyography ( EMG ) during active knee extension . Results The no tourniquet group had significantly less pain in the early post-operative period compared to the tourniquet group . There was no difference in Oxford knee score , range of motion , or thigh and knee swelling up to 12 months post-operatively . Quadriceps function , measured by surface EMG , was compromised for the first six months post-surgery by tourniquet use . The radiological cement mantle at the bone prosthesis interface at 12-month follow-up was not affected by the absence of a tourniquet . Conclusions We believe that it is safe and beneficial for our patients to routinely perform TKA without a tourniquet BACKGROUND : We previously provided evidence that extending an overnight continuous femoral nerve block to 4 days after tricompartment knee arthroplasty ( TKA ) provides clear benefits during the perineural infusion in the immediate postoperative period . However , it remains unknown if the extended infusion improves subsequent health-related quality of life between 7 days and 12 mo . METHODS : Patients undergoing TKA received a femoral perineural infusion of ropivacaine 0.2 % from surgery until the following morning , at which time patients were r and omized to either continue perineural ropivacaine ( n = 25 ) or normal saline ( n = 25 ) in a double-masked fashion . Patients were discharged with their catheter and a portable infusion pump , and catheters were removed on postoperative day 4 . Health-related quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) Index preoperatively and then at 7 days , as well as 1 , 2 , 3 , 6 , and 12 mo after surgery . The WOMAC evaluates three dimensions of health-related quality of life : pain , stiffness , and physical functional disability . For inclusion in the analysis , we required a minimum of 4 of the 6 time points , including day 7 and at least 2 of mo 3 , 6 , and 12 . RESULTS : The two treatment groups had similar WOMAC scores for the mean area under the curve calculations ( point estimate for the difference in mean area under the curve for the two groups [ overnight infusion group−extended infusion group ] = 1.2 , 95 % confidence interval : −5.6 to + 8.0 ; P = 0.72 ) and at all individual time points ( P > 0.05 ) . CONCLUSIONS : We found no evidence that extending an overnight continuous femoral nerve block to 4 days improves ( or worsens ) subsequent health-related quality of life between 7 days and 12 mo after TKA . ( Clinical Trials.gov number , NCT00135889 . OBJECTIVES We prospect ively evaluated the effects of continuous passive motion ( CPM ) started after two different time intervals following total knee arthroplasty ( TKA ) on short- and long-term results , in comparison with st and ard physical therapy . METHODS Eighty-six patients were r and omized to three groups following TKA for primary osteoarthritis . The control group ( n=28 ) received only conventional physical therapy . Group I and II , each consisting of 29 patients , were treated with conventional physical therapy combined with CPM that was started on the first and third postoperative days , respectively , and continued until discharge with three one-hour sessions daily . Preoperative and postoperative measurements of the knee range of motion were recorded . Clinical and functional results were assessed using the Knee Society rating system . The patients were followed-up for at least two years ( range 26 to 52 months ) . RESULTS The duration of CPM was 22 hours in group I , and 19 hours in group II ( p>0.05 ) . Knee flexion values measured in the CPM groups on day 3 and at discharge showed significant differences with those of the control group , but no significant differences were found between the groups after the first postoperative month in this respect ( p>0.05 ) . The mean duration to reach 100 degrees of passive knee flexion ( p=0.03 ) and the mean length of hospital stay ( p=0.04 ) in the CPM groups were shorter by three and two days compared to the control group , respectively . Clinical and functional knee scores showed significant improvements in all the groups postoperatively ( p<0.001 ) , but there were no significant differences between the groups with respect to pre- and postoperative knee scores ( p>0.05 ) . CONCLUSION Even though CPM protocol s applied following TKA may shorten the length of hospital stay , CPM applications do not offer additional short- and long-term benefits over st and ard physical therapy with respect to knee flexion and clinical and functional results Background : Previously , we have demonstrated that extending a continuous femoral nerve block ( cFNB ) from overnight to 4 days after total knee arthroplasty ( TKA ) provides clear benefits during the infusion , but not subsequent to catheter removal . However , there were major limitations in generalizing the results of that investigation , and we subsequently performed a very similar study using a multicenter format , with many health care providers , in patients on general orthopedic wards , thus greatly improving inference of the results to the general population . Not surprisingly , the perioperative/short-term outcomes differed greatly from the first , more limited study . We now present a prospect i ve follow-up study of the previously published , multicenter , r and omized controlled clinical trial to investigate the possibility that an extended ambulatory cFNB decreases long-term pain , stiffness , and functional disability after TKA , which greatly improves inference of the results to the general population . Methods : Subjects undergoing TKA received a cFNB with ropivacaine 0.2 % from surgery until the following morning , at which time patients were r and omized to continue either perineural ropivacaine ( n = 28 ) or normal saline ( n = 26 ) . Patients were discharged with their catheter and a portable infusion pump , and catheters were removed on postoperative day 4 . Health-related quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis Index preoperatively and then at 7 days , as well as 1 , 2 , 3 , 6 , and 12 months after surgery . This index evaluates pain , stiffness , and physical functional disability . For inclusion in the analysis , we required a minimum of 4 of the 6 time points , including day 7 and at least 2 of months 3 , 6 , and 12 . Results : The 2 treatment groups had similar Western Ontario and McMaster Universities Osteoarthritis scores for the mean area-under-the-curve calculations ( point estimate for the difference in mean area under the curve for the 2 groups [ overnight infusion group − extended infusion group ] = 3.8 ; 95 % confidence interval , −3.8 to + 11.3 ; P = 0.32 ) and at all individual time points ( P > 0.05 ) . Conclusions : This investigation found no evidence that extending an overnight cFNB to 4 days improves ( or worsens ) subsequent pain , stiffness , or physical function after TKA in patients of multiple centers convalescing on general orthopedic wards Background and Objectives Continuous femoral nerve block is a well-accepted technique for regional analgesia after total-knee replacement . However , many patients still experience considerable pain at the popliteal space and at the medial aspect of the knee . The goal of this study is to evaluate whether a psoas compartment catheter provides better postoperative analgesia than a femoral nerve catheter does and whether it is as effective as the combination of a femoral and a sciatic nerve catheter and , thus , improves functional outcome . Methods Ninety patients who underwent total-knee replacement under st and ardized general anesthesia participated in this prospect i ve r and omized study . Group FEM received a continuous femoral nerve block , group FEM/SCI received a combination of a femoral and a sciatic continuous nerve block , and group PSOAS received a continuous psoas compartment block . Patient-controlled analgesia with piritramide was available for 48 hours . Maximal bending and extending of the knee and walking distance was assessed during the first 7 days . A st and ardized telephone survey was conducted after 9 to12 months to evaluate residual pain and functional outcome . Results Postoperative opioid consumption during 48 hours was significantly less in the FEM/SCI group ( median : 18 mg ; 25th/75th percentile : 6/40 ) compared with the FEM group ( 49 mg ; 25/66 ) and the PSOAS group ( 44 mg ; 30/62 ) ( P = .002 ) . Postoperative pain scores were not different , and no differences occurred with respect to short-term or long-term functional outcome . Conclusion The FEM/SCI catheter is superior to FEM and PSOAS catheter with respect to reduced analgesic requirements after total-knee replacement , but functional outcome does not differ with those 3 continuous regional analgesia techniques Objective In orthopedic surgery , it is well known that the use of intrathecal morphine ( ITM ) leads to an improved quality of postoperative analgesia . Little is known how this improved analgesia affects the long-term course after surgery . Study design A r and omized , double-blind trial . Setting Academic medical center . Subjects Forty-nine patients undergoing total hip or knee replacement surgery in spinal anesthesia . Methods Patients were r and omly assigned to receive either 0.1 mg ( n=16 ) or 0.2 mg ( n=16 ) morphine sulfate intrathecally or physiological saline ( n=17 ) added to 3 mL 0.5 % isobaric bupivacaine for spinal anesthesia . As a function of the quality of the short-term postoperative analgesia , the effect on recovery and quality of life was evaluated at various time points up to 26 weeks after surgery . Results In both ITM groups , the additionally required postoperative systemic morphine dose was significantly reduced compared with the placebo group ( P=0.004 ) . One week after operation , patients with ITM reported significantly less pain at rest ( P=0.01 ) compared to the placebo group . At discharge , in comparison with the 0.1 mg ITM and placebo group , the 0.2 mg ITM group showed a higher degree of impairment regarding pain , stiffness , and physical function of the respective joint ( P=0.02 ) . Over the further follow-up period of 6 months after surgery , recovery and the quality of life did not differ significantly between the three study groups ( P>0.2 ) . Conclusion Morphine ( 0.1 mg ) as adjunct to 0.5 % bupivacaine for spinal anesthesia is effective to produce a pronounced postoperative analgesia with a beneficial analgesic effect up to 1 week after surgery . With this study design , the different quality of postoperative analgesia had no effect on quality of life and recovery in patients over the 6-month follow-up period . In the medium term , ITM may induce hyperalgesic effects BACKGROUND AND PURPOSE The primary purpose of this r and omized controlled trial was to determine which method of mobilization - ( 1 ) st and ardized exercises ( SE ) and continuous passive motion ( CPM ) , ( 2 ) SE and slider board ( SB ) therapy , using an inexpensive , nontechnical device that requires minimal knee active range of motion ( ROM ) , or ( 3 ) SE alone-achieved the maximum degree of knee ROM in the fIrst 6 months following primary total knee arthroplasty ( TKA ) . The secondary purpose was to compare health-related quality of life among these 3 groups . SUBJECTS The subjects were 120 patients ( n=40/group ) who received a TEA at a teaching hospital between June 1997 and July 1998 and who agreed to participate in the study . METHODS Subjects were examined preoperatively , at discharge , and at 3 and 6 months after surgery . The examination consisted of measurement of knee ROM and completion of the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index and the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS The 3 treatment groups were similar with respect to age , sex , and diagnosis at the start of the study . There were no differences in knee ROM or in WOMAC Osteoarthritis Index or SF-36 scores at any of the measurement intervals . The rate of postoperative complications also was not different among the groups . DISCUSSION AND CONCLUSION When postoperative rehabilitation regimens that focus on early mobilization of the patient are used , adjunct ROM therapies ( CPM and SB ) that are added to daily SE sessions are not required . Six months after TEA , patients attain a satisfactory level of knee ROM and function Introduction There is no consensus on the position of the knee joint while performing wound closure after total knee arthroplasty ( TKA ) . Further , there are no studies focusing on the association between early functional outcomes and different wound closure strategies . Therefore , we investigated the effects of tourniquet and knee position during wound closure on early recovery of range of motion ( ROM ) after primary TKA . To our knowledge , this is the first study to evaluate the influence of both tourniquet and knee position during wound closure in primary TKA . Methods One hundred-twenty eligible patients were consecutively enrolled in this study and r and omly divided into four groups according to wound closure strategy . Wound closure was either performed with the knee in flexion at 90 ° or in full extension , with the combination of an inflated or deflated tourniquet . Visual analogue score ( VAS ) , knee ROM , ROM recovery , knee society score ( KSS ) , and wound complications were evaluated in the early postoperative period . Results After the first postoperative week , ROM recovery in the group with knee in extension and inflated tourniquet was significantly lesser than the two groups with deflated tourniquets . Between the first and fourth postoperative weeks , ROM recovery in the group with knee inflection and deflated tourniquet was significantly higher than the two groups with knee in extension . After the first postoperative week , the visual analog score ( VAS ) for pain in the group with knee inflection and deflated tourniquet was significantly lesser than the two groups with inflated tourniquets . The differences in the outcomes between the four groups were not significant after the fourth postoperative week . The incidence of wound complications and KSS were not significantly different between the four groups . Conclusion Following TKA , wound closure with the knee in flexion and after deflating the tourniquet significantly decreased postoperative pain and promoted the recovery of ROM in the early postoperative period Patients with knee osteoarthritis present with reduced quadriceps muscle strength , which is partially responsible for impaired function and disability . Although total knee replacement ( TKR ) is an effective surgical procedure , residual muscle weakness is not usually addressed and may persist for years postoperatively . This article reports the results of a prospect i ve , r and omized , controlled trial evaluating the effect of electric muscle stimulation of the vastus medialis on the speed and effort of walking , quality of life , and knee performance in patients undergoing TKR . Seventy patients who underwent TKR were r and omly divided into 2 groups . Patients in group A received electric muscle stimulation and st and ard physiotherapy for 6 weeks , while patients in group B received physiotherapy only . All patients were assessed with both subjective and objective clinical scales preoperatively and at 6 , 12 , and 52 weeks postoperatively . Patients in group A demonstrated a statistically significant increase in walking speed , Oxford Knee Score , and American Knee Society function score compared to those in group B at 6 weeks ( P=.003 , .001 , and .001 , respectively ) and at 12 weeks ( all P=.001 ) . A statistically significant increase in the SF-36 physical component summary score was observed at 6 , 12 , and 52 weeks ( all P=.001 ) . Three patients found the sensation of the electrical stimulation uncomfortable and ab and oned its use . No skin reactions and surgical site infections were observed . Electrical stimulation of the vastus medialis muscle in addition to conventional physiotherapy improves functional recovery and early rehabilitation after TKR OBJECTIVES To determine the effect of guided imagery ( GI ) on functional outcomes of total knee replacement ( TKR ) , explore psychological and neuroimmune mediators , and assess feasibility of study implementation . DESIGN Investigator-blinded , r and omized , placebo-controlled pilot study . SETTING S Hospital , surgeon 's office , participant 's home . PARTICIPANTS 82 persons undergoing TKR . INTERVENTIONS Audiorecordings of TKR-specific GI scripts or placebo-control audiorecordings of audiobook segments . OUTCOME MEASURES Gait velocity and Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) Function scale . RESULTS Outcomes for 58 participants ( 29 receiving GI and 29 controls ) were analyzed at 6 months after surgery . The most frequent reason for noncompletion was protocol -driven exclusion at 6 months for having the contralateral knee replaced before the study endpoint ( n = 15 ) . With imaging ability as a moderator , gait velocity , but not WOMAC Function score , was significantly improved at 6 months in the GI group . Participants in the GI group , but not the control group , had lower WOMAC Pain scores at 3 weeks after surgery than at baseline . Hair cortisol concentration was significantly lower at 6 months after surgery than at baseline in the GI group but not the control group . GI group participants had lower treatment adherence but greater treatment credibility than the control group . CONCLUSION R and omized controlled trials of GI in the TKR population are feasible , but inclusion /exclusion criteria influence attrition . Further studies are needed to elaborate this study 's findings , which suggest that guided imagery improves objective , but not patient-reported , outcomes of TKR . Hair cortisol concentration results suggest that engagement in a time-limited guided imagery intervention may contribute to stress reduction even after the intervention is terminated . Further investigation into optimal content and dosing of GI is needed INTRODUCTION Post total knee replacement pain control using parenteral opioids results in significant side effects like nausea and vomiting . Periarticular injections are used to control pain without these side effects . This study aim ed to evaluate the safety and efficacy of periarticular steroid injection in patients undergoing total knee arthroplasty , as well as assess the patient 's functional outcomes over a period of two years . METHODS A total of 100 patients who underwent total knee arthroplasty were r and omised into two groups . The treatment group received periarticular infiltration with triamcinolone acetonide , bupivacaine and epinephrine . The control group received only bupivacaine and epinephrine . The postoperative analgesic regime was st and ardised for all patients . The immediate postoperative outcomes evaluated included pain score , morphine consumption , time to ambulation , straight leg raise , range of motion and duration of hospital stay . Longer-term outcomes were assessed at 1 , 3 , 6 and 24 months using the SF-36 question naire and Oxford Knee Score . RESULTS Patients in the treatment group had significantly lower pain scores , reduced morphine consumption and earlier discharge . They also had better range of knee motion and were able to regain muscular strength earlier . There was no increase in major complications such as infection or tendon rupture in the treatment group . There was no difference between the groups with regard to the medium-term outcomes of up to two years . CONCLUSION This modality of pain control is safe and efficacious for post total knee replacement pain control A vigorous rehabilitation program following discharge from the hospital is necessary for patients having a total knee arthroplasty to maintain and improve range of motion and function . To compare the effectiveness of the continuous passive motion ( CPM ) machine as a home therapy program versus professional physical therapy , a prospect i ve , comparative , r and omized clinical study of 103 consecutive primary total knee arthroplasties in 80 patients ( 23 bilateral ) was performed . The CPM group consisted of 37 patients ( 49 knees ) , and the physical therapy group consisted of 43 patients ( 54 knees ) . At 2 weeks , knee flexion was similar in the two groups , but a flexion contracture was noted in the CPM group ( 4.2 degrees ) . This difference is felt by the authors to be clinical ly insignificant . At 6 months , there were no differences in knee scores , knee flexion , presence of flexion contracture , or extensor lag between the two groups . The cost for the CPM machine group was $ 10,582 ( $ 286 per patient ) , and the cost for professional therapy was $ 23,994 ( $ 558 per patient ) . We conclude that the CPM machine after the hospital discharge of patients having total knee replacement is an adequate rehabilitation alternative with lower cost and with no difference in results compared with professional therapy Purpose Severe post-operative pain is one of the main problems after total knee arthroplasty . In this study , we investigated the effect of a peri-articular multimodal drugs injections pre-emptively on post-operative pain control and knee functions following total knee arthroplasty . Methods and material sThis study was a double-blind r and omized clinical trial . Eligible cases including 137 patients —aged 30 to 80 years old — were r and omly divided into one of two groups : the drug group received a cocktail consisting of bupivacaine hydrochloride , morphine sulphate , epinephrine , and ketorolac . The control group received epinephrine only . The injections were given 15 minutes before incision . Joint range of motion ( ROM ) and the severity of pain by using visual analog scale ( VAS ) of 1 to 10 and patient ’s facial expression , were assessed in the pre-operative visit , after 24 hours , 48 hours , and six weeks after operation . Knee Society score ( KSS ) was recorded before the operation , six weeks , and six months after the operation for each patient . Results The data of VAS showed no significant difference between the groups before operation but there was statistically significant difference between the two groups at 24 hours , 48 hours , and six weeks after the operation . In KSS , difference was not significant between the two groups before the operation and six months after surgery while our results showed a statistically significant difference between groups six weeks after the operation . In ROM , there was no significant difference between the groups before operation . There was a statistically significant difference between the two groups at 24 hours , 48 hours and six weeks after the operation . Complications were recorded at six weeks after surgery . Conclusion Peri-articular multimodal injection including bupivacaine , morphine , and ketorolac preferably with pre-emptive injection method provided proper post-operative pain relief , less opioid consumption , and better early rehabilitation following TKA at 48 hours after surgery . Level of study Level Abstract Introduction A r and omised , double-blind clinical trial was conducted comparing the efficacy of tranexamic acid ( TXA ) as a single intravenous bolus or a continuous infusion to patients undergoing total knee arthroplasty ( TKA ) . Study hypothesis was that a second dose of TXA would not offer any clinical benefits over the single infusion . Material s and methods One hundred and six patients were r and omised to a single intraoperative dose of 30 mg/kg tranexamic acid ( OS group , n = 54 ) , or to a loading dose of 10 mg/kg tranexamic acid followed 2 h later by a continuous 2 mg/kg/h infusion for 20 h ( OD group , n = 52 ) . The primary outcome was blood loss calculated from haematological values and perioperative transfusions . Secondary outcomes included the occurrence of major complications within the first postoperative year . Results All patients completed tranexamic acid therapy without adverse events . The mean blood loss was 1,148 ± 585 ml in group OS and 1,196 ± 614 ml in group OD ( p = 0.68 ) . No patients received a transfusion . There were no occurrences of major complications up to 6-weeks follow-up . Conclusions The study demonstrated that a single bolus of tranexamic acid 30 mg/kg is as effective as a continuous infusion in patients undergoing tranexamic acid . The single application of tranexamic acid as part of routine care is recommended Purpose The purpose s of this study were to compare the pain score , systemic opioid consumption , and range of motion ( ROM ) between the group where the use of continuous femoral nerve block ( CFNB ) was discontinued on postoperative day 3 ( POD 3 ) and the group where it was discontinued on POD 7 within an established clinical pathway for postoperative recovery after total knee arthroplasty ( TKA ) and to assess the treatment-related side effects and complications , as well as the functional status of these two groups of patients at 2 years after surgery . Methods This prospect i ve , r and omized , double-blinded trial compared the analgesic efficacy and the functional outcomes between group A ( n = 30 ) where continuous femoral nerve block was performed until POD 3 ( discontinued prior to the initiation of range of motion ( ROM ) exercises ) and group B ( n = 33 ) , where the continuous femoral nerve block was performed until POD 7 ( discontinued during the ROM exercise ) after TKA . Results The resting pain scores of group B were lower than those of group A but there was no significant difference between the two groups ( n.s . , P = 0.387 ) . However , the peak pain scores during ROM exercise , beginning on POD3 through to POD14 , were significantly lower in group B than in group A ( P = 0.001 ) . The cumulative morphine IV-PCA requirements through the POD 2 were similar in the two groups ( n.s . , P = 0.811 ) . However , the cumulative oral oxycodone consumption during hospitalization was significantly lower in group B than in group A , P < 0.0001 . Group B showed significantly greater satisfaction with their method of analgesia than group A ( P = 0.001 ) . Group A scored 2.0 ( 2.0–3.0 ) , whereas group B scored 1.0 ( 1.0–2.0 ) . At 2 years , there was no significant difference in the functional outcomes ( the knee flexion and extension angle , the Knee Society Score , and WOMAC pain , stiffness , and function scale ) . Conclusion The study group who received 7-day continuous femoral nerve block after TKA showed superior analgesia and higher patient satisfaction during the hospital stay than those given 3-day continuous femoral nerve block . Despite the additional time , effort and cost to place and manage continuous femoral nerve catheters , the 7-day continuous femoral nerve block can be recommended as an effective and safe regional component of a multimodal analgesia strategy after TKA.Level of evidence II Purpose The purpose of this study was to determine whether platelet-rich plasma ( PRP ) might prevent blood loss and postoperative pain and expedite wound healing following total knee arthroplasty ( TKA ) . Methods Forty consecutive patients with knee arthritis who were matched for age , sex and body mass index ( BMI ) were r and omly allocated to either receive or not receive PRP application over the wound , including capsule , medial and lateral recesses , during TKA . Postoperative haemoglobin , blood loss , blood transfusion , visual analogue scale ( VAS ) score , wound score , Knee Society Score ( KSS ) and Western Ontario and McMaster Osteoarthritis Index ( WOMAC ) score were recorded and evaluated . Results The platelet-rich plasma and control groups comprised 17 and 23 patients , respectively . The PRP group recorded significantly less reduction in haemoglobin and need for blood transfusion ( p = 0.00 and p = 0.001 , respectively ) , experienced less pain ( p = 0.00 ) and required fewer narcotics than the control ( p = 0.00 ) . There was significant difference in range of motion ( ROM ) at three months ( p = 0.01 ) , no significant difference in wound scores ( p = 0.311 ) and significant difference in KSS and WOMAC scores at 12 weeks ( p = 0.00 , 0.00 ) . However no significant difference was found at six months . Conclusions PRP has significant effect in preventing blood loss , postoperative pain and need for narcotics after TKA and has a positive effect on short-term clinical outcome In an initial r and omised controlled trial ( RCT ) we segregated 180 patients to one of two knee positions following total knee replacement ( TKR ) : six hours of knee flexion using either a jig or knee extension . Outcome measures included post-operative blood loss , fall in haemoglobin , blood transfusion requirements , knee range of movement , limb swelling and functional scores . A second RCT consisted of 420 TKR patients r and omised to one of three post-operative knee positions : flexion for three or six hours post-operatively , or knee extension . Positioning of the knee in flexion for six hours immediately after surgery significantly reduced blood loss ( p = 0.002 ) . There were no significant differences in post-operative range of movement , swelling , pain or outcome scores between the various knee positions in either study . Post-operative knee flexion may offer a simple and cost-effective way to reduce blood loss and transfusion requirements following TKR . We also report a caution ary note regarding the potential risks of prolonged knee flexion for more than six hours observed during clinical practice in the intervening period between the two trials , with 14 of 289 patients ( 4.7 % ) reporting lower limb sensory neuropathy at their three-month review OBJECTIVE To evaluate if the timing of aquatic therapy influences clinical outcomes after total knee arthroplasty ( TKA ) or total hip arthroplasty ( THA ) . DESIGN Multicenter r and omized controlled trial with 3- , 6- , 12- , and 24-month follow-up . SETTING Two university hospitals , 1 municipal hospital , and 1 rural hospital . PARTICIPANTS Patients ( N=465 ) undergoing primary THA ( n=280 ) or TKA ( n=185 ) : 156 men , 309 women . INTERVENTION Patients were r and omly assigned to receive aquatic therapy ( pool exercises aim ed at training of proprioception , coordination , and strengthening ) after 6 versus 14 days after THA or TKA . MAIN OUTCOME MEASURES Primary outcome was self-reported physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) at 3- , 6- , 12- , and 24-months postoperatively . Results were compared with published thresholds for minimal clinical ly important improvements . Secondary outcomes included the Medical Outcomes Study 36-Item Short-Form Health Survey , Lequesne-Hip/Knee-Score , WOMAC-pain and stiffness scores , and patient satisfaction . RESULTS Baseline characteristics of the 2 groups were similar . Analyzing the total study population did not result in statistically significant differences at all follow-ups . However , when performing sub analysis for THA and TKA , opposite effects of early aquatic therapy were seen between TKA and THA . After TKA all WOMAC subscales were superior in the early aquatic therapy group , with effect sizes of WOMAC physical function ranging from .22 to .39 . After THA , however , all outcomes were superior in the late aquatic therapy group , with WOMAC effect sizes ranging from .01 to .19 . However , the differences between treatment groups of these subanalyses were not statistically significant . CONCLUSIONS Early start of aquatic therapy had contrary effects after TKA when compared with THA and it influenced clinical outcomes after TKA . Although the treatment differences did not achieve statistically significance , the effect size for early aquatic therapy after TKA had the same magnitude as the effect size of nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis of the knee . However , the results of this study do not support the use of early aquatic therapy after THA . The timing of physiotherapeutic interventions has to be clearly defined when conducting studies to evaluate the effect of physiotherapeutic interventions after TKA and THA We report a prospect i ve r and omly controlled trial to examine the effectiveness of continuous passive motion ( CPM ) in improving postoperative function and range of movement after total knee arthroplasty ( TKA ) . We allocated 53 patients ( 57 knees ) to one of three postoperative regimes : no CPM ( n = 19 ) ; CPM at 0 to 40 degrees ( 0 to 40 CPM ; n = 18 ) ; and CPM at 0 to 70 degrees ( 0 to 70 CPM ; n = 20 ) . Those in the CPM groups had CPM for 48 hours and all patients had an identical regime of physiotherapy . There was an even distribution of various cemented and cementless TKAs in each group . Patients were assessed preoperatively and at one week and at one year postoperatively . At one week , there was a statistically significant increase in the range of flexion and total range of movement in the 0 to 70 CPM group compared with the no-CPM group . At one year we found no significant differences in mean flexion , overall range of movement , fixed flexion deformity or functional results in the three groups . Those who had CPM had a significant increase in analgesic requirement ( p = 0.04 ) . There was an increased mean blood drainage postoperatively in those who had 0 to 70 CPM ( 1558 ml ) compared with those with no CPM ( 956 ml ) ( t = 2.96 , p = 0.005 ) and with 0 to 40 CPM ( 1017 ml ) ( t = 2.62 , p = 0.01 ) . Our findings show that CPM had no significant advantage in terms of improving function or range of movement , and that its use increased blood loss and analgesic requirements Rehabilitation following total knee arthroplasty ( TKA ) is a costly , cumbersome , and often painful process . Physical therapy contributes to the successful outcome of TKA but can be expensive . Alternative methods of obtaining good functional results that help minimize costs are desirable . Neuromuscular electrical stimulation ( NMES ) is a potential option . Neuromuscular electrical stimulation has been shown to increase quadriceps muscle strength and activation following TKA . Functional scores also improve following TKA when NMES is added to conventional therapy protocol s vs therapy alone . The authors hypothesized that rehabilitation managed by a physical therapist would not result in a functional advantage for patients undergoing TKA when compared with NMES and an unsupervised at-home range of motion exercise program and that patient satisfaction would not differ between the 2 groups . Seventy patients were r and omized into a postoperative protocol of conventional physical therapy with a licensed therapist , including range of motion exercises and strengthening exercises , or into a program of NMES and range of motion exercises performed at home without therapist supervision . Noninferiority of the NMES program was obtained 6 weeks postoperatively ( Knee Society pain/function scores , Western Ontario and McMaster Universities Osteoarthritis Index , flexion ) . Noninferiority was shown 6 months postoperatively for all parameters . The results suggest that rehabilitation managed by a physical therapist results in no functional advantage or difference in patient satisfaction when compared with NMES and an unsupervised at-home range of motion program . Neuromuscular electrical stimulation and unsupervised at-home range of motion exercises may provide an option for reducing the cost of the postoperative TKA recovery process without compromising quadriceps strength or patient satisfaction Background : Tourniquet use during primary total knee arthroplasty is thought to reduce intraoperative blood loss and improve visibility . Our goal was to investigate whether tourniquet use is necessary for controlling intraoperative blood loss when alternatives such as tranexamic acid ( TXA ) are available . Methods : One hundred and fifty patients were equally r and omized to 3 groups . Group A was treated with a tourniquet as well as multiple doses of intravenous TXA ( 20 mg/kg 5 to 10 minutes before the skin incision and 10 mg/kg 3 , 6 , 12 , and 24 hours later ) along with 1 g of topical TXA , Group B was treated the same as Group A but without the tourniquet , and Group C was treated with the tourniquet only . Results : The amount of intraoperative blood loss was similar for the 3 groups . Group B had significantly less hidden blood loss than Group A ( p = 0.018 ) and Group C ( p < 0.001 ) . No significant differences ( p > 0.05 ) were observed between Group A and Group B with regard to total blood loss , drainage volume , intraoperative blood loss , transfusion rate , or maximum change in the hemoglobin ( Hb ) level . We also found significantly more benefits for Group B compared with Groups A and C with regard to postoperative swelling ratio , levels of inflammatory biomarkers , visual analog scale ( VAS ) pain scores , range of motion at discharge , Hospital for Special Surgery ( HSS ) score , and patient satisfaction . There were no significant differences ( p > 0.05 ) in the deep venous thrombosis or pulmonary embolus rates among the 3 groups . More wound secretion was observed in the groups in which a tourniquet was used . Conclusions : Patients treated with multiple doses of intravenous and topical TXA without a tourniquet had less hidden blood loss , a lower ratio of postoperative knee swelling , less postoperative knee pain , lower levels of inflammatory biomarkers , better early knee function , and even better early satisfaction than those treated with a tourniquet . Long-term follow-up should be performed to evaluate the effects on prosthetic fixation and long-term survival of total knee arthroplasty performed without a tourniquet . Level of Evidence : Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence Objectives : Ketamine and nefopam has been documented to decrease pain intensity and improve rehabilitation after total knee arthroplasty ( TKA ) . We conducted a follow-up study of a previously r and omized clinical trial to determine the prevalence and risk factors of chronic pain 1 year after TKA and to assess the role of perioperative administration of ketamine and nefopam . Material s and Methods : The original r and omized , double-blind trial evaluated postoperative pain in 75 patients scheduled for TKA who received either a 48-hour infusion of ketamine or nefopam compared with placebo . The current study has evaluated patients at 6 and 12 months for the presence of chronic pain defined as a visual analogue scale ≥40 mm during a stair-climbing test . Other outcomes were incidence of neuropathic pain evaluated ( DN4 score ) , active flexion of the knee , and functional outcome ( KOOS-PS score ) . Results : A total of 69 patients completed the trial . The prevalence of chronic pain at 12 months was 17.4 % ( 95 % confidence interval [ CI ] , 10.2%-27.9 % ) without difference between the ketamine ( 12.5 % ) , nefopam ( 13.7 % ) , and placebo groups ( 26.1 % ) . Prevalence of neuropathic pain was 10.2 % ( 95 % CI , 3%-17.3 % ) . Ketamine reduced DN4 scores ( P=0.02 ) , increased knee flexion ( P=0.0007 ) , and KOOS-PS scores ( P<0.0001 ) compared with placebo . A visual analogue scale score ≥60 mm in the postoperative period was the only risk factor associated with the occurrence of chronic pain ( odds ratio 4.54 ; 95 % CI , 1.17 - 17.67 ) . Discussion : After TKA , the intensity of postoperative pain is a risk factor of chronic pain on movement . Intraoperative ketamine seems to improve long-term results of rehabilitation in this setting Several recent reports suggest that pain-related catastrophizing is a risk factor for poor acute pain outcomes following surgical interventions . However , it has been less clear whether levels of catastrophizing influence longer-term postoperative outcomes . Data were analyzed from a relatively small number ( n=43 ) of patients who underwent total knee replacement and were followed for 12 months after their surgery . Previous research has suggested that high levels of both catastrophizing and depression are associated with elevated acute postoperative pain complaints among patients undergoing knee surgery . In this sample , catastrophizing and depression at each of the assessment points were studied as prospect i ve predictors of pain ( both global pain ratings and pain at night ) at the subsequent assessment point over the course of one year . The predictive patterns differed somewhat across measures of pain reporting ; depressive symptoms were unique predictors of greater global pain complaints , while catastrophizing was a specific and unique predictor of elevated nighttime pain . While surgical outcomes following total knee replacement are , on average , quite good , a significant minority of patients continue to experience long-term pain . The present findings suggest that high levels of catastrophizing and depression may promote enhanced pain levels , indicating that interventions design ed to reduce catastrophizing and depressive symptoms may have the potential to further improve joint replacement outcomes AIMS This non-blinded r and omised controlled trial compared the effect of patient-controlled epidural analgesia ( PCEA ) versus local infiltration analgesia ( LIA ) within an established enhanced recovery programme on the attainment of discharge criteria and recovery one year after total knee arthroplasty ( TKA ) . The hypothesis was that LIA would increase the proportion of patients discharged from rehabilitation by the fourth post-operative day but would not affect outcomes at one year . PATIENTS AND METHODS A total of 242 patients were r and omised ; 20 were excluded due to failure of spinal anaesthesia leaving 109 patients in the PCEA group and 113 in the LIA group . Patients were review ed at six weeks and one year post-operatively . RESULTS There was no difference in the proportion of patients discharged from rehabilitation by the fourth post-operative day , ( 77 % in the PCEA group , 82 % in the LIA group , p = 0.33 ) , mean length of stay ( four days in each group , p = 0.540 ) , day of first mobilisation ( p = 0.013 ) or pain ( p = 0.278 ) . There was no difference in mean Oxford Knee Scores ( 41 points in each group , p = 0.915 ) or the rate of complications in the two groups . CONCLUSION Both techniques provided adequate pain relief , enabled early mobilisation and accelerated rehabilitation and good patient-reported outcomes up to one year post-operatively . PCEA and LIA are associated with similar clinical outcomes following TKA . Cite this article : Bone Joint J 2016;98-B1189 - 96 Background and purpose — Aseptic loosening is a main cause of late revision in total knee replacement ( TKR ) . Migration of implants as measured by radiostereometric analysis ( RSA ) can predict future loosening . This migration is associated with bone resorption . Denosumab is a human monoclonal antibody that binds to receptors on osteoclast precursors and osteoclasts . This prevents osteoclast formation , result ing in less bone resorption in cortical and trabecular bone . We investigated whether denosumab can reduce migration of TKR , as measured with RSA . Patients and methods — In this 2-center , r and omized , double-blind placebo-controlled trial , 50 patients with osteoarthritis of the knee were treated with an injection of either denosumab ( 60 mg ) or placebo 1 day after knee replacement surgery and again after 6 months . RSA was performed postoperatively and after 6 , 12 , and 24 months . The primary effect variable was RSA maximal total point motion ( MTPM ) after 12 months . We also measured other RSA variables and the knee osteoarthritis outcome score ( KOOS ) . Results — The primary effect variable , MTPM after 12 months , showed that migration in the denosumab group was statistically significantly less than in the controls . Denosumab MTPM 12 months was reduced by one-third ( denosumab : median 0.24 mm , 10 % and 90 % percentiles : 0.15 and 0.41 ; placebo : median 0.36 mm , 10 % and 90 % percentiles : 0.20 and 0.62 ) . The secondary MTPM variables ( 6 and 24 months ) also showed a statistically significant reduction in migration . There was no significant difference in MTPM for the period 12–24 months . KOOS sub-variables were similiar between denosumab and placebo after 12 and 24 months . Interpretation — Denosumab reduces early migration in total knee replacement , as in previous trials using bisphosphonates . As migration is related to the risk of late loosening , denosumab may be beneficial for long-term results We have carried out a prospect i ve r and omised , single blind clinical trial to investigate the effect of continuous passive motion on range of knee flexion , lack of extension , pain levels and analgesic use after total knee replacement surgery . 85 subjects were r and omly allocated to control or study group . All subjects followed the existing rehabilitation protocol , which permits immediate active range of motion exercises and mobilisation with the study group using continuous passive motion for 1 h , twice a day . Outcome measures employed were range of motion , pain assessed on a visual analogue scale and analgesic use according to the WHO ladder . Blinded evaluation was carried out preoperatively , at time of discharge from hospital , 6 weeks , 6 and 12 months postoperation . No significant difference was observed between groups at all time intervals for each outcome variable using Wilcoxon Rank sum tests . The results substantiate previous findings that short duration continuous passive motion following total knee arthroplasty does not influence outcome of range of motion or reported pain OBJECTIVE To clarify the effects of tourniquet use on pain , early rehabilitation , blood loss , incidence rate of thrombosis in primary total knee arthroplasty ( TKA ) through a r and omized controlled trial . METHODS Between Janurary 2014 and August 2015 , 168 patients with knee osteoarthritis undergoing primary TKA were r and omly allocated to tourniquet group ( n = 84 ) or non-tourniquet group ( n = 82 ) . There was no significant difference in gender , age , body mass index , affected side , osteoarthritis grading , disease duration , preoperative range of motion ( ROM ) , visual analogue scale ( VAS ) , Hospital for Special Surgery ( HSS ) score , and hemoglobin ( Hb ) between 2 groups ( P > 0.05 ) . The operation time , hospitalization time , 90 ° knee flexion time , straight leg lifting time , and ambulation time were compared between 2 groups . Intraoperative blood loss , Hb decrease , postoperative VAS score , HSS score , ROM , and postoperative complications were recorded and compared . RESULTS There was no significant difference in operation time ( t = -1.353 , P = 0.178 ) . The patients were followed up 3 - 20 months ( mean , 12 months ) in tourniquet group , and 3 - 22 months ( mean , 13 months ) in non-tourniquet group . No significant difference was found in Hb decrease ( t = -1.855 , P = 0.066 ) and transfusion rate ( 23.81 % of tourniquest group vs. 25.61 % of non-tourniquest group ) ( χ² = 0.072 , P = 0.788 ) between 2 groups . Significant difference was found in the incidence rate of thrombosis between tourniquet and non-tourniquet groups ( 10.71 % vs. 2.44 % ) ( χ² = 4.592 , P = 0.032 ) , and the intraoperative blood loss of tourniquet group was significantly less than that of non-tourniquet group ( t = -16.066 , P = 0.000 ) . The 90 ° knee flexion time , straight leg lifting time , ambulation time , and hospitalization time of tourniquet group were significantly later than those of non-tourniquet group ( P < 0.05 ) . The tourniquet group had significantly higher VAS score at 3 , 5 , 7 , and 14 days after operation ( P < 0.05 ) and lower HSS score at 28 days after operation ( t = -4.192 , P = 0.000 ) than non-tourniquet group , but there was no significant difference in the ROM between 2 groups ( t = 0.676 , P = 0.500 ) . CONCLUSION The use of a tourniquet during TKA will increase knee pain and thrombotic events , but can not decrease total blood loss and transfusion rate . A tourniquet use during TKA is unfavorable for early rehabilitation progress We conducted a prospect i ve study to investigate the immediate and 2-year outcomes of total knee arthroplasty patients who received continuous femoral nerve block ( FNB ) for analgesia . Sixty patients undergoing unilateral total knee arthroplasty were r and omized into 3 groups and received high-dose continuous FNB , low-dose continuous FNB , or no FNB . In the immediate postoperative period , we studied their pain scores , cumulative morphine use , any FNB-related complications , time of first ambulation , and patient satisfaction . At 2 years , we assessed their functional outcomes with Oxford knee question naire and Knee Society clinical rating system . Immediately after surgery , there was less pain , higher satisfaction , and lower morphine use among patients on continuous FNB regardless of ropivacaine dosage used . At 2 years , there were no significant differences in functional outcomes There remains a lack of r and omized controlled trials comparing methods of perioperative analgesia for total knee arthroplasty . To address this deficiency , a blinded , r and omized controlled trial was conducted to compare the use of femoral nerve block ( group F ) and local anesthetic ( group L ) . A sample of 55 patients who met the inclusion criteria were r and omized to either group . No significant differences in the most severe pain score or 36-Item Short Form Health Survey , The Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , or Oxford scores were observed between groups . However , the Knee Society score was significantly higher in group F. In addition , group F used significantly fewer micrograms of intravenous fentanyl in the first 24 hours . Balancing the risks of femoral nerve block with those of increased systemic narcotic delivery should be performed on a case-by-case basis An RCT pilot- study was conducted to assess efficacy of a 48-h continuous local infiltration of intra-articular bupivacaine ( 0.5 % at 2 cc/h ) versus placebo ( 0.5 % saline at 2 cc/h ) in decreasing PCA morphine consumption following TKA . Secondary outcomes included 48-h VAS pain , opioid side effects , length of stay , and knee function scores up to 1-year postoperatively . Of 67 r and omized patients , 49 completed the trial including 24 bupivacaine , and 25 placebo patients . Mean 48-h PCA morphine consumption did not differ significantly between treatment ( 39 mg ± 27.1 ) and placebo groups ( 53 mg ± 30.4 ) ( P = .137 ) . The intervention did not improve pain scores , or any other outcome studied . Given study results we would conclude that analgesia outcomes with a multimodal analgesia regimen are not significantly improved by adding 48 h of 0.5 % bupivacaine infiltration at 2 cc/h We report the findings of a r and omised controlled triple-blind pilot study of intraoperative ketamine infusion combined with spinal anaesthesia on the prevalence of persisting post surgical pain following total knee arthroplasty surgery . Twelve patients were r and omised to receive either ketamine or placebo in association with spinal anaesthesia for total knee arthroplasty . All patients also received general anaesthesia . More patients were pain-free at six months in the ketamine group ( three of five ) compared to the control group ( two of seven ) . Perioperative data collected during the study suggested that the addition of intraoperative ketamine might also improve the quality of recovery . Although no statistical analysis was undertaken due to the small numbers , these preliminary findings suggest that the use of intraoperative systemic ketamine in association with spinal anaesthesia for the reduction of persisting post surgical pain deserves further study BACKGROUND Venography is currently used to assess the incidence of deep vein thrombosis ( DVT ) in dose-finding and confirmatory trials of new antithrombotic agents . Central ly adjudicated , complete compression ultrasound ( CCUS ) could be a non-invasive alternative to venography . OBJECTIVES A sub study of two , similarly design ed , phase IIb trials of a novel , oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to vali date CCUS against venography . PATIENTS / METHODS Patients received study drugs until m and atory , bilateral venography was performed 7 + /- 2 days after surgery . CCUS was performed within 24 h after venography by sonographers blinded to the venography result . Sonographers were trained and certified for the st and ardized examination and documentation procedure . Venograms and sonograms were adjudicated central ly at different sites by two independent readers ; discrepancies between readers were resolved by consensus . RESULTS A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials ( n = 1435 ) : 19 % of venograms and 20 % of sonograms were not evaluable . The observed frequency of any DVT was 18.9 % with venography and 11.5 % with CCUS . Sensitivity of CCUS compared with venography was 31.1 % for any DVT ( 95 % confidence interval 23.4 , 38.9 ) , 21.0 % ( 2.7 , 39.4 ) for proximal DVT , and 30.8 % ( 23.1 , 38.6 ) for distal DVT . The figures for specificity were 93.0 % ( 91.0 , 95.1 ) , 98.7 % ( 98.0 , 99.5 ) , and 93.3 % ( 91.5 , 95.3 ) , respectively . CONCLUSIONS Based on these results , central ly adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs Background and Objectives This is a follow-up to determine long-term outcomes after total knee arthroplasty ( TKA ) in patients enrolled in a previous r and omized trial that found reduced postoperative pain after addition of sciatic nerve block to continuous femoral nerve block for TKA . Methods Physical function after TKA was evaluated at 3 and 12 months in patients ( n = 89 ) receiving continuous femoral nerve block alone ( group F ) , combined with a single-injection ( group Fs ) or continuous sciatic nerve block ( group FCS ) after TKA , until the second postoperative day . Physical function , stiffness , and pain were measured by using Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , Oxford Knee Score 12-item knee question naires , and visual analog scale at rest and during mobilization before TKA and 3 and 12 months afterward . Post hoc , a median split on poor functioning ( WOMAC ) was analyzed . Results Western Ontario and McMaster Universities Osteoarthritis Index , Oxford Knee Score 12-item knee , and visual analog scale scores improved significantly in all patients , without any differences among groups . Median ( range ) WOMAC at 3 months were in group F , 83 ( 20–97 ) ; group Fs , 72 ( 25–99 ) ; and group , FCS 76 ( 28–100 ) and at 12 months 87 ( 35–98 ) , 77 ( 43–100 ) , and 89 ( 35–100 ) , respectively . Conclusions No differences were detected in the secondary outcomes we examined . Thus , improved postoperative outcome did not translate into improved functional outcome or long-term pain OBJECTIVE To evaluate the effect of inpatient aquatic physiotherapy in addition to usual ward physiotherapy on the recovery of strength , function , and gait speed after total hip or knee replacement surgery . DESIGN Pragmatic r and omized controlled trial with blinded 6-month follow-up . SETTING Acute-care private hospital . PARTICIPANTS People ( n=65 ) undergoing primary hip or knee arthroplasty ( average age , 69.6+/-8.2y ; 30 men ) . INTERVENTIONS Participants were r and omly assigned to receive supplementary inpatient physiotherapy , beginning on day 4 : aquatic physiotherapy , nonspecific water exercise , or additional ward physiotherapy . MAIN OUTCOME MEASURES Strength , gait speed , and functional ability at day 14 . RESULTS At day 14 , hip abductor strength was significantly greater after aquatic physiotherapy intervention than additional ward treatment ( P=.001 ) or water exercise ( P=.011 ) . No other outcome measures were significantly different at any time point in the trial , but relative differences favored the aquatic physiotherapy intervention at day 14 . No adverse events occurred with early aquatic intervention . CONCLUSIONS A specific inpatient aquatic physiotherapy program has a positive effect on early recovery of hip strength after joint replacement surgery . Further studies are required to confirm these findings . Our research indicates that aquatic physiotherapy can be safely considered in this early postoperative phase Abstract Patients undergoing total knee arthroplasty often experience substantial postoperative pain , which may delay functional recovery and hospital discharge . We recently reported the short-term analgesic efficacy of a single-injection femoral nerve block after spinal anesthesia in total knee arthroplasty . We have now followed 30 patients a minimum of 1 year to determine the functional outcome and pain relief after femoral and obturator nerve block after total knee arthroplasty . Patients undergoing primary unilateral total knee arthroplasty were r and omized to one of three treatment groups : ( 1 ) femoral nerve block ; ( 2 ) obturator nerve block ; or ( 3 ) placebo ( sham block ) . At 6 weeks and 1 year , all three groups had similar total Hospital for Special Surgery knee scores and similar subscores such as range of motion , daily function , and resting and dynamic pain . The data support the usefulness of a peripheral nerve blockade in the context of a multimodal analgesic regimen and a tailored rehabilitation program to individual patients and institutions . Level of Evidence : Level III , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence Objective : Pregabalin is effective in several neuropathic pain syndromes . This trial evaluated its efficacy , safety , and tolerability for treatment of painful HIV-associated neuropathy . Methods : This r and omized , double-blind , placebo-controlled , parallel-group trial included a 2-week double-blind dose-adjustment ( 150–600 mg/day BID ) phase , a 12-week double-blind maintenance phase , and an optional 3-month open label extension phase . The primary efficacy measure was the mean Numeric Pain Rating Scale ( NPRS ) score , an 11-point numeric rating scale . Secondary measures included Patient Global Impression of Change ( PGIC ) and sleep measurements . Results : Baseline mean NPRS score was 6.93 for patients r and omized to pregabalin ( n = 151 ) and 6.72 for those to placebo ( n = 151 ) . Pregabalin average daily dosage ( SD ) was 385.7 ( 160.3 ) mg/d . At endpoint , pregabalin and placebo showed substantial reductions in mean NPRS score from baseline : −2.88 vs −2.63 , p = 0.3941 . Pregabalin had greater improvements in NPRS score relative to placebo at weeks 1 ( −1.14 vs −0.69 , p = 0.0131 ) and 2 ( −1.92 vs −1.43 , p = 0.0393 ) , and at weeks 7 ( −3.22 vs −2.53 p = 0.0307 ) and 8 ( −3.33 vs −2.53 , p = 0.0156 ) . At all other time points , differences between groups were not significant . Sleep measurements and 7-item PGIC did not differ among treatment groups ; however , collapsed PGIC scores showed 82.8 % of pregabalin and 66.7 % of placebo patients rated themselves in 1 of the 3 “ improved ” categories ( p = 0.0077 ) . Somnolence and dizziness were the most common adverse events with pregabalin . Conclusions : Pregabalin was well-tolerated , but not superior to placebo in the treatment of painful HIV neuropathy . Factors predicting analgesic response in HIV neuropathy warrant additional research . Classification of Evidence : This Class II trial showed that pregabalin is not more effective than placebo in treatment of painful HIV neuropathy Background Multimodal cocktail periarticular injection ( MCPI ) with a large volume of low concentration local anesthetics , adrenaline , and anti‐inflammatory agents such as non‐steroidal anti‐inflammatory drug or steroids have shown good pain control and improvement in range of motion after surgery . This study compares the efficacy of pain control after total knee arthroplasty , using multimodal cocktail periarticular injection with steroid or without steroid . Methods This is a prospect i ve , double‐blinded , r and omized and control study . Seventy‐two patients with osteoarthritis that met clinical criteria for total knee arthroplasty were recruited into the study , and were r and omized to receive either multimodal cocktail periarticular injection with steroid or without steroid . Pain was assessed by visual analogue scale ( VAS ) at preoperative and postoperative at rest , and during activity . The range of motion was recorded preoperatively and postoperatively . The amount of daily and cumulative morphine consumption were measured by patient‐controlled analgesia in the first 72 hours postoperatively . The duration of celecoxib usage was also recorded at the last follow‐up . Results There were no differences between the non‐steroid and steroid groups with regard to VAS at rest and during activity , or range of motion , at any postoperative observation time . The postoperative Knee Society Knee Score in the steroid group improved significantly as compared with that in non‐steroid group at the one‐month ( 84.1±13.1 and 65.9±12.1 ; P < 0.0045 ) , three‐month follow‐up ( 90.2±16.3 and 72.5±16.6 ; P < 0.0027 ) , but after postoperative six‐month the Knee Society Knee Score showed no significant difference between the groups . There was no significant difference in consumption of the morphine about daily or total consumption within 72 hours between the two groups . The duration of celecoxib usage in patients in the steroid group was significantly shorter than that in the non‐steroid group ( ( 7.2±0.7 ) compared with ( 10.5±1.9 ) weeks ; P=0.012 ) . Conclusion The patients who received the steroid injection had faster rehabilitation and less non‐steroidal anti‐inflammatory drugs consumption The authors report the results of a prospect i ve r and omized clinical trial using continuous passive motion after total knee arthroplasty . One hundred twenty patients were assigned r and omly to one treatment group : No continuous passive motion ( Group I ) , continuous passive motion from 0 ° to 50 ° and increased as tolerated ( Group II ) , and continuous passive motion from 70 ° to 110 ° ( Group III ) . The continuous passive motion was initiated in the recovery room and was maintained for a maximum of 24 hours at which point all patients began identical postoperative physiotherapy regimens . Patients were assessed preoperatively , during their hospital stay , at 6 weeks , 12 weeks , 26 weeks , and 52 weeks after their surgery . There were no statistical differences between any of the treatment groups regarding cumulative analgesic requirements , range of motion at any measured interval , length of stay ( Group I , 5.1 days ; Group II , 5.2 days ; Group III , 5 days ) or Knee Society scores . The current study does not support the use of short-term continuous passive motion after total knee replacement . A st and ard and a high flexion continuous passive motion protocol failed to show any advantage over physiotherapy alone in the parameters evaluated Background Pain management after surgery has been used as a sales argument for the use of COX-2 inhibitors , but their potential positive and negative effects have not been fully investigated . We thus conducted a controlled evaluation of the effect of celecoxib on perioperative blood loss , pain relief and consumption of analgesics , range of motion , and subjective outcome in conjunction with total knee replacement ( TKR ) . Method 50 patients were r and omized to either placebo or celecoxib ( 200 mg ) preoperatively and then twice daily . Total blood loss was calculated by the Hb balance method , taking the patient 's pre- and postoperative hemoglobin and blood volume into account . Pain scores ( VAS ) , range of motion , and subjective outcome ( KOOS ) were monitored postoperatively and during the first year after surgery . Results No differences in total , hidden , or drainage blood loss were found between the groups . There were 30 % lower pain scores during the first 4 weeks after surgery and lower morphine consumption after surgery in the celecoxib group , while no effect was seen on pain , range of motion , and subjective outcome at the 1 year follow-up . Interpretation Celecoxib does not increase perioperative blood loss but reduces pain during the postoperative period after TKR . It is not necessary to discontinue celecoxib before surgery . The postoperative use of celecoxib did not increase range of motion or subjective outcome 1 year after TKR Background and Objectives Despite multiple clinical trials comparing the adductor canal block ( ACB ) with femoral nerve block ( FNB ) for total knee arthroplasty , none looked at the aforementioned nerve blocks from early functional results to up to 6 months after surgery . Methods For this prospect i ve , double-blind , r and omized , single-center trial , we enrolled 98 patients set to undergo total knee arthroplasty . The patients were r and omized , with 93 patients included in the intention-to-treat analysis . Subjects received injections of both ACB and an FNB , with 1 containing 30 mL of saline ( placebo ) and the other 30 mL of local anesthetic ( treatment ) depending on r and omization . Adductor canal block and FNB were compared using percentage of baseline maximum voluntary isovolumetric contraction ( MVIC ) of the quadriceps muscle retained at 6 ( primary endpoint ) , 24 , and 48 hours and 6 months postoperatively . Secondary endpoints also included Timed Up and Go , range of motion , 6-minute walking test , pain score , and postoperative pain medication use . Results Percent MVIC retained was significantly higher in ACB patients at 6 ( P < 0.0001 ) and 24 hours ( P < 0.0001 ) . Comparing Timed Up and Go results yielded significant difference between treatment groups at 6 hours ( P = 0.0213 ) and 24 hours ( P = 0.0424 ) . Pain scores , pain medication intake , range of motion , and 6-minute walking test were not significantly different between the treatment groups . A linear relationship exists between the change in quadriceps MVIC and pain score in the ACB group , with increasing pain leading to a decreased MVIC ( P = 0.0039 ) . Conclusions The ACB showed better preservation of quadriceps muscle strength and improved ambulation in the first 24 hours postoperatively without compromising pain control Background The current practice in elective orthopaedics does not routinely include psychological interventions despite evidence that psychological factors such as personality , anxiety , depression and negative thinking styles can influence outcomes and recovery from surgery . The objective of this paper was to review the effectiveness of psychological interventions used in conjunction with total hip ( THA ) and knee arthroplasty ( TKA ) , in improving patient reported joint outcomes . Methods An extensive literature search was conducted according to Preferred Reporting Items for Systematic review s and Meta-Analyses guidelines . Search terms included psychology , interventions , and orthopaedics . Articles were included if they were r and omised controlled trials ( RCTs ) of psychological interventions involving active patient participation measured with patient reported joint outcomes in patients undergoing hip or knee arthroplasty . Results A total of 19,489 titles were screened . Seven studies met the inclusion criteria and were included . Five of seven studies did not show improvements in patient reported outcomes after surgery . Specifically , psycho-education alone was not effective at improving patient reported joint outcomes in two out of two studies . Conclusion The current literature does not support routine psychological interventions for TKA and THA . However , it should be noted that the literature for psychological interventions in conjunction with TKA and THA is still in its infancy . This gap in the literature is surprising , considering the importance of the role of psychological factors in recovery . Further RCTs with long term follow ups , multidisciplinary involvement , and more comprehensive and focused interventions that go beyond educating patients are needed . Future studies should account for the dem and effect , include measures of psychological variables to determine whether psychological interventions are more beneficial for some patients compared to others , and compare the different modes of delivery and timing of interventions to determine the optimal nature and duration of psychological interventions for TKA and THA Background : Pain catastrophizing has been identified as a prognostic indicator of poor outcome following knee arthroplasty . Interventions to address pain catastrophizing , to our knowledge , have not been tested in patients undergoing knee arthroplasty . The purpose of this study was to determine whether pain coping skills training in persons with moderate to high pain catastrophizing undergoing knee arthroplasty improves outcomes 12 months postoperatively compared with usual care or arthritis education . Methods : A multicenter , 3-arm , single-blinded , r and omized comparative effectiveness trial was performed involving 5 university-based medical centers in the United States . There were 402 r and omized participants . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) Pain Scale , measured at baseline , 2 months , 6 months , and 12 months following the surgical procedure . Results : Participants were recruited from January 2013 to June 2016 . In 402 participants , 66 % were women and the mean age of the participants ( and st and ard deviation ) was 63.2 ± 8.0 years . Three hundred and forty-six participants ( 90 % of those who underwent a surgical procedure ) completed a 12-month follow-up . All 3 treatment groups had large improvements in 12-month WOMAC pain scores with no significant differences ( p > 0.05 ) among the 3 treatment arms . No differences were found between WOMAC pain scores at 12 months for the pain coping skills and arthritis education groups ( adjusted mean difference , 0.3 [ 95 % confidence interval ( CI ) , −0.9 to 1.5 ] ) or between the pain coping and usual-care groups ( adjusted mean difference , 0.4 [ 95 % CI , −0.7 to 1.5 ] ) . Secondary outcomes also showed no significant differences ( p > 0.05 ) among the 3 groups . Conclusions : Among adults with pain catastrophizing undergoing knee arthroplasty , cognitive behaviorally based pain coping skills training did not confer pain or functional benefit beyond the large improvements achieved with usual surgical and postoperative care . Future research should develop interventions for the approximately 20 % of patients undergoing knee arthroplasty who experience persistent function-limiting pain . Level of Evidence : Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence BACKGROUND Total knee arthroplasty ( TKA ) is usually associated with severe postoperative pain , which can prevent rehabilitation of patients ' knee function and influence the satisfaction of surgery . Local infiltration analgesia ( LIA ) as a new method to managing postoperative pain has been applied in clinical practice recently . However , the safety and efficacy of LIA compared with femoral nerve block ( FNB ) in postoperative pain management of TKA still remains controversial . Thus , we conducted an original clinical trial to compare LIA and FNB . METHOD One hundred fifty-seven patients undergoing TKA were enrolled in a r and omized , double-blind , single-center study . The patients received either FNB ( group A ) or periarticular infiltration of local anesthetic ( group B ) . The morphine consumption used in patient-controlled analgesia after surgery , postoperative Visual Analogue Scale ( VAS ) , Knee Society Score , and range of motion before and after surgery in both groups were analyzed , as well as the adverse effects . RESULTS Group A consisted 78 patients , and group B contained 79 patients . The patients ' characteristics including age and body mass index had no significant difference ( P > .05 ) . Morphine consumption , VAS at rest , range of motion , and Knee Society Score were similar between the 2 groups . Our study showed group B , the local anesthetic group had less VAS with movement on postoperative day 1 ( P = .01 ) than that of group A , which means a better pain control . Because of the study design , the surgery time showed no significant difference . Eighteen patients in group A and 21 patients in group B experienced mild-to-medium nausea or vomiting . One patient in group B had dizziness and one patient in group A suffered a neuropraxic injury to the femoral nerve . No urinary retention case was seen during inpatient days . There were no significant differences between the 2 groups about side effects . CONCLUSIONS Our research showed that no significant differences were observed between the 2 treatment groups . LIA could provide a similar analgesic effect to FNBs with a low incidence of complications OBJECTIVE The purpose of this study was to compare continuous femoral nerve analgesia to oral opioid analgesics after discontinuation of epidural analgesia following total knee replacement . DESIGN R and omized prospect i ve controlled parallel group trial . Setting . Large tertiary university teaching hospital in a major Midwestern city . Subjects . Sixty-two subjects were r and omized to receive neuraxial anesthesia followed by either oral analgesics ( N = 31 ) or continuous femoral nerve analgesia ( N = 31 ) . INTERVENTIONS After discontinuation of epidural anesthesia on the morning after surgery , continuous femoral nerve analgesia ( CFA ) , ropivacaine 25 mg bolus and 5 mg/h infusion was initiated . Catheters were removed 24 hours later . All subjects received oral opioid analgesics as needed . OUTCOME MEASURES The primary outcome measure was knee flexion at 1 month . Physical therapy assessment s , pain scores , opioid consumption , and patient satisfaction were assessed during hospitalization . Knee flexion , pain scores , and opioid consumption were collected at 1 , 6 , and 12 months , and health-related quality of life was collected at 6 and 12 months . RESULTS ; The median difference ( 95 % CI ) in the change in knee flexion from baseline was 7.5 ( 0 to 15 ) degrees greater after CFA ( P = 0.04 ) at 1 month . CFA subjects had greater compliance with physical therapy , reduced pain scores , and opioid requirements during hospitalization . Thromboembolic events occurred in 0/31 CFA vs 4/31 non-CFA subjects ( P = 0.04 ) . CONCLUSIONS CFA for 24 hours following discontinuation of epidural analgesia was associated with lower pain scores , greater compliance with physical therapy , increased range of motion , reduced opioid analgesia use , and greater patient satisfaction during hospitalization . The increased flexion of the operated joint was still evident at 1 month postoperatively Background The goal of this work was to investigate the effects of different methods of using pneumatic tourniquet on reducing blood loss in patients undergoing cemented total knee arthroplasty ( TKA ) . Methods One hundred and fifty patients undergoing unilateral cemented TKA were r and omly divided into three groups ( 50 patients per group ) . The tourniquet was used during the entire operation ( Group A ) , used from the beginning of operation to the completion of joint replacement ( Group B ) , and from the beginning of osteotomy to the completion of arthroplasty ( Group C ) . The following parameters were recorded : intraoperative blood loss ( IBL ) , postoperative blood loss ( PBL ) , hidden blood loss ( HBL ) , and total blood loss ( TBL ) ; operation time and tourniquet time ; incidence of postoperative complications ; and hospital for special surgery ( HSS ) score . Results IBL , HBL , and TBL in group C was significantly less than that in group B ( all P < 0.05 ) . Tourniquet time in group C was significantly less than that in groups A and B ( all P < 0.05 ) . The incidence of tourniquet-related complications in group C ( 6 % ) was relatively lower than that in group A ( 10 % ) during hospitalization ( P > 0.05 ) . Post-operative HSS scores at 2 weeks after the operation in group C was significantly higher than that in group A and group B ( all P < 0.05 ) . Conclusions Our results suggest that using a tourniquet from the beginning of osteotomy to the completion of arthroplasty could significantly reduce TBL in TKA , and decrease the incidence of complications ; thereby facilitating early post-operative functional recovery Background The recovery of quadriceps muscle force and function after total knee arthroplasty ( TKA ) is suboptimal , which predisposes patients to disability with increasing age . Objective The purpose of this investigation was to evaluate the efficacy of quadriceps muscle neuromuscular electrical stimulation ( NMES ) , initiated 48 hours after TKA , as an adjunct to st and ard rehabilitation . Design This was a prospect i ve , longitudinal r and omized controlled trial . Methods Sixty-six patients , aged 50 to 85 years and planning a primary unilateral TKA , were r and omly assigned to receive either st and ard rehabilitation ( control ) or st and ard rehabilitation plus NMES applied to the quadriceps muscle ( initiated 48 hours after surgery ) . The NMES was applied twice per day at the maximum tolerable intensity for 15 contractions . Data for muscle strength , functional performance , and self-report measures were obtained before surgery and 3.5 , 6.5 , 13 , 26 , and 52 weeks after TKA . Results At 3.5 weeks after TKA , significant improvements with NMES were found for quadriceps and hamstring muscle strength , functional performance , and knee extension active range of motion . At 52 weeks , the differences between groups were attenuated , but improvements with NMES were still significant for quadriceps and hamstring muscle strength , functional performance , and some self-report measures . Limitations Treatment volume was not matched for both study arms ; NMES was added to the st and ard of care treatment . Furthermore , testers were not blinded during testing , but used st and ardized scripts to avoid bias . Finally , some patients reached the maximum stimulator output during at least one treatment session and may have tolerated more stimulation . Conclusions The early addition of NMES effectively attenuated loss of quadriceps muscle strength and improved functional performance following TKA . The effects were most pronounced and clinical ly meaningful within the first month after surgery , but persisted through 1 year after surgery |
10,851 | 20,149,474 | Our data showed that the addition of cetuximab to chemotherapy would improve overall survival and overall response rate .
It may provide new option for clinical treatment for untreated advanced non-small-cell lung cancer .
The side effects of E-chemo are predictable and manageable | PURPOSE To compare the efficacy and toxicities of chemotherapy plus cetuximab ( Erbitux , E ; E-chemo ) with chemotherapy alone ( chemo alone ) in patients with previously untreated advanced non-small-cell lung cancer ( NSCLC ) . | PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib ( Iressa [ ZD1839 ] ; AstraZeneca , Wilmington , DE ) , a novel epidermal growth factor receptor tyrosine kinase inhibitor , in patients with pretreated advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This was a r and omized , double-blind , parallel-group , multicenter phase II trial . Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens ( at least one containing platinum ) were r and omly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily . RESULTS Efficacy was similar for the 250- and 500-mg/d groups . Objective tumor response rates were 18.4 % ( 95 % confidence interval [ CI ] , 11.5 to 27.3 ) and 19.0 % ( 95 % CI , 12.1 to 27.9 ) ; among evaluable patients , symptom improvement rates were 40.3 % ( 95 % CI , 28.5 to 53.0 ) and 37.0 % ( 95 % CI , 26.0 to 49.1 ) ; median progression-free survival times were 2.7 and 2.8 months ; and median overall survival times were 7.6 and 8.0 months , respectively . Symptom improvements were recorded for 69.2 % ( 250 mg/d ) and 85.7 % ( 500 mg/d ) of patients with a tumor response . Adverse events ( AEs ) at both dose levels were generally mild ( grade 1 or 2 ) and consisted mainly of skin reactions and diarrhea . Drug-related toxicities were more frequent in the higher-dose group . Withdrawal due to drug-related AEs was 1.9 % and 9.4 % for patients receiving gefitinib 250 and 500 mg/d , respectively . CONCLUSION Gefitinib showed clinical ly meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients . At 250 mg/d , gefitinib had a favorable AE profile . Gefitinib 250 mg/d is an important , novel treatment option for patients with pretreated advanced NSCLC [ corrected CONTEXT More persons in the United States die from non-small cell lung cancer ( NSCLC ) than from breast , colorectal , and prostate cancer combined . In pre clinical testing , oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor ( EGFR ) , a mediator of cell signaling , and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib . OBJECTIVE To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib . DESIGN , SETTING , AND PATIENTS Double-blind , r and omized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers . Patients ( N = 221 ) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens . INTERVENTION Daily oral gefitinib , either 500 mg ( administered as two 250-mg gefitinib tablets ) or 250 mg ( administered as one 250-mg gefitinib tablet and 1 matching placebo ) . MAIN OUTCOME MEASURES Improvement of NSCLC symptoms ( 2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [ FACT-L ] instrument ) and tumor regression ( > 50 % decrease in lesion size on imaging studies ) . RESULTS Of 221 patients enrolled , 216 received gefitinib as r and omized . Symptoms of NSCLC improved in 43 % ( 95 % confidence interval [ CI ] , 33%-53 % ) of patients receiving 250 mg of gefitinib and in 35 % ( 95 % CI , 26%-45 % ) of patients receiving 500 mg . These benefits were observed within 3 weeks in 75 % of patients . Partial radiographic responses occurred in 12 % ( 95 % CI , 6%-20 % ) of individuals receiving 250 mg of gefitinib and in 9 % ( 95 % CI , 4%-16 % ) of those receiving 500 mg . Symptoms improved in 96 % of patients with partial radiographic responses . The overall survival at 1 year was 25 % . There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement ( P = .26 ) , radiographic tumor regression ( P = .51 ) , and projected 1-year survival ( P = .54 ) . The 500-mg dose was associated more frequently with transient acne-like rash ( P = .04 ) and diarrhea ( P = .006 ) . CONCLUSIONS Gefitinib , a well-tolerated oral EGFR-tyrosine kinase inhibitor , improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy e19011 Background : The phase III BMS099 trial investigated cetuximab ( C ) added to taxane/carboplatin ( TC ) for 1st line treatment of advanced NSCLC . Progression-free survival ( PFS ) was not significantly different with C ; response rate ( RR ) was significantly higher . Median overall survival ( OS ) was longer , with a difference not statistically significant , but similar in magnitude to the significant OS improvement from the FLEX trial ( cisplat/vinorelb±C ) . A secondary objective of the BMS099 study was to assess the effect of C on Lung Cancer Symptoms ( LCS ) . METHODS Chemonaïve patients ( pts ) with stage IIIB/IV NSCLC ( any histology or EGFR expression status ) were r and omized to TC±C. LCS were measured using the functional assessment of cancer treatment-lung cancer subscale question naire ( FACT-LCS ) , given at baseline and before each therapy cycle until disease progression ( scoring 7 symptoms : breath loss , weight loss , clear thinking , coughing , appetite , chest tightness , breath ease , on a 0 - 4 scale ) . The main endpoints were rates of symptom response/progression ( ≥ 2 point improvement/decrease from baseline in 2 consecutive assessment s ) , compared between arms with a stratified Cochran-Mantel-Haenszel ( CMH ) test ; a stratified log-rank test was used to compare time to symptomatic progression . A Wei-Lachin test was used to compare between arms the changes from baseline in LCS score , and a longitudinal model was constructed to measure treatment effect on those score changes . RESULTS With 676 patients r and omized , the baseline compliance rates for the FACT-LCS question naire were 99.4 % and 99.1 % for CTC and TC respectively , decreasing by week 18 to 74.0 % and 66.4 % . Baseline FACT-LCS scores were similar across treatment arms ( median , 19.0 ) . Symptom response rates were similar with CTC vs TC ( 32.6 % vs 28.5 % , CMH P=0.26 ) , and time to symptomatic progression was not significantly different ( log-rank P=0.58 ) . Changes from baseline in FACT-LCS scores did not differ significantly between arms ( Wei Lachin P=0.912 ; longitudinal model P=0.81 ) . CONCLUSIONS The addition of C to TC for the 1st treatment of advanced NSCLC result ed in similar symptom response/progression rates and did not affect trends in LCS score changes throughout treatment . [ Table : see text ] PURPOSE Epidermal growth factor receptor ( EGFR ) gene copy number detected by fluorescent in situ hybridization ( FISH ) has proven to be useful for selection of non-small-cell lung cancer ( NSCLC ) patients for treatment with EGFR tyrosine kinase inhibitors . Here , we evaluate EGFR FISH as a predictive marker in NSCLC patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus chemotherapy . PATIENTS AND METHODS Two hundred twenty-nine chemotherapy-naive patients with advanced-stage NSCLC were enrolled onto a phase II selection trial evaluating sequential or concurrent chemotherapy ( paclitaxel plus carboplatin ) with cetuximab . RESULTS EGFR FISH was assessable in 76 patients with available tumor tissue and classified as positive ( four or more gene copies per cell in > /= 40 % of the cells or gene amplification ) in 59.2 % . Response ( complete response/partial response ) was numerically higher in FISH-positive ( 45 % ) versus FISH-negative ( 26 % ) patients ( P = .14 ) , whereas disease control rate ( complete response/partial response plus stable disease ) was statistically superior ( 81 % v 55 % , respectively ; P = .02 ) . Patients with FISH-positive tumors had a median progression-free survival time of 6 months compared with 3 months for FISH-negative patients ( P = .0008 ) . Median survival time was 15 months for the FISH-positive group compared with 7 months for patients who were FISH negative . ( P = .04 ) . Furthermore , survival favored FISH-positive patients receiving concurrent therapy . CONCLUSION These results are the first to suggest that EGFR FISH is a predictive factor for selection of NSCLC patients for cetuximab plus chemotherapy . Prospect i ve validation of these findings is warranted PURPOSE Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors have demonstrated antitumor activity in patients with non-small-cell lung cancer ( NSCLC ) . This study examined the safety profile of the monoclonal antibody EGFR inhibitor , cetuximab , when added to paclitaxel and carboplatin in untreated patients with stage IV NSCLC . Secondary objectives included efficacy and paclitaxel and carboplatin pharmacokinetics during cetuximab treatment . PATIENTS AND METHODS Patients with tumor evidence of EGFR by immunohistochemistry , performance status of 0 to 2 , and measurable disease received paclitaxel 225 mg/m2 with carboplatin area under the curve = 6 on day 1 every 3 weeks . Cetuximab was administered at 400 mg/m2 , 1 week before paclitaxel and carboplatin , then weekly at 250 mg/m2 . The regimen continued until disease progression or intolerable toxicity . RESULTS Thirty-one of 32 enrolled patients were treated . The most common cetuximab toxicity was rash in 84 % of patients ( grade 3 in 13 % ) . Pharmacokinetic sampling did not reveal an interaction between carboplatin , paclitaxel , and cetuximab . An objective response was observed in eight patients ( 26 % ) . With a median follow-up of 19 months , the median time to progression was 5 months , median survival was 11 months , and the 1- and 2-year survival rates were 40 % and 16 % , respectively . CONCLUSION The combination of cetuximab , paclitaxel , and carboplatin was safe and well tolerated in this population of stage IV patients . The response rate , time to progression , and median survival were slightly superior to historical controls treated with paclitaxel and carboplatin alone . A r and omized phase II trial has completed accrual BACKGROUND Use of cetuximab , a monoclonal antibody targeting the epidermal growth factor receptor ( EGFR ) , has the potential to increase survival in patients with advanced non-small-cell lung cancer . We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer . METHODS In a multinational , multicentre , open-label , phase III trial , chemotherapy-naive patients ( > or=18 years ) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were r and omly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy . Chemotherapy was cisplatin 80 mg/m(2 ) intravenous infusion on day 1 , and vinorelbine 25 mg/m(2 ) intravenous infusion on days 1 and 8 of every 3-week cycle ) for up to six cycles . Cetuximab-at a starting dose of 400 mg/m(2 ) intravenous infusion over 2 h on day 1 , and from day 8 onwards at 250 mg/m(2 ) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred . The primary endpoint was overall survival . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00148798 . FINDINGS Between October , 2004 , and January , 2006 , 1125 patients were r and omly assigned to chemotherapy plus cetuximab ( n=557 ) or chemotherapy alone ( n=568 ) . Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group ( median 11.3 months vs 10.1 months ; hazard ratio for death 0.871 [ 95 % CI 0.762 - 0.996 ] ; p=0.044 ) . The main cetuximab-related adverse event was acne-like rash ( 57 [ 10 % ] of 548 , grade 3 ) . INTERPRETATION Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer . FUNDING Merck PURPOSE Erlotinib is a highly specific epidermal growth factor receptor ( HER1/EGFR ) tyrosine kinase inhibitor . This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response , survival , and symptom improvement . PATIENTS AND METHODS Fifty-seven patients received an oral , continuous daily dose of 150 mg of erlotinib . Assessment s of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria . The European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 , supplemented with a lung cancer module , Quality of Life Question naire LC13 , was used to measure health-related quality of life . Additional analyses were performed to identify predictors of response and survival . RESULTS The objective response rate was 12.3 % ( 95 % CI , 5.1 % to 23.7 % ) . Responses were observed regardless of type or number of prior chemotherapy regimens . Median survival time was 8.4 months ( 95 % CI , 4.8 to 13.9 months ) , and the 1-year survival rate was 40 % ( 95 % CI , 28 % to 54 % ) . Erlotinib therapy was associated with tumor-related symptom improvement . The drug was well tolerated ; drug-related cutaneous rash and diarrhea were observed in 75 % and 56 % of patients , respectively . One patient experienced toxicity consisting of severe grade 3 rash and diarrhea . Time since diagnosis and good performance status were significant predictors of survival in a multivariate Cox proportional hazards model , whereas HER1/EGFR staining intensity was not . Additionally , survival correlated with the occurrence and severity of rash . CONCLUSION Erlotinib was active and well tolerated in this patient population , and further clinical development is clearly warranted . Cutaneous rash seems to be a surrogate marker of clinical benefit , but this finding should be confirmed in ongoing and future studies Background : Cetuximab has demonstrated synergy with taxanes in pre clinical models ; as well as single agent activity . We assessed the activity of cetuximab with carboplatin and paclitaxel given on a 4-week schedule , in advanced , chemo-naive non-small cell lung cancer . Patients and Methods : This phase II , single arm , multi-institution study featured st and ard dosage of cetuximab 400 mg/m2 day 1 , then 250 mg/m2 with paclitaxel ( 100 mg/m2/wk , for 3 weeks ) , and carboplatin ( area under curve = 6 ) day 1 of each 28 day cycle . After 4 to 6 cycles , in the absence of disease progression or excess toxicity , cetuximab was continued weekly . Primary end point was response rate . Results : Fifty-three patients ( median age 63 , 51 % male ) participated . Response rate was 57 % ( 3 complete response and 27 partial response ) . At a median follow-up of 12.5 months , the estimated overall survival is 13.8 months ( 95 % CI : 9.08–16.02 ) with an event-free survival rate of 5.53 months ( 95 % CI : 4.77–7.99 ) , 18.9 % remain free from progression at 1 year . Improved survival was associated with female gender , absence of prior radiation , PS 0 and epidermal growth factor receptor expression . Toxicities included rash ( 28 % grade 3 ) , nail changes ( 3.7 % grade 3 ) , hypomagnesemia ( 7.5 % grade 3 and 3.7 % grade 4 ) , and neutropenia ( 25 % grade 3 and 13 % grade 4 ) in addition to other typical side effects anticipated with paclitaxel/carboplatin . There were no grade 5 toxicities . Conclusion : Combination of cetuximab/paclitaxel/carboplatin in non-small cell lung cancer was well tolerated and clinical ly active with manageable toxicities . This unique schedule , integrating weekly paclitaxel and cetuximab has not yet been tested in a r and omized trial PURPOSE This multicenter , open-label , phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-naïve , epidermal growth factor receptor-positive , stage IV non-small-cell lung cancer . Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate , time to progression , and overall survival . PATIENTS AND METHODS Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab , carboplatin , and gemcitabine . An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week , followed by weekly doses of 250 mg/m2 . Carboplatin ( area under the curve = 5 , day 1 ) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks . Patients were evaluated for tumor response after every two cycles of therapy . RESULTS The most frequently reported adverse events related to cetuximab included an acne-like rash ( 88.6 % ) , dry skin ( 34.3 % ) , asthenia and skin disorders ( 31.4 % ) , mucositis/stomatitis ( 25.7 % ) , fever/chills ( 20 % ) , and nausea/vomiting ( 17.1 % ) . The majority of these toxicities were mild to moderate . One patient withdrew from the study because of a grade 3 allergic reaction . Myelosuppression was the most frequently observed toxicity related to chemotherapy . Responses among 35 assessable patients included 10 partial responses ( 28.6 % ) . Twenty-one patients had stable disease . The median time to progression was 165 days , and the median overall survival was 310 days . CONCLUSION The combination of cetuximab , carboplatin , and gemcitabine was well tolerated with an acceptable toxicity profile . Most grade 3 adverse events were attributable to chemotherapy . The response rate and median survival are encouraging and warrant additional investigation |
10,852 | 22,152,587 | CONCLUSION While data are limited , there is no evidence to suggest that hormonal contraceptive use among women with sickle cell disease is associated with an increased risk of clinical complications | BACKGROUND Women with sickle cell disease have an increased risk of pregnancy-related complications and need safe , effective contraceptive methods to prevent unintended pregnancy .
STUDY DESIGN We conducted a systematic review to examine the safety of hormonal and intrauterine contraceptive use among women with sickle cell disease . | People with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations , but it is unknown whether they experience an increased risk of venous thromboembolism . We conducted a case-control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics . All subjects were assayed for hemoglobin S and hemoglobin C genotypes . The prevalence of the S allele was 0.070 and 0.032 for case patients and controls , respectively ( P < .001 ) . The odds that a patient had sickle cell trait were approximately twice that of a control , indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype ( odds ratio = 1.8 with 95 % confidence interval , 1.2 - 2.9 ) . The odds ratio for pulmonary embolism and sickle cell trait was higher , 3.9 ( 2.2 - 6.9 ) . The prevalence of sickle cell disease was also increased among case patients compared with controls . We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7 % OBJECTIVE Our purpose was to determine the rate of preeclampsia in women who are positive for sickle cell trait . STUDY DESIGN All African-American women were tested for sickle cell trait with the " sickledex " screen at the fist prenatal visit and prospect ively enrolled in this study from March 1994 to June 1995 . " Sickledex " screens were confirmed with hemoglobin electrophoresis . Demographic data were collected at the time of enrollment . Outcome data , including preeclampsia ( as defined by The American College of Obstetricians and Gynecologists criteria ) , gestational age at delivery , birth weight , and postpartum endometritis were collected immediately post partum . Assuming a 10 % rate of positive sickle cell trait , 1100 patients were required to demonstrate a doubling in the rate of preeclampsia with 80 % power and p < 0.05 . The Student t test , the Mann-Whitney U test , chi 2 analysis , and Fisher 's exact tests were used for statistical analysis . RESULTS Of 1584 women enrolled in the study , 162 were positive for sickle cell trait . Sickle cell trait-positive women were older than the sickle cell trait-negative women ( 24.4 + /- 4.6 vs 23.0 + /- 4.4 years , p < 0.001 ) , but there was no significant difference in parity . The rate of preeclampsia was significantly increased in sickle cell-positive women ( 24.7 % vs 10.3 % , p < 0.0001 ) . There was no significant difference in the rate of chronic hypertension , diabetes , or smoking . Parous sickle cell-positive women more frequently gave a history of preeclampsia in a previous pregnancy ( 21.4 % vs 9.3 % , p < 0.0001 ) . There was a statistically significant decrease in gestational age at delivery and birth weight in sickle cell trait-positive women ( 36.7 + /- 2.7 vs 37.7 + /- 3.0 weeks , p < 0.0001 ; and 3082 + /- 591 vs 3369 + /- 573 gm , p < 0.0001 ) . The rate of postpartum endometritis was significantly increased in the women positive for sickle cell trait ( 12.3 % vs 5.1 % , p < 0.001 ) , although both groups had a similar cesarean section rate ( 14.8 % vs 12.6 % , not significant ) . CONCLUSION This is the first prospect i ve study to demonstrate that sickle cell trait-positive women are at significantly higher risk for development of perinatal complications that have traditionally been associated with sickle disease Forty-three homozygous ( SS ) female sickle cell anemic patients with a history of at least one painful crisis per month and desiring a reversible contraceptive were administered DMPA/3 months or Microgynon monthly . A third group of 16 surgically sterilized patients served as control . Patients were followed for 1 year to assess possible effects of the contraceptives on the patients ' painful crises . No changes were observed in any of the groups in the hematological parameters . At the end of the study , 70 % of the patients receiving DMPA were pain-free and only 16 % of those still reporting painful crises rated them as intense . Patients receiving Microgynon also had an amelioration of the painful crises , although at a lower rate ; after 12 months , 45.5 % still experienced some crises . Although less marked than in the other groups , 50.5 % of the control patients also reported an improvement of their painful crisis , which may be a result of closer medical care Objective To determine the maternal and fetal outcomes of pregnancy in women with sickle cell disease . Methods The subjects were part of a cohort recruited from 19 centers for a prospect i ve study of the clinical course of sickle cell disease . Each participant was evaluated using a structured protocol in which steady-state data and information on both sickle- and non-sickle-related events were colleted . The rates of antepartum and intrapartum complications were tallied for pregnancies carried to delivery . Fetal outcome was assessed according to gestational age , birth weight , and Apgar score . Differences among genotypes in event rates were assessed using Fisher exact test . Differences in gestational age and birth weight , and predictors of these outcomes , were assessed using analyses of covariance . Results Two hundred eighty-six of the 445 reported pregnacies proceeded to delivery . Non-sickle-related antepartum and intrapartum complication rates were comparable with those of African-American women who did not have sickle cell disease . One of the two deaths observed during this study was directly related to the presence of sickle cell disease . Rates of maternal morbidity from sickle cell disease were the same during pregancy as during the nonpregnant state . Ninety-nine percent of those pregnancies carried to delivery result ed in a live birth . Twenty-one percent of the infants born to women of the SS genotype were small for gestational age ( SGA ) . Preclampsia and acute anemic events were identified as risk factors for SGA infants . Conclusion Those caring for women with sickle cell disease should support them if they desire to have children 16 male and 28 female patients experiencing moderately severe pain during episodes of sickle-cell disease at least once in 3 months with little or no fever or exacerbations of jaundice were selected for a cross-over trial of low doses of steriods against saline solution . The patients each completed 4 - 6 months of treatment . All patients were on regular folates and had high or normal serum-iron values . Weights ranged from 24 - 134 pounds and ages from 2 - 35 years . Male patients were r and omly assigned to either testosterone in oil ( 10 mg in 1 ml ) or physiological sodium chloride solution ( 1 ml ) . Females were r and omly assigned to progesterone in oil ( 10 mg in 1 ml ) or physiological saline solution . A score was computed each month reflecting the severity , duration , and frequency of episodes of pain . About 80 % of the individuals on steriods had good responses and about the same proportion of the sodium chloride group had very poor responses . 22 of the original 31 patients stopped taking saline injections after the 1st 2 weeks . The packed-cell volumes in the steroid group rose during the period of steroid injections , while there was no appreciable change in the sodium chloride group . There were no sex differences in the pattern of response and no deleterious side effects were noted OBJECTIVE To assess the safety of Norplant contraceptive implant use by women with mild-moderate homozygous sickle cell disease ( HbSS ) . METHOD Prospect i ve observation of women pre- and post-insertion of Norplant , with each woman serving as her own control . PARTICIPANTS 25 women 18 - 40 years of age who attended a hospital sickle cell clinic ; post-insertion data were available for 23 women . OUTCOME MEASURES Changes in hematologic parameters including PCV , MCV , reticulocytes , ISCs , HbF and bilirubin ; changes in biochemical parameters including HDL cholesterol , aspartate transaminase , alkaline phosphate , serum creatinine and serum albumin . RESULT With a mean follow-up of 12.4 months ( range 1 - 29 months ) , there were no clinical ly or statistically significant group or individual changes in the hematologic or biochemical parameters after Norplant insertion . CONCLUSION Norplant appears to be a safe and appropriate contraceptive for women with mild-moderate HbSS disease |
10,853 | 25,456,155 | Potassium appears to improve endothelial function with a dose of > 40 mmol/d , however the mechanisms for this effect remain unclear .
Potassium may improve measures of vascular function however this effect may be dependent on the effect of potassium on blood pressure .
The effect of fruit and vegetables on endothelial function independent of confounding variables is less clear .
Increased fruit and vegetable intake may improve vascular function only in high risk population s. CONCLUSION Increasing dietary potassium appears to improve vascular function but the effect of increasing fruit and vegetable intake per se on vascular function is less clear | AIM To review the relationships between : 1 ) Potassium and endothelial function ; 2 ) Fruits and vegetables and endothelial function ; 3 ) Potassium and other measures of vascular function ; 4 ) Fruits and vegetables and other measures of vascular function . | Background —Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations . Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events . This study was design ed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease . Methods and Results —Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . The effect of the coadministration of vitamin C ( 24 mg/min ) was assessed in a subgroup of 179 patients . Cardiovascular events , including death from cardiovascular causes , myocardial infa rct ion , ischemic stroke , coronary angioplasty , and coronary or peripheral bypass operation , were studied during a mean follow-up period of 4.5 years . Patients experiencing cardiovascular events ( n=91 ) had lower vasodilator responses to acetylcholine ( P < 0.001 ) and sodium nitroprusside ( P < 0.05 ) , but greater benefit from vitamin C ( P < 0.01 ) . The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P = 0.001 ) , the effect of vitamin C ( P = 0.001 ) , and age ( P = 0.016 ) remained independent predictors of cardiovascular events . Conclusions —Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease . These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity OBJECTIVES The study was done to determine whether radial artery applanation tonometry can be used as a noninvasive method of assessing global endothelial function . BACKGROUND ; It is known that beta(2)-receptor stimulation results in endothelial release of nitric oxide . Furthermore , for over a century glyceryl trinitrate ( GTN ) has been known to markedly affect the arterial pressure waveform , even in the absence of significant blood pressure ( BP ) changes . Therefore , it was hypothesized that the change in the peripheral pressure waveform , as measured using tonometry and quantified using the augmentation index ( AIx ) and in response to Salbutamol ( Salb ) , would allow assessment of global endothelial function . METHODS The study contained three parts . In the first study , Salb ( 400 microg ) was administered to 11 healthy subjects via inhalation after either intravenous N-omega-nitro-monomethyl-L-arginine ( L-NMMA ) ( 3 mg/kg over 5 min ) or control solution ( normal saline ) in the supine , rested , fasted condition . The BP , heart rate and waveform responses were recorded each 5 min following Salb for 20 min . Next , GTN was given and responses recorded 5 min later . In the second study , both the reproducibility of Salb and the GTN responses were assessed in 9 subjects studied twice on separate days . In the third study , the Salb and GTN responses of 12 subjects with angiographic coronary artery disease ( CAD ) were compared with 10 age-matched control subjects with no atherosclerotic risk factors . RESULTS After control infusion , AIx decreased following Salb , from 50.8 + /- 4.3 % to 44.8 + /- 4.2 % , a change of -11.8 + /- 3.7 % , p < 0.01 . After L-NMMA , AIx did not significantly change following Salb ( 54.2 + /- 5.1 % vs. 52.9 + /- 5.3 % , -2.0 + /- 3.1 % ) . The GTN-induced decreases in AIx were similar after either infusion ( 35.1 + /- 3.3 % vs. 36.5 + /- 3.3 % ) . Reproducibility of Salb-induced changes in AIx between studies performed on separate days was good ( r = 0.80 , p < 0.01 ) . Salb-induced changes in AIx in CAD patients were significantly less compared to control subjects ( -2.4 + /- 1.9 % vs. -13.2 + /- 2.4 % , respectively , p < 0.002 ) . The GTN-induced changes were not significantly different ( -27.6 + /- 4.2 vs. -38.9 + /- 4.4 % , p = 0.07 ) . CONCLUSIONS The peripheral arterial pressure waveform is sensitive to beta(2)-stimulation . Changes are related to nitric oxide release , are reproducible and can distinguish between clinical subject groups . Arterial waveform changes following Salb may thus provide a noninvasive method of measuring " global " arterial endothelial function Epidemiological studies indicate that diets rich in fruits and vegetables ( F&V ) are protective against CVD . Puréed F&V products retain many beneficial components , including flavonoids , carotenoids , vitamin C and dietary fibres . The present study aim ed to establish the physiological effects of acute ingestion of a F&V purée-based drink ( FVPD ) on vasodilation , antioxidant status , phytochemical bioavailability and other CVD risk factors . A total of twenty-four subjects , aged 30 - 70 years , completed the r and omised , single-blind , controlled , crossover test meal study . Subjects consumed 400 ml of the FVPD , or a fruit-flavoured sugar-matched control , after following a low-flavonoid diet for 5 d. Blood and urine sample s were collected throughout the study day , and vascular reactivity was assessed at 90 min intervals using laser Doppler iontophoresis . The FVPD significantly increased plasma vitamin C ( P= 0·002 ) and total nitrate/nitrite ( P= 0·001 ) concentrations . There was a near significant time by treatment effect on ex vivo LDL oxidation ( P= 0·068 ) , with a longer lag phase after consuming the FVPD . During the 6 h after juice consumption , the antioxidant capacity of plasma increased significantly ( P= 0·003 ) and there was a simultaneous increase in plasma and urinary phenolic metabolites ( P < 0·05 ) . There were significantly lower glucose and insulin peaks after ingestion of the FVPD compared with control ( P= 0·019 and 0·003 ) and a trend towards increased endothelium-dependent vasodilation following FVPD consumption ( P= 0·061 ) . Overall , FVPD consumption significantly increased plasma vitamin C and total nitrate/nitrite concentrations , with a trend towards increased endothelium-dependent vasodilation . Puréed F&V products are useful vehicles for increasing micronutrient status , plasma antioxidant capacity and in vivo NO generation , which may contribute to CVD risk reduction Background — Observational evidence has consistently linked increased fruit and vegetable consumption with reduced cardiovascular morbidity ; however , there is little direct trial evidence to support the concept that fruit and vegetable consumption improves vascular function . This study assessed the dose-dependent effects of a fruit and vegetable intervention on arterial health in subjects with hypertension . Methods and Results — After a 4-week run-in period during which fruit and vegetable intake was limited to 1 portion per day , participants were r and omized to consume either 1 , 3 , or 6 portions daily for the next 8 weeks . Endothelium-dependent and -independent arterial vasodilator responses were assessed by venous occlusion plethysmography in the brachial circulation before and after intervention . Compliance was monitored with serial contemporaneous 4-day food records and by measuring concentrations of circulating dietary biomarkers . A total of 117 volunteers completed the 12-week study . Participants in the 1- , 3- , and 6-portions/d groups reported consuming on average 1.1 , 3.2 , and 5.6 portions of fruit and vegetables , respectively , and serum concentrations of lutein and & bgr;-cryptoxanthin increased across the groups in a dose-dependent manner . For each 1-portion increase in reported fruit and vegetable consumption , there was a 6.2 % improvement in forearm blood flow responses to intra-arterial administration of the endothelium-dependent vasodilator acetylcholine ( P=0.03 ) . There was no association between increased fruit and vegetable consumption and vasodilator responses to sodium nitroprusside , an endothelium-independent vasodilator . Conclusions — The present study illustrates that among hypertensive volunteers , increased fruit and vegetable consumption produces significant improvements in an established marker of endothelial function and cardiovascular prognosis BACKGROUND Although numerous human studies have shown consistent effects of some polyphenol-rich foods on several intermediate markers for cardiovascular diseases , it is still unknown whether their action could be specifically related to polyphenols . OBJECTIVE We investigated the effect of orange juice and its major flavonoid , hesperidin , on microvascular reactivity , blood pressure , and cardiovascular risk biomarkers through both postpr and ial and chronic intervention studies . DESIGN Twenty-four healthy , overweight men ( age 50 - 65 y ) were included in a r and omized , controlled , crossover study . Throughout the three 4-wk periods , volunteers daily consumed 500 mL orange juice , 500 mL control drink plus hesperidin ( CDH ) , or 500 mL control drink plus placebo ( CDP ) . All measurements and blood collection s were performed in overnight-fasted subjects before and after the 4-wk treatment periods . The postpr and ial study was conducted at the beginning of each experimental period . RESULTS Diastolic blood pressure ( DBP ) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP ( P = 0.02 ) , whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast . However , both orange juice and CDH ingestion significantly improved postpr and ial microvascular endothelial reactivity compared with CDP ( P < 0.05 ) when measured at the peak of plasma hesperetin concentration . CONCLUSIONS In healthy , middle-aged , moderately overweight men , orange juice decreases DBP when regularly consumed and postpr and ially increases endothelium-dependent microvascular reactivity . Our study suggests that hesperidin could be causally linked to the beneficial effect of orange juice . This trial is registered at clinical trials.gov as NCT00983086 OBJECTIVES Our objective was to determine if long-term daily administration of phytonutrient supplements can prevent the immediate adverse impact of a high-fat meal and increase the production of nitric oxide . BACKGROUND Ingestion of a high-fat meal impairs flow-mediated vasodilation of the brachial artery for at least 4 h ; however , co-ingestion of vitamin antioxidants or a green salad has been shown to prevent this effect . METHODS Flow-mediated brachial artery reactivity test ( BART ) both before and 3 h after a 900 calorie 50 g fat meal was evaluated in 38 healthy volunteers ( age 36.4 + /- 10.1 years ) . Subjects were r and omized to four weeks of daily supplementation with a powdered fruit vegetable juice concentrate ( Juice Plus [ JP ] ) along with a complex supplement providing nutritional antioxidants and various herbal extracts ( Vineyard [ V ] ) , JP alone , or a matching placebo . At three and four weeks , BART was repeated both before and after the high-fat meal . Serum nitrate/nitrite concentrations were measured at baseline and at four weeks . RESULTS Four weeks of the JP-V combination blunted the detrimental effect of the high-fat meal ( -47.5 + /- 23.4 % at baseline vs. -1.7 + /- 9.7 % at four weeks [ p < 0.05 ] ) . Four weeks of JP alone had a similar beneficial effect ( -45.1 + /- 19.7 % at baseline vs. -16.6 + /- 10.3 % at four weeks [ p < 0.05 ] ) , whereas there was no substantial effect of the placebo . In the subjects treated with supplements , concentrations of serum nitrate/nitrite increased from 78 + /- 39 to 114 + /- 62 microm/l ( p < 0.02 ) . CONCLUSIONS Daily ingestion of modest amounts of a fruit/vegetable juice concentrate with or without adjunctive phytonutrient supplementation can reduce the immediate adverse impact of high-fat meals on flow-mediated vasoactivity and increase nitrate/nitrite blood concentration K-rich fruit and vegetables may lower blood pressure ( BP ) and improve vascular function . A r and omised controlled trial ( IS RCT N50011192 ) with a cross-over design was conducted in free-living participants with early stages of hypertension ( diastolic BP>80 and < 100 mmHg , not receiving BP-lowering medication ) to test this hypothesis . Following a 3-week run-in period on a control diet , each subject completed four dietary 6-week dietary interventions ( control+placebo capsules , an additional 20 or 40 mmol K(+)/d from fruit and vegetables or 40 mmol potassium citrate capsules/d ) using a Latin square design with a washout period ≥ 5 weeks between the treatment periods . Out of fifty-seven subjects who were r and omised , twenty-three male and twenty-five female participants completed the study ; compliance to the intervention was corroborated by food intake records and increased urinary K(+ ) excretion ; plasma lipids , vitamin C , folate and homocysteine concentrations , urinary Na excretion , and body weight remained were unchanged . On the control diet , mean ambulatory 24 h systolic/diastolic BP were 132·3 ( sd 12·0)/81·9 ( ( SD ) 7·9 ) mmHg , and changes ( Bonferroni 's adjusted 95 % CI ) compared with the control on the diets providing 20 and 40 mmol K(+)/d as fruit and vegetables were 0·8 ( - 3·5 , 5·3)/0·8 ( - 1·9 , 3·5 ) and 1·7 ( - 3·0 , 5·3)/1·5 ( - 1·5 , 4·4 ) , respectively , and were 1·8 ( - 2·1 , 5·8)/1·4 ( - 1·6 , 4·4 ) mmHg on the 40 mmol potassium citrate supplement , and were not statistically significant . Arterial stiffness , endothelial function , and urinary and plasma isoprostane and C-reactive protein ( CRP ) concentrations did not differ significantly between the diets . The present study provides no evidence to support dietary advice to increase K intake above usual UK intakes in the subjects with early stages of hypertension To evaluate the role of the sodium pump in resistance control in vivo , we studied vascular responses to potassium , which produces vasodilation by the activation of vascular Na+ , K(+)-ATPase , in normotensive volunteers receiving a high salt diet compared with volume-depleted subjects receiving diuretic treatment . Forearm blood flow was measured by strain-gauge plethysmography during small increments in local concentrations of potassium with intrabrachial arterial infusions of KCl . Infusions of 0.12 and 0.24 mEq/min KCl increased forearm blood flow and decreased forearm vascular resistance in a dose-dependent fashion . But the simultaneous intrabrachial arterial infusion of 2 micrograms/min ouabain , a Na+,K(+)-ATPase inhibitor , could blunt the decremental response of vascular resistance to 0.12 mEq/min KCl . The decrements of vascular resistance with KCl infusions divided by the initial resistance were significantly less with ouabain compared with those without ouabain ( 43 + /- 4 % versus 57 + /- 3 % , p < 0.01 ) . This suggests that potassium produces vasodilation by the activation of vascular Na+,K(+)-ATPase activity . Similarly , salt loading ( 180 mEq NaCl for 7 days ) after treatment with diuretics could attenuate percent decrements of resistance with KCl infusions ( 39 + /- 3 % versus 53 + /- 2 % , p < 0.01 ) , whereas vascular resistance responses to sodium nitroprusside , a nonspecific vasodilator , and to verapamil , a calcium antagonist , did not change with salt loading after volume depletion . Therefore , salt loading could attenuate forearm vascular response to potassium specifically , as did the administration of ouabain . ( ABSTRACT TRUNCATED AT 250 WORDS Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease . Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways , which may improve endothelial function and lower blood pressure . Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach . Their combined effect in the circulation is unclear . Here , our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status , endothelial function , and blood pressure . A r and omized , controlled , crossover trial with healthy men and women ( n=30 ) was conducted . The acute effects of four energy-matched treatments ( control , apple , spinach , and apple+spinach ) , administered in r and om order , were compared . Measurements included plasma nitric oxide status , assessed by measuring S-nitrosothiols+other nitrosylated species ( RXNO ) and nitrite , blood pressure , and endothelial function , measured as flow-mediated dilatation of the brachial artery . Results are means and 95 % CI . Relative to control , all treatments result ed in higher RXNO ( control , 33 nmol/L , 26 , 42 ; apple , 51 nmol/L , 40 , 65 ; spinach , 86 nmol/L , 68 , 110 ; apple+spinach , 69 nmol/L , 54 , 88 ; P<0.01 ) and higher nitrite ( control , 35 nmol/L , 27 , 46 ; apple , 69 nmol/L , 53 , 90 ; spinach , 99 nmol/L , 76 , 129 ; apple+spinach , 80 nmol/L , 61 , 104 ; P<0.01 ) . Compared to control , all treatments result ed in higher flow-mediated dilatation ( P<0.05 ) and lower pulse pressure ( P<0.05 ) , and apple and spinach result ed in lower systolic blood pressure ( P<0.05 ) . No significant effect was observed on diastolic blood pressure . The combination of apple and spinach did not result in additive effects on nitric oxide status , endothelial function , or blood pressure . In conclusion , flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status , enhance endothelial function , and lower blood pressure acutely , outcomes that may benefit cardiovascular health BACKGROUND AND AIMS Oxidative stress has been advocated as a major cause for cardiovascular disease ( CVD ) , and low plasma antioxidant concentrations are associated with endothelial dysfunction , the first step towards atherosclerosis . However , although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD , supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk . The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation ( FMD ) in volunteers at low cardiovascular risk . METHODS AND RESULTS In a crossover trial , 24 subjects ( 13 women , mean age 61 ± 3 years ) , received , in a r and omised order , a 14-day high ( HT ) and a 14-day low ( LT ) antioxidant diets , with a 2-week wash-out ( WO ) in between . Both diets were comparable in daily portions of fruits and vegetables , and in alcohol , fibre and macronutrient intake , but differed in their total antioxidant capacity . Before and after each diet , anthropometrics , blood pressure , fasting plasma glucose , lipid profile , hepatic enzymes , circulating antioxidant concentrations , high sensitivity C-reactive protein ( hs-CRP ) and FMD were assessed . FMD increased significantly during the HT diet compared to the LT ( p < 0.000 ) . FMD values were 2.3 % higher after HT compared with LT ( p < 0.001 ) after adjustment for age , gender and diet order . α-tocopherol increased significantly ( p < 0.05 ) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly ( p < 0.05 and p < 0.01 , respectively ) during the HT diet , compared with the LT diet . CONCLUSIONS A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk , which may further reduce their risk of CVD An increase in nitrate intake can augment circulating nitrite and nitric oxide . This may lead to lower blood pressure and improved vascular function . Green leafy vegetables , such as spinach , are rich sources of nitrate . We aim ed to assess the acute effects of a nitrate-rich meal containing spinach on arterial stiffness and blood pressure in healthy men and women . Twenty-six participants aged 38 - 69years were recruited to a r and omized controlled cross-over trial . The acute effects of two energy-matched ( 2000kJ ) meals , administered in r and om order , were compared . The meals were either high nitrate ( 220 mg of nitrate derived from spinach [ spinach ] ) or low nitrate [ control ] . Outcome measurements were performed pre-meal and at specific time points up to 210min post meal . Spinach result ed in an eightfold increase in salivary nitrite and a sevenfold increase in salivary nitrate concentrations from pre-meal ( P<0.001 ) to 120min post meal . Spinach compared with control result ed in higher large artery elasticity index ( P<0.001 ) , and lower pulse pressure ( P<0.001 ) and systolic blood pressure ( P<0.001 ) . Post meal carotid-femoral pulse wave velocity ( P=0.07 ) , augmentation index ( P=0.63 ) , small artery elasticity index ( P=0.98 ) and diastolic blood pressure ( P=0.13 ) were not significantly altered by spinach relative to control . Therefore , consumption of a nitrate-rich meal can lower systolic blood pressure and pulse pressure and increase large artery compliance acutely in healthy men and women . If sustained , these effects could contribute to better cardiovascular health It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model . Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans . The aim of the study was to investigate the effect of one portion ( 300 g ) of blueberries on selected markers of oxidative stress and antioxidant protection ( endogenous and oxidatively induced DNA damage ) and of vascular function ( changes in peripheral arterial tone and plasma nitric oxide levels ) in male subjects . In a r and omized cross-over design , separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly . Before and after consumption ( at 1 , 2 , and 24 hours ) , blood sample s were collected and used to evaluate anthocyanin absorption ( through mass spectrometry ) , endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells ( through the comet assay ) , and plasma nitric oxide concentrations ( through a fluorometric assay ) . Peripheral arterial function was assessed by means of Endo-PAT 2000 . Blueberries significantly reduced ( P < .01 ) H(2)O(2)-induced DNA damage ( -18 % ) 1 hour after blueberry consumption compared to control . No significant differences were observed for endogenous DNA damage , peripheral arterial function and nitric oxide levels after blueberry intake . In conclusion , one portion of blueberries seems sufficient to improve cell antioxidant defense against DNA damage , but further studies are necessary to underst and their role on vascular function & NA ; Current methods for assessing vasomotor endothelial function are impractical for use in large studies . We tested the hypothesis that pulse‐wave analysis ( PWA ) combined with provocative pharmacological testing might provide an alternative method . Radial artery waveforms were recorded and augmentation index ( AIx ) was calculated from derived aortic waveforms . Thirteen subjects received sublingual nitroglycerin ( NTG ) , inhaled albuterol , or placebo . Twelve subjects received NTG , albuterol , and placebo separately during an infusion of NG‐monomethyl‐L‐arginine ( LNMMA ) or norepinephrine . Twenty‐seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol . Endothelial function was assessed by PWA and forearm blood flow in 27 subjects . Albuterol and NTG both significantly and repeatably reduced AIx ( P<0.001 ) . Only the response to albuterol was inhibited by LNMMA ( −9.8±5.5 % vs −4.7±2.7 % ; P=0.02 ) . Baseline AIx was higher in the hypercholesterolemic subjects , who exhibited a reduced response to albuterol ( P=0.02 ) but not to NTG when compared with matched controls . The responses to albuterol and acetylcholine were correlated ( r=0.5 , P= 0.02 ) . Consistent with an endothelium‐dependent effect , the response to albuterol was substantially inhibited by LNMMA . Importantly , the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra‐arterial acetylcholine . This methodology provides a simple , repeatable , noninvasive means of assessing endothelial function in vivo OBJECTIVE To compare the effects of short-term dietary supplementation with tomato juice , vitamin E , and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein ( C-RP ) and cell adhesion molecules in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS There were 57 patients with well-controlled type 2 diabetes aged < 75 years treated with placebo for 4 weeks and then r and omized to receive tomato juice ( 500 ml/day ) , vitamin E ( 800 U/day ) , vitamin C ( 500 mg/day ) , or continued placebo treatment for 4 weeks . Susceptibility of LDL to oxidation ( lag time ) and plasma concentrations of lycopene , vitamin E , vitamin C , C-RP , vascular cell adhesion molecule 1 , and intercellular adhesion molecule 1 were measured at the beginning of the study , after the placebo phase , and at the end of the study . RESULTS Plasma lycopene levels increased nearly 3-fold ( P = 0.001 ) , and the lag time in isolated LDL oxidation by copper ions increased by 42 % ( P = 0.001 ) in patients during supplementation with tomato juice . The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E ( 54 % ) . Plasma C-RP levels decreased significantly ( -49 % , P = 0.004 ) in patients who received vitamin E. Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study . CONCLUSIONS This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E , which also decreases plasma levels of C-RP , a risk factor for myocardial infa rct ion , in patients with diabetes . These findings may be relevant to strategies aim ed at reducing risk of myocardial infa rct ion in patients with diabetes Background —Increasing extracellular K+ concentration within and just above the physiological range hyperpolarizes and relaxes vascular smooth muscle in vitro . These actions involve inwardly rectifying potassium channels ( KIR ) and Na+/K+ ATPase , which are inhibited , respectively , by Ba2 + and ouabain . The role ( if any ) of KIR in controlling human resistance vessel tone is unknown , and we investigated this in the forearm . Methods and Results —Blood flow was measured by plethysmography in healthy men . Drugs and electrolytes were infused through the brachial artery . BaCl2 ( 4 & mgr;mol/min , also used in subsequent experiments ) increased Ba2 + plasma concentration in the infused forearm to 50±0.8 & mgr;mol/L ( mean±SEM ) and reduced blood flow by 24±4 % ( n=8 , P < 0.001 ) without causing systemic effects . Ouabain ( 2.7 nmol/min ) , alone and with BaCl2 , reduced flow by 10±2 % and 28±3 % , respectively ( n=10 ) . Incremental infusions of KCl ( 0.05 , 0.1 , and 0.2 mmol/min ) increased flow from baseline by 1.0±0.2 , 2.0±0.4 , and 4.2±0.5 mL/min per deciliter forearm , respectively . Responses to KCl ( 0.2 mmol/min ) were inhibited by BaCl2 , alone and plus ouabain , by 60±9 % and 88±6 % , respectively ( both P ≤0.01 ) . In control experiments , norepinephrine ( 240 pmol/min ) reduced blood flow by 24±2 % but had no significant effect on K+-induced vasodilation . BaCl2 , alone or with ouabain , did not significantly influence responses to verapamil or nitroprusside . Conclusions —Ba2 + increases forearm vascular resistance . K+-induced vasodilation is selectively inhibited by Ba2 + and almost abolished by Ba2 + plus ouabain , suggesting a role for KIR and Na+/K+ ATPase in controlling basal tone and in K+-induced vasorelaxation in human forearm resistance vessels Epidemiological studies suggest that consumption of tomato products reduces the risk of CVD via antioxidant , hypocholesterolaemic and anti-inflammatory mechanisms . Although experimental data also describe beneficial effects on endothelial function , clinical data in human subjects are lacking . To test the hypothesis that tomato ingestion ameliorates endothelial function , we r and omised healthy non-smoking postmenopausal women to consume a buttered roll with and without tomato purée ( 70 g ) in a cross-over design . Endothelial-dependent flow-mediated dilation ( FMD ) and endothelial-independent nitro-mediated dilation of the brachial artery were assessed with high-resolution ultrasound ( 13 MHz linear array transducer ) . Acute ( 24 h ) and long-term ( 7 d ) effects were examined after daily consumption of the described meal . Nineteen volunteers completed the protocol and provided technically suitable ultrasound measurement data . Plasma lycopene levels increased from 0·30 ( sem 0·04 ) ( baseline ) to 0·42 ( sem 0·04 ) and to 0·74 ( sem 0·06 ) μm after 24 h and 7 d , respectively , with tomato purée consumption . These data indicated an effective absorption of the tomato product . However , both acute and long-term tomato purée consumption had no effects on endothelium-dependent or -independent dilation of the brachial artery . In addition , we found no correlation between lycopene plasma levels and FMD . In conclusion , consumption of tomato products associated with a significant increase in plasma lycopene levels had no effects on endothelial function in healthy postmenopausal women To determine the effects of potassium supplementation on endothelial function , cardiovascular risk factors , and bone turnover and to compare potassium chloride with potassium bicarbonate , we carried out a 12-week r and omized , double-blind , placebo-controlled crossover trial in 42 individuals with untreated mildly raised blood pressure . Urinary potassium was 77±16 , 122±25 , and 125±27 mmol/24 hours after 4 weeks on placebo , potassium chloride , and potassium bicarbonate , respectively . There were no significant differences in office blood pressure among the 3 treatment periods , and only 24-hour and daytime systolic blood pressures were slightly lower with potassium chloride . Compared with placebo , both potassium chloride and potassium bicarbonate significantly improved endothelial function as measured by brachial artery flow-mediated dilatation , increased arterial compliance as assessed by carotid-femoral pulse wave velocity , decreased left ventricular mass , and improved left ventricular diastolic function . There was no significant difference between the 2 potassium salts in these measurements . The study also showed that potassium chloride reduced 24-hour urinary albumin and albumin : creatinine ratio , and potassium bicarbonate decreased 24-hour urinary calcium , calcium : creatinine ratio , and plasma C-terminal cross-linking telopeptide of type 1 collagen significantly . These results demonstrated that an increase in potassium intake had beneficial effects on the cardiovascular system , and potassium bicarbonate may improve bone health . Importantly , these effects were found in individuals who already had a relatively low-salt and high-potassium intake BACKGROUND AND AIMS Endothelial dysfunction , as assessed by flow mediated dilatation ( FMD ) is an early event in atherosclerosis and an independent predictor of cardiovascular events . The effect of potassium supplementation on endothelial function and blood pressure ( BP ) in the postpr and ial state is not known . The aim of this study was to assess endothelial function using FMD in healthy volunteers . METHODS AND RESULTS Thirty-two normotensive volunteers received a meal with 36 mmol potassium ( High K ) and a control 6 mmol potassium ( Low K ) meal on 2 separate occasions in a r and omized order . FMD and BP were measured while participants were fasting and at 30 , 60 , 90 and 120 min after the meal . There was a postpr and ial decrease in FMD in both groups . FMD decreased overall less after the High K meal compared to the Low K meal ( meal effect p < 0.05 ) . Both meals produced a postpr and ial decrease in BP at 30 min which returned to baseline levels by 120 min . No significant differences in BP were observed between meals . FMD and systolic BP were negatively correlated at 90 ( r = -0.54 - 0.55 , p < 0.01 ) and 120 min ( r = -0.42 - 0.56 , p < 0.01 ) after both meals . CONCLUSIONS A high potassium meal , which contains a similar amount of potassium as 2.5 serves of bananas , can lessen the postpr and ial reduction in brachial artery FMD when compared to a low potassium meal BACKGROUND AND AIMS Increased potassium intake is related to reduced blood pressure ( BP ) and reduced stroke rate . The effect of increased dietary potassium on endothelial function remains unknown . The aim was to determine the effect of increased dietary potassium from fruit and vegetables on endothelial function . METHODS AND RESULTS Thirty five healthy men and women ( age 32 ± 12 y ) successfully completed a r and omised cross-over study of 2 × 6 day diets either high or low in potassium . Flow mediated dilatation ( FMD ) , BP , pulse wave velocity ( PWV ) , augmentation index ( AI ) and a fasting blood sample for analysis of Intercellular Adhesion Molecule-1 ( ICAM-1 ) , E-selectin , asymmetric dimethylarginine ( ADMA ) and endothelin-1 were taken on completion of each intervention . Dietary change was achieved by including bananas and potatoes in the high potassium and apples and rice/pasta in the low potassium diet . Dietary adherence was assessed using 6 day weighed food diaries and a 24 h urine sample . The difference in potassium excretion between the two diets was 48 ± 32 mmol/d ( P = 0.000 ) . Fasting FMD was significantly improved by 0.6 % ± 1.5 % following the high compared to the low potassium diet ( P = 0.03 ) . There were no significant differences in BP , PWV , AI , ICAM-1 , ADMA or endothelin-1 between the interventions . There was a significant reduction in E-selectin following the high ( Median = 5.96 ng/ml ) vs the low potassium diet ( Median = 6.24 ng/ml ) , z = -2.49 , P = 0.013 . CONCLUSION Increased dietary potassium from fruit and vegetables improves FMD within 1 week in healthy men and women but the mechanisms for this effect remain unclear . CLINICAL TRIAL REGISTRY ACTRN12612000822886 Pomegranate juice may improve cardiovascular risk because of its content of antioxidant polyphenols . We conducted a r and omized placebo-controlled parallel study to examine the effect of pomegranate juice on pulse wave velocity ( PWV ) , blood pressure ( BP ) and plasma antioxidant status ( ferric reducing power ; FRAP ) in 51 healthy adults ( 30–50 years ) . Participants consumed 330 ml/day of pomegranate juice or control drink for four weeks . Measurements were made at baseline and at four weeks . There was no effect of the intervention on PWV ( P = 0.694 ) and plasma FRAP ( P = 0.700 ) . However , there was a significant fall in systolic blood pressure ( −3.14 mmHg , P < 0.001 ) , diastolic blood pressure ( −2.33 mmHg P < 0.001 ) and mean arterial pressure ( −2.60 mmHg , P < 0.001 ) . Change in weight was similar in the two groups over the intervention period ( P = 0.379 ) . The fall in BP was not paralleled by changes in concentration of serum angiotensin converting enzyme . We conclude that pomegranate juice supplementation has benefits for BP in the short term , but has no effect on PWV . The mechanism for the effect is uncertain Endothelial dysfunction might be an important and early event in the pathogenesis of major cardiovascular diseases . Therefore , the evaluation of endothelial function in humans may be of great clinical relevance . Usual methods for that purpose are either invasive and /or technically dem and ing . In the dermal microcirculation , endothelial function may be assessed noninvasively from the laser Doppler measurement of increases in blood flow after either the transdermal application of acetylcholine by iontophoresis , or the release of transient arterial occlusion ( reactive hyperemia ) . An endothelium-independent response may be provided by the iontophoresis of sodium nitroprusside . This approach is notable for technical simplicity , but of uncertain reproducibility . Sixteen young , healthy , nonsmoking males were examined in the fasting state . Changes in skin blood flow were measured with a laser Doppler imager during the iontophoresis of acetylcholine and sodium nitroprusside , as well as during reactive hyperemia , on two different days , at each of two different sites on the volar face of the forearm . Nonspecific effects related to the stimulation of terminal nerve fibers by the iontophoretic current were suppressed by prior surface anesthesia . The iontophoresis of acetylcholine and sodium nitroprusside induced a seven- to eightfold increase in dermal blood flow . The corresponding figure for peak reactive hyperemia was approximately fourfold . The mean coefficients of variation of responses recorded on different days , on the same site , in the same individual were < 10 % for iontophoresis of acetylcholine and for peak reactive hyperemia , and between 10 and 20 % for iontophoresis of sodium nitroprusside . This day-to-day variation was significantly smaller than the site-to-site variation ( p < 0.01 for all three responses ) . Endothelium-dependent and -independent responses of dermal blood flow evaluated with laser Doppler imaging are highly reproducible from day to day , at least in healthy nonsmoking young male subjects , and provided some simple pre caution s are observed , foremost among which is the strict st and ardization of the recording site . These observations may have implication s for the testing of endothelial function in clinical studies Background / Objectives : To study the bioavailability of anthocyanins and the effects of a 20 % blackcurrant juice drink on vascular reactivity , plasma antioxidant status and other cardiovascular disease risk markers . Subjects/ Methods : The study was a r and omised , cross-over , double-blind , placebo-controlled acute meal study . Twenty healthy volunteers ( 11 females and 9 males ) were recruited , and all subjects completed the study . Fasted volunteers consumed a 20 % blackcurrant juice drink ( 250 ml ) or a control drink following a low-flavonoid diet for the previous 72 h. Vascular reactivity was assessed at baseline and 120 min after juice consumption by laser Doppler imaging ( LDI ) . Plasma and urine sample s were collected periodically over an 8-h period for analysis , with a final urine sample collected at 24 h. The cross-over was performed after a 4-week washout . Results : There were no significant effects of the 20 % blackcurrant juice drink on acute measures of vascular reactivity , biomarkers of endothelial function or lipid risk factors . Consumption of the test juice caused increases in plasma vitamin C ( P=0.006 ) , and urinary anthocyanins ( P<0.001 ) . Delphinidin-3-rutinoside and cyanidin-3-rutinoside were the main anthocyanins excreted in urine with delphinidin-3-glucoside also detected . The yield of anthocyanins in urine was 0.021±0.003 % of the dietary intake of delphinidin glycosides and 0.009±0.002 % of the dietary intake of cyanidin glycosides . Conclusions : The juice consumption did not have a significant effect on vascular reactivity . Anthocyanins were present at low concentrations in the urine , and microbial metabolites of flavonoids were detected in plasma after juice consumption BACKGROUND Smoking is associated with impaired vascular function . Concord grape juice ( CGJ ) , a rich source of flavonoids , can modify cardiovascular risk factors . Endothelial function and arterial stiffness are surrogate markers of arterial health . We examined the impact of CGJ on arterial wall properties in healthy smokers . METHODS We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on 3 occasions ( day 0 ( baseline ) , day 7 , and day 14 ) in a r and omized , placebo-controlled , double-blind , crossover study . Measurements were taken before ( pSm ) , immediately after ( Sm0 ) , and 20 minutes after ( Sm20 ) cigarette smoking . Endothelial function was evaluated by flow-mediated dilation ( FMD ) of the brachial artery . Carotid-femoral pulse wave velocity ( PWV ) was measured as an index of aortic stiffness . RESULTS Compared with placebo , treatment with CGJ result ed in a significant improvement in pSm values of FMD ( P = 0.02 ) and PWV ( P = 0.04 ) . At baseline , smoking decreased FMD in both the CGJ group ( P < 0.001 ) and the placebo group ( P < 0.001 ) . Compared with placebo , CGJ treatment prevented the acute smoking-induced decrease in FMD on day 7 ( P = 0.02 ) and day 14 ( P < 0.001 ) . Moreover , at baseline , smoking induced a significant elevation in PWV in both the CGJ group ( P = 0.02 ) and the placebo group ( P = 0.04 ) . Treatment with CGJ prevented the smoking-induced elevation in PWV on day 7 ( P = 0.003 ) and day 14 ( P < 0.001 ) . CONCLUSIONS CGJ consumption improved endothelial function and vascular elastic properties of the arterial tree in healthy smokers and attenuated acute smoking-induced impairment of arterial wall properties BACKGROUND Oxidative and inflammatory stresses are involved in the pathogenesis of atherosclerosis . The consumption of fruit and vegetables is associated with improved health and reduced cardiovascular risk . Red oranges have a high content of antioxidant and antiinflammatory substances , but there is a paucity of data concerning their effects on cardiovascular biomarkers in subjects with increased cardiovascular risk . OBJECTIVE We investigated the effect of red orange juice intake on endothelial function , oxidative stress , and markers of inflammation in subjects with increased cardiovascular risk . DESIGN Nineteen nondiabetic subjects with increased cardiovascular risk ( aged 27 - 56 y ) were included in a r and omized , placebo-controlled , single-blind crossover study and compared with 12 healthy , nonobese control subjects . In 2 periods of 7 d each with a 3-d interval , each participant alternatively received 500 mL red orange juice/d and 500 mL placebo/d in a r and om sequence . All measurements were performed in the morning after overnight fasting . RESULTS Endothelial function , which was measured as flow-mediated dilation , significantly improved and was normalized ( 5.7 % compared with 7.9 % ; P < 0.005 ) after 1 wk of red orange juice consumption . Similarly , concentrations of high-sensitivity C-reactive protein , IL-6 , and TNF-α significantly decreased ( P < 0.001 ) . Red orange juice had no significant effect on nitric oxide plasma concentrations . CONCLUSION A 7-d consumption of red orange juice ameliorates endothelial function and reduces inflammation in nondiabetic subjects with increased cardiovascular risk . This trial was registered at biomed central .com as IS RCT N39987296 The authors investigated effects of excessive salt intake and potassium supplementation on ambulatory arterial stiffness index ( AASI ) and endothelin-1 ( ET-1 ) in salt-sensitive and non-salt-sensitive individuals . AASI and symmetric AASI ( s-AASI ) were used as indicators of arterial stiffness . Plasma ET-1 levels were used as an index of endothelial function . Chronic salt-loading and potassium supplementation were studied in 155 normotensive to mild hypertensive patients from rural northern China . After 3 days of baseline investigation , participants were maintained sequentially for 7 days each on diets of low salt ( 51.3 mmol/d ) , high salt ( 307.7 mmol/d ) , and high salt+potassium ( 60 mmol/d ) . Ambulatory 24-hour blood pressure ( BP ) and plasma ET-1 were measured at baseline and on the last 2 days of each intervention . High-salt intervention significantly increased BP , AASI , s-AASI ( all P<.001 ) ; potassium supplementation reversed increased plasma ET-1 levels . High-salt-induced changes in BP , s-AASI , and plasma ET-1 were greater in salt-sensitive individuals . Potassium supplementation decreased systolic BP and ET-1 to a significantly greater extent in salt-sensitive vs non-salt-sensitive individuals ( P<.001 ) . Significant correlations were identified between s-AASI and ET-1 change ratios in response to both high-salt intervention and potassium supplementation ( P<.001 ) . Reducing dietary salt and increasing daily potassium improves arterial compliance and ameliorates endothelial dysfunction Background / objectives : Epidemiological studies suggest that apple consumption is associated with a reduction in cardiovascular disease risk . Apple polyphenols may contribute to explain these effects . Endothelial dysfunction has been associated with early stage of atherosclerosis and polyphenols from various dietary sources have been shown to reverse it . The aim of the present study was to investigate the effect of the consumption of a polyphenol-rich apple on endothelial function . Subjects/ methods : In all , 30 hypercholesterolemic volunteers were included in a double-blind , r and omized crossover trial . They successively consumed 40 g of two lyophilized apples , polyphenol-rich and polyphenol-poor , providing respectively 1.43 and 0.21 g polyphenols per day during two 4-week periods separated by a 4-week washout period . Results : Brachial artery flow-mediated vasodilation ( FMD ) was assessed at the beginning and at the end of each intervention period . FMD did not differ between the polyphenol-rich and the polyphenol-poor apples , neither did the other cardiovascular disease risk factors ( plasma lipids , homocysteine , antioxidant capacity ) . Conclusions : These data suggest that over a 4-week period , the consumption of a polyphenol-rich apple does not improve vascular function in hypercholesterolemic patients Summary . Background : High intake of vegetables and fruits is associated with decreased risk of coronary heart disease . Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits , such as flavonoids . Aim of the study : To study the effects of high and low intake of vegetables , berries and apple on platelet function and inflammatory markers . Methods : The study was a r and omised , controlled parallel human dietary intervention with healthy female and male volunteers ( n = 77 , 19–52 y ) . Nineteen healthy volunteers served as controls . The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables , berries and apple and rich either in linoleic acid ( 11 % of energy , en% ) or oleic acid ( 12 en% ) . Blood and three 24-hour urine sample s were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation . Results : No differences between the treatment groups were seen in platelet count or volume , markers of platelet activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide , protein kinase C activity , urinary 2,3-dinor-thromboxane B2 excretion , plasma P-selectin ) , plasma intercellular adhesion molecule-1 , sensitive C-reactive protein , or antiphospholipid antibodies . Conclusions : The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables , berries and apple do not differ in their effects on platelets or inflammation Consumption of tomato products is linked to beneficial outcomes through antioxidant and anti-inflammatory mechanisms . The aim of this study was to determine whether a 14-day period of tomato paste supplementation would improve endothelial function . Nineteen volunteers ( mean age , 39 ± 13 years ; 8 men/11 women ) were studied in a r and omized ( exposure sequence ) , single-blind ( operator ) , crossover design . The study consisted of a supplementation arm ( 70 g tomato paste containing 33.3 mg of lycopene ) and a control arm , during which no tomato paste was added to their regular diet . Volunteers maintained their regular diet during study arms . Two-week washout periods preceded each arm . Flow-mediated dilatation ( FMD ) measured by brachial artery ultrasonography was used as an estimate of endothelial function at day 1 ( acute response ) and day 15 ( midterm response ) . Plasma lipid peroxides were measured with a photometric enzyme-linked immunosorbent assay as an index of total oxidative status . Tomato supplementation led to an overall FMD increase compared with the control period ( P = .047 for repeated- measures 3 × 2 analysis of variance ) . At day 1 , FMD was not significantly increased ( P = .329 ) . By day 15 , tomato supplementation result ed in an increase in FMD by 3.3 % ± 1.4 % , whereas at the control arm , FMD declined by -0.5 % ± 0.6 % ( P = .03 ) ; magnitudes of change are absolute FMD values . Total oxidative status decreased at the end of the supplementation period compared with baseline values ( P = .038 ) . Daily tomato paste consumption exerts a beneficial midterm but not short-term effect on endothelial function . Further studies are warranted to explore the effects of tomato paste on endothelial dilation in different age groups and comorbidities BACKGROUND AND AIMS Public health campaigns recommend increased fruit and vegetable ( FV ) consumption as an effective means of cardiovascular risk reduction . During an 8 week r and omised control trial among hypertensive volunteers , we noted significant improvements in endothelium-dependent vasodilatation with increasing FV consumption . Circulating indices of inflammation , endothelial activation and insulin resistance are often employed as alternative surrogates for systemic arterial health . The responses of several such biomarkers to our previously described FV intervention are reported here . METHODS AND RESULTS Hypertensive volunteers were recruited from medical outpatient clinics . After a common 4 week run-in period during which FV consumption was limited to 1 portion per day , participants were r and omised to 1 , 3 or 6 portions daily for 8 weeks . Venous blood sample s for biomarker analyses were collected during the pre and post-intervention vascular assessment s. A total of 117 volunteers completed the 12 week study . Intervention-related changes in circulating levels of high sensitivity C-reactive protein ( hsCRP ) , soluble intracellular adhesion molecule-1 ( sICAM-1 ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , von Willebr and factor ( vWF ) and plasminogen activator inhibitor-1 ( PAI-1 ) did not differ significantly between FV groups . Similarly , there were no significant between group differences of change in homeostasis model assessment ( HOMA ) scores . CONCLUSIONS Despite mediating a significant improvement in acetylcholine induced vasodilatation , increased FV consumption did not affect a calculated measure of insulin resistance or concentrations of the circulating biomarkers measured during this study . Functional indices of arterial health such as endothelium-dependent vasomotion are likely to provide more informative cardiovascular end-points during short-term dietary intervention trials BACKGROUND Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk . OBJECTIVE The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease . DESIGN We completed an acute pilot study with no placebo ( n = 15 ) and a chronic placebo-controlled crossover study ( n = 44 ) that examined the effects of cranberry juice on vascular function in subjects with coronary artery disease . RESULTS In the chronic crossover study , subjects with coronary heart disease consumed a research preparation of double-strength cranberry juice ( 54 % juice , 835 mg total polyphenols , and 94 mg anthocyanins ) or a matched placebo beverage ( 480 mL/d ) for 4 wk each with a 2-wk rest period between beverages . Beverage order was r and omly assigned , and participants refrained from consuming other flavonoid-containing beverages during the study . Vascular function was measured before and after each beverage , with follow-up testing ≥12 h after consumption of the last beverage . Mean ( ±SD ) carotid-femoral pulse wave velocity , a measure of central aortic stiffness , decreased after cranberry juice ( 8.3 ± 2.3 to 7.8 ± 2.2 m/s ) in contrast with an increase after placebo ( 8.0 ± 2.0 to 8.4 ± 2.8 m/s ) ( P = 0.003 ) . Brachial artery flow-mediated dilation , digital pulse amplitude tonometry , blood pressure , and carotid-radial pulse wave velocity did not change . In the uncontrolled pilot study , we observed improved brachial artery flow-mediated dilation ( 7.7 ± 2.9 % to 8.7 ± 3.1 % , P = 0.01 ) and digital pulse amplitude tonometry ratio ( 0.10 ± 0.12 to 0.23 ± 0.16 , P = 0.001 ) 4 h after consumption of a single 480-mL portion of cranberry juice . CONCLUSIONS Chronic cranberry juice consumption reduced carotid femoral pulse wave velocity-a clinical ly relevant measure of arterial stiffness . The uncontrolled pilot study suggested an acute benefit ; however , no chronic effect on measures of endothelial vasodilator function was found . This trial was registered at clinical trials.gov as NCT00553904 Data suggest that polyphenol-rich products may improve endothelial function and other cardiovascular health risk factors . Grape and wine contain high amounts of polyphenols , but effects of these polyphenols have hardly been investigated in isolation in r and omized controlled studies . Our objective in this study was to test the chronic effect of polyphenol-rich solids derived from either a wine grape mix or grape seed on flow-mediated dilation ( FMD ) . Blood pressure and other vascular function measures , platelet function , and blood lipids were secondary outcomes . Thirty-five healthy males were r and omized in a double-blind , placebo-controlled crossover study consisting of three 2-wk intervention periods separated by 1-wk washout periods . The test products , containing 800 mg of polyphenols , were consumed as capsules . At the end of each intervention period , effects were measured after consumption of a low-fat breakfast ( ~751 kJ , 25 % fat ) and a high-fat lunch ( ~3136 kJ , 78 % fat ) . After the low-fat breakfast , the treatments did not significantly affect FMD . The absolute difference after the wine grape solid treatment was -0.4 % ( 95 % CI = -1.8 to 0.9 ; P = 0.77 ) and after grape seed solids , 0.2 % ( 95 % CI = -1.2 to 1.5 ; P = 0.94 ) compared with after the placebo treatment . FMD effects after the high-fat lunch and effects on secondary outcomes also showed no consistent differences between both of the grape solids and placebo treatment . In conclusion , consumption of grape polyphenols has no major impact on FMD in healthy men . Future studies should address whether grape polyphenols can improve FMD and other cardiovascular health risk factors in population s with increased cardiovascular risk BACKGROUND Fruit and vegetable-rich diets are associated with a reduced cardiovascular disease ( CVD ) risk . This protective effect may be a result of the phytochemicals present within fruits and vegetables ( F&V ) . However , there can be considerable variation in the content of phytochemical composition of whole F&V depending on growing location , cultivar , season and agricultural practice s , etc . Therefore , the present study investigated the effects of consuming fruits and vegetables as puree-based drinks ( FVPD ) daily on vasodilation , phytochemical bioavailability , antioxidant status and other CVD risk factors . FVPD was chosen to provide a st and ardised source of F&V material that could be delivered from the same batch to all subjects during each treatment arm of the study . METHODS Thirty-nine subjects completed the r and omised , controlled , cross-over dietary intervention . Subjects were r and omised to consume 200 mL of FVPD ( or fruit-flavoured control ) , daily for 6 weeks with an 8-week washout period between treatments . Dietary intake was measured using two 5-day diet records during each cross-over arm of the study . Blood and urine sample s were collected before and after each intervention and vasodilation assessed in 19 subjects using laser Doppler imaging with iontophoresis . RESULTS FVPD significantly increased dietary vitamin C and carotenoids ( P < 0.001 ) , and concomitantly increased plasma α- and β-carotene ( P < 0.001 ) with a near-significant increase in endothelium-dependent vasodilation ( P = 0.060 ) . CONCLUSIONS Overall , the findings obtained in the present study showed that FVPD were a useful vehicle to increase fruit and vegetable intake , significantly increasing dietary and plasma phytochemical concentrations with a trend towards increased endothelium-dependent vasodilation Objective Postmenopausal women have increased arterial stiffness ( brachial-ankle pulse wave velocity [ baPWV ] ) and wave reflection . L-Citrulline supplementation reduces baPWV but not brachial blood pressure . Peripheral vasodilators decrease wave reflection amplitude or second systolic peak ( SBP2 ) in radial artery and aorta , which are related to aortic systolic blood pressure ( SBP ) . We examined the effects of L-citrulline – rich watermelon supplementation on baPWV , wave reflection characteristics , and aortic SBP in postmenopausal women . Methods In a r and omized cross-over study , 12 postmenopausal women ( mean [ SE ] age , 57 [ 1 ] y ; mean [ SE ] body mass index , 38.1 [ 2.1 ] kg/m2 ; mean [ SE ] SBP , 153 [ 4 ] mm Hg ) were assigned to watermelon supplementation ( L-citrulline/L-arginine 6 g/d ) or placebo supplementation for 6 weeks . Before and after each intervention , baPWV , aortic SBP , aortic diastolic blood pressure , aortic SBP2 , radial SBP2 , and aortic and radial augmentation indices were measured using applanation tonometry . Results baPWV ( −1.2 [ 0.3 ] m/s , P < 0.001 ) , aortic SBP ( −10 [ 3 ] mm Hg , P < 0.01 ) , and aortic diastolic blood pressure ( −7 [ 1 ] mm Hg , P < 0.001 ) decreased after watermelon supplementation compared with placebo . Although radial and aortic augmentation indices were unaffected , radial and aortic SBP2 decreased ( −10 [ 3 ] mm Hg , P < 0.01 ) after watermelon supplementation compared with placebo . The reduction in aortic SBP was correlated with reductions in radial SBP2 ( r = 0.99 , P < 0.001 ) and aortic SBP2 ( r = 0.98 , P < 0.001 ) . The decreases in baPWV correlated with reductions in radial SBP2 ( r = 0.57 , P < 0.01 ) and aortic SBP2 ( r = 0.64 , P < 0.01 ) . Conclusions Watermelon supplementation reduces arterial stiffness and aortic SBP by reducing pressure wave reflection amplitude in obese postmenopausal women with hypertension Purpose Wild blueberries ( WB ) ( Vaccinium angustifolium ) are rich sources of polyphenols , such as flavonols , phenolic acids and anthocyanins ( ACNs ) , reported to decrease the risk of cardiovascular and degenerative diseases . This study investigated the effect of regular consumption of a WB or a placebo ( PL ) drink on markers of oxidative stress , inflammation and endothelial function in subjects with risk factors for cardiovascular disease . Methods Eighteen male volunteers ( ages 47.8 ± 9.7 years ; body mass index 24.8 ± 2.6 kg/m2 ) received according to a cross-over design , a WB ( 25 g freeze-dried powder , providing 375 mg of ACNs ) or a PL drink for 6 weeks , spaced by a 6-week wash-out . Endogenous and oxidatively induced DNA damage in blood mononuclear cells , serum interleukin levels , reactive hyperemia index , nitric oxide , soluble vascular adhesion molecule concentration and other variables were analyzed . Results Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases ( from 12.5 ± 5.6 % to 9.6 ± 3.5 % , p ≤ 0.01 ) and the levels of H2O2-induced DNA damage ( from 45.8 ± 7.9 % to 37.2 ± 9.1 % , p ≤ 0.01 ) , while no effect was found after the PL drink . No significant differences were detected for markers of endothelial function and the other variables under study . Conclusions In conclusion , the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage . Future studies should address in greater detail the role of WB in endothelial function . This study was registered at www.is rct n.org as IS RCT N47732406 Abstract Background . Potassium is the main intracellular cation , which contributes to keeping the intracellular membrane potential slightly negative and elicits contraction of smooth , skeletal and cardiac muscle . A change in potassium intake modifies both cardiovascular and renal tubular function . The purpose of the trial was to investigate the effect of dietary potassium supplementation , 100 mmol daily in a r and omized , placebo-controlled , crossover trial of healthy participants during two periods of 28 days duration . The participants ( N = 21 ) received a diet that was st and ardized regarding energy requirement , and sodium and water intake . Methods . 24-hour ambulatory blood pressure ( ABP ) and applanation tonometry were used to assess blood pressure , pulse wave velocity ( PWV ) , augmentation index ( AIx ) and central blood pressure ( CBP ) . Immunoassays were used for measurements of plasma concentrations of vasoactive hormones : renin ( PRC ) , angiotensin II ( Ang II ) , aldosterone ( Aldo ) , atrial natriuretic peptide ( ANP ) , vasopressin ( AVP ) , pro-brain natriuretic peptide (pro-BNP),endothelin ( Endo ) , urinary excretions of aquaporin 2 ( AQP2 ) , cyclic AMP ( cAMP ) , and the β-fraction of the epithelial sodium channel ( ENaCß ) . Results . AQP2 excretion increased during potassium supplementation , and free water clearance fell . The changes in urinary potassium excretion and urinary AQP2 excretion were significantly and positively correlated . Aldo increased . GFR , u-ENaC- β , PRC , Ang II , ANP , BNP , Endo , blood pressure and AI were not significantly changed by potassium supplementation , whereas PWV increased slightly . Conclusions . Potassium supplementation changed renal tubular function and increased water absorption in the distal part of the nephron . In spite of an increase in aldosterone in plasma , blood pressure remained unchanged after potassium supplementation . Clinical Trials . Gov Identifier : BACKGROUND Observed associations between increased fruit and vegetable ( F&V ) consumption , particularly those F&Vs that are rich in flavonoids , and vascular health improvements require confirmation in adequately powered r and omized controlled trials . OBJECTIVE This study was design ed to measure the dose-response relation between high-flavonoid ( HF ) , low-flavonoid ( LF ) , and habitual F&V intakes and vascular function and other cardiovascular disease ( CVD ) risk indicators . DESIGN A single-blind , dose-dependent , parallel r and omized controlled dietary intervention study was conducted . Male and female low-F&V consumers who had a ≥ 1.5-fold increased risk of CVD ( n = 174 ) were r and omly assigned to receive an HF F&V , an LF F&V , or a habitual diet , with HF and LF F&V amounts sequentially increasing by 2 , 4 , and 6 ( + 2 , + 4 , and + 6 ) portions/d every 6 wk over habitual intakes . Microvascular reactivity ( laser Doppler imaging with iontophoresis ) , arterial stiffness [ pulse wave velocity , pulse wave analysis ( PWA ) ] , 24-h ambulatory blood pressure , and biomarkers of nitric oxide ( NO ) , vascular function , and inflammation were determined at baseline and at 6 , 12 , and 18 wk . RESULTS In men , the HF F&V diet increased endothelium-dependent microvascular reactivity ( P = 0.017 ) with + 2 portions/d ( at 6 wk ) and reduced C-reactive protein ( P = 0.001 ) , E-selectin ( P = 0.0005 ) , and vascular cell adhesion molecule ( P = 0.0468 ) with + 4 portions/d ( at 12 wk ) . HF F&Vs increased plasma NO ( P = 0.0243 ) with + 4 portions/d ( at 12 wk ) in the group as a whole . An increase in F&Vs , regardless of flavonoid content in the groups as a whole , mitigated increases in vascular stiffness measured by PWA ( P = 0.0065 ) and reductions in NO ( P = 0.0299 ) in the control group . CONCLUSION These data support recommendations to increase F&V intake to ≥ 6 portions daily , with additional benefit from F&Vs that are rich in flavonoids , particularly in men with an increased risk of CVD |
10,854 | 32,197,823 | Comparable results in terms of peri-implant attachment dimensions between test and control groups were found , except for a significantly higher apical junctional epithelium to coronal bone to implant ( ajE-CBI ) distance for chemically modified acid-etched compared with titanium machined surfaces .
Non-meta-analyzable and /or qualitative results highlighted some improved properties also for microgrooved and oxidized surfaces .
Limited data from animal studies suggest that some characteristics of the transmucosal implant components may affect peri-implant soft-tissue adhesion and stabilization but do not allow definitive conclusions . | STATEMENT OF PROBLEM How the properties of the implant-abutment unit may affect the peri-implant soft-tissue seal , whose stability is considered key to safeguarding the implant from bacterial contamination and preserve peri-implant health conditions , is unclear .
PURPOSE The purpose of this systematic review and meta- analysis of animal studies was to investigate whether material and surface properties of transmucosal implant components can influence the peri-implant soft-tissue adhesion at a histological level . | The aim of this study of the present experiment was to study the marginal periimplant tissues at intentionally non-submerged ( 1-stage implants ) and initially submerged and subsequently exposed implants ( 2-stage implants ) . 5 beagle dogs , about 1-year-old , were used , 3 months after the extraction of the m and ibular premolars , fixtures of the Astra Tech Implants Dental System , the Brånemark System and the Bonefit -- ITI system were installed . In each m and ibular quadrant , 1 fixture of each implant system was installed in a r and omised order . The installation procedure followed the recommendations given in the manuals for each system . Thus , following installation , the bone crest coincided with the fixture margin of the Astra Tech Implants Dental System and the Brånemark System , whereas the border between the plasma sprayed and the machined surface of the Bonefit-ITI implant system was positioned at the level of the bone crest . Following a healing period of 3 months , abutment connection was carried out in the 2-stage systems ( the Astra Tech Implants Dental System and the Brånemark system ) . A 6-month period of plaque control was initiated . The animals were sacrificed and biopsies representing each important region dissected . The tissue sample s were prepared for light microscopy and exposed to histometric and morphometric measurements . The mucosal barrier which formed to the titanium surface following 1-stage and 2-stage implant installations comprised an epithelial and a connective tissue component , which for that 3 systems studied , had similar dimensions and composition . The amount of lamellar bone contained in the periimplant region close to the fixture part of the 3-implant systems was almost identical . It is suggested that correctly performed implant installation may ensure proper conditions for both and hard tissue healing , and that the geometry of the titanium implant seems to be of limited importance OBJECTIVES To ( i ) investigate the influence of different extensions of a laser microgrooved abutment zone on connective tissue attachment and ( ii ) assess the impact of a repeated abutment dis-/reconnection on soft- and hard-tissue healing . MATERIAL S AND METHODS Titanium implants were inserted epicrestally in the lower jaws of six dogs . Healing abutments with either partially ( LP ) or completely ( LC ) laser microgrooved margins or machined surface margins ( M ) were r and omly allocated either to a single (1 × )/repeated ( 2 × ) dis-/reconnection at 4 and 6 weeks ( test ) , respectively , or left undisturbed ( control ) . At 6 and 8 weeks , histomorphometrical ( e.g. most coronal level of bone in contact with the implant [ CBI ] , subepithelial connective tissue attachment [ STC ] ) and immunohistochemical ( Collagen Type-I [ CI ] ) parameters were assessed . RESULTS At control sites , LP/LC groups revealed lower mean CBL ( 8 weeks , 0.95 ± 0.51 vs. 0.54 ± 0.63 vs. 1.66 ± 1.26 mm ) , higher mean STC ( 8 weeks , 82.58 ± 24.32 % vs. 96.37 ± 5.12 % vs. 54.17 ± 8.09 % ) , but comparable CI antigen reactivity . A repeated abutment manipulation was associated with increased mean CBL ( 8 weeks , 1.53 ± 1.09 vs. 0.94 ± 0.17 vs. 1.06 ± 0.34 mm ) , decreased STC ( 8 weeks , 57.34 ± 43.06 % vs. 13.26 ± 19.04 % vs. 37.76 ± 37.08 % ) and CI values . CONCLUSIONS It was concluded that ( i ) LC > LP abutments enhanced subepithelial connective tissue attachment and preserved crestal bone levels , ( ii ) repeated abutment dis-/reconnection during the initial healing phase ( 4 - 6 weeks ) may be associated with increased soft- and hard-tissue changes and ( iii ) LP and LC should be considered using a one abutment , one time approach Limited information exists regarding soft tissue and hard tissue responses to abutments with different material composition . The aim of this study is to evaluate soft and hard tissue responses to titanium and polymer healing abutments over a 3-month period . Sixteen patients were included in this prospect i ve trial . Implants were provisionalized with either titanium or polymer healing abutments . Changes of marginal bone level and soft tissue dimensions were recorded at implant installation and at 3 months Previous research has demonstrated the effectiveness of laser-ablated microgrooves placed on implant collars to support direct connective tissue attachments to altered implant surfaces . Such a direct connective tissue attachment serves as a physiologic barrier to the apical migration of the junctional epithelium and prevents crestal bone resorption . The current prospect i ve pre clinical trial sought to evaluate bone and soft tissue healing patterns when laser-ablated microgrooves were placed on the abutment . A canine model was selected for comparison to previous investigations that examined the negative bone and soft tissue sequelae of the implant-abutment microgap . The results demonstrate significant improvement in peri-implant hard and soft tissue healing compared to traditional machined abutment surfaces OBJECTIVE To evaluate the marginal soft and hard tissue healing at titanium and Polyetheretherketone ( PEEK ) healing implant abutments over a 4-month period . MATERIAL AND METHODS In six Labrador dogs , all m and ibular premolars and first molars were extracted . After 4 months of healing , flaps were elevated , and two implants were installed at each side of the m and ible , one in the premolar and the other in the molar regions . Four different types of healing abutments were positioned on the top of each implant : ( i ) titanium ( Ti ) ; ( ii ) PEEK material bonded to a base made of titanium ( Ti-P ) , r and omly positioned in the premolar region ; ( iii ) PEEK , pristine ( P ) ; and ( iv ) PEEK , roughened ( P-R ) , r and omly positioned in the molar region . The flaps were sutured to allow a non-submerged healing , and after 4 months , the animals were sacrificed and ground sections obtained for histological evaluation . RESULTS A higher resorption of the buccal bone crest was observed at the PEEK bonded to a base made of titanium abutments ( 1.0 ± 0.3 mm ) compared to those made of titanium ( 0.3 ± 0.4 mm ) . However , similar dimensions of the peri-implant mucosa and similar locations of the soft tissues in relation to the implant shoulder were observed . No statistically significant differences were seen in the outcomes when the pristine PEEK was compared with the roughened PEEK abutments . The mean apical extension of the junctional epithelium did not exceed the implant shoulder at any of the abutment types used . CONCLUSIONS The coronal level of the hard and soft tissues allows the conclusion that the use of PEEK as healing abutments may be indicated OBJECTIVE Microorganisms harboring the oral cavity , mainly those related to periodontal diseases , are the most potential etiologic factor of failure in long-term implant treatment . The material used for abutment components may influence the adhesion and colonization of microbial species . The aim of this in vivo investigation was to evaluate the biofilm formation on machined ( MPT ) or cast titanium ( CPT ) and zirconia abutments ( Zc ) . METHODS Six healthy subjects were enrolled in this r and omized crossover clinical investigation . The study was conducted in three phases according to abutment surface evaluated . Each subject used an individual oral splint containing four disks of the same tested substrate , two located in the anterior and two in the posterior region , totalizing 12 specimens for subject . Participants were asked to use the removable intraoral splint during 24 h. DNA checkerboard hybridization method was used to identify and quantify 38 bacterial species colonizing formed biofilm on the abutment substrates . RESULTS Pathogens and non-pathogens species were found colonizing the three substrates surfaces . Fusobacterium nucleatum , Neisseria mucosa , Porphyromonas aeruginosa , Peptostreptococcus anaerobios , Staphylococcus aureus , Streptococcus gordonii , Streptococcus parasanguinis , and Tanerella forsythia were the only species with no significant differences over the tested material s ( P > 0.05 ) . All the other target species presented significant differences sought by Friedman test ( P < 0.0001 ) . CONCLUSIONS There was a significant difference in the total bacterial count between the three groups . CPT presented the higher mean counts , followed by MPT and Zc . CPT group also showed a higher mean incidence of species than MPT and Zc . The anterior or posterior region of disks placement did not show significant differences in relation to bacterial adhesion OBJECTIVE The aim of the present study was to analyze the soft tissue barrier formed to implant abutments made of different material s. MATERIAL AND METHODS Six Labrador dogs , about 1 year old , were used . All m and ibular premolars and the first , second and third maxillary premolars were extracted . Three months later four implants ( OsseoSpeed , 4.5 x 9 mm , Astra Tech Dental , Mölndal , Sweden ) were placed in the edentulous premolar region on one side of the m and ible and healing abutments were connected . One month later , the healing abutments were disconnected and four new abutments were placed in a r and omized order . Two of the abutments were made of titanium ( Ti ) , while the remaining abutments were made of ZrO(2 ) or AuPt-alloy . A 5-months plaque control program was initiated . Three months after implant surgery , the implant installation procedure and the subsequent abutment shift were repeated in the contra-lateral m and ibular region . Two months later , the dogs were euthanized and biopsies containing the implant and the surrounding soft and hard peri-implant tissues were collected and prepared for histological analysis . RESULTS It was demonstrated that the soft tissue dimensions at Ti- and ZrO(2 ) abutments remained stable between 2 and 5 months of healing . At Au/Pt-alloy abutment sites , however , an apical shift of the barrier epithelium and the marginal bone occurred between 2 and 5 months of healing . In addition , the 80-mum-wide connective tissue zone lateral to the Au/Pt-alloy abutments contained lower amounts of collagen and fibroblasts and larger fractions of leukocytes than the corresponding connective tissue zone of abutments made of Ti and ZrO(2 ) . CONCLUSION It is suggested that the soft tissue healing to abutments made of titanium and ZrO(2 ) is different to that at abutments made of AuPt-alloy OBJECTIVES To investigate ( i ) the impact of different titanium implant surfaces on soft tissue integration over 6 months , and ( ii ) the influence of frequent clinical probing during the healing phase on the established mucosal seal . MATERIAL AND METHODS St and ardized clinical probing was r and omly performed ( 12 dogs , probing versus control ) at different transmucosal surfaces [ machined ( M ) , s and -blasted/acid-etched ( SLA ) , and chemically modified acid-etched ( modA ) , modSLA ] at 2 , 4 , 8 , and 12 weeks ( i.e. 1 x , 2 x , 3 x , and 4 x ) . Histomorphometrical analysis ( e.g. mucosal margin ( PM ) - apical extension of the junctional epithelium ( aJE ) , PM - coronal level of bone-to-implant contact ( CBI ) was performed at 4 , 8 , 12 , and 24 weeks . RESULTS While M and SLA groups revealed a split formation , epithelial cells and connective tissue were in close contact to modA and modSLA surfaces . Frequent clinical probing ( i.e. 3 x and 4 x ) increased mean pocket depths , PM-aJE , and aJE-CBI values in all groups and markedly disrupted the epithelial and connective tissue attachment . CONCLUSIONS It was concluded that irrespective of the surface characteristics , a frequent clinical probing at short intervals during the healing phase was associated with dimensional and structural changes of the mucosal seal |
10,855 | 23,056,128 | Vital pulp therapy was the most important topic amongst endodontic high level evidence articles | INTRODUCTION This study aim ed to evaluate patents as well as high level research es including systematic review s/meta-analyses and r and omized controlled clinical trials ( RCT ) published in scientific journals by Iranians endodontic . | Effective management of severe endodontic pain is often a major problem . The analgesic effect of ketorolac tromethamine ( Toradol , 10 mg p.o . ) was compared with acetaminophen codeine ( 325 mg/15 mg p.o . ) in patients with severe pain due to acute apical periodontitis in a double-blind clinical study . A total of 66 patients presenting with severe pain ( defined as 7 cm and more using a visual analog scale ) were r and omly assigned to receive either ketorolac tromethamine or acetaminophen codeine ( 33 patients in each group ) , and recorded their pain score once every 10 min for 90 min after administration . Results indicate that patients in the ketorolac group had significantly less pain than those who received acetaminophen codeine ( p = 0.005 ) The purpose of this noninferiority trial was to compare postoperative pain relief after one-visit root canal therapy ( O RCT ) with a pulpotomy performed with a new endodontic calcium-enriched mixture cement ( PCEM ) in human permanent molars with irreversible pulpitis . A total of 407 selected patients were r and omly allocated into the O RCT group ( n = 202 ) or the PCEM group ( n = 205 ) . Numerical Rating Scale question naires were used to record pain intensity ( PI ) by the patients during the first 7 days after treatment . While there was no statistically significant difference in the mean PI at baseline between the two study groups ( P = 0.45 ) , changes in mean PI were significantly different between them ( P < 0.001 ) . In the O RCT group , pain relief was achieved after 36 h [ 95 % confidence interval ( CI ) , 27.00–45.00 ] , compared to 18 h in the PCEM group ( 95 % CI , 15.00–21.00 ) , a significant difference ( P < 0.01 ) . Comparison of the mean PI sum recorded over 7 days showed that patients in the O RCT group experienced significantly more pain than those in the PCEM group ( P < 0.001 ) ; a similar difference was observed for pain in response to percussion tests ( P < 0.001 ) . Treatment with PCEM thus had the better pain-reducing effects than O RCT in irreversible pulpitis cases Purpose The aim of this study was to compare the effect of white mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomised primary molars . Methods In this clinical trial study , 60 lower second primary molars of 46 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) and FC ( control ) groups by r and om numbered table . Following removal of the coronal pulp and haemostasis , the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps . The teeth of both groups were restored with stainless steel crowns . Children arrived for clinical and radiographic follow-up evaluation after 6 , 12 and 24 months . Results The treated teeth in FC group ( n = 18 ) were clinical ly and radiographically successful after 24 months . The radiographic follow-up evaluation revealed one failure ( furcation involvement ) in 18 molars treated with MTA after 24 months . The treated teeth in MTA group were clinical ly successful 24 months postoperatively . Pulp canal obliteration was observed in one of the teeth treated with MTA and four of the teeth treated with FC . Conclusion MTA could be used as a safe medicament for pulpotomy in cariously exposed primary molars and could be a substitute for FC Objectives Root canal therapy ( RCT ) and tooth extraction have been conventional treatment options for management of human mature teeth with irreversible pulpitis . Excellent short-term treatment outcomes of vital pulp therapy with calcium-enriched mixture cement ( VPT/CEM ) , as a new treatment option , on postoperative pain relief was demonstrated ; if intermediate- and long-term treatment outcomes of the new treatment are also non-inferior compared to RCT , then VPT/CEM may become a viable treatment option for management of mature teeth with irreversible pulpitis . Material s and methods In 23 healthcare centers , 407 9- to 65-year-old patients were r and omly allocated into two study arms including one-visit RCT ( reference treatment ; n = 202 ) and VPT/CEM ( alternative treatment ; n = 205 ) . Six- and twelve-month clinical and radiographic successes were assessed . Results Mean follow-up times at 6- and 12-month follow-ups were “ 6.70 ± 0.68 and 6.72 ± 0.71 months ” and “ 12.96 ± 0.67 and 12.90 ± 0.66 months ” in the available cases of RCT and VPT/CEM arms , respectively . Favorable clinical success rates in the two study arms did not show statistical difference ; however , the radiographic success rate in the VPT/CEM was significantly greater than RCT arm at the two follow-ups ( P < 0.001 ) . The patients ’ age had no effect on the treatment outcomes ( P = 0.231 ) . Conclusions Treatment outcomes of VPT/CEM may be superior to RCT in mature molars with irreversible pulpitis . The performance of bio material s such CEM cement may assist in the shift towards more biologic treatments . Clinical relevance VPT/CEM may be a realistic alternative treatment for human mature molar teeth with symptoms of irreversible pulpitis ; the use of VPT/CEM is highly beneficial for patients as well as general dentists OBJECTIVE To conduct a r and omized clinical trial to compare the post-operative pain experience as well as clinical and radiographic outcomes of pulpotomy in human permanent molars with irreversible pulpitis using calcium enriched mixture ( CEM ) cement or mineral trioxide aggregate ( MTA ) . MATERIAL S AND METHODS A total of 413 patients met the inclusion criteria and consented to participate . The patients were r and omly allocated into two study arms : MTA pulpotomy ( PMTA : n = 208 ) and CEM pulpotomy ( PCEM : n = 205 ) . Numerical rating scale question naires were utilized by the patients to record pain intensity ( PI ) over 7 days post-operatively . The patients were followed-up for 12 months to assess the clinical and radiographic outcomes of treatment . The data was analyzed using Chi-square , Cohen 's kappa and t-tests . RESULTS There was no significant difference in the mean PI recorded during the 7 post-operative days between the two study arms ( p = 0.221 ) . The clinical and radiographic success rates for PMTA at 12-month follow-up were 98 and 95 % , respectively ; and 97 and 92 % for PCEM , respectively . There was no significant differences in clinical ( p = 0.7 ) and radiographic ( p = 0.4 ) success rates between the two arms . CONCLUSIONS Excellent treatment outcomes occurred in molar teeth with irreversible pulpitis undergoing pulpotomy with MTA and CEM bio material Acute pain and swelling following endodontic treatment are a challenge for both the patient and the dentist . According to previous studies , the incidence of flare-ups increases after endodontic treatment of teeth with necrotic pulps . Calcium hydroxide is currently used as a multi- purpose drug in root canal therapy . The aim of this study was to evaluate the incidence and severity of flare-ups after treatment of pulpless teeth using calcium hydroxide as an intracanal dressing . Sixty patients with single-root necrotic teeth participated in this study . These patients were r and omly divided into three groups of 20 . The patients were treated in Group A in a single-visit approach , in group B with a two-visit approach without any intracanal dressing and group C with a two-visit approach using calcium hydroxide as an intracanal dressing for one week . All of the patients were followed for 72 hours after each treatment session . The information about the incidence and severity of pain and swelling was recorded in tables , using a modified Visual Analogue Scale for pain severity measurement and a scale with four degrees for measuring the severity of swelling . The data were analyzed by chi-square test and GENMODE procedure INTRODUCTION Achieving pulp anesthesia with irreversible pulpitis is difficult . This study evaluated whether nonsteroidal anti-inflammatory drugs assist local anesthesia . METHODS In a r and omized double-blinded clinical trial , 150 patients ( 50 per group ) with irreversible pulpitis were given placebo , 600 mg ibuprofen , or 75 mg indomethacin 1 hour before local anesthesia . Each patient recorded their pain score on a visual analog scale before taking the medication , 15 minutes after anesthesia in response to a cold test , during access cavity preparation and during root canal instrumentation . No or mild pain at any stage was considered a success . Data were analyzed by the chi-square and analysis of variance tests . RESULTS Overall success rates for placebo , ibuprofen , and indomethacin were 32 % , 78 % , and 62 % , respectively ( p < 0.001 ) . Ibuprofen and indomethacin were significantly better than placebo ( p < 0.01 ) . There was no difference between ibuprofen and indomethacin ( p = 0.24 ) . CONCLUSIONS Premedication with ibuprofen and indomethacin significantly increased the success rates of inferior alveolar nerve block anesthesia for teeth with irreversible pulpitis AIM To compare the treatment outcomes of calcium-enriched mixture ( CEM ) cement and mineral trioxide aggregate ( MTA ) as pulp dressing bio material s in vital pulpotomy of carious primary molars . STUDY DESIGN split-mouth r and omised clinical trial . MATERIAL S AND METHODS Forty children aged 4 - 8 years with 2 carious teeth requiring pulpotomy were selected and r and omly assigned to MTA ( n = 40 ) or CEM ( n = 40 ) groups . After coronal pulp removal , the remaining radicular pulp was covered with an appropriate bio material ; the teeth were then permanently restored . Clinical /radiographic success/failures were blindly evaluated at 6- , 12- and 24-month follow-ups . STATISTICS the recorded data were analyzed with McNemar test and GEE . RESULTS A total of 36 , 33 and 35 patients were available for 6- , 12- and 24-month follow-ups , respectively . At the 12-month follow-up only one and three teeth in the CEM and MTA groups had pathologic external root resorption , respectively . The resorbed teeth were then missed due to extraction /exfoliation at the 24-month follow-up ; all other treated teeth were sign/symptom-free . Overall , clinical and radiographic outcomes in both MTA/CEM groups were comparable at the three follow-ups without significant differences . Time had no significant effect on the success . CONCLUSION MTA and CEM demonstrated favourable treatment outcomes for pulpotomy of carious primary molars ; CEM may be an effective pulp dressing bio material BACKGROUND Amitriptyline is one of the most common tricyclic antidepressants , which binds to pain sensory nerve fibers close to the sodium channel ; hence , it could interact to some degree with receptors of local anesthetics . This study was design ed to assess the additional analgesic effects of 2 % Amitriptyline local gel administration in irreversible pulpitis pain of the molars . MATERIAL S AND METHODS This study was a r and omized , double-blind clinical trial that was performed on 56 consented adult patients who did not receive enough analgesia after a lidocaine nerve block for their tooth pulpitis pain . Patients were treated with 0.2 ml of either 2 % amitriptyline or placebo , which was directly injected into their m and ibular molar pulp chamber after they had received two routine lidocaine injections . Patients were asked to score their pain as a mark on a 10-cm Visual Analogue Scale ( VAS ) at different timepoints : 0 ( just before gel administration ) , 1 , 3 , 5 , 7 , and 9 minutes after the treatments . RESULTS There was a 92.5 % decrease in VAS scores of patients 9 minutes after amitriptyline administration compared to Time 0 , while in the placebo group this difference was only 13.5 % . Further , in the amitriptyline group , the VAS score at all timepoints was statistically different from Time 0 ( P < 0.01 ) . The overall pain reduction and its trend was significantly higher in the amitriptyline group compared with the placebo group ( P < 0.001 ) . CONCLUSION Inter-pulp space administration of amitriptyline 2 % gel for completing analgesia in irreversible pulpitis pain could be effective and useful as a conjunctive therapy to injections of local anesthetics Previous papers in this series on evidence -based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically search ing for evidence . The next step , critical appraisal of the evidence , is made easier if one underst and s the basic concepts of clinical research design . The strongest design , especially for questions related to therapeutic or preventive interventions , is the r and omized , controlled trial . Questions relating to diagnosis , prognosis and causation are often studied with observational , rather than experimental , research design s. The strongest study design should be used whenever possible . Rules have been established to grade research evidence . This paper , the fourth in the series , presents an overview of research methodology most commonly used in the dental literature INTRODUCTION The purpose of the present study was the immunohistochemical study of fibronectin ( FN ) and tenascin ( TN ) in human tooth pulp capped with mineral trioxide aggregate ( MTA ) and novel endodontic cement ( NEC ) ( calcium enriched mixture cement ) after 2 and 8 weeks . METHODS Thirty-two premolar teeth that were scheduled for extraction for orthodontic reasons were exposed and capped with either MTA or NEC . The teeth were r and omly divided into 4 groups : group 1 ( NEC for 2 weeks ) , group 2 ( NEC for 8 weeks ) , group 3 ( MTA for 2 weeks ) , and group 4 ( MTA for 8 weeks ) . After capping the exposed pulps with either NEC ( groups 1 and 2 ) or MTA ( groups 3 and 4 ) , half of the specimens underwent extraction and were prepared for histologic and immunohistochemical evaluation for FN and TN after 2 weeks , and the remaining half were assessed after 8 weeks . FN and TN expression was scored by a blinded pathologist on a scale of I-IV , and the results were analyzed by the Wilcoxon and Mann-Whitney U statistical tests . RESULTS FN and TN staining was observed in all 4 experimental groups , and there was no significant difference between expression of FN and TN in any groups . FN and TN staining was observed in the dentinal bridge matrix after 2 weeks under MTA . Expression of both markers reduced significantly after 8 weeks under MTA , and staining was observed only in unmineralized parts of dentinal bridge . FN and TN expression was observed in the matrix of the dentinal bridge after 2 weeks under NEC , and staining of both markers was reduced after 8 weeks compared with 2 weeks . The staining pattern of TN in NEC groups was higher than in MTA groups in both time intervals . However , the difference was not significant . CONCLUSIONS The present study demonstrated that both MTA and NEC are suitable bio material s for direct pulp capping and are able to stimulate dentinal bridge formation . Moreover , the role of FN and TN as 2 major components of the matrix of a reparative dentinal bridge was observed AIM To compare the outcome after 6 months of the application of formocresol ( FC ) or mineral trioxide aggregate ( MTA ) during pulpotomy in primary molar teeth . METHODOLOGY A maximum of 126 children ( aged 5 - 9 years ) with carious primary teeth that required pulpotomy were selected . Following r and omization , a st and ard pulpotomy preparation was undertaken , and the coronal pulp removed and bleeding arrested . In the FC group , cotton balls , soaked in FC , were placed for 5 min , and then the pulp chamber was filled with Zonalin , a pulpotomy agent . In the MTA group , a 1-mm-thick paste of MTA was used as a pulpotomy agent . The crowns in both groups were restored with amalgam or glass ionomer . The teeth of 100 patients were evaluated and compared clinical ly and radiographically after 3 and 6 months . RESULTS No signs of clinical failure were observed at the 3- and 6-month follow-up appointments in either group . There were no significant differences in the radiographic findings of the teeth and surrounding tissue at the 3-month follow-up . However , at the 6-month follow-up , significantly more cases ( P = 0.036 ) with root resorption were seen in the FC group ; no cases of resorption occurred amongst the MTA cases . The surrounding tissue showed radiographic signs of post-treatment disease in four FC cases ; none was seen in the MTA cases . CONCLUSION After 6 months , pulpotomy with MTA was associated with fewer cases of root resorption and post-treatment disease . MTA appears to be a reliable alternative material for pulpotomy in primary molar teeth Introduction Based on Iran ’s 20-year prospect i ve national vision document , Iran may be seen as the most developed country in science and technology in the region by 2025 . In this report , bibliometric indicators are used to compare the research productivity in endodontics between Iran and 28 selected Asian countries . Material s and Methods Medical Subject Headings keyword- search ing of PubMed up to 2012 was conducted to compare the scientific publications in Iran and neighboring countries ( Middle East , Middle Asia , Caucasus and EMRO countries ) . Highest 5 PubMed -indexed endodontic journals were also search ed to retrieve the number of published articles of the top five countries . Data were extracted , tabulated and compared to identify the ranks as well as trends . Results The results confirm that there are many differences in scientific endodontic publications between the studied countries ; Iran ranked second in endodontic research productivity compared to Turkey in 2011 . However , Iran attained first place in 2010 as well as the most positive publication trend in PubMed -indexed endodontic journals . Conclusion Although Iran was in second rank in the region last year , the positive trend in published endodontic research papers is considered a sign of future success in acquiring Iran ’s vision Context : Vital pulp therapy has been known as one of the treatment options to preserve pulp after being exposed by trauma or caries . Aim : To investigate human pulpal response to white and grey mineral trioxide aggregate ( WMTA , GMTA ) and Dycal ( MTA ) as pulp capping agents . Setting and Design : Human volunteers were participated in this r and omized clinical trial . Material s and Methods : This study was conducted on 90 intact first and second premolars of human maxillary and m and ibular teeth . The teeth were r and omly assigned into three groups of 30 each . Under local anesthesia , teeth were exposed and capped either with GMTA , WMTA , or Dycal . After 30 , 60 , and 90 days 10 teeth of each group were extracted and prepared for histologic observation . Statistical Analysis : Histopathologic data were analyzed by χ2 , Kruskal Wallis and Mann Whitney tests . Results : the calcified bridge in teeth that were capped with GMTA was significantly thicker than Dycal at 30 and 60 days ( P= 0.015 and P=0.002 , respectively ) ; whereas WMTA showed significantly thicker calcified bridge than Dycal at 90 days ( P=0.02 ) . In addition , GMTA specimens showed significantly less inflammation compared to Dycal sample s at 90 days interval ( P=0.019 ) . No significant difference was found between GMTA and WMTA in terms of calcified bridge thickness and pulp inflammatory response to the capping material s ( P>0.05 ) . Conclusions : Based on the result of this study , both types of MTA can be suggested as the material s of choice for direct pulp capping procedure instead of Dycal as hard setting calcium hydroxide cement OBJECTIVE To compare clinical and radiographic outcomes of pulpotomy treatment using calcium-enriched mixture ( CEM ) cement and mineral trioxide aggregate ( MTA ) in carious-exposed vital immature permanent first molars . DESIGN Fifty-one immature molars with clinical carious exposure with symptomatic/asymptomatic pulpitis met the inclusion criteria and r and omly assigned to one of the treatment groups ( CEM [ 26 teeth ; 59 roots ] , MTA [ 25 teeth ; 59 roots ] ) . After performing pulpotomy and covering the radicular pulps with the bio material s , all teeth were permanently restored . Blinded clinical and radiographic evaluations were performed at 6 and 12 months after operation for signs of success or failure . Radiographs were evaluated for complete/partial apical closure . The data were analysed using chi-square test and generalized estimating equation ( GEE ) model . RESULTS There was no significant difference at the baseline between the two experimental groups . All available cases ( 49 teeth ) showed pulp survival and signs of continuous root development after 12 months . Overall , complete apical closure ( apexogenesis ) occurred in 76.8 % and 73.8 % of radiographically interpreted roots in CEM cement and MTA groups , respectively . There was no statistical difference in terms of radiographic outcomes between two groups . CONCLUSIONS Calcium-enriched mixture cement and MTA showed similar performance in pulpotomy of immature caries-exposed permanent molars BACKGROUND Vital pulpotomy is a single-stage procedure defined as the surgical amputation of the coronal portion of exposed vital pulp , usually as a means of preserving the vitality and function of the remaining radicular portion . OBJECTIVES The aim of this study was to compare the clinical and radiographic success rates for electrosurgical vs formocresol pulpotomy in human primary molar teeth . SETTING S AND DESIGN This was a prospect i ve , r and omized clinical trial . MATERIAL S AND METHODS In this r and omized clinical trial , pulpotomies were performed on 70 primary molars in children aged 5 - 10 years . The teeth were treated using either a conventional formocresol ( 35 teeth ) or electrosurgical technique ( 35 teeth ) . Following the pulpotomy procedure , the teeth were evaluated for clinical and radiographic success for three , six and nine months . The teeth were evaluated for the presence of pain , abscess , fistula , mobility , internal and external resorption , and radiolucency . STATISTICAL ANALYSIS The data were assessed with Fishers ' Exact test . RESULTS After nine months of follow-up , the clinical and radiographic success rates were 96 and 84 % respectively in the electrosurgical group and 100 and 96.8 % respectively in the formocresol group . There was no statistically significant difference between the success rates in the two groups ( P > 0.05 ) . CONCLUSIONS Our results showed the failure rates for electrosurgical pulpotomy to be equal to those for formocresol pulpotomy . Although electrosurgical pulpotomy is a nonpharmacological technique giving favorable results , it is still a preservative technique . Further studies using larger sample s and longer evaluation periods are recommended OBJECTIVE The aim of this study was to assess the efficacy of inferior alveolar nerve ( IAN ) block combined with buccal infiltration for m and ibular molars with irreversible pulpitis . METHODOLOGY Eighty-four patients were r and omly assigned to 3 groups of 28 patients each . Lidocaine 2 % with 1:80,000 epinephrine was used for all injections . Group I patients received an IAN block with 1.8 mL of anesthetic . Group II patients received an IAN block using 3.6 mL. Group III patients received 1.8 mL as an IAN block and 1.8 mL as a buccal infiltration . A visual analogue scale was used to rate pain before anesthesia and discomfort experienced before and during access cavity preparation . Data were analyzed by chi-square , ANOVA , Kruskal-Wallis , and Mann-Whitney tests . RESULTS The success rates for groups I to III were 14.8 % , 39.3 % , and 65.4 % , respectively . Group III had significantly better anesthesia compared with group I ( P < .05 ) . CONCLUSION Combining an IAN block and a buccal infiltration injection provided more effective anesthesia in m and ibular molars with irreversible pulpitis . However , some cases may still require further anesthesia to prevent pain during endodontic treatment INTRODUCTION Effective management of endodontic pain represents a continuing challenge . This study evaluates the use of a preoperative , single oral dose of prednisolone for the prevention and control of postendodontic pain . METHODS Forty patients were r and omly assigned to 2 groups , placebo and prednisolone ( 30 mg ) . The medications were administered 30 minutes before the start of st and ard endodontic treatment . Postoperative pain was assessed after 6 , 12 , and 24 hours by using a visual analogue scale . RESULTS The outcome showed that prednisolone result ed in a statistically significant reduction in postendodontic pain at 6 , 12 , and 24 hours ( P < .0001 ) . No side effects were reported for any of the medications used . CONCLUSIONS This study suggests that a preoperative , single oral dose of prednisolone substantially reduced postendodontic pain . Further studies are needed to evaluate the applicability of these findings to other clinical conditions , single- versus multiple-visit endodontic treatment , and drug regimens R and omised controlled trials ( RCTs ) are regarded as the best study design s to test the efficacy of medical and dental intervention . Many reports , however , have shown that at the moment the quality of dental RCT reports is still poor , and further efforts to improve it are necessary . It has been suggested that trials that are not well design ed provide biased estimates of the treatment effects and that a journal 's impact factor is not related to the quality of RCTs published . For these reasons , before trusting RCT reports , a careful assessment of the study selected is needed . R and omisation , blinding , allocation concealment , drop outs analysis are essential quality components of RCTs . Many systems for RCTs quality assessment are available . In this report the concept of quality of RCTs will be critically evaluated and the most commonly used instruments available for quality assessment of RCTs in dental research will be review ed OBJECTIVES The aims of this study were to evaluate iodoform base material s for root canal treatment of necrotic primary teeth , and to compare them with traditionally used zinc oxide and eugenol ( ZOE ) . SAMPLE AND METHODS Zinc oxide and eugenol and Vitapex ( a premixed calcium hydroxide and iodoform paste ) were compared for root canal treatment in 52 necrotic primary teeth in two groups of children with a mean age of 5 years and 8.4 months . All the patients were followed-up clinical ly and radiographically 3 months and 10 - 16 months postoperatively . RESULTS The overall success rates of Vitapex and ZOE were 100 % and 78.5 % , respectively . Using Fisher 's Exact Test , the difference was statistically significant ( P < 0.05 ) . CONCLUSION Both ZOE and Vitapex gave encouraging results . Vitapex , however , can be used more safely whenever there is a doubt about the patient 's return for follow-up The purpose of this study was to eluci date whether premedication therapy with acetaminophen-codeine or ibuprofen is able to increase the depth of anesthesia in inflamed teeth . Sixty patients with the diagnosis of irreversible pulpitis in 1 m and ibular tooth requiring root canal therapy ( RCT ) were selected . Two other teeth in the same quadrant were selected as controls . An electric pulp tester ( EPT ) was used to evaluate pulp sensitivity at the baseline and after drug administration and anesthesia injection . The subjects were divided into 3 groups r and omly , and in each group 1 of the 3 drugs including acetaminophen-codeine , ibuprofen , and placebo were administered 1 hour before anesthesia delivery . After 1 hour , anesthesia was injected and after a waiting period , the EPT measurement was recorded . The reversed EPT scale was used to evaluate the depth of anesthesia achieved during RCT . Data were analyzed to statistically compare the results before and after intervention in cases and controls of each group and among different groups . Significanly lower tooth sensitivity levels ( TSLs ) were observed after intervention in acetaminophen-codeine and ibuprofen groups , which was more significant in the ibuprofen group . The comparison of inflamed teeth TSLs in the acetaminophen-codeine group and the placebo group after anesthesia and drug administration showed significant differences ( P = .001 ) . This comparison between ibuprofen and placebo groups also showed significant differences ( P approximately 0 ) . Also , significantly lower TSL of inflamed teeth was observed in the ibuprofen group in comparison with the acetaminophen-codeine group ( P = .002 ) . This study reflected preoperative administration of ibuprofen , if not contraindicated , as a drug of choice 1 hour before local anesthesia injection as an effective method for achieving a deep anesthesia during RCT of teeth with irreversible pulpitis INTRODUCTION Obtaining a correct working length is critical to the success of endodontic therapy . The aim of this clinical study was to compare the effect of working length determination using electronic apex locator or working length radiograph on the length adequacy of final working length as well as the final obturation . METHODS A total of 84 patients with 188 canals were r and omized into two groups ; in group 1 , the working length was determined by working length radiograph , whereas in group 2 , it was determined by the Raypex5 electronic apex locator ( VDW , Munich , Germany ) . Length adequacy was assessed in each group for master cone and final obturation radiography and categorized into short , acceptable , and over cases . RESULTS There was no statistically significant difference between the rates of acceptable ( master cone radiography : group 1 = 82.1 % and group 2 = 90.4 % ; final radiography : group 1 = 85.7 % and group 2 = 90.4 % ) and short cases ( master cone radiography : group 1 = 7.1 % and group 2 = 8.7 % ; final radiography : group 1 = 1.2 % and group 2 = 1 % ) between the two groups . Over cases in master cone radiography were significantly more in group 1 ( 10.7 % ) than group 2 ( 1 % ) ( χ² , p = 0.00 ) . However , this category did not show a significant difference for final obturation between group 1 ( 13.1 % ) and group 2 ( 8.7 % ) . CONCLUSION The results of endodontic treatment using the Raypex5 electronic apex locator are quite comparable , if not superior , to radiographic length measurement regarding the rates of acceptable and short cases . Furthermore , in addition to reducing the radiographic exposure , electronic apex locators are superior in reducing overestimation of the root canal length |
10,856 | 29,045,191 | Although RTH improved muscle size and strength , this protocol did not provide significant benefit over resistance training in normoxia . | Abstract Recent studies have reported that resistance training in hypoxia ( RTH ) may augment muscle size and strength development .
However , consensus on the effects of RTH via systematic review and meta- analysis is not yet available .
This work aim ed to systematic ally review studies which have investigated using RTH versus normoxic resistance training ( NRT ) to improve muscular size and strength , and to perform a meta- analysis to determine the effect of RTH on these adaptive parameters . | Abstract Hypoxia is an important modulator of endurance exercise‐induced oxidative adaptations in skeletal muscle . However , whether hypoxia affects resistance exercise‐induced muscle adaptations remains unknown . Here , we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training , including muscle cross‐sectional area ( CSA ) , one‐repetition maximum ( 1RM ) , muscular endurance , and makers of mitochondrial biogenesis and angiogenesis , such as peroxisome proliferator‐activated receptor‐γ coactivator‐1α ( PGC‐1α ) , citrate synthase ( CS ) activity , nitric oxide synthase ( NOS ) , vascular endothelial growth factor ( VEGF ) , hypoxia‐inducible factor‐1 ( HIF‐1 ) , and capillary‐to‐fiber ratio . Sixteen healthy male subjects were r and omly assigned to either a normoxic resistance training group ( NRT , n = 7 ) or a hypoxic ( 14.4 % oxygen ) resistance training group ( HRT , n = 9 ) and performed 8 weeks of resistance training . Blood and muscle biopsy sample s were obtained before and after training . After training muscle CSA of the femoral region , 1RM for bench‐press and leg‐press , muscular endurance , and skeletal muscle VEGF protein levels significantly increased in both groups . The increase in muscular endurance was significantly higher in the HRT group . Plasma VEGF concentration and skeletal muscle capillary‐to‐fiber ratio were significantly higher in the HRT group than the NRT group following training . Our results suggest that , in addition to increases in muscle size and strength , HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle To test the hypothesis that severe hypoxia during low-resistance/high-repetition strength training promotes muscle hypertrophy , 19 untrained males were assigned r and omly to 4 weeks of low-resistance/high-repetition knee extension exercise in either normoxia or in normobaric hypoxia ( FiO2 0.12 ) with recovery in normoxia . Before and after the training period , isokinetic strength tests were performed , muscle cross-sectional area ( MCSA ) measured ( magnetic resonance imaging ) and muscle biopsies taken . The significant increase in strength endurance capacity observed in both training groups was not matched by changes in MCSA , fibre type distribution or fibre cross-sectional area . RT-PCR revealed considerable inter-individual variations with no significant differences in the mRNA levels of hypoxia markers , glycolytic enzymes and myosin heavy chain isoforms . We found significant correlations , in the hypoxia group only , for those hypoxia marker and glycolytic enzyme mRNAs that have previously been linked to hypoxia-specific muscle adaptations . This is interpreted as a small , otherwise undetectable adaptation to the hypoxia training condition . In terms of strength parameters , there were , however , no indications that low-resistance/high-repetition training in severe hypoxia is superior to equivalent normoxic training This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions ( corresponding to an altitude of 3,850 m ) . Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer . Muscle biopsies were taken , and performance tests were carried out before and after the training period . Similar increases in maximal O(2 ) uptake ( 8.3 - 13.1 % ) and maximal power output ( 11.4 - 20.8 % ) were found in all groups . RT-PCR revealed elevated mRNA concentrations of the alpha-subunit of hypoxia-inducible factor 1 ( HIF-1 ) after both high- ( + 82.4 % ) and low (+78.4%)-intensity training under hypoxic conditions . The mRNA of HIF-1alpha(736 ) , a splice variant of HIF-1alpha newly detected in human skeletal muscle , was shown to be changed in a similar pattern as HIF-1alpha . Increased mRNA contents of myoglobin ( + 72.2 % ) and vascular endothelial growth factor ( + 52.4 % ) were evoked only after high-intensity training in hypoxia . Augmented mRNA levels of oxidative enzymes , phosphofructokinase , and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions . Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training . Fine-tuning of the training response is recognized at the molecular level , and with less sensitivity also at the structural level , but not at global functional responses like maximal O(2 ) uptake or maximal power output PURPOSE Recent studies have shown that low-intensity resistance training with vascular occlusion ( kaatsu training ) induces muscle hypertrophy . A local hypoxic environment facilitates muscle hypertrophy during kaatsu training . We postulated that muscle hypertrophy can be more efficiently induced by placing the entire body in a hypoxic environment to induce muscle hypoxia followed by resistance training . METHODS Fourteen male university students were r and omly assigned to hypoxia ( Hyp ) and normoxia ( Norm ) groups ( n = 7 per group ) . Each training session proceeded at an exercise intensity of 70 % of 1 repetition maximum ( RM ) , and comprised four sets of 10 repetitions of elbow extension and flexion . Students exercised twice weekly for 6 wk and then muscle hypertrophy was assessed by magnetic resonance imaging and muscle strength was evaluated based on 1RM . RESULTS Muscle hypertrophy was significantly greater for the Hyp-Ex ( exercised flexor of the hypoxia group ) than for the Hyp-N ( nonexercised flexor of the hypoxia group ) or Norm-Ex flexor ( P < .05 , Bonferroni correction ) . Muscle hypertrophy was significantly greater for the Hyp-Ex than the Hyp-N extensor . Muscle strength was significantly increased early ( by week 3 ) in the Hyp-Ex , but not in the Norm-Ex group . CONCLUSION This study suggests that resistance training under hypoxic conditions improves muscle strength and induces muscle hypertrophy faster than under normoxic conditions , thus representing a promising new training technique In skeletal muscle , phosphocreatine ( PCr ) recovery from submaximal exercise has become a reliable and accepted measure of muscle oxidative capacity . During exercise , O2 availability plays a role in determining maximal oxidative metabolism , but the relationship between O2 availability and oxidative metabolism measured by 31P-magnetic resonance spectroscopy ( MRS ) during recovery from exercise has never been studied . We used 31P-MRS to study exercising human gastrocnemius muscle under conditions of varied fractions of inspired O2 ( FIO2 ) to test the hypothesis that varied O2 availability modulates PCr recovery from submaximal exercise . Six male subjects performed three bouts of 5-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery in a 1.5-T magnet while breathing three different FIO2 concentrations ( 0.10 , 0 . 21 , and 1.00 ) . Under each FIO2 treatment , the PCr recovery time constants were significantly different , being longer in hypoxia [ 33 . 5 + /- 4.1 s ( SE ) ] and shorter in hyperoxia ( 20.0 + /- 1.8 s ) than in normoxia ( 25.0 + /- 2.7 s ) ( P < /= 0.05 ) . End-exercise pH was not significantly different among the three treatments ( 7.08 + /- 0.01 for 0.10 , 7.04 + /- 0.01 for 0.21 , and 7.04 + /- 0.02 for 1.00 ) . These results demonstrate that PCr recovery is significantly altered by FIO2 and suggest that , after submaximal exercise , PCr recovery , under normoxic conditions , is limited by O2 availability 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 Purpose The aim of this study was to analyze the effect of hypoxia on metabolic and acid – base balance , blood oxygenation , electrolyte , and half-squat performance variables during high-resistance circuit ( HRC ) training . Methods Twelve resistance-trained subjects participated in this study . After a 6RM testing session , participants performed three r and omized trials of HRC : normoxia ( NORM : FiO2 = 0.21 ) , moderate hypoxia ( MH : FiO2 = 0.16 ) , or high hypoxia ( HH : FiO2 = 0.13 ) , separated by 72 h of recovery in normoxic conditions . HRC consisted of two blocks of three exercises ( Block 1 : bench press , deadlift and elbow flexion ; Block 2 : half-squat , triceps extension , and ankle extension ) . Each exercise was performed at 6RM . Rest periods lasted for 35 s between exercises , 3 min between sets , and 5 min between blocks . Peak and mean force and power were determined during half-squat . Metabolic , acid – base balance , blood oxygenation and electrolyte variables , arterial oxygen saturation ( SaO2 ) , and rating of perceived exertion ( RPE ) were measured following each block . Results During the first set , peak force and power were significantly lower in HH than MH and NORM ; whereas in the second set , mean and peak force and power were significantly lower in HH than NORM . At the end of the HRC training session , blood lactate and RPE in HH were significantly higher than in MH and NORM . SaO2 , pH , HCO3− , and pO2 values were significantly lower in all hypoxic conditions than in NORM . Conclusion These results indicate that simulated hypoxia during HRC exercise reduce blood oxygenation , pH , and HCO3− , and increased blood lactate ultimately decreasing muscular performance Abstract The aim of the present study was to evaluate the effects of a 6 week resistance training protocol under hypoxic conditions ( FiO2 = 12.9 % , 4000 m ) on muscle hypertrophy . The project included 12 resistance trained male subjects , r and omly divided into two experimental groups . Group 1 ( n = 6 ; age 21 ± 2.4 years ; body height [ BH ] 178.8 ± 7.3 cm ; body mass [ BM ] 80.6 ± 12.3 kg ) and group 2 ( n = 6 ; age 22 ± 1.5 years ; BH 177.8 ± 3.7 cm ; BM 81.1 ± 7.5 kg ) . Each group performed resistance exercises alternately under normoxic and hypoxic conditions ( 4000 m ) for 6 weeks . All subjects followed a training protocol that comprised two training sessions per week at an exercise intensity of 70 % of 1RM ; each training session consisted of eight sets of 10 repetitions of the bench press and barbell squat , with 3 min rest periods . The results indicated that strength training in normobaric hypoxia caused a significant increase in BM ( p < 0.01 ) and fat free mass ( FFM ) ( p < 0.05 ) in both groups . Additionally , a significant increase ( p < 0.05 ) was observed in IGF-1 concentrations at rest after 6 weeks of hypoxic resistance training in both groups . The results of this study allow to conclude that resistance training ( 6 weeks ) under normobaric hypoxic conditions induces greater muscle hypertrophy compared to training in normoxic conditions OBJECTIVES To investigate the effect of blood flow restriction or normobaric hypoxic exposure combined with low-load resistant exercise ( LRE ) , on muscular strength and endurance . DESIGN A r and omised controlled trial . METHODS Well-trained netball players ( n=30 ) took part in a 5 weeks training of knee flexor and extensor muscles in which LRE ( 20 % of one repetition maximum ) was combined with ( 1 ) an occlusion pressure of approximately 230mmHg around the upper thigh ( KT , n=10 ) , ( 2 ) hypoxic air to generate blood oxyhaemoglobin levels of approximately 80 % ( HT , n=10 ) or ( 3 ) with no additional stimulus ( CT , n=10 ) . The training was of the same intensity and amount in all groups . One to five days before and after training , participants performed a series of strength and endurance tests of the lower limbs ( 3-s maximal voluntary contraction [ MVC3 ] , area under 30-s force curve [ MVC30 ] , number of repetitions at 20 % 1RM [ Reps201RM ] ) . In addition , the cross-sectional area ( CSA ) of the quadriceps and hamstrings were measured . RESULTS Relative to CT , KT and HT increased MVC3 ( 11.0±11.9 % and 15.0±13.1 % ) , MVC30 ( 10.2±9.0 % and 18.3±17.4 % ) and Reps201RM ( 28.9±23.7 % and 23.3±24.0 % , mean±90 % confidence interval ) after training . CSA increased by 6.6±4.5 % , 6.1±5.1 % and 2.9±2.7 % in the KT , HT and CT groups respectively . CONCLUSIONS LRE in conjunction with KT or HT can provide substantial improvements in muscle strength and endurance and may be useful alternatives to traditional training practice Abstract Ramos-Campo , DJ , Rubio-Arias , JÁ , Freitas , TT , Camacho , A , Jiménez-Diaz , JF , and Alcaraz , PE . Acute physiological and performance responses to high-intensity resistance circuit training in hypoxic and normoxic conditions . J Strength Cond Res 31(4 ) : 1040–1047 , 2017—The aim of this study was to analyze physical performance and physiological variables during high-intensity resistance circuit training ( HRC ) with the addition of 2 levels ( moderate and high ) of systemic hypoxia . Twelve resistance-trained young male subjects participated in the study . After a 6 repetition maximum testing session , participants performed 3 r and omized trials of HRC : normoxia ( NORM : fraction of inspired oxygen [ FiO2 ] = 0.21 ; ∼0 m altitude ) , moderate hypoxia ( MH : FiO2 = 0.16 ; ∼2.100 m altitude ) , or high hypoxia ( HH : FiO2 = 0.13 ; ∼3.800 m altitude ) , as controlled by a hypoxic generator . Bench press force , heart rate and heart rate variability , rating of perceived exertion , resting metabolic rate , energy cost , and countermovement jump were assessed in each session . Heart rate variability in HH was significantly lower ( st and ard deviation of all normal NN intervals [ intervals between two “ normal ” beats ] = 111.9 vs. 86.7 milliseconds ; st and ard deviation of the difference between consecutive NN intervals = 19.5 vs. 17.0 milliseconds ; p ⩽ 0.05 ) in comparison with NORM . There were significant differences in rating of perceived exertion between NORM and HH ( 11.6 vs. 13.8 points ) . Peak and mean force on the bench press were significantly lower ( p ⩽ 0.05 ) in HH when compared with MH ( peak : 725 vs. 488 N ; mean : 574 vs. 373 N ) . Energy cost was significantly higher ( p ⩽ 0.01 ) in both hypoxic conditions compared with NORM ( NORM : 10.4 ; MH : 11.7 ; HH : 13.3 kJ·min−1 ) . There were no differences between conditions in heart rate and countermovement jump variables . These results indicate that hypoxic stimuli during HRC exercise alter physical performance and physiological variables and affect how strenuous the exercise is perceived to be . High-intensity resistance circuit training in hypoxia increases the stress on the performance and physiological responses , and these differences must be taken into account to avoid an excessive overload Abstract Scott , BR , Slattery , KM , Sculley , DV , Hodson , JA , and Dascombe , BJ . Physical performance during high-intensity resistance exercise in normoxic and hypoxic conditions . J Strength Cond Res 29(3 ) : 807–815 , 2015—This study aim ed to determine whether different levels of hypoxia affect physical performance during high-intensity resistance exercise or subsequent cardiovascular and perceptual responses . Twelve resistance-trained young men ( age , 25.3 ± 4.3 years ; height , 179.0 ± 4.5 cm ; body mass , 83.4 ± 9.1 kg ) were tested for 1 repetition maximum ( 1RM ) in the back squat and deadlift . Following this , participants completed 3 separate r and omized trials of 5 × 5 repetitions at 80 % 1RM , with 3 minutes rest between sets , in normoxia ( NORM ; fraction of inspired oxygen [ FIO2 ] = 0.21 ) , moderate-level hypoxia ( FIO2 = 0.16 ) , or high-level hypoxia ( FIO2 = 0.13 ) by a portable hypoxic unit . Peak and mean force and power variables were monitored during exercise . Arterial oxygen saturation ( SpO2 ) , heart rate ( HR ) , and rating of perceived exertion ( RPE ) were assessed immediately following each set . No differences in force or power variables were evident between conditions . Similar trends were evident in these variables across each set and across the exercise session in each condition . SpO2 was lower in hypoxic conditions than in NORM , whereas HR was higher following sets performed in hypoxia . There were no differences between conditions in RPE . These results indicate that a hypoxic stimulus during high-intensity resistance exercise does not alter physical performance during repetitions and sets or affect how strenuous exercise is perceived to be . This novel training strategy can be used without adversely affecting the physical training dose experienced and may provide benefits over the equivalent training in NORM It has been reported that exercise under hypoxic conditions elevates acute growth hormone secretion after exercise compared with that under normoxic conditions . This study examined the influence of resistance training under moderate hypoxic conditions on muscle thickness , strength and hormonal responses . Thirteen healthy men were assigned into two groups matched for physical fitness level and then r and omized into two groups that performed exercise under normoxic ( FiO2 = 20·9 % ) or hypoxic ( FiO2 = 12·7 % ) conditions . Three sets of elbow extensions with unilateral arm were performed to exhaustion at a workload of a 10 repetition maximum with 1‐minute intervals for 3 days per week for 8 weeks . The thickness of the biceps and triceps brachii was determined using B‐mode ultrasound before and after training . Blood sampling was carried out before and after exercise , as well as during the first and last training sessions . Increase in the thickness of the triceps brachii in trained arm was significantly greater in the hypoxic group than in the normoxic group . The 10 repetition maximum was significantly increased not only in the trained arm but also in the untrained arm in both groups . Serum growth hormone concentrations after exercise were significantly higher in the hypoxic group than in the normoxic group on both the first and last training sessions . These findings suggest that hypoxic resistance training elicits more muscle hypertrophy associated with a higher growth hormone secretion , but that the greater muscle hypertrophy did not necessarily contribute a greater gain of muscle strength Maximal power ( Pmax ) levels and the effects of the manipulation of training variables on power output in rugby league football players were investigated in 5 studies . In study 1 , players of 3 different ability levels were assessed for Pmax during explosive bench press throws . Pmax levels were a significant descriptor of playing ability within the sport . In study 2 , the effect of contrast loading was investigated during jump squats . The result was a significant ( p < 0.05 ) increase in power output in the investigated load . In study 3 , the effect of an ascending vs. descending order of loads during explosive bench press throws was investigated . An ascending order result ed in a significantly higher power output for the heaviest load , whereas the descending order result ed in a significantly higher power output for the lightest load . In study 4 , the relationship between measures of upper-body strength , power , and speed was investigated in athletes from 3 different levels of playing ability . Strength , power , and speed were significantly correlated overall ; however , the relationships were greater in the more experienced training group . In study 5 , it was found that stronger athletes utilized a lower percentage of 1 repetition maximum ( 1RM ; 46–51 % ) to attain Pmax than less strong athletes ( 58–69 % ) |
10,857 | 19,653,883 | Results indicate that physiotherapy exercise after discharge following total hip replacement has the potential to benefit patients .
Conclusion Insufficient evidence exists to establish the effectiveness of physiotherapy exercise following primary hip replacement for osteoarthritis . | Abstract Background Physiotherapy has long been a routine component of patient rehabilitation following hip joint replacement .
The purpose of this systematic review was to evaluate the effectiveness of physiotherapy exercise after discharge from hospital on function , walking , range of motion , quality of life and muscle strength , for osteoarthritic patients following elective primary total hip arthroplasty . | 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 Postoperative length of stay ( LOS ) may be affected by more intensive physical therapy following surgery . This study was design ed to assess whether LOS could be affected by weekend physical therapy following surgery in patients who had undergone total hip arthroplasty ( THA ) or total knee arthroplasty ( TKA ) . Weekend coverage for these patients was made possible by increased staffing in the Physical Therapy Department . The study group consisted of 84 patients who had undergone THA or TKA and had physical therapy treatment the weekend following surgery . The Control group consisted of 53 patients who had undergone THA or TKA prior to the implementation of the weekend intervention program . A retrospective chart audit was used to obtain pertinent information about control group patients . In the total sample mean LOS following weekend therapy ( 10.84 days ) was significantly different ( p < 0.05 ) from mean LOS prior to implementation of the study ( 12.28 days ) . Significant decreases in postoperative LOS were also found within the two subgroups of patients who had undergone THA and TKA . The results indicate that physical therapy treatment the weekend following THA or TKA significantly decreases postoperative LOS when physical therapy re sources are increased to accommo date this increase in coverage OBJECTIVE To compare treadmill training with partial body-weight support ( TT-BWS ) and conventional physical therapy ( PT ) in ambulatory patients with hip arthroplasty . DESIGN R and omized controlled trial . SETTING Rehabilitation center . PARTICIPANTS Eighty patients with a fully loadable implant who could walk independently with crutches after unilateral total hip arthroplasty were r and omized to receive either TT-BWS ( treatment group ) or conventional PT ( controls ) , for 10 working days . INTERVENTIONS Each patient received 45 minutes of individualized PT , either treadmill training plus PT in the experimental or PT alone in the control group . MAIN OUTCOME MEASURES The Harris score , recorded by blind assessors , served as the primary outcome measure . Secondary outcome measures were the hip extension deficit , gait velocity , gait symmetry , affected hip abductor power ; hip abductor amplitude of electromyographic activation ; and the interval from surgery to ab and oning crutches . RESULTS At the end of training , the treatment group 's Harris score was 13.6 points higher ( P<.0001 ) than the control group 's score . Further , hip extension deficit was 6.8 degrees less ( P<.0001 ) , gait symmetry was 10 % greater ( P=.001 ) , affected hip abductor was stronger ( Medical Research Council grade s 4.24 vs 3.73 ; P<.0001 ) , and the amplitude of gluteus medius activity was 41.5 % greater ( P=.001 ) than those measures for controls . Gait velocity did not differ in the 2 groups . These significant differences in favor of the treatment group persisted at 3 and 12 months . The treatment group ab and oned crutches sooner than the control group ( 3 vs 8wk ) . In the treatment group , 39 patients finished treatment , 35 appeared at 3 , and 26 at 12 months for follow-up . In the control group , the corresponding numbers were 40 , 35 , and 24 patients , respectively . CONCLUSION TT-BWS is more effective than conventional PT at restoring symmetrical independent walking after hip replacement The ability to develop muscle force rapidly may be a very important factor to prevent a fall and to perform other tasks of daily life . However , information is still lacking on the range of training-induced neuromuscular adaptations in elderly humans recovering from a period of disuse . Therefore , the present study examined the effect of three types of training regimes after unilateral prolonged disuse and subsequent hip-replacement surgery on maximal muscle strength , rapid muscle force [ rate of force development ( RFD ) ] , muscle activation , and muscle size . Thirty-six subjects ( 60 - 86 yr ) were r and omized to a 12-wk rehabilitation program consisting of either 1 ) strength training ( 3 times/wk for 12 wk ) , 2 ) electrical muscle stimulation ( 1 h/day for 12 wk ) , or 3 ) st and ard rehabilitation ( 1 h/day for 12 wk ) . The nonoperated side did not receive any intervention and thereby served as a within-subject control . Thirty subjects completed the trial . In the strength-training group , significant increases were observed in maximal isometric muscle strength ( 24 % , P < 0.01 ) , contractile RFD ( 26 - 45 % , P < 0.05 ) , and contractile impulse ( 27 - 32 % , P < 0.05 ) . No significant changes were seen in the two other training groups or in the nontrained legs of all three groups . Mean electromyogram signal amplitude of vastus lateralis was larger in the strength-training than in the st and ard-rehabilitation group at 5 and 12 wk ( P < 0.05 ) . In contrast to traditional physiotherapy and electrical stimulation , strength training increased muscle mass , maximal isometric strength , RFD , and muscle activation in elderly men and women recovering from long-term muscle disuse and subsequent hip surgery . The improvement in both muscle mass and neural function is likely to have important functional implication s for elderly individuals This preliminary study examined , in a restricted r and omized trial , the effects of a 6-week arm-crank rehabilitation training program in elderly osteoarthrosis patients after total hip arthroplasty , first on physiological and perceptual responses and second on physical function . Two groups of patients were studied : a training group ( N = 7 , mean age = 74.9 yr , st and ard deviation [ SD ] = 5.0 yr ) who followed a training program in addition to traditional rehabilitation , and a control group who followed traditional rehabilitation only ( N = 7 mean age = 75.4 yr , SD = 5.1 yr ) . At the beginning of the training program , the heart rate and the perceived exertion were not significantly correlated during the exercise session . However , at the end of the training program , five patients had a significant heart rate/perceived exertion relationship ( p < 0.05 ) . Furthermore , positive effects of the arm-crank rehabilitation training program were observed on cardioventilatory and functional responses in the training group compared with the control group . These results suggest that after an habituation period , most of our elderly osteoarthrosis patients experienced physical sensations that were connected to physiological responses . Therefore , perceived exertion could be useful in these patients to regulate exercise intensity , especially at the end of and after the rehabilitation period To determine the effect of minimal exercise on functional fitness following total hip replacement in elderly women , 20 women ( 13 exercisers , 7 controls ) who had undergone unilateral or bilateral hip replacement surgery for primary osteoarthritis were studied . An exercise treadmill test with respiratory gas and blood lactate analyses , and a field test of walking speed on a measured course , were administered before and after a twice weekly exercise programme of three months ' duration . Markers of cardiorespiratory fitness , including peak achieved oxygen uptake ( VO2 ) and ventilatory and lactate thresholds were measured . Maximum self-selected walking speed was also measured over a flat course . Peak VO2 increased in the exercise group when compared to baseline ( P < 0.05 ) but did not differ from the control group . The exercise group significantly improved their walking speed by 10.1 % compared with non-exercising controls ( 1.41 vs 1.20 m/sec , P < 0.05 ) , and increased VO2 at lactate threshold . The improvements occurred despite the twice weekly exercise sessions being below the recommended frequency of exercise for improving cardiorespiratory fitness . Minimal exercise in elderly women after hip surgery can substantially improve submaximal exercise capacity , as well as walking speed Providing physical therapy service on Sundays is a much debated topic among hospital administrators . The purpose of this study was to determine if 7 days per week of physical therapy coverage results in shorter lengths of stay and differing discharge status than 6 days per week . A total of 140 subjects with hip or knee arthroplasty participated ; there were 80 in the 6-day groups and 60 in the 7-day groups . Data on postoperative length of stay , discharge destination , and discharge disposition were collected by retrospective medical record review . The Mann-Whitney U test was used to test for differences in length of stay data , and the chi-squared test was used to test for differences in discharge disposition and discharge destination . No significant differences in postoperative length of stay , discharge destination , nor discharge disposition existed between the 6- and 7-day physical therapy coverage hip or knee arthroplasty groups . However , the power of the statistical tests applied was low . This study provides no evidence that 7-day per week physical therapy results in shortened postoperative length of stay , differing discharge destination , nor differing discharge disposition for patients undergoing hip or knee arthroplasty OBJECTIVE To investigate the influence of an arm-interval exercise program for the upper limbs on health status and walking ability in elderly patients after total hip arthroplasty . DESIGN A r and omized controlled investigation . After surgery , a control group started a general rehabilitation program , and a training group combined it with an arm-interval exercise program . SUBJECTS Fourteen patients ( age 75.1 + /- 4.8 years ) were r and omly assigned to the control group ( n = 7 ) and the training group ( n = 7 ) . METHODS A Western Ontario and MacMaster University ( WOMAC ) Osteoarthritis Index was completed and an incremental exercise test on an arm crank ergometer was also performed 1 month before ( T(-1 ) ) and 2 months after surgery ( T2 ) . Moreover , a 6-minute walk test was performed at T2 . RESULTS Both groups significantly improved all dimensions of WOMAC , except in WOMAC physical function subscale in the control group . The training group covered a significantly longer distance in the walking test than the control group and also presented significantly higher VO2 peak value at T2 . Correlation analyses indicate that VO2 peak value and the distance covered in the 6-minute walking test were significantly associated with functional status . After calculating the ratio distance covered/score at WOMAC physical function , we observed a significantly higher ratio value in the training group than in the control group . CONCLUSION Preliminary results indicate that the improvement in physical fitness and functional status of the training group seems to be associated with better health status Organized physiotherapy starting two months after uncomplicated total hip replacements for primary arthrosis did not improve the rehabilitation . Six months after surgery there were no significant differences between 14 patients with and 16 patients without physiotherapy regarding improvement of passive hip motion , or hip or knee muscle strength of the operated limb . Neither were there any differences in walking ability or activities of daily living OBJECTIVE To assess the efficacy of a home exercise program in increasing hip muscle strength , walking speed , and function in patients more than 1.5 years after total hip replacement ( THR ) . DESIGN R and omized controlled trial . SETTING Kinesiology laboratory . PARTICIPANTS Fifty-three patients with unilateral THR were r and omly assigned to the training ( n=26 ) and control ( n=27 ) groups . Patients in the training group were further divided into exercise-high ( n=13 ) and exercise-low ( n=13 ) compliance groups according to their practice ratio ( high , > or = 50 % ) . INTERVENTION The training group underwent a 12-week home program that included hip flexion range of motion exercises for both hip joints ; strengthening exercises for bilateral hip flexors , extensors , and abductors ; and a 30-minute walk every day . The control group did not receive any training . MAIN OUTCOME MEASURES Strength of bilateral hip muscles , free and fast walking speeds while walking over 3 different terrains , and functional performance were assessed by using a dynamometer , videotape analysis , and the functional activity part of the Harris Hip Score , respectively , before and after the 12-week period . RESULTS Subjects in the exercise-high compliance group showed significantly ( P < .05 ) greater improvement in muscle strength for the operated hip , fast walking speed , and functional score than those in the exercise-low compliance and control groups . CONCLUSIONS The design ed home program was effective in improving hip muscle strength , walking speed , and function in patients after THR who practice d the program at least 3 times a week , but adherence to this home program may be a problem OBJECTIVE To investigate the effects of a late-phase exercise program for patients who underwent total hip arthroplasty ( THA ) 4 to 12 months earlier . DESIGN A single-blind , r and omized controlled trial . SETTING Exercises were performed in subjects ' homes . Exercise instruction and measurements taken before and after the trial were performed in an outpatient research and treatment center . PARTICIPANTS Convenience sample of 34 adults 4 to 12 months post-THA r and omly allocated to experimental or control groups . Twenty-eight subjects completed the study . INTERVENTION An 8-week , hip-exercise intervention , during which the control group received basic isometric and active range of motion exercises ; the experimental group received strength and postural stability exercises . MAIN OUTCOME MEASURES Score on the 12-Item Hip Question naire ; fear of falling ; hip flexor , extensor , abductor , and knee extensor muscle torque ; and postural stability in single stance . RESULTS There was a statistically significant improvement in all measures of self-perceived function , muscle strength ( hip flexors , 24.4 % ; hip extensors , 47.8 % ; hip abductors , 41.2 % ; knee extensors , 23.4 % ) , and postural stability ( 36.8 % ) in the experimental group and no significant change in the control group . Neither group had statistically significant changes in fear of falling measures . CONCLUSIONS An exercise program emphasizing weight bearing and postural stability significantly improved muscle strength , postural stability , and self-perceived function in patients 4 to 12 months after THA CONTEXT Inpatient rehabilitation after elective hip and knee arthroplasty is often necessary for patients who can not function at home soon after surgery , but how soon after surgery inpatient rehabilitation can be initiated has not been studied . OBJECTIVE To test the hypothesis that high-risk patients undergoing elective hip and knee arthroplasty would incur less total cost and experience more rapid functional improvement if inpatient rehabilitation began on postoperative day 3 rather than day 7 , without adverse consequences to the patients . DESIGN R and omized controlled trial conducted from 1994 to 1996 . SETTING Tertiary care center . PARTICIPANTS A total of 86 patients undergoing elective hip or knee arthroplasty and who met the following criteria for being high risk : 70 years of age or older and living alone , 70 years of age or older with 2 or more comorbid conditions , or any age with 3 or more comorbid conditions . Of the 86 patients , 71 completed the study . INTERVENTIONS R and om assignment to begin inpatient rehabilitation on postoperative day 3 vs postoperative day 7 . MAIN OUTCOME MEASURES Total length of stay and cost from orthopedic and rehabilitation hospital admissions , functional performance in hospitals using a subset of the functional independence measure , and 4-month follow-up assessment using the R AND 36-item health survey I and the functional status index . RESULTS Patients who completed the study and began inpatient rehabilitation on postoperative day 3 exhibited shorter mean ( + /-SD ) total length of stay ( 11.7+/-2.3 days vs 14.5+/-1.9 , P<.001 ) , lower mean ( + /-SD ) total cost ( $ 25891+/-$3648 vs $ 27762+/-$3626 , P<.03 ) , more rapid attainment of short-term functional milestones between days 6 and 10 ( 36.2+/-14.4 m ambulated vs 21.4+/-13.3 m , P<.001 ; 4.8+/-0.8 mean transfer functional independence measure score vs 4.3+/-0.7 , P<.01 ) , and equivalent functional outcome at 4-month follow-up . CONCLUSION These data showed that high-risk individuals were able to tolerate early intensive rehabilitation , and this intervention yielded faster attainment of short-term functional milestones in fewer days using less total cost A prospect i ve study was conducted to quantitatively measure the relative muscle torque strengths in 20 consecutive women with unilateral osteoarthritic hips and 20 consecutive men with unilateral osteonecrotic hips before and after primary cementless total hip arthroplasty . Maximal isometric torque strengths in the muscles of flexion , extension , and abduction around the hip joint were measured preoperatively and postoperatively at six months and one year , using a Cybex 340 dynamometer . The results showed improved muscle function after total hip arthroplasty in both diseased and healthy hips . In the diseased hips , all muscle groups improved significantly , from 150 to 250 % of the preoperative levels , at six months and one year postoperatively , except in the osteoarthritic women , in whom the improvement at six months was minimal . Preoperatively , all muscle groups in the diseased hips were weaker than those in the uninvolved hips , especially in the osteonecrotic men ( 51 - 79 % of healthy side ) . In both groups , however , the torques strengths of the diseased hips had not caught up to the healthy hips in the one-year follow-up period ( 84 - 89 % in the osteonecrotic male group , and 79 - 81 % in the osteoarthritic female group ) . The authors recommended that muscle strengthening exercises for the hip should be continued for at least one year , and perhaps longer , after total hip arthroplasty Objective : To assess the feasibility of comparing two types of exercise regime aim ing to improve mobility and function following knee arthroplasty . Design : A single-blind r and omized controlled trial . Subjects : Patients with primary , unilateral knee osteoarthritis undergoing elective knee joint replacement . Intervention : Home-based traditional exercise group ( TEG ) or home-based functional exercise group ( FEG ) following discharge from hospital . Outcome measures : These included goniometry ; a knee-specific pain score , leg extensor power and a walking test . Patients were followed up at three , six and 12 months after surgery . Results : Forty-seven patients met the study criteria , 24 were r and omized to the TEG and 23 to the FEG . There were marked improvements in mobility , leg extensor power and pain in the year after surgery ( MANOVA p < 0.001 ) . There were no statistically significant differences between the two exercise groups . Knee flexion decreased during the follow-up period and had not recovered by 12 months . Retention of patients was a problem , with nearly 50 % lost to follow-up at 12 months . These patients were assessed as having low motivation during inpatient rehabilitation ( p < 0.05 ) . Conclusions : There were trends in favour of the FEG that were of clinical relevance . A definitive study would need a sample size of at least 100 patients in each arm . It is essential to develop strategies to combat loss to follow-up OBJECTIVE To study the effect of a home program of physical therapy . DESIGN Nonr and omized control trial . SETTING Home based . PATIENTS Subjects had total hip arthroplasty ( THA ) for hip osteoarthritis ( hip-OA ) without THA failure , or cardiopulmonary , neurological , or cognitive problems . Twenty-three subjects ( mean age 63.4 years ; mean post-THA period 793 days , 6 to 48 months ) were divided into 3 groups matching with age , gender , and postoperative periods . INTERVENTION The 6-week home program included range of motion ( ROM ) exercises , and low resistance isometric and eccentric exercises of hip abductors . Physical therapists prescribed ROM and isometric exercises for group A , all programs for group B , and no programs for the control group . The programs were modified every 2 weeks as necessary . MAIN OUTCOME MEASURE Hip ROM , maximum isometric hip abduction torque measured by Cybex II , gait speed , and cadence were evaluated . RESULTS The practice ratio of the program was about 70 % for both groups . Maximum isometric torque improved in the THA side of group A ( p < .01 ) and the control group ( p < .05 ) , and on both sides in group B ( p < .01 ) . Gait speed and cadence also improved significantly . No correlation coefficient existed between practice days and the improvement ratio of the maximum torque . CONCLUSION The home program was effective in long-term post-THA The purpose of this prospect i ve , r and omized study was to apply an 8-week customized exercise program to patients ( Group E ) scheduled for total hip arthroplasty , followed by a postsurgery exercise program , and show the effect on functional recovery compared with control subjects ( Group C ) who received no additional exercise apart from routine in-hospital physical therapy . Strength , range of motion , and physical function tests were completed by 57 patients at Week 8 and Week 1 before surgery and at Weeks 3 , 12 , and 24 postoperatively . No differences between the exercise and control groups were observed at baseline . By 1 week before surgery , patients in Group E had shown significant improvements for Western Ontario and McMaster Universities Osteoarthritis Index ( total score , stiffness , and physical function components ) , and combined hip strength . Patients in Group E had improved hip flexion range of motion in the diseased hip compared with patients in Group C. Significant differences in outcome measures between Group E and Group C were observed throughout the postoperative phase from Weeks 3 to 24 . The current study showed that customized perioperative exercise programs are well tolerated by patients with end-stage hip arthritis , and are effective in improving early recovery of physical function after total hip arthroplasty CONTEXT Preliminary study results suggest that osteopathic manipulative treatment ( OMT ) may reduce pain , improve ambulation , and increase rehabilitation efficiency in patients undergoing knee or hip arthroplasty . OBJECTIVE To determine the efficacy of OMT in patients who recently underwent surgery for knee or hip osteoarthritis or for a hip fracture . DESIGN R and omized controlled trial involving hospital and postdischarge phases . SETTING Hospital-based acute rehabilitation unit . PATIENTS A total of 42 women and 18 men who were hospitalized between October 1998 and August 1999 . INTERVENTION Patients were r and omly assigned to groups that received either OMT or sham treatment in addition to st and ard care . Manipulation was individualized and performed according to study guidelines regarding frequency , duration , and technique . MAIN OUTCOME MEASURES Changes in Functional Independence Measure ( FIM ) scores and in daily analgesic use during the rehabilitation unit stay ; length of stay ; rehabilitation efficiency -- defined as the FIM total score change per rehabilitation unit day ; and changes in Medical Outcomes Study Short Form-36 scores from rehabilitation unit admission to 4 weeks after discharge . RESULTS Of 19 primary outcome measures , the only significant difference between groups was decreased rehabilitation efficiency with OMT ( 2.0 vs 2.6 FIM total score points per day ; P = .01 ) . Stratified analyses demonstrated that poorer OMT outcomes were confined to patients with osteoarthritis who underwent total knee arthroplasty ( length of stay , 15.0 vs 8.3 days ; P = .004 ; rehabilitation efficiency , 2.1 vs 3.4 FIM total score points per day ; P < .001 ) . CONCLUSION The OMT protocol used does not appear to be efficacious in this hospital rehabilitation population OBJECTIVES : To determine a cut off value for changes in radiological joint space width that allowed definition of radiological progression of hip osteoarthritis not related to measurement method errors and , thereafter , to determine factors predictive of radiological progression of hip osteoarthritis and to evaluate the correlations between clinical and radiological parameters . METHODS : A prospect i ve , longitudinal ( one year duration ) , multicentre study was made of patients with osteoarthritis of the hip ( American College of Rheumatology criteria ) . Data on clinical activity ( pain , functional impairment ) , demographic data ( age , gender , body mass index ) , and femoral head migration ( superolateral , superomedial , concentric ) were collected when the patient entered the study ; radiological grade ( joint space width in millimetres at the narrowest point using a 0.1 mm graduated magnifying glass , evaluated by a single observer unaware of the chronology of the films ) was recorded at the patient 's entry to the study and after one year . RESULTS : Analysis of the means of the differences between two analyses performed by a single observer of 30 pairs of radiographs ( one performed after an interval of one year ) ( 0.06 ( SD 0.23 ) ) suggested that a change of more than 0.56 mm ( 2 SD ) after a one year follow up could define progression of osteoarthritis of the hip . Of the 508 patients recruited , 461 ( 91 % ) completed the one year follow up and radiological progression was observed in 102 ( 22 % ) . The factors predictive of radiological progression that were identified in the multivariate analysis were : radiological joint space width at entry < or = 2 mm , superolateral migration of the femoral head , female gender , Lequesne 's functional index > 10 , age at entry > 65 years ( odds ratios 2.11 , 4.25 , 2.51 , 2.66 , 1.90 , respectively ) . The level of clinical parameters ( pain , functional impairment ) and the amount of symptomatic treatment required ( non-steroidal anti-inflammatory drugs and analgesic intake ) accounted for 20 % ( p < 0.0001 ) of the variability of the changes in radiological joint space width over the one year study period . CONCLUSION : These data suggest that radiological progression of hip osteoarthritis could be defined by a change in joint space width of at least 0.6 mm after a one year follow up period , is correlated with the changes in clinical status of the patients , and is related not only to demographic data ( age , gender ) , but also to some specific characteristics of osteoarthritis ( localisation , radiological severity , clinical activity ) BACKGROUND Lately , the number of systematic review s published has increased substantially . Many systematic review s exclude trials published in language s other than English . However , there is little empirical evidence to support this action . We looked for differences in the completeness of reporting between trials published in other language s and those published in English , to see whether the exclusion of trials published in other language s is justified . METHODS We compared completeness of reporting , design characteristics , and analytical approaches of 133 r and omised controlled trials ( RCTs ) published in English between 1989 and 1994 and 96 published in French , German , Italian , or Spanish during the same time . RCTs were identified by h and search ing of journals ( seven in English and six in the other language s ) . FINDINGS We found no significant differences between trials published in English and other- language trials for any single item in the completeness of reporting scale ( r and omisation , double-blinding , withdrawals ) , or for the overall score ( percentage of maximum possible score 51.0 % for trials in English , 46.2 % for trials in other language s ; 95 % CI for difference -1.1 to 10.5 ) . Other- language trials were more likely than English- language trials to have adult participants , to use two or more interventions , and to compare two or more active treatments without an untreated control group . Trials in other language s were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation . INTERPRETATION These results provide evidence for inclusion of all trial reports , irrespective of the language in which they are published , in systematic review s. Their inclusion is likely to increase precision and may reduce systematic errors . We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic review |
10,858 | 24,710,215 | These techniques are mainly used for soft tissue analysis , evaluation of bone grafting , and changes in the craniofacial skeleton .
Digital dental casts are used to evaluate treatment and changes over time .
Available evidence implies that 3D imaging methods can be used for documentation of CLP patients .
No data are available yet showing that 3D methods are more informative than conventional 2D methods . | BACKGROUND Current guidelines for evaluating cleft palate treatments are mostly based on two-dimensional ( 2D ) evaluation , but three-dimensional ( 3D ) imaging methods to assess treatment outcome are steadily rising .
OBJECTIVE To identify 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate . | BACKGROUND Alveolar bone grafting is a st and ard procedure used to achieve good occlusion for both functional and aesthetic purpose s in patients with cleft lip and palate . At the past , main methods used to evaluate bone bridge formation after bone grafting are radiographs , such as dental , occlusal , and panoramic . PURPOSE To evaluate bone bridge both qualitatively and quantitatively , we used CT scans ( conventional and QCT ) . Quantitative computed tomography ( QCT ) has previously been used for measuring bone mineral density of the lumbar vertebrae . PATIENTS AND METHODS The study comprised 26 male and 15 female patients who underwent alveolar bone grafting . We analyzed bone bridge with regard to four factors : marginal bone level , vertical height , anteroposterior bone width and bone mineral density using dental radiographs , and CT scans such as conventional and QCT . The clinical results of orthodontic treatment were evaluated more than 2 years postoperatively . RESULTS Orthodontic treatment was considered to be successful when the bone bridge satisfied the following criteria : marginal bone level > = 3 , vertical height > = 6.5 mm , anteroposterior bone width > = 5 mm , and bone mineral density < 350 mg Ca(5 ) ( PO(4 ) ) OH/mL. CONCLUSION we could predict the prognosis of patients ' orthodontic treatment in early stage after bone grafting PURPOSE The aim of this study was to assess the 3-dimensional facial surface changes after cleft alveolar bone grafting with digital surface photogrammetry . PATIENTS AND METHODS In a prospect i ve study , 22 patients with cleft lip and palate underwent alveolar bone grafting . Before the procedure and 6 weeks postoperatively and before the continuation of orthodontic treatment , 3-dimensional images were taken with digital surface photogrammetry . Seven st and ard craniofacial l and marks on the nose and the upper lip were identified . Their spatial change because of bone grafting was assessed . Statistical analysis was performed with analysis of variance and t test . RESULTS A significant increase in anterior projection on the operative side ( P < .05 ) was found for the labial insertion points of the alar base ( subalare ) . No significant changes were detected for the position of the labial l and marks . CONCLUSION Our results show 3-dimensionally that there is a positive influence of the alveolar bone graft on the projection of the alar base on the cleft side Yardsticks have been developed to measure dental arch relations in cleft lip and palate ( CLP ) patients as diagnostic proxies for the underlying skeletal relationship . Travelling with plaster casts to compare results between CLP centres is inefficient so the aim of this study was to investigate the reliability of using digital models or photographs of dental casts instead of plaster casts for rating dental arch relationships in children with complete bilateral cleft lip and palate ( CBCLP ) . Dental casts of children with CBCLP ( n=20 ) were included . Plaster casts , digital models and photographs of the plaster casts were available for all the children at 6 , 9 , and 12 years of age . All three record formats were scored using the bilateral cleft lip and palate ( BCLP ) yardstick by four observers in r and om order . No significant differences were found for the BCLP yardstick scores among the three formats . The interobserver weighted kappa scores were between 0.672 and 0.934 . Comparison between the formats per observer result ed in weighted kappa scores between 0.692 and 0.885 . It is concluded that digital models and photographs of dental casts can be used for rating dental arch relationships in patients with CBCLP . These formats are a reliable alternative for BCLP yardstick assessment s on conventional plaster casts OBJECTIVES To evaluate the reliability of clinical assessment , two-dimensional color transparencies and three-dimensional imaging for evaluating the residual facial deformity in patients with repaired complete unilateral cleft lip and palate ( UCLP ) and compare the ratings of facial deformity made by health care professionals with those made by lay assessors . PATIENTS AND PARTICIPANTS Thirty-one r and omly selected subjects aged 10 to 30 years with repaired complete UCLP . Five professionals and five laypersons evaluated each subject 's residual cleft-related facial deformity using clinical assessment , two-dimensional color transparencies , and three-dimensional images . MAIN OUTCOME MEASURES The facial deformity of the full face , lip , nose , and midface were scored using a 5-point ordinal scale on two occasions with a 1-month interval . Intra- and interexaminer agreements were calculated from weighted kappa statistics . Bootstrap permutation tests were used to detect any differences in agreement . RESULTS Assessment of facial deformity showed good reproducibility across the three assessment media ( kappa = 0.42 to 0.83 , SE 0.08 ) . Clinical assessment among lay assessors , however , was poor to moderate ( kappa = 0.16 to 0.58 , SE 0.07 ) . For all assessors , there was no difference in the two non clinical media relative to the st and ard clinical assessment for assessment s of the full face ( p = .377 ) . For assessment s of the lip or nose , transparency scores were in greater agreement with the clinical scores than were the three-dimensional assessment scores ( p = .017 and .011 , respectively ) . For rating the midface , the three-dimensional scores were in greater agreement with the clinical scores than were the color transparencies scores ( p = .047 ) . CONCLUSIONS In comparison with lay assessors , clinical assessment among professionals was more reproducible . This was not so for non clinical media . The equivalence of using the color transparencies and three-dimensional media relative to the clinical assessment depends on the region of the face being considered Aim : Rapid Maxillary Expansion ( RME ) and Delaire facemask are a well-established treatment method for patients with cleft lip and palate and Class III malocclusion . Several roentgenocephalometric studies on skeletal effects of this therapy are known . However , there are no systematic studies on soft tissue changes . The aim of this study was to analyze three-dimensionally the soft tissue changes in facial morphology of children with cleft lip and palate and Class III malocclusion under therapy with RME and Delaire facemask . Patients and Method : A prospect i ve longitudinal clinical trial was undertaken . 29 children between 4.1 and 6.4 years were divided into four groups : eight patients with unilateral cleft lip and palate ( group 1 ) , six patients with isolated cleft palate ( group 2 ) , eight patients with Class III malocclusion ( group 3 ) . The mean treatment period with RME and Delaire mask was 8.2 months . Seven untreated children with no need of orthodontic treatment were chosen as the control ( group 4 ) . Two 3D images , one at the beginning and one at the end of the study , were generated with the DSP 400 © imaging system . Both images were superimposed ten times and measured ten times . Results : We detected significant forward rotation and forward displacement of the soft tissue in the lower midface with the dentoalveolar areas in all patient groups . No significant asymmetric forward displacement of the soft tissue in the maxilla could be verified in the lower or upper midface , not even in the unilateral cleft lip and palate patients . Among the groups , the Class III malocclusion patients showed greater maxillary soft tissue changes . Conclusion : The RME and the Delaire facemask demonstrated the greatest effectiveness in the lower midface soft tissue in terms of forward displacement and forward rotation in the cleft lip and palate patients , particularly in the Class III patients . The 3D data allowed us to discriminatively interpret the effects of the orthopedic mask on the entire maxillary complex and maxillary alveolar process . In the unilateral cleft lip and palate patients , there was descriptively both symmetric and asymmetric advancement of the midface soft tissue . ZusammenfassungZiel : Die Gaumennahterweiterung ( GNE ) und Delaire-Maske stellen ein etabliertes Therapieverfahren bei Patienten mit Lippen- Kiefer-Gaumen-(LKG-)Spalten und Klasse-III-Anomalien dar . Viele röntgenkephalometrische Studien zum skelettalen Effekt dieser Therapie liegen vor . Systematische Untersuchungen zu Weichgewebeveränderungen fehlen jedoch . Ziel dieser Studie war es , die Weich gewebeveränderungen der Gesichtsmorphologie von Kindern mit Spaltbildungen und Klasse-III-Anomalien unter Therapie mit GNE und Delaire-Maske dreidimensional aufzuzeigen . Patienten und Method ik : Es wurde eine klinische prospektive Longitudinaluntersuchung mit 29 in vier Gruppen eingeteilten Kindern zwischen 4,1 und 6,4 Jahren durchgeführt . Acht Patienten mit einseitiger LKG-Spalte ( Gruppe 1 ) , sechs mit isolierter Gaumenspalte ( Gruppe 2 ) und acht mit Klasse-III-Anomalie ( Gruppe 3 ) wurden i m Durchschnitt 8,2 Monate mit GNE und Delaire-Maske beh and elt und untersucht . Sieben unbeh and elte Kinder ohne kieferorthopädischen Beh and lungsbedarf dienten als Kontrolle ( Gruppe 4 ) . Zwei 3D-Abbildungen , eine zum Untersuchungsbeginn und eine zum Untersuchungsende , wurden mit dem DSP-400 © -System generiert , zehnfach überlagert und zehnfach vermessen . Ergebnisse : In allen Gruppen konnte eine signifikante Vorschwenkung und Vorverlagerung des Weichgewebes i m unteren Mittelgesicht mit den dento-alveolären Bereichen nachgewiesen werden . Keine signifikante asymmetrische Vorverlagerung der Maxilla , weder i m unteren noch i m oberen Mittelgesicht , konnte beobachtet werden – auch nicht bei den einseitigen LKG-Spalten . Zwischen den Gruppen zeigten die Klasse-III-Patienten die größeren maxillären Weichgewebeveränderungen . Schlussfolgerungen : Die GNE und die Delaire-Maske zeigten bei den Spaltpatienten und vor allem bei den Klasse-III-Patienten eine deutliche Beeinflussbarkeit auf das Weichgewebe i m Sinne einer Vorverlagerung und einer Vorschwenkung i m unteren Mittelgesicht . Die Wirkungen der orthopädischen Maske auf den gesamten Maxillakomplex sowie auf den maxillären Alveolarfortsatz ließen sich anh and der 3D- Date n unterschiedlich interpretieren . Bei einseitigen LKG-Spalten kam es i m Mittelgesicht deskriptiv sowohl zu symmetrischer als auch asymmetrischer Vorverlagerung des Weichgewebes OBJECTIVE To supply quantitative information about the facial soft tissues of adult operated patients with cleft lip and palate ( CLP ) . DESIGN , SETTING , AND PATIENTS The three-dimensional coordinates of soft tissue facial l and marks were obtained using an electromagnetic digitizer in 18 Caucasian patients with CLP ( 11 males and 7 females aged 19 to 27 years ) and 162 healthy controls ( 73 females and 89 males aged 18 to 30 years ) . From the l and marks , 15 facial dimensions and two angles were calculated . Data were compared with those collected in healthy individuals by computing z-scores . Two summary anthropometric measurements for quantifying craniofacial variations were assessed in both the patients and reference subjects : the mean z-score ( an index of overall facial size ) , and its SD , called the craniofacial variability index ( an index of facial harmony ) . RESULTS In treated patients with CLP , facial size was somewhat smaller than in normal individuals , but in all occasions the mean z-score fell inside the normal interval ( mean + /- 2 SD ) . Almost all patients had a craniofacial variability index larger than the normal interval , indicating a global disharmonious appearance . Overall , in patients pronasale , subnasale , and pogonion were more posterior , the nose was shorter and larger , the face was narrower , and the soft tissue profile and upper lip were flatter than in the reference population . CONCLUSIONS The facial soft tissue structures of adult operated patients with CLP differed from those of normal controls of the same age , sex , and ethnic group . In this patient group , surgical corrections of CLP failed to provide a completely harmonious appearance , even if the deviations from the reference were limited . Further analyses of larger groups of patients are needed Objective To evaluate three-dimensional nasal morphology following primary reconstruction in children with unilateral cleft lip and palate relative to contemporaneous noncleft data . Design Prospect i ve , cross-sectional , controlled study . Setting Glasgow Dental Hospital and School , Faculty of Medicine , Glasgow University . Patients and Participants Two groups of 3-year-old children ( 21 with unilateral cleft lip and palate and 96 controls ) with facial images taken using a three-dimensional , vision-based capture technique . Method Three-dimensional images of the face were reflected so the cleft was on the left side to create a homogeneous group for statistical analysis . Three-dimensional coordinates of anthropometric l and marks were extracted from facial images by a single operator . A set of linear measurements was used to compare cleft and control subjects on right and left sides , adjusting for sex differences . Results The mean nasal base width and the width of the nostril floor on right and left sides differed significantly between control and unilateral cleft lip and palate groups . The measurements were greater in children with unilateral cleft lip and palate . The differences in the mean nasal height and mean nasal projection between the groups were not statistically significant . Mean columellar lengths were different between the left and right sides in children with unilateral cleft lip and palate . Conclusions There were significant nasal deformities following the surgical repair of unilateral cleft lip and palate PURPOSE This study radiographically evaluated the quantity and quality of secondary alveolar bone grafts from the anterior iliac crest to maxillary alveolar clefts in cleft lip and palate patients with the use of computed tomography . PATIENTS AND METHODS A 1-year prospect i ve study was conducted by using 14 unilateral and bilateral cleft lip and palate patients . Axial and coronal computed tomography ( CT ) scans were obtained during the immediate postoperative phase and at 1-year follow-up . RESULTS This study showed that the average alveolar cleft requires a bone graft volume ranging from 0.9 to 3.6 cm3 , with a mean volume of 2.10 cm3 . The percentage of bone loss derived from the linear dimensional changes to the alveolar bone graft between the immediate postoperative and follow-up CT scans were as follows : 17.9 % in maximal bone height , 29.9 % in maximal anteroposterior bone width , and 13.7 % in maximal transverse width . As compared with the linear measurements , the volumetric analysis showed a disproportional amount of volume loss equaling 43.7 % and 42.5 % in the coronal and axial studies , respectively . This showed a total average volume loss of 43.1 % at approximately 1 year after the secondary alveolar cleft repair . However , as the canine tooth erupts through the bone graft , it can account for up to 53.4 % of the total average volume loss . All 14 patients ( 17 clefts ) showed bone bridging between the alveolar cleft radiographically , with good incorporation and maturation of the bone graft , and no recurrence of the oronasal fistula . CONCLUSION The CT scan is a valuable radiographic imaging modality to assess and follow the clinical outcome of secondary alveolar bone grafting Objective To evaluate nasal morphology , symmetry , and nostril shape in patients with unilateral cleft lip and palate following mixed-dentition alveolar bone grafting . Design Prospect i ve stereophotogrammetric study . Setting Hospital-based . Patients Thirty-nine patients with a history of repaired unilateral cleft lip and palate who received an iliac crest alveolar bone graft were recruited prospect ively to participate in the study . Each patient served as his/her own control . Interventions Partial facial impressions of all patients were acquired before and a minimum of 6 months after the alveolar bone grafting procedure . Image acquisition and analysis of the casts constructed from these models were carried out using three-dimensional stereophotogrammetry . Main Outcome Measures Surface-based registration s and linear measurements were performed to assess nasal morphology and nostril shape . A modified Procrustes technique was used to determine the change in nasal symmetry . A two-tailed , paired t test and an analysis of covariance were used to assess statistical significance . Results Significant side-to-side asymmetry exists in the nasal region of patients with unilateral cleft lip and palate , both before and after alveolar bone grafting . No significant changes were observed between pre – alveolar bone graft and post – alveolar bone graft images based on linear measurements , asymmetry scores , and registration s. Gender and surgeon were not significant factors . Conclusion Under the conditions of this study , mixed-dentition alveolar bone grafting appears to have no significant long-term effect on nasal morphology , symmetry , or nostril shape This prospect i ve cross-sectional , case-controlled morphometric study investigated three-dimensional facial morphological variation among and between 8- and 12-year-old children [ 40 with a unilateral cleft lip and palate ( UCLP ) , 23 with a unilateral cleft lip and alveolus ( UCLA ) , 19 with a bilateral cleft lip and palate ( BCLP ) , and 21 with an isolated cleft palate ( ICP ) ] . Eighty gender- and age-matched individuals comprised the control group . The mean shape of each group was computed using generalized Procrustes analysis ( GPA ) . Differences in shape between group means were assessed using multivariate analysis of variance and permutation tests , and shape differences were visualized for interpretation using warpings of the gr and mean shape and transformation grids computed using thin plate splines ( TPA ) . Statistically significant differences between the mean facial shapes and forms ( shape plus size ) of all groups were found . The greatest difference was in the BCLP group and the second greatest in the UCLP group . The study of asymmetry indicated different degrees and differences in the nature of asymmetry that characterize different cleft lip and palate ( CLP ) deformities . Principal component analyses ( PCA ) of form space and of means , plus reflected means , were informative with respect to the differences in facial size and shape and asymmetry between these groups . The results highlight differences in the aetiology of ICP and CLP groups and underline the potential value of statistical shape analysis in assessing the outcomes of CLP treatment Objective Three-dimensional analysis of palate size and shape in patients with complete unilateral cleft lip and palate ( UCLP ) at the stage of permanent dentition . Subjects Thirty r and omly selected dental casts of boys approximately 15 years old with complete UCLP and 28 dental casts of normal boys of the same age . Interventions All patients underwent lip repair according to Tennison with primary periosteoplasty ( mean age 8.5 months ) and palate repair by pushback and pharyngeal flap surgery ( mean age 4.9 years ) . Main Outcome Measures Data on the palate height in 210 defined locations . Results The palate in patients with UCLP was narrower throughout its whole extent , more anteriorly than posteriorly . From the canines posteriorly , it was also lower , and the difference as compared with controls increased in a posterior direction up to the level of second premolars ( up to 30 % ) and then slightly diminished ( to 21 % between the first molars ) . The reduction of area of transverse sections reached 45 % between premolars and 39 % between first molars . The palate in the anterior portion was highest on the cleft side and in a posterior direction the maximum height of the palate shifted toward the midline and even beyond that line toward the noncleft side . Palatal height did not depend on dentoalveolar arch width . Conclusion The smaller width and height of the palate confirm the substantially reduced space for the tongue in patients with UCLP . The reduction is only slightly larger than in previously examined patients with isolated cleft palate . Palatal vault is asymmetrical , highest anteriorly on the cleft side and posteriorly on the noncleft side OBJECTIVE This objective of this study was to determine the effect of presurgical nasoalveolar molding on long-term nasal shape in complete unilateral clefts . DESIGN The study was retrospective , and the subjects were chosen at r and om . Nasal casts of the subjects were scanned in three dimensions . Each nose was best fit to its mirror image , and a numerical asymmetry score was determined . SETTING All patients were treated at the Institute of Reconstructive Plastic Surgery , NYU Medical Center , New York , New York . PATIENTS The study subjects ( n = 10 ) were selected from a group that had undergone presurgical nasal molding in conjunction with alveolar molding . The control subjects ( n = 10 ) were selected from a group that had undergone presurgical alveolar molding alone . INTERVENTIONS All subjects underwent presurgical orthopedic treatment until the age of approximately 4 months at which time the primary surgery was performed . MAIN OUTCOME MEASURE The nasal shape following nasal molding should be more symmetrical than if molding had not been done . RESULTS The mean asymmetry index for the nasoalveolar molding group was 0.74 , and the control group was 1.21 . This difference was statistically significant ( p < .05 ) . CONCLUSIONS Presurgical nasoalveolar molding significantly increases the symmetry of the nose . The increase in symmetry is maintained long term into early childhood . The limitations of this study include ( 1 ) asymmetry alone is not an adequate shape result in most situations , ( 2 ) the children evaluated in this study were not fully grown , and ( 3 ) the control group was not age matched Objective : To evaluate the clinical application of three-dimensional ( 3D ) imaging for the analysis of a broad variety of cleft lips and to conduct a systematic analysis . Design : This was a prospect i ve study using a noncontact 3D laser scanner to acquire the preoperative 3D facial profiles . The data sets were analyzed qualitatively and quantitatively . The data were expressed by ratios and scores . Patients : Forty nonse date d patients ( 1 to 39 years , average age 2.7 years ) with unilateral cleft lip , cleft lip and alveolus , or complete unilateral cleft in Cambodia . Results : The acquired 3D data sets ( mean acquisition time : 2.5 seconds ) from facial surfaces were of diagnostic quality in 27 of 40 patients ( average age , 14.2 years ) . In these cases all anatomical structures could be mapped precisely by means of l and mark positioning in the range of millimeters . A new method of systematic analysis could be elaborated , allowing for data set expression independent of size and growth factors . In children under age 3 , the measuring procedure was of limited value because of motion artifacts and was successful in only 6 % ( 1 of 15 ) of these patients . Conclusion : The system offers a solid and precise tool for 3D imaging of the complex cleft lip anatomy in compliant patients and is useful for preoperative cleft assessment and follow-up . However , the application is limited in moving infants or uncooperative adults because of scanning time and acquisition method . The development of motion tracking and faster devices could eliminate motion artifacts Abstract The objective of the current study was to assess the outcome of the alveolar bone grafting ( ABG ) in patients with cleft palate . Thirty-one patients with complete unilateral cleft lip and palate were prospect ively divided into 2 groups according to the timing of surgery : ( 1 ) secondary ABG ( SABG ) , undertaken during mixed dentition ( n = 16 ) ; and ( 2 ) tertiary ABG ( TABG ) , undertaken during permanent dentition ( n = 15 ) . Septum height was assessed using cone beam computed tomography in 3 views ( buccal , intermediate , palatal ) and classified according to the modified Bergl and Index , which scores the results into 5 types according to the height of the neoformed bone septum ( excellent : septum with a normal height ; good : septum with minor deficiency ; regular : marginal defect of > 25 % of the root length ; bad : bone deficiency on the nasal aspect ; and failure ) . In the SABG group , 6 to 12 months postoperatively , 75 % of the patients were classified as having excellent/good conditions and 25 % as having regular/bad conditions . No patients were observed as having failure conditions . In the TABG group , 53 % of the patients were classified as having excellent/good , 21 % were classified as having regular/bad conditions , and 26 % were classified as having failure conditions . Significantly better outcomes were observed for the SABG group when compared with the TABG group . In conclusion , the age at which ABG is performed is a factor that impacts on the surgical outcome . Specifically , increasing age is associated with worse outcomes Objective The aim of this study was to investigate the influence of facial asymmetry on how an adult population with unilateral cleft lip and palate ( CLP ) perceived themselves and were perceived by others . Patients and Methods 3D facial data of 30 adult patients with cleft lip and palate ( CLP ) was scanned and st and ardized extra- and intraoral photographs were taken . The measured degree of 3D asymmetry was computed for the entire face , midface and lower face . Subjective estimates regarding facial symmetry , attractiveness as well as satisfaction and a desire or indication for further treatment were surveyed by means of a question naire filled out by patients and an assessment group ( 10 orthodontists , 10 oral and maxillofacial ( OM ) surgeons , 15 laypersons ) . Results The study ’s results show that the largest degree of asymmetry was found in the midface of CLP patients . The vast majority of the patients were dissatisfied with their facial appearance , and patients , experts and laypersons expressed great interest in and a need of correction . We observed tangible incongruence between how the patients perceived their own faces and how others perceived them . Conclusions Asymmetry , especially in the midface , appears to detract from how facial appearance is self-perceived and perceived by others , which explains the primary desire for or need of nose correction . The self-perception of patients affected by CLP does not correlate with objective results or how others perceive them . Clinicians should be open to adult patients ’ requests for correction , but the patient‘s self-perception should also be critically explored . ZusammenfassungZielZiel der Studie war es , den Einfluss der fazialen Asymmetrie auf die Selbst- und Fremdwahrnehmung bei Erwachsenen mit einseitiger Lippen-Kiefer-Gaumen-(LKG-)Spalte , nach Beh and lungsabschluss zu untersuchen . Patienten und Method ikVon 30 erwachsenen Patienten mit LKG-Spalte wurden 3-D-Gesichts date n erhoben sowie st and ardisierte extra- und intraorale Fotografien angefertigt . Der gemessene 3-D-Asymmetriegrad wurde von dem gesamten Gesicht , dem Mittel- und dem Untergesicht berechnet . Subjektive Einschätzungen bezüglich der fazialen Symmetrie , Attraktivität sowie Zufriedenheit und weitere/r Beh and lungswunsch/-indikation wurden mittels Fragebogen von den Patienten und einer Beurteilergruppe ( 10 Kieferorthopäden , 10 MKG-Chirurgen , 15 Laien ) erhoben . ErgebnisseDie Ergebnisse der Studie zeigen , dass der größte Anteil der Asymmetrie i m Mittelgesicht bei Patienten mit LKG-Spalte zu finden war . Der weitaus größte Teil der Patienten war unzufrieden mit dem fazialen Erscheinungsbild , und es best and ein hoher Korrekturwunsch bzw . -bedarf vonseiten der Patienten , Experten und Laien . Eine deutliche Inkongruenz konnte zwischen der fazialen Selbstwahrnehmung des Spaltträgers und der Fremdwahrnehmung nachgewiesen werden . SchlussfolgerungenInsbesondere eine Asymmetrie i m Mittelgesicht scheint die Fremd- und Selbstwahrnehmung des fazialen Aussehens negativ zu beeinflussen , wodurch sich der Korrekturwunsch bzw . -bedarf primär nach einer Nasenkorrektur erklären lässt . Patienten mit LKG-Spalten verfügen über eine Selbstwahrnehmung , die nicht mit den objektiven Ergebnissen bzw . der Fremdwahrnehmung korreliert . Der Kliniker sollte den Korrekturwünschen des erwachsenen Patienten offen gegenüberstehen , jedoch auch das Selbstbild des Patienten kritisch hinterfragen OBJECT The aim of this study was to evaluate the clinical application of three-dimensional ( 3D ) imaging and morphological analysis with subsequent individual therapy planning and postoperative 3D symmetry control in comparison with data from non-cleft persons . DESIGN This was a prospect i ve study using a 3D surface-imaging and evaluation system in cleft patients and non-cleft persons . The pre- and postoperative 3D facial profiles were recorded from the patients using a 3D laser scanner . The preoperative 3D image was analyzed qualitatively and quantitatively for an individual therapy planning . On the basis of ratios and scores , based on empirical regions of interest , the technique of cleft repair was design ed individually . The postoperative result was evaluated regarding symmetry . The surgically created soft tissue shift was defined quantitatively and visualized with vectors . The postoperative symmetry was compared with 3D data from a group of non-cleft persons of the same ethnical group . PATIENTS Eleven patients ( mean age 13.8 years , median 13 , minimum 2 , maximum 41 years ) with either a unilateral isolated cleft lip , a cleft lip and alveolus or a complete unilateral cleft lip , alveolus and palate and 25 non-cleft persons ( 8 children between 4 and 12 years , 17 adults ( 9 men , 8 women ) between 18 and 50 years ) . All these persons investigated were Asians of Khmer origin . RESULTS The analysis permitted quantitative 3D evaluation . The 3D anthropometric data of the non-cleft Khmer persons were collected and named the gold st and ard of symmetry in this ethnical group . All postoperative 3D images reached symmetrical values within the range of the normal cohort . Soft tissue shifts from pre- to postoperative sites could be visualized . CONCLUSION A new method for registration was described enabling follow-up registration in patients when growing older . This 3D soft tissue analysis can be a useful tool in quantitative analysis and objective follow-up control in cleft patients . It offers deeper insight into the complex morphology to be treated and could contribute to individualisation of surgical procedures INTRODUCTION A resorbable collagen matrix with recombinant human bone morphogenetic protein ( rhBMP-2 ) was compared with traditional iliac crest bone graft for the closure of alveolar defects during secondary dental eruption . METHODS Sixteen patients with unilateral cleft lip and palate , aged 8 to 12 years , were selected and r and omly assigned to group 1 ( rhBMP-2 ) or group 2 ( iliac crest bone graft ) . Computed tomography was performed to assess both groups preoperatively and at months 6 and 12 postoperatively . Bone height and defect volume were calculated through Osirix Dicom Viewer ( Pixmeo , Apple Inc. ) . Overall morbidity was recorded . RESULTS Preoperative and follow-up examinations revealed progressive alveolar bone union in all patients . For group 1 , final completion of the defect with a 65.0 % mean bone height was detected 12 months postoperatively . For group 2 , final completion of the defect with an 83.8 % mean bone height was detected 6 months postoperatively . Dental eruption routinely occurred in both groups . Clinical complications included significant swelling in three group 1 patients ( 37.5 % ) and significant donor-site pain in seven group 2 patients ( 87.5 % ) . CONCLUSIONS For this select group of patients with immature skeleton , rhBMP-2 therapy result ed in satisfactory bone healing and reduced morbidity compared with traditional iliac crest bone grafting Objective : The aim of this study was to assess the outcome of bone grafting using a corticocancellous block of iliac crest to reconstruct the support for the deformed , volume-deficient alar base in treated patients with unilateral cleft lip and palate ( UCLP ) . The main outcome being measured was nasal symmetry . Design : This was a prospect i ve study using a noninvasive three-dimensional stereophotogrammetry system ( C3D ) to assess the position of the alar base . Images were captured immediately preoperatively and at 6 months following the augmentation of the alar base with a block of bone graft . These images were used to calculate facial symmetry scores and were compared using a two sample Student 's t test to assess the efficacy of the surgical method in reducing facial/nasal asymmetry . Patients : This investigation was conducted on 18 patients with one patient failing to attend for follow-up . The results for 17 patients are presented . Results : Facial symmetry scores improved significantly following the insertion of the bone graft at the deficient alar base ( p = 0.005 ) . Conclusions : 3D stereophotogrammetry is a noninvasive , accurate , and archiveable method of assessing facial form and surgical change . Nasal symmetry can be quantified and measured reliably with this tool . Bone grafting to the alar base region of treated UCLP patients with volume deficiency produces improvement in nasal symmetry Objective : To assess the radiographic outcome of secondary alveolar bone grafting in individuals with nonsyndromic unilateral or bilateral cleft lip and palate using cone beam computed tomography . Methods : This prospect i ve study was conducted at the University of California at San Francisco Center for Craniofacial Anomalies on 21 consecutive nonsyndromic complete cleft lip and palate individuals between 8 and 12 years of age who required alveolar bone grafting . Seventeen unilateral and four bilateral cleft lip and palate individuals had preoperative and postoperative cone beam computed tomography scans that were analyzed using Amira 3.1.1 software . Results : The average volume of the preoperative alveolar cleft defect in unilateral cleft lip and palate was 0.61 cm3 , and the combined average volume of the right and left alveolar cleft defects in bilateral cleft lip and palate was 0.82 cm3 . The average percentage bone fill in both unilateral cleft lip and palate and bilateral cleft lip and palate was 84 % . The outcome of alveolar bone grafting was assessed in relation to ( 1 ) type of cleft , ( 2 ) size of preoperative cleft defect , ( 3 ) presence or absence of lateral incisor , ( 4 ) root development stage of the maxillary canine on the cleft side , ( 5 ) timing , and ( 6 ) surgeon . None of these parameters significantly influenced the radiographic outcome of alveolar bone grafting . Conclusions : Secondary alveolar bone grafting of the cleft defect in our center was successful , based on radiographic outcome using cone beam computed tomography scans . Volume rendering using cone beam computed tomography and Amira software is a reproducible and practical method to assess the preoperative alveolar cleft volume and the adequacy of bone fill postoperatively The decision for lip revision surgery in patients with repaired cleft lip/palate is based on surgeons ’ subjective evaluation of lip disability . An objective evaluation would be highly beneficial for the assessment of surgical outcomes . In this study , the effects of lip revision on circumoral movements were objective ly quantified . The hypothesis was that lip revision increases scarring and impairment . The study was a non-r and omized clinical trial that included patients with cleft lip who had revision , patients with cleft lip who did not , and non-cleft control individuals . Three-dimensional facial movements were measured . Revision patients were measured before and after surgery . Other individuals were measured at similar intervals . Regression models were fit to summary measurements , and changes were modeled . Patients with repaired cleft lip/palate had fewer mean movements than control individuals . Lip revision did not worsen mean movements ; however , individual patients ’ movements varied from ‘ improvement ’ to ‘ no change ’ to ‘ worse ’ relative to those of control individuals In cleft lip and palate patients the shape of the nose invariably changes in three dimensions ( 3D ) due to rhinoplastic surgery . The purpose of this study was to evaluate stereophotogrammetry as a 3D method to document volumetric changes of the nose in patients with a cleft lip ( CL ) or cleft lip and palate ( CLP ) after secondary open rhinoplasty . 12 patients with unilateral CL or CLP were enrolled in the study prospect ively . 3D facial images were acquired using 3D stereophotogrammetry preoperatively and 3 months postoperatively . A 3D cephalometric analysis of the nose was performed and volumetric data were acquired . The reliability of the method was tested by performing an intra- and inter-observer analysis . Left , right and total nasal volumes and symmetry were compared . No statistically significant differences ( p<0.05 ) were found within and between observers for the measured volumes and symmetry . Postoperatively , the total volume of the nose increased significantly , especially the volume at the cleft side . No significant volume difference pre- and postoperatively was found for the non-cleft side . The symmetry of the nose improved significantly . 3D stereophotogrammetry is a sensitive , quick , non-invasive method for evaluating volumetric changes of the nose in patients with cleft lip or cleft lip and palate Objectives To clarify the need for secondary alveolar bone grafting ( ABG ) in incomplete alveolar clefts identified clinical ly from its appearance and test the usefulness of alveolar ridge notching in the edentulous stage as a predictor for ABG . Design A prospect i ve , cross-sectional study comparing three groups of patients at two stages . Patients Twenty-four patients with unilateral incomplete cleft of primary palate who underwent either no surgery or cheiloplasty only . Methods Cleft severity was assessed at two stages . Initially , the appearance of untreated clefts was assessed before cheiloplasty or at 3 months of age in the patient without cheiloplasty and grade d by severity into three groups . Later alveolar bone defects were assessed with computed tomography in the primary or mixed dentition period . A decision regarding the requirement for ABG was then made . Finally , the relationship between untreated clefts and the need for ABG was determined . Main Outcome Measures Nine ( 75 % ) of 12 patients with alveolar ridge notching in the edentulous stage were diagnosed as fulfilling the criteria for ABG . Results The alveolar bone defects correlated with the severity of untreated cleft conditions ( Spearman r = 0.65 , p = .002 ) . The need for ABG was greater in patients with alveolar ridge notching , compared with those without notching ( 9/12 versus 0/12 , p = .00034 ) . Conclusions Most patients with incomplete alveolar clefts clinical ly identified in the edentulous stage required ABG , and alveolar ridge notching in the edentulous stage could therefore serve as a predictor for ABG OBJECTIVE Three-dimensional analysis of palate size and shape in patients with isolated cleft palate at the stage of permanent dentition . DESIGN Cross-sectional study using Fourier transform profilometry . SUBJECTS Twenty-nine r and omly selected dental casts of approximately 15-year-old boys with isolated cleft palate and 28 dental casts of normal boys of the same age . INTERVENTIONS All patients were operated on by the same method ( pushback and pharyngeal flap surgery ) at a mean age of 4.5 years . MAIN OUTCOME MEASURES Data on the palate height in 210 defined locations ( pixels ) . RESULTS The palate in isolated clefts is narrower throughout its whole extent and lower from the level of the first premolars . The difference , as compared with controls , increases in a posterior direction . At the level of the first molars , palatal height is reduced by one-quarter , the area of the transversal section by more than one-third . The shaping of the palate vault is , on average , symmetrical with a marked interindividual variability . Palatal height does not depend on the width of the dentoalveolar arch , and the height of the primary palate is not reduced . CONCLUSION The smaller width and reduced height from the level of the first premolars posteriorly confirm the substantially reduced space available for the tongue in patients with isolated cleft palate . Deviations are on the average symmetrical , and the anterior part of the palate is not shallower BACKGROUND The aim of this study was to evaluate symmetry of the lip and nose in patients with CUCLP after primary cheiloseptoplasty ( Afroze technique ) , in comparison to non-cleft controls . METHODOLOGY In this prospect i ve study , forty-four patients with operated non-syndromic CUCLP were included . The control group consisted of 44 volunteers without cleft defects of approximately the same age and sex . Primary septoplasty was performed in conjunction with the cleft lip ( CL ) repair using the Afroze incision . 3D facial images were acquired using 3D stereophotogrammetry . After a 3D cephalometric analysis of the lip and nose was performed in both groups , linear and volumetric data were acquired . Lip and nose symmetry were calculated and compared using Student`s t-tests as well as the Chi square test . RESULTS For all measurements , the control group was up to 36 % closer to perfect symmetry compared to the CUCLP group after primary surgery . This difference was statistically significant . CONCLUSIONS After primary cheiloseptoplasty according to the Afroze technique in patients with CUCLP , asymmetry in the nose and lip area still exists as compared to non-cleft controls . Although non-cleft individuals also show some degree of asymmetry , the results of this study stress the difficulty in obtaining near normal symmetrical relations Objective The objective of this study was to describe the threedimensional morphology of the maxilla of patients with bilateral cleft lip and palate treated by a delayed cleft closure in the deciduous dentition . They were compared to a eugnathic control group . Patients and Methods Thirty-two study casts of complete bilateral cleft lip and palate from the archive of the former Wolfgang-Rosenthal Clinic Thallwitz were scanned in three-dimensions and compared to an equally large eugnathic control group . The mean age of the study group was 4.92 years , and that of the control group 5.02 years . Dimensions were recorded using a reflex microscope according to specific l and marks . Results The study group exhibited transversal anterior compression and posterior over-development of the dental arch . We observed conspicuously more frequent , marked inward rotation of the left lateral segment together with broadly-scattered data . We were unable to establish a correlation between the anterior and posterior dental arch widths . In the sagittal dimension , the mean position of the premaxilla was in no way different than that of the control group . Vertically we noted a difference in the level between the premaxilla and lateral segments . The premaxilla was situated significantly more caudally than the lateral segments . Conclusions Even when cleft palate closure is delayed , the result is maxillary constriction and vertical deviation of the cleft segments . The large individual scatter of deviations dem and s a greatly individualized , differentiated concept for later maxillary development . ZusammenfassungZielZiel der Untersuchung war die Charakterisierung der dreidimensionalen Morphologie des Kiefers von Patienten mit doppelseitigen Lippen-Kiefer-Gaumen-(LKG-)Spalten bei spätem Spaltverschluss i m Milchgebiss . Es erfolgte eine Gegenüberstellung mit einer eugnathen Vergleichsgruppe . Patienten und Method ikAus dem Archiv der früheren Wolfgang-Rosenthal-Klinik Thallwitz wurden 32 Modelle von doppelseitigen durchgehenden LKG-Spalten dreidimensional vermessen und einer gleich großen Kontrollgruppe Eugnather gegenübergestellt . Das mittlere Alter der Untersuchungsgruppe lag bei 4,92 Jahren , das der Kontrollgruppe bei 5,02 Jahren . Die Vermessung erfolgte mit einem Reflexmikroskop anh and eingeführter Messpunkte . ErgebnisseTransversal fielen eine anteriore Kompression und eine posteriore Überentwicklung des Zahnbogens der Untersuchungsgruppe auf . Auffällig war eine häufigere ausgeprägte Einschwenkung des linken lateralen Segments bei großer Streuung der Messwerte . Ein Zusammenhang zwischen anteriorer und po steriorer Zahnbogenbreite konnte nicht hergestellt werden . In der sagittalen Dimension wies die mittlere Position der Prämaxilla keinen Unterschied zur Kontrollgruppe auf . Vertikal wurde ein Niveauunterschied zwischen Prämaxilla und lateralen Segmenten nachgewiesen . Die Prämaxilla lag signifikant kaudaler als die lateralen Segmente . SchlussfolgerungenAuch bei spätem Gaumenverschluss tritt eine Kompression des Kiefers und vertikale Lageabweichung der Spaltsegmente auf . Die große individuelle Streuung der Abweichungen erfordert eine stark individualisierte und differenzierte Konzeption für die Nachentwicklung des Oberkiefers Objective : Secondary bone grafting plays an important role in the dental rehabilitation of patients with clefts of the lip , alveolus , and palate . A major complication of this surgical technique is resorption of the grafted bone transplant . Conventional two-dimensional radiographs are often inconclusive and do not demonstrate the true deficit . The main objective of this study was to evaluate the amount and exact location of bone loss on the basis of three-dimensional models over a period of 3 years . Design : Twenty-four patients with unilateral cleft palate were included in this prospect i ve study . Axial computed tomography scans of all patients were taken immediately preoperatively , and 1 , 2 , and 3 years postoperatively . Volumetric analysis was performed on three-dimensional models of the cleft defects and the bone bridges using three-dimensional computed tomography . Interventions : All patients were treated by secondary alveolar bone grafting prior to eruption of the permanent canine . Results : Extensive bone resorption was found in the bucco-palatal dimension of the alveolar portion of the transplant . The success rate of secondary bone grafting was high in cases of rapid orthodontic gap closures . The mean bone loss in the first year after surgery was 49.5 % . The transplants remained almost constant in the following 2 years . Conclusions : Radiographic scales based on orthopantomography only evaluate the vertical dimension of the transplants . This study , however , showed that bone resorption in the transversal dimension is clearly underestimated with conventional two-dimensional radiographs Objective : This is a retrospective study regarding the effect of alveolar bone grafting ( ABG ) on morphological changes in the bony structure of the nose in alveolar and palatal cleft patients . Methods : Sixty-five r and omly selected adults were included in the present study . Of the 65 subjects , 21 had no congenital anomaly and were design ated as the control group ( n = 21 ; mean age 22.4 ± 4.3 years ) . Forty-four had unilateral complete clefts of the alveolus and palate on the left side . The patients with clefts were further divided into two subgroups based on presence or absence of ABG in their histories . These groups were termed the ABG(+ ) group ( n = 24 ; mean age 20.3 ± 2.5 years ) and the ABG(− ) group ( n = 20 ; mean age 32 ± 4.5 years ) , respectively . An anatomical structure that constitutes the bony component of the nose was defined . This structure , composed of the nasal bones and part of the frontal process of the maxilla , was termed the BSEN ( bony structure of the external nose ) . The symmetry of the BSEN was assessed quantitatively by performing morphological measurements on computerized tomographic images of each patient 's skull , and these measurements were compared among the control , ABG(+ ) , and ABG(− ) groups . Results : The BSEN presented more symmetric features in the ABG(+ ) group patients than in the ABG(− ) group patients . Conclusion : ABG improves symmetry of the BSEN . This finding justifies ABG in terms of cosmetic improvement of the external nose in patients with unilateral complete alveolar and palatal clefts Objectives The aim of this study was to demonstrate the clinical applicability of limited cone beam computed tomography ( Dental 3D-CT ) for assessment of bone-grafted alveolar cleft . Patients and Methods Seventeen bone bridges were examined after alveolar bone grafting in 13 patients with cleft lip and palate . All bone bridges , including cleft-adjacent teeth , were examined by plain radiography and the Dental 3D-CT imaging system . Results The plain radiographs showed the approximate condition of the bone bridge and cleft-adjacent teeth . The Dental 3D-CT images clearly showed precise three-dimensional ( 3D ) morphology of the bone bridge , 3D relationships between the bone bridge and the roots of cleft-adjacent teeth , and their periodontal condition . In addition , the conditions surrounding dental implants installed in the bone bridge could be observed three-dimensionally . Conclusions The results indicate that the Dental 3D-CT imaging system is suitable for clinical assessment of alveolar bone grafting before and after installation of dental implants or orthodontic treatment of the cleft-adjacent teeth Objective To evaluate three-dimensional lip morphology , following primary reconstruction in children with unilateral cleft lip and palate relative to contemporaneous noncleft data . Design Prospect i ve , cross-sectional , controlled study . Setting Glasgow Dental Hospital and School , University of Glasgow , U.K. Patients and Participants Two groups of 3-year-old children ( 21 with unilateral cleft lip and palate and 96 controls ) with facial images taken using a three-dimensional vision-based capture technique . Method Three-dimensional images of the face were reflected so the cleft was on the left side to create a homogeneous group for statistical analysis . Three-dimensional coordinates of anthropometric l and marks were extracted from facial images . Three-dimensional , generalized Procrustes superimposition was implemented and a set of linear measurements were used to compare cleft and control subjects for right and left sides , adjusting for sex differences . Results Crista philtri on both the cleft and noncleft sides were displaced laterally and posteriorly ; there was also a statistically significant increase in philtrum width . No significant differences between cleft and control regarding the cutaneous height of the upper lip . The lip in the cleft patients was flatter than in the noncleft individuals , with less prominence of labialis superioris . Conclusions Stereophotogrammetry allows detection of residual dysmorphology following cleft repair . There was significant increase of the philtrum width . The lip appeared flatter and more posterior displaced in unilateral cleft lip and palate patients compared with controls |
10,859 | 26,381,375 | The highest risk of recrudescence was observed in areas of emerging artemisinin resistance and very low transmission intensity .
Current artemether-lumefantrine dosing recommendations achieve day 7 lumefantrine concentrations ≥200 ng/ml and high cure rates in most uncomplicated malaria patients . | Achieving adequate antimalarial drug exposure is essential for curing malaria .
Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy .
However , the ‘ therapeutic ’ day 7 lumefantrine concentration threshold needs to be defined better , particularly for important patient and parasite sub- population s. The WorldWide Antimalarial Resistance Network ( WWARN ) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria , to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations . | Background Safety surveillance of widely used artemisinin-based combination therapy ( ACT ) is essential , but tolerability data in the over five years age group are largely anecdotal . Methods Two open-label , r and omized trials were conducted in Nimba County , Liberia : i ) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years ( Study -T ) , and , ii ) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months ( Study -E ) . In both studies patients were r and omized to fixed-dose artesunate-amodiaquine ( ASAQ Winthrop ® ) or artemether-lumefantrine ( AL , Coartem ® ) , respectively . Clinical - and laboratory-adverse events ( AEs ) were recorded until day 28 . Results Study -T : most patients experienced at least one AE . Severe AEs were few , primarily asymptomatic blood system disorders or increased liver enzyme values . No treatment or study discontinuation occurred . Mild or moderate fatigue ( 39.8 % vs 16.3 % , p < 0.001 ) , vomiting ( 7.1 % vs 1.6 % , p < 0.001 ) , nausea ( 3.2 % vs 1.0 % , p = 0.01 ) , and anaemia ( 14.9 % vs 9.8 % , p = 0.01 ) were more frequently recorded in the ASAQ versus AL arm . Study -E : mild or moderate AEs were common , including anaemia , fatigue , vomiting or diarrhoea . The few severe events were asymptomatic blood system disorders and four clinical events ( pneumonia , malaria , vomiting and stomatitis ) . Conclusion Both ASAQ and AL were well tolerated in patients of all age groups . No unexpected AEs occurred . Certain mild or moderate AEs were more frequent in the ASAQ arm . St and ardised safety surveillance should continue for all forms of ACT.Trial registration The protocol s were registered with Current Controlled Trials , under the identifier numbers IS RCT N40020296 , IS RCT N51688713 , ( http://www.controlled-trials.com ) Background Malaria is a very important cause of anaemia in tropical countries . Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration . For comparisons across studies , it is often necessary to derive one measure from the other . Methods Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries , to assess the haemoglobin/haematocrit relationship at different time points in malaria . Using a linear r and om effects model , a conversion equation for haematocrit was derived based on 3,254 measurements from various time points ( ranging from day 0 to day 63 ) from 1,810 patients with simultaneous measurements of both parameters . Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion . Results A good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin . On average , haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference ( ± SD ) of -0.69 ( ± 1.3 ) for children under the age of 5 ( n = 1,440 measurements from 449 patients ) . Conclusion Based on this large data set , an accurate and robust conversion factor both in acute malaria and in convalescence was obtained . The commonly used threefold conversion is also valid Background Home-management of malaria ( HMM ) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa . However , limited data are available on the effectiveness of using artemisinin-based combination therapy ( ACT ) within the HMM strategy . The aim of this study was to assess the effectiveness of artemether-lumefantrine ( AL ) , presently the most favoured ACT in Africa , in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania , when provided by community health workers ( CHWs ) and administered unsupervised by parents or guardians at home . Methods An open label , single arm prospect i ve study was conducted in two rural villages with high malaria transmission in Kibaha District , Tanzania . Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test ( RDT ) were provisionally enrolled and provided AL for unsupervised treatment at home . Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and review ed weekly by the CHWs during 42 days . Primary outcome measure was PCR corrected parasitological cure rate by day 42 , as estimated by Kaplan-Meier survival analysis . This trial is registered with Clinical Trials.gov , number NCT00454961 . Results A total of 244 febrile children were enrolled between March-August 2007 . Two patients were lost to follow up on day 14 , and one patient withdrew consent on day 21 . Some 141/241 ( 58.5 % ) patients had recurrent infection during follow-up , of whom 14 had recrudescence . The PCR corrected cure rate by day 42 was 93.0 % ( 95 % CI 88.3%-95.9 % ) . The median lumefantrine concentration was statistically significantly lower in patients with recrudescence ( 97 ng/mL [ IQR 0 - 234 ] ; n = 10 ) compared with reinfections ( 205 ng/mL [ 114 - 390 ] ; n = 92 ) , or no parasite reappearance ( 217 [ 121 - 374 ] ng/mL ; n = 70 ; p ≤ 0.046 ) . Conclusions Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective , which provides evidence base for scaling-up implementation of HMM with AL in Tanzania BACKGROUND Adherence to antimalarial drug regimens is improved by simple dosing . If the fixed antimalarial drug combination artemether-lumefantrine ( AL ) could be given once daily , this should improve adherence and thus effectiveness and lower the risk of selecting for resistance . METHODS In an open r and omized study , 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days . The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves ( AUC ) . Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles . RESULTS Lumefantrine pharmacokinetic profiles were obtained for 36 patients . The AUC((0 - ->infinity ) ) of the once-daily regimen was 30 % lower than that in the conventional regimen ( P = 0.011 ) with a median ( range ) value of 306 ( 114 - 5781 ) microg/ml h , compared with 432 ( 308 - 992 ) microg/ml h. There was no significant difference in the peak plasma concentrations reached . PCR-adjusted cure rate estimates at day 42 of follow-up were 94 % ( 95 % CI : 84 - 100 ) in the six-dose arm and 85 % ( 70 - 100 ) in the three-dose arm ( P = 0.3 ) . CONCLUSION Artemether-lumefantrine efficacy is reduced by once-daily dosing , because absorption of lumefantrine is dose limited . At currently recommended doses , this antimalarial should be given twice daily in a 3-day regimen , with food containing fat Objectives Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions . We investigated drug – drug interactions between artemether/lumefantrine and efavirenz or nevirapine . Methods We performed a cross-over study in which HIV-infected adults received st and ard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state . Artemether , dihydroartemisinin , lumefantrine , efavirenz and nevirapine plasma concentrations were measured and compared . Results Efavirenz significantly reduced artemether maximum concentration ( Cmax ) and plasma AUC ( median 29 versus 12 ng/mL , P < 0.01 , and 119 versus 25 ng · h/mL , P < 0.01 ) , dihydroartemisinin Cmax and AUC ( median 120 versus 26 ng/mL , P < 0.01 , and 341 versus 84 ng · h/mL , P < 0.01 ) , and lumefantrine Cmax and AUC ( median 8737 versus 6331 ng/mL , P = 0.03 , and 280 370 versus 124 381 ng · h/mL , P < 0.01 ) . Nevirapine significantly reduced artemether Cmax and AUC ( median 28 versus 11 ng/mL , P < 0.01 , and 123 versus 34 ng · h/mL , P < 0.01 ) and dihydroartemisinin Cmax and AUC ( median 107 versus 59 ng/mL , P < 0.01 , and 364 versus 228 ng · h/mL , P < 0.01 ) . Lumefantrine Cmax and AUC were non-significantly reduced by nevirapine . Artemether/lumefantrine reduced nevirapine Cmax and AUC ( median 8620 versus 4958 ng/mL , P < 0.01 , and 66 329 versus 35 728 ng · h/mL , P < 0.01 ) , but did not affect efavirenz exposure . Conclusions Co-administration of artemether/lumefantrine with efavirenz or nevirapine result ed in a reduction in artemether , dihydroartemisinin , lumefantrine and nevirapine exposure . These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine . Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . Background To date no comparative trials have been done , to our knowledge , of fixed-dose artemisinin combination therapies ( ACTs ) for the treatment of Plasmodium falciparum malaria in pregnancy . Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world . The objective of this study was to compare the efficacy , tolerability , and safety of artemether-lumefantrine , the most widely used fixed ACT , with 7 d artesunate monotherapy in the second and third trimesters of pregnancy . Methods and Findings An open-label r and omised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d ( AL ) or artesunate monotherapy 7 d ( AS7 ) was conducted in Karen women in the border area of northwestern Thail and who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy . The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery , as estimated by Kaplan-Meier survival analysis . Infants were assessed at birth and followed until 1 y of life . Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy . Both regimens were very well tolerated . The cure rates ( 95 % confidence interval ) for the intention to treat ( ITT ) population were : AS7 89.2 % ( 82.3%–96.1 % ) and AL 82.0 % ( 74.8%–89.3 % ) , p = 0.054 ( ITT ) ; and AS7 89.7 % ( 82.6%–96.8 % ) and AL 81.2 % ( 73.6%–88.8 % ) , p = 0.031 ( per- protocol population ) . One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up . Birth outcomes and infant ( up to age 1 y ) outcomes did not differ significantly between the two groups . The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL . Conclusion The current st and ard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with uncomplicated falciparum malaria , but efficacy was inferior to 7 d artesunate monotherapy and was unsatisfactory for general deployment in this geographic area . Reduced efficacy probably results from low drug concentrations in later pregnancy . A longer or more frequent AL dose regimen may be needed to treat pregnant women effectively and should now be evaluated . Parasitological endpoints in clinical trials of any antimalarial drug treatment in pregnancy should be extended to delivery or day 42 if it comes later . Trial Registration : Current Controlled Trials IS RCT Background The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies . Methods On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P. falciparum malaria in a r and omized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008 . ( IS RCT N88705995 ) Results The proportion of patients with residual parasitemia on day 1 rose from 55 % in 2005–2006 to 87 % in 2007–2008 ( odds ratio , 5.4 , 95%CI , 2.7–11.1 ; P<0.001 ) and from 81 % to 95 % ( OR , 4.1 , 95%CI , 1.7–9.9 ; P = 0.002 ) in the DHA-PPQ and AM-LM groups , respectively . In parallel , Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7 % to 14 % ( P = 0.1 ) and from 6 % to 15 % ( P = 0.05 ) with DHA-PPQ and AM-LM , respectively . Coinciding with decreasing transmission in the study area , clinical tolerance to parasitemia ( defined as absence of fever ) declined between 2005–2006 and 2007–2008 ( OR body temperature > 37.5 ° C , 2.8 , 1.9–4.1 ; P<0.001 ) . Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof . Conclusions The significant , albeit small , decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity , to the coincident reduction in population -level clinical immunity , or both . Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better underst and ing of the mechanisms underlying reduced parasite clearance rates . Trial Registration Controlled-Trials.com IS RCT CONTEXT Combination therapy is now widely advocated as first-line treatment for uncomplicated malaria in Africa . However , it is not clear which treatment regimens are optimal or how to best assess comparative efficacies in highly endemic areas . OBJECTIVE To compare the efficacy and safety of 3 leading combination therapies for the treatment of uncomplicated malaria . DESIGN , SETTING , AND PARTICIPANTS Single-blind r and omized clinical trial , conducted between November 2004 and June 2006 , of treatment for all episodes of uncomplicated malaria in children in an urban community in Kampala , Ug and a. A total of 601 healthy children ( aged 1 - 10 years ) were r and omly selected and were followed up for 13 to 19 months , receiving all medical care at the study clinic . INTERVENTIONS Study participants were r and omized to receive 1 of 3 combination therapies ( amodiaquine plus sulfadoxine-pyrimethamine , amodiaquine plus artesunate , or artemether-lumefantrine ) when diagnosed with their first episode of uncomplicated malaria . The same assigned treatment was given for all subsequent episodes . MAIN OUTCOME MEASURE 28-Day risk of parasitological failure ( unadjusted and adjusted by genotyping to distinguish recrudescence from new infection ) for each episode of uncomplicated malaria treated with study drugs . RESULTS Of enrolled children , 329 of 601 were diagnosed with at least 1 episode of uncomplicated malaria , and 687 episodes of Plasmodium falciparum malaria were treated with study drugs . The 28-day risk of treatment failure ( unadjusted by genotyping ) for individual episodes of malaria were 26.1 % ( 95 % CI , 21.1%-32.1 % ) for amodiaquine plus sulfadoxine-pyrimethamine , 17.4 % ( 95 % CI , 13.1%-23.1 % ) for amodiaquine plus artesunate , and 6.7 % ( 95 % CI , 3.9%-11.2 % ) for artemether-lumefantrine ( P<.05 for all pairwise comparisons ) . When only recrudescent treatment failures were considered , the risks of failure were 14.1 % ( 95 % CI , 10.3%-19.2 % ) , 4.6 % ( 95 % CI , 2.5%-8.3 % ) , and 1.0 % ( 95 % CI , 0.3%-4.0 % ) for the same order of study drugs , respectively ( P < or = .008 for all pairwise comparisons , except amodiaquine plus artesunate vs artemether-lumefantrine , P = .05 ) . There were no deaths or cases of severe malaria . Significant reductions in anemia ( 9.3 % [ 95 % CI , 7.0%-12.0 % ] at enrollment vs 0.6 % [ 95 % CI , 0.1%-2.2 % ] during the last 2 months of follow-up ; P<.001 ) and asymptomatic parasitemia ( 18.6 % [ 95 % CI , 15.5%-22.1 % ] at enrollment vs 2.3 % [ 95 % CI , 1.5%-3.5 % ] during the last 2 months of follow-up ; P<.001 ) were observed according to routine testing . CONCLUSIONS Artemether-lumefantrine was the most efficacious treatment for uncomplicated malaria in the study population . With all study regimens , the provision of prompt and reasonably effective facility-based treatment was associated with good outcomes in long-term health measures . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N37517549 BACKGROUND Our study examined the relative contributions of host , pharmacokinetic , and parasitological factors in determining the therapeutic response to artemether-lumefantrine ( AL ) . METHODS On the northwest border of Thail and , patients with uncomplicated Plasmodium falciparum malaria were enrolled in prospect i ve studies of AL treatment ( 4- or 6-dose regimens ) and followed up for 42 days . Plasma lumefantrine concentrations were measured by high performance liquid chromatography ; malaria parasite pfmdr1 copy number was quantified using a real-time polymerase chain reaction assay ( PCR ) , and in vitro drug susceptibility was tested . RESULTS All treatments result ed in a rapid clinical response and were well tolerated . PCR-corrected failure rates at day 42 were 13 % ( 95 % confidence interval [ CI ] , 9.6%-17 % ) for the 4-dose regimen and 3.2 % ( 95 % CI , 1.8%-4.6 % ) for the 6-dose regimen . Increased pfmdr1 copy number was associated with a 2-fold ( 95 % CI , 1.8 - 2.4-fold ) increase in lumefantrine inhibitory concentration(50 ) ( P=.001 ) and an adjusted hazard ratio for risk of treatment failure following completion of a 4-dose regimen , but not a 6-dose regimen , of 4.0 ( 95 % CI , 1.4 - 11 ; P=.008 ) . Patients who had lumefantrine levels below 175 ng/mL on day 7 were more likely to experience recrudescence by day 42 ( adjusted hazard ratio , 17 ; 95 % CI , 5.5 - 53 ) , allowing prediction of treatment failure with 75 % sensitivity and 84 % specificity . The 6-dose regimen ensured that therapeutic levels were achieved in 91 % of treated patients . CONCLUSIONS The lumefantrine plasma concentration profile is the main determinant of efficacy of artemether-lumefantrine . Amplification in pfmdr1 determines lumefantrine susceptibility and , therefore , treatment responses when plasma lumefantrine levels are subtherapeutic Background Prospect i ve efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development . The in vivo efficacy of artesunate-amodiaquine ( ASAQ ) fixed-dose combination ( FDC ) was compared to that of artemether-lumefantrine ( AL ) among children aged six to 59 months in Nimba County , Liberia , where Plasmodium falciparum malaria is endemic and efficacy data are scarce . Methods An open-label , r and omized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC ( ASAQ Winthrop ® ) to AL ( Coartem ® ) in 300 children aged six to 59 months with uncomplicated falciparum malaria . Inclusion was between December 2008 and May 2009 . R and omization ( 1:1 ) was to a three-day observed oral regimen ( ASAQ : once a day ; AL : twice a day , given with fatty food ) . Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured . Results The day 42 genotyping-adjusted cure rate estimates were 97.3 % [ 95 % CI : 91.6 - 99.1 ] for ASAQ and 94.2 % [ 88.1 - 97.2 ] for AL ( Kaplan-Meier survival estimates ) . The difference in day 42 cure rates was −3.1 % [ upper limit 95 % CI : 1.2 % ] . These results were confirmed by observed proportion of patients cured at day 42 on the per- protocol population . Parasite clearance was 100 % ( ASAQ ) and 99.3 % ( AL ) on day 3 . The probability to remain free of re-infection was 0.55 [ 95 % CI : 0.46 - 0.63 ] ( ASAQ ) and 0.66 [ 0.57 - 0.73 ] ( AL ) ( p = 0.017 ) . Conclusions Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL . The proportion of patients with re-infection was high in both arms in this highly endemic setting . In 2010 , ASAQ FDC was adopted as the first-line national treatment in Liberia . Continuous efficacy monitoring is recommended . Trial registration The protocol s were registered with Current Controlled Trials , under the identifier numbers IS RCT N51688713 , IS RCT N40020296 BACKGROUND Malaria in pregnancy is associated with maternal and fetal morbidity and mortality . In 2006 , WHO recommended use of artemisinin-based combination treatments during the second or third trimesters , but data on efficacy and safety in Africa were scarce . We aim ed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara , Ug and a. METHODS We did an open-label , r and omised , non-inferiority trial between October , 2006 , and May , 2009 , at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Ug and a. Pregnant women were r and omly assigned ( 1:1 ) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine , and were followed up weekly until delivery . Our primary endpoint was cure rate at day 42 , confirmed by PCR . The non-inferiority margin was a difference in cure rate of 5 % . Analysis of efficacy was for all r and omised patients without study deviations that could have affected the efficacy outcome . This study was registered with Clinical Trials.gov , number NCT00495508 . FINDINGS 304 women were r and omly assigned , 152 to each treatment group . By day 42 , 16 patients were lost to follow-up and 25 were excluded from the analysis . At day 42 , 137 ( 99.3 % ) of 138 patients taking artemether-lumefantrine and 122 ( 97.6 % ) of 125 taking quinine were cured-difference 1.7 % ( lower limit of 95 % CI -0.9 ) . There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group . INTERPRETATION Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy . FUNDING Médecins Sans Frontières and the European Commission As artemether/lumefantrine is now deployed as the first-line treatment for uncomplicated falciparum malaria in Bangladesh , information on its efficacy and adherence to its use is important . A r and omised controlled non-inferiority trial comparing directly observed treatment ( DOT ) and non-directly observed treatment ( NDOT ) was conducted in 320 patients with uncomplicated falciparum malaria in B and arban Hill Tract District , Bangladesh . Both regimens showed similar high levels of PCR-corrected 42-day parasitological and clinical cure rates ( 99.3 % in the NDOT group and 100 % in the DOT group ; P=0.49 ) . Survival analysis for the time to recurrence of infection showed no difference between treatment groups ( log rank , P=0.98 ) . Adherence , as assessed by counting remaining tablets and oral interviews , was 93 % in the NDOT group and was confirmed by Day 7 lumefantrine concentrations . Adherence was independent of educational level . Patients with plasma lumefantrine concentrations < 280 ng/ml at Day 7 were at greater risk for re-infection ( relative risk 5.62 ; P=0.027 ) . The efficacy of artemether/lumefantrine for the treatment of uncomplicated falciparum malaria in Bangladesh is high and is similar for DOT and NDOT . Adherence to therapy is high BACKGROUND Human immunodeficiency virus ( HIV ) protease inhibitors show activity against Plasmodium falciparum in vitro . We hypothesized that the incidence of malaria in HIV-infected children would be lower among children receiving lopinavir-ritonavir-based antiretroviral therapy ( ART ) than among those receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART . METHODS We conducted an open-label trial in which HIV-infected children 2 months to 5 years of age who were eligible for ART or were currently receiving NNRTI-based ART were r and omly assigned to either lopinavir-ritonavir-based ART or NNRTI-based ART and were followed for 6 months to 2 years . Cases of uncomplicated malaria were treated with artemether-lumefantrine . The primary end point was the incidence of malaria . RESULTS We enrolled 176 children , of whom 170 received the study regimen : 86 received NNRTI-based ART , and 84 lopinavir-ritonavir-based ART . The incidence of malaria was lower among children receiving the lopinavir-ritonavir-based regimen than among those receiving the NNRTI-based regimen ( 1.32 vs. 2.25 episodes per person-year ; incidence-rate ratio , 0.59 ; 95 % confidence interval [ CI ] , 0.36 to 0.97 ; P=0.04 ) , as was the risk of a recurrence of malaria after treatment with artemether-lumefantrine ( 28.1 % vs. 54.2 % ; hazard ratio , 0.41 ; 95 % CI , 0.22 to 0.76 ; P=0.004 ) . The median lumefantrine level on day 7 after treatment for malaria was significantly higher in the lopinavir-ritonavir group than in the NNRTI group . In the lopinavir-ritonavir group , lumefantrine levels exceeding 300 ng per milliliter on day 7 were associated with a reduction of more than 85 % in the 63-day risk of recurrent malaria . A greater number of serious adverse events occurred in the lopinavir-ritonavir group than in the NNRTI group ( 5.6 % vs. 2.3 % , P=0.16 ) . Pruritus occurred significantly more frequently in the lopinavir-ritonavir group , and elevated alanine aminotransferase levels significantly more frequently in the NNRTI group . CONCLUSIONS Lopinavir-ritonavir-based ART as compared with NNRTI-based ART reduced the incidence of malaria by 41 % , with the lower incidence attributable largely to a significant reduction in the recurrence of malaria after treatment with artemether-lumefantrine . Lopinavir-ritonavir-based ART was accompanied by an increase in serious adverse events . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ; Clinical Trials.gov number , NCT00978068 . ) ABSTRACT The objective of this study was to conduct a prospect i ve population pharmacokinetic and pharmacodynamic evaluation of lumefantrine during blinded comparisons of artemether-lumefantrine treatment regimens in uncomplicated multidrug-resistant falciparum malaria . Three combination regimens containing an average adult lumefantrine dose of 1,920 mg over 3 days ( four doses ) ( regimen A ) or 2,780 mg over 3 or 5 days ( six doses ) ( regimen B or C , respectively ) were given to 266 Thai patients . Detailed observations were obtained for 51 hospitalized adults , and sparse data were collected for 215 patients of all ages in a community setting . The population absorption half-life of lumefantrine was 4.5 h. The model-based median ( 5th and 95th percentiles ) peak plasma lumefantrine concentrations were 6.2 ( 0.25 and 14.8 ) μg/ml after regimen A , 9.0 ( 1.1 and 19.8 ) μg/ml after regimen B , and 8 ( 1.4 and 17.4 ) μg/ml after regimen C. During acute malaria , there was marked variability in the fraction of drug absorbed by patients ( coefficient of variation , 150 % ) . The fraction increased considerably and variability fell with clinical recovery , largely because food intake was resumed ; taking a normal meal close to drug administration increased oral bioavailability by 108 % ( 90 % confidence interval , 64 to 164 ) ( P , 0.0001 ) . The higher-dose regimens ( B and C ) gave 60 and 100 % higher areas under the concentration-time curves ( AUC ) , respectively , and thus longer duration s for which plasma lumefantrine concentrations exceeded the putative in vivo MIC of 280 μg/ml ( median for regimen B , 252 h ; that for regimen C , 298 h ; that for regimen A , 204 h [ P , 0.0001 ] ) and higher cure rates . Lumefantrine oral bioavailability is very dependent on food and is consequently poor in acute malaria but improves markedly with recovery . The high cure rates with the two six-dose regimens result ed from increased AUC and increased time at which lumefantrine concentrations were above the in vivo MIC The efficacy and safety of the 6-dose regimen of artemether-lumefantrine were assessed in an open r and omized trial in children and adults presenting with acute , uncomplicated Plasmodium falciparum malaria in Thail and between November 1997 and March 1998 . 200 patients were enrolled in 2 centres : 150 received artemether-lumefantrine ( i.e. , a median total dose of 9.6 mg/kg [ interquartile range 8.7 - 10.7 ] and 57.9 mg/kg of lumefantrine [ 52.4 - 64.0 ] ) and 50 the st and ard combination of artesunate ( 12 mg/kg over 3 d ) and mefloquine ( 25 mg/kg ) . All patients had rapid initial clinical and parasitological responses . The 28 d cure rates were high : 97.7 % ( 95 % confidence interval [ 95 % CI ] 93.5 - 99.5 % ) for artemether-lumefantrine and 100 % ( 95 % CI 92.5 - 100 % ) for artesunate-mefloquine . The 6-dose regimen of artemether-lumefantrine was better tolerated than , and as effective as , artesunate-mefloquine , the current st and ard treatment in this area of multidrug-resistant P. falciparum malaria ABSTRACT The relationship between malnutrition and malaria in young children is under debate , and no studies evaluating the association between malnutrition and response to artemisinin-based combination therapies ( ACTs ) have been published . We evaluated the association between malnutrition and response to antimalarial therapy in Ug and an children treated with ACTs for repeated episodes of malaria . Children aged 4 to 12 months diagnosed with uncomplicated malaria were r and omized to dihydroartemisinin-piperaquine ( DP ) or artemether-lumefantrine ( AL ) and followed for up to 2 years . All HIV-exposed and HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis ( TS ) . The primary exposure variables included height-for-age and weight-for-age z scores . Outcomes included parasite clearance at days 2 and 3 and risk of recurrent parasitemia after 42 days of follow-up . Two hundred ninety-two children were r and omized to DP or AL , result ing in 2,013 malaria treatments . Fewer than 1 % of patients had a positive blood smear by day 3 ( DP , 0.2 % ; AL , 0.6 % [ P = 0.18 ] ) . There was no significant association between height-for-age or weight-for-age z scores and a positive blood smear 2 days following treatment . For children treated with DP but not on TS , decreasing height-for-age z scores of < −1 were associated with a higher risk of recurrent parasitemia than a height-for-age z score of > 0 ( hazard ratio [ HR ] for height-for-age z score of < −1 and ≥−2 = 2.89 [ P = 0.039 ] ; HR for height-for-age z score of < −2 = 3.18 [ P = 0.022 ] ) . DP and AL are effective antimalarial therapies in chronically malnourished children in a high-transmission setting . However , children with mild to moderate chronic malnutrition not taking TS are at higher risk for recurrent parasitemia and may be considered a target for chemoprevention ABSTRACT An open , r and omized comparison of artemether-benflumetol ( CGP 56 697 ; Novartis ) with artesunate-mefloquine was conducted in 617 patients with acute uncomplicated multidrug-resistant falciparum malaria on the western border of Thail and . Both treatments rapidly and reliably cleared fever and parasitemia , and there was no significant difference in the initial therapeutic response parameters . Parasite genotyping was used to distinguish recrudescences from new infections . The 63-day cure rate for artesunate-mefloquine ( 94 % ) was significantly higher than the cure rate for artemether-benflumetol ( 81 % ) ( P < 0.001 ) . Both regimens were well tolerated . Nausea , vomiting , dizziness , sleep disorders , and other neurological side effects were between two and four times more common in the artesunate-mefloquine group than in the artemether-benflumetol group ( P < 0.001 ) . Artemether-benflumetol is effective and very well tolerated in the treatment of multidrug-resistant falciparum malaria . A higher dose than that used in the present study may improve efficacy BACKGROUND Malaria control is difficult where there is intense year-round transmission of multiple plasmodium species , such as in Papua New Guinea . METHODS Between April 2005 and July 2007 , we conducted an open-label , r and omized , parallel-group study of conventional chloroquine-sulfadoxine-pyrimethamine and artesunate-sulfadoxine-pyrimethamine , dihydroartemisinin-piperaquine , and artemether-lumefantrine in children in Papua New Guinea 0.5 to 5 years of age who had falciparum or vivax malaria . The primary end point was the rate of adequate clinical and parasitologic response at day 42 after the start of treatment with regard to Plasmodium falciparum , after correction for reinfections identified through polymerase-chain-reaction ( PCR ) genotyping of polymorphic loci in parasite DNA . Secondary end points included the rate of adequate clinical and parasitologic response at day 42 with regard to P. vivax without correction through PCR genotyping . RESULTS Of 2802 febrile children screened , 482 with falciparum malaria and 195 with vivax malaria were included . The highest rate of adequate clinical and parasitologic response for P. falciparum was in the artemether-lumefantrine group ( 95.2 % ) , as compared with 81.5 % in the chloroquine-sulfadoxine-pyrimethamine group ( P=0.003 ) , 85.4 % in the artesunate-sulfadoxine-pyrimethamine group ( P=0.02 ) , and 88.0 % in the dihydroartemisinin-piperaquine group ( P=0.06 ) . The rate of adequate clinical and parasitologic response for P. vivax in the dihydroartemisinin-piperaquine group ( 69.4 % ) was more than twice that in each of the other three treatment groups . The in vitro chloroquine and piperaquine levels that inhibited growth of local P. falciparum isolates by 50 % correlated significantly ( P<0.001 ) . Rash occurred more often with artesunate-sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine than with chloroquine-sulfadoxine-pyrimethamine ( P=0.004 for both comparisons ) . CONCLUSIONS The most effective regimens were artemether-lumefantrine against P. falciparum and dihydroartemisinin-piperaquine against P. vivax . The relatively high rate of treatment failure with dihydroartemisinin-piperaquine against P. falciparum may reflect cross-resistance between chloroquine and piperaquine . ( Australian New Zeal and Clinical Trials Registry number , ACTRN12605000550606 . BACKGROUND We assessed the efficacy , effectiveness and safety of artemether-lumefantrine , which is the most widely used artemisinin-based combination therapy in Africa , against Plasmodium falciparum malaria during an extended follow-up period after initial and repeated treatment . METHODS We performed an open-label r and omized trial of artemether-lumefantrine with supervised ( n=180 ) and unsupervised intake ( n=179 ) in children < 5 years of age with uncomplicated falciparum malaria in rural Tanzania . Recurrent infections between day 14 and day 56 were retreated within the same study arm . Main end points were polymerase chain reaction (PCR)-corrected cure rates by day 56 and day 42 after initial and repeated treatment , respectively , as estimated by survival analysis . RESULTS The PCR-corrected cure rate after initial treatment was 98.1 % ( 95 % confidence interval [ CI ] , 94.2%-99.4 % ) after supervised and 95.1 % ( 95 % CI , 90.7%-98.1 % ) after unsupervised intake ( P=.29 ) . After retreatment of recurrent infections , the cure rates were 92.9 % ( 95 % CI , 81.8%-97.3 % ) and 97.6 % ( 95 % CI , 89.3%-98.8 % ) , respectively ( P=.58 ) . Reinfections occurred in 46.9 % ( 82 of 175 ) versus 50.9 % of the patients ( relative risk [ RR ] , 0.92 [ 95 % CI , 0.74 - 1.14 ] ; P=.46 ) after initial therapy and 32.4 % ( 24 of 74 ) versus 39.0 % ( 32 of 82 ) ( RR , 0.83 [ 95 % CI , 0.54 - 1.27 ] ; P=.39 ) after retreatment . Median blood lumefantrine concentrations in supervised and unsupervised patients on day 7 were 304 versus 194 ng/mL ( P<.001 ) after initial treatment and 253 versus 164 ng/mL ( P=.001 ) after retreatment . Vomiting was the most commonly reported drug-related adverse event ( in 1 % of patients ) after both initial and repeated treatment . CONCLUSIONS Artemether-lumefantrine was highly efficacious even after unsupervised administration , despite significantly lower lumefantrine concentrations , compared with concentration achieved with supervised intake , and was well-tolerated and safe after initial and repeated treatment . CLINICAL TRIAL REGISTRATION IS RCT N69189899 OBJECTIVE To determine the efficacy of artemether-lumefantrine malaria treatment , as an alternative to artesunate + mefloquine , which is becoming ineffective in some areas of the Thai-Cambodian border . METHODS Two studies were conducted to monitor the efficacy of artemether-lumefantrine in Sampov Lun referral hospital , Battambang Province , in 2002 and 2003 , and one study was conducted to assess the efficacy of mefloquine + artesunate in 2003 for comparison . The studies were performed according to the WHO st and ardized protocol with a follow-up of 28 days . The therapeutic efficacy tests were complemented with in vitro tests and in 2003 , with the measurement of lumefantrine plasma concentration at day 7 for the patients treated with artemether-lumefantrine . RESULTS A total of 190 patients were included : 55 were treated with artemether-lumefantrine in 2002 ( AL2002 ) , 80 with artemether-lumefantrine and food supplementation in 2003 ( AL2003 ) and 55 with artesunate + mefloquine in 2003 ( AM2003 ) . With the per- protocol analysis , the cure rate was 71.1 % in study AL2002 , 86.5 % in study AL2003 and 92.4 % in study AM2003 . All the data were PCR corrected . The artemether-lumefantrine cure rate was unexpectedly low in 2002 , but it increased with food supplementation in 2003 . There was a significant difference ( P = 0.02 ) in lumefantrine plasma concentrations between adequate clinical and parasitological responses and treatment failure cases . In vitro susceptibility to lumefantrine was reduced for isolates sample d from patients presenting with treatment failure , but the difference was not statistically different from isolates sample d from patients who were successfully treated . CONCLUSION Treatment failure cases of artemether-lumefantrine are most probably because of low levels of lumefantrine blood concentration . Further investigations are necessary to determine whether resistance of Plasmodium falciparum isolates to lumefantrine is present in the region The new oral fixed combination artemether-lumefantrine ( CGP 56697 ) has proved to be an effective and well-tolerated treatment of multi-drug resistant Plasmodium falciparum malaria , although cure rates using the four-dose regimen have been lower than with the currently recommended alternative of artesunate-mefloquine . Two six-dose schedules ( total adult dose = 480 mg of artemether and 2,880 mg of lumefantrine ) were therefore compared with the previously used four-dose regimen ( 320 mg of artemether and 1,920 mg of lumefantrine ) in a double-blind trial involving 359 patients with uncomplicated multidrug-resistant falciparum malaria . There were no differences between the three treatment groups in parasite and fever clearance times , and reported adverse effects . The two six-dose regimens gave adjusted 28-day cure rates of 96.9 % and 99.12 % , respectively , compared with 83.3 % for the four-dose regimen ( P < 0.001 ) . These six-dose regimens of artemether-lumefantrine provide a highly effective and very well-tolerated treatment for multidrug-resistant falciparum malaria Background : The antiretroviral drug efavirenz ( EFV ) and the antimalarial artemisinin-based combination therapy artemether – lumefantrine ( AL ) are commonly co-administered to treat HIV and malaria . EFV is a known inducer of cytochrome P450 3A4 , which converts artemether to dihydroartemisinin ( DHA ) that is also active and metabolizes longer acting lumefantrine ( LR ) . A study in healthy volunteers was completed to address the concern that EFV impacts AL pharmacokinetics ( PKs ) . Methods : Adults received AL ( 80/480 mg twice daily ) for 3-days before and during EFV co-administration ( 600 mg daily for 26 days ) with intensive PK for artemether , DHA , and LR conducted after the last AL dose for each period . EFV PK was evaluated with and without AL . PK parameters were estimated using noncompartmental methods . Results : Twelve subjects completed the 2-period study . PK exposure for artemether , DHA , and LR [ as estimated by the area under the concentration time curve ( AUClast ) ] decreased or trended toward decrease with EFV , compared with when administered alone [ −51 % ( P = 0.084 ) , −46 % ( P = 0.005 ) , and −21 % ( P = 0.102 ) , respectively ] . Day-7 LR levels , previously deemed predictive of treatment success , were 46 % lower ( P = 0.002 ) with EFV , but the LR half-life was unchanged . EFV PK exposure was minimally altered after AL co-administration [ AUC0–24 hrs decreased by 17 % ( P = 0.034 ) ] . Conclusions : Exposure to DHA , but not LR , was significantly lower during EFV-AL co-administration compared with that during administration of AL alone . These findings may have implication s for the treatment efficacy of AL , particularly in children . However , the observed modest changes probably do not warrant dosage adjustment during co-administration of AL with EFV BACKGROUND The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa . However , its effectiveness has not been assessed in the field , and could be compromised by poor adherence , incorrect timing of doses , and insufficient intake of fatty foods with every dose . Our aim , therefore , was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions , compared with its efficacy when given under supervision to in patients with acute uncomplicated falciparum malaria . METHODS We did a r and omised trial to compare the efficacy , safety , and pharmacokinetics of artemether-lumefantrine when given in a supervised ( all doses observed with fatty-food intake ; n=313 ) or unsupervised ( first dose supervised followed by outpatient treatment with nutritional advice ; n=644 ) setting to patients of all ages ( weight > 10 kg ) with acute , uncomplicated falciparum malaria in Mbarara , Ug and a. Our primary endpoint was 28 day , PCR-adjusted , parasitological cure rate . Analysis was by intention to treat and evaluability analysis . FINDINGS 38 patients were lost to follow-up and one withdrew consent . Day-28 cure rates were 97.7 % ( 296 of 303 ) and 98.0 % ( 603 of 615 ) in the supervised and unsupervised groups , respectively . We recorded 15 non-severe , drug-related adverse events , all of which resolved . INTERPRETATION Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice . If used as first-line treatment , artemether-lumefantrine could make a substantial contribution to malaria control in Africa , though cost is an issue ABSTRACT The pharmacokinetic and pharmacodynamic properties of a new pediatric formulation of artemether-lumefantrine , dispersible tablet , were determined within the context of a multicenter , r and omized , parallel-group study . In an exploratory approach , we compared a new pediatric formulation with the tablet formulation administered crushed in the treatment of African children with uncomplicated Plasmodium falciparum malaria . Patients were r and omized to 3 different dosing groups ( weights of 5 to < 15 kg , 15 and < 25 kg , and 25 to < 35 kg ) . Treatment was administered twice daily over 3 days . Plasma concentrations of artemether and its active metabolite , dihydroartemisinin ( DHA ) , were determined at 1 and 2 h after the first dose of dispersible ( n = 91 ) and crushed ( n = 93 ) tablets . A full pharmacokinetic profile of lumefantrine was reconstituted on the basis of 310 ( dispersible tablet ) and 315 ( crushed tablet ) plasma sample s , collected at 6 different time points ( 1 sample per patient ) . Dispersible and crushed tablets showed similar artemether and DHA maximum concentrations in plasma ( Cmax ) for the different body weight groups , with overall means of 175 ± 168 and 190 ± 168 ng/ml , respectively , for artemether and 64.7 ± 58.1 and 63.7 ± 65.0 ng/ml , respectively , for DHA . For lumefantrine , the population Cmax were 6.3 μg/ml ( dispersible tablet ) and 7.7 μg/ml ( crushed tablet ) , whereas the areas under the concentration-time curves from time zero to the time of the last quantifiable plasma concentration measured were 574 and 636 μg · h/ml , respectively . For both formulations , descriptive quintile analyses showed no apparent association between artemether/DHA Cmax and parasite clearance time or between the lumefantrine Cmax and the occurrence of adverse events or corrected QT interval changes . The results suggest that the dispersible tablet provides adequate systemic exposure to artemether , DHA , and lumefantrine in African children with uncomplicated P. falciparum malaria BACKGROUND Recent clinical trials in the Lao People 's Democratic Republic have demonstrated that chloroquine and sulfadoxine-pyrimethamine , which are national malaria treatment policy , are no longer effective in the treatment of uncomplicated Plasmodium falciparum malaria . METHODS A r and omized comparison of 3 oral antimalarial combinations -- chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine -- with 42-day follow-up period , was conducted among 330 patients with acute uncomplicated falciparum malaria in southern Laos . RESULTS The 42-day cure rates , as determined by intention-to-treat analysis and adjusted for reinfection , were 100 % , 97 % , and 93 % for the groups receiving artesunate plus mefloquine , artemether-lumefantrine , and chloroquine plus sulfadoxine-pyrimethamine , respectively . Of 8 patients receiving chloroquine plus sulfadoxine-pyrimethamine who experienced treatment failure , 6 had early treatment failure . The mean parasite clearance time was significantly longer in patients treated with chloroquine plus sulfadoxine-pyrimethamine ( 2.9 days ; 95 % confidence interval [ CI ] , 2.8 - 3.0 days ) than in those treated with artesunate plus mefloquine ( 2.07 days ; 95 % CI , 2.0 - 2.1 days ; P<.001 ) and artemether-lumefantrine ( 2.08 days ; 95 % CI , 2.0 - 2.1 days ; P<.001 ) . Cure rates with artemether-lumefantrine were high despite low mean daily dietary fat intake ( 13.8 g ; 95 % CI , 12.5 - 15.1 g ) and day 7 plasma lumefantrine concentrations ( 0.47 mu g/mL ; 95 % CI , 0.38 - 0.56 mu g/mL ) . CONCLUSION Oral artesunate plus mefloquine and artemether-lumefantrine are highly effective for the treatment of uncomplicated falciparum malaria in Laos The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune population s are not well defined . In this study , 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute , uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine . The parasitologic cure rate at 28 days was 96.0 % for the per protocol population ( 119/124 patients ) . Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours , respectively . No patient had gametocytes after Day 7 . Treatment was well tolerated ; most adverse events were mild to moderate and seemed to be related to malaria . There were few serious adverse events , none of which were considered to be drug-related . No significant effects on ECG or laboratory parameters were observed . In conclusion , the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum malaria in nonimmune patients In r and omized clinical trials , subjects are recruited at multiple study centres . Factors that vary across centres may exert a powerful independent influence on study outcomes . A common problem is how to incorporate these centre effects into the analysis of censored time-to-event data . We survey various methods and find substantial advantages in the gamma frailty model . This approach compares favourably with competing methods and appears minimally affected by violation of the assumption of a gamma-distributed frailty . Recent computational advances make use of the gamma frailty model a practical and appealing tool for addressing centre effects in the analysis of multicentre trials The pharmacokinetics of benflumetol as a fixed combination , artemether-benflumetol ( CGP 56697 ) , following three regimens [ regimen A : four tablets at 0 , 8 , 24 and 48 h ( 320 mg artemether , 1,920 mg benflumetol ) ; regimen B : two tablets at 0 , 8 , 24 and 48 h ( 160 mg artemether , 960 mg benflumetol ) ; regimen C : four tablets at 0 , 8 and 24 h ( 240 mg artemether , 1,440 mg benflumetol ) ] were investigated in 39 patients with acute uncomplicated falciparum malaria . All patients showed a rapid initial response with a median parasite clearance time of 40 , 41 and 39.5 h and a fever clearance time of 27.8 , 32 and 24.5 h for regimens A , B and C , respectively . In nine patients ( two , four and three patients in regimens A , B and C , respectively ) , however , parasitemia reappeared in the peripheral blood smear between days 9 and 23 . The pharmacokinetics of benflumetol were highly variable , with coefficients of variation in pharmacokinetic parameters ranging from 14.9 % to 144 % . Absorption and elimination of benflumetol were relatively slow . Median Cmax per dose ( first dose ) was significantly higher in regimen B ( 6.29 ng/ml/mg dose ) than in regimen A ( 2.6 ng/ml/mg dose ) and regimen C ( 3.06 ng/ml/mg dose ) . Mean T1/2z in regimen C ( 2.65 h ) was significantly shorter than in regimen A ( 4.5 h ) and regimen B ( 3.89 h ) . In patients on regimens A and B who showed a sensitive response , plasma concentrations of benflumetol were significantly higher than in those with treatment failure ABSTRACT Artemether-lumefantrine has become one of the most widely used antimalarial drugs in the world . The objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multidrug-resistant Plasmodium falciparum malaria on the northwestern border of Thail and . Burmese and Karen women ( n = 103 ) with P. falciparum malaria and in the second and third trimesters of pregnancy were treated with artemether-lumefantrine ( 80/480 mg ) twice daily for 3 days . All patients provided five capillary plasma sample s for drug quantification , and the collection times were r and omly distributed over 14 days . The concentration-time profiles of lumefantrine were assessed by nonlinear mixed-effects modeling . The treatment failure rate ( PCR-confirmed recrudescent infections at delivery ) was high ; 16.5 % ( 95 % confidence interval , 9.9 to 25.1 ) . The population pharmacokinetics of lumefantrine were described well by a two-compartment open model with first-order absorption and elimination . The final model included interindividual variability in all pharmacokinetic parameters and a linear covariate relationship between the estimated gestational age and the central volume of distribution . A high proportion of all women ( 40 % , 41/103 ) had day 7 capillary plasma concentrations of < 355 ng/ml ( which corresponds to approximately < 280 ng/ml in venous plasma ) , a threshold previously associated with an increased risk of therapeutic failure in nonpregnant patients in this area . Predictive modeling suggests that a twice-daily regimen given for 5 days would be preferable in later pregnancy . In conclusion , altered pharmacokinetic properties of lumefantrine contribute to the high rates of failure of artemether-lumefantrine treatment in later pregnancy . Dose optimization is urgently needed AIMS To investigate the pharmacokinetic and pharmacodynamic properties of artemether and benflumetol in a fixed combination tablet ( CGP 56697 ) and to offer an explanation for the lower than expected cure rate in a Thai clinical trial . METHODS Two hundred and sixty patients were enrolled into a r and omized , double-blind , parallel group , dose-finding trial . CGP 56697 was given orally , either as : A , 4 x 4 tablets over 48 h ; B , 4 x 2 tablets over 48 h or C , 3 x 4 tablets over 24 h. Each tablet contained artemether 20 mg amd benflumetol 120 mg . The pharmacokinetics were determined using a population -based approach combining full profiles ( 42 patients ) and sparse data ( 218 patients ) . Parasite clearance time and 28 day cure rate were correlated with the derived pharmacokinetic parameters . RESULTS The median absorption half-life of benflumetol was 5.3 h , with a tmax of 10 h and terminal elimination half-life of 4.5 days . For artemether ( and its metabolite , dihydroartemisinin ) , the corresponding values were 1.9 ( 1.9 ) h , 1.8 ( 1.2 ) h , and 0.84 ( 0.43 ) h. The variability in bioavailability of artemether and dihydroartemisinin was large both between doses and between patients , but was less pronounced for benflumetol . Compared with the first dose , benflumetol bioavailability was estimated to increase three-fold by the third and fourth doses . Higher artemether or dihydroartemisinin AUC was found to decrease parasite clearance time . Higher benflumetol AUC was found to significantly increase the chance of cure . CONCLUSIONS Using a population -based approach it was confirmed that the pharmacokinetic and pharmacodynamic properties of benflumetol and artemether differ markedly . Benflumetol AUC is associated with cure and the effect of benflumetol when coadministered with artemether is to prevent recrudescence . The mode of action of benflumetol is consistent with its longer elimination half-life . A short course of low-dose artemether , which is rapidly absorbed and has a short elimination half-life , produced effective parasite clearance . The complementary pharmacokinetic and pharmacodynamic properties of benflumetol and artemether was the main rationale for developing a fixed-dose combination . While the 4 x 4 dose regimen is very effective in most endemic areas , the poorer absorption ( 2.5 fold lower than in China ) and the more resistant parasites in Thail and require higher doses of this drug BACKGROUND In 2008 , Guinea-Bissau introduced artemether-lumefantrine for treatment of uncomplicated malaria . Previously , 3 times the st and ard dose of chloroquine , that was probably efficacious against Plasmodium falciparum with the resistance-associated chloroquine-resistance transporter ( pfcrt ) 76 T allele , was routinely used . The present study compared the efficacy and tolerability of a double st and ard dose of chloroquine with the efficacy and tolerability of artemether-lumefantrine . METHODS In a r and omized open-label clinical trial , artemether-lumefantrine or chloroquine ( 50 mg/kg ) were given as 6 divided doses over 3 days to children aged 6 months--15 years who had uncomplicated P. falciparum monoinfection . Drug concentrations were measured on day 7 . P. falciparum multidrug resistance gene N86Y and pfcrt K76 T alleles were identified . RESULTS The polymerase chain reaction-adjusted day 28 and 42 treatment efficacies were 162 ( 97 % ) of 168 and 155 ( 97 % ) of 161 , respectively , for artemether-lumefantrine and 150 ( 95 % ) of 158 and 138 ( 94 % ) of 148 , respectively , for chloroquine . When parasites with resistance-associated pfcrt 76 T were treated , the day 28 efficacy of chloroquine was 87 % . No severe drug-related adverse events were detected . Symptom resolution was similar with both treatments . CONCLUSIONS Both treatments achieved the World Health Organization-recommended efficacy for antimalarials that will be adopted as policy . High-dose chloroquine treatment regimes should be further evaluated with the aim of assessing chloroquine as a potential partner drug to artemisinin derivatives . Clinical trials registration . NCT00426439 Forty-two healthy subjects were r and omized in a parallel three-group design trial to investigate potential electrocardiographic and pharmacokinetic interactions between the new antimalarial co-artemether , a combination of artemether and lumefantrine ( both of which are predominantly metabolized through CYP3A4 ) , and mefloquine , another antimalarial described as a substrate ( and possible inhibitor ) of CYP3A4 . Subjects were assigned to one of the three possible treatment groups ( i.e. , co-artemether alone or mefloquine alone or the combination of both ) . The dosage was 1000 mg mefloquine ( divided into three doses over 12 h ) followed 12 h later by six applications of co-artemether ( 40 mg artemether+480 mg lumefantrine each ) over 60 h. The study medications were generally well tolerated after all treatments . Concomitant administration with mefloquine caused statistically significant lower ( around 30 - 40 % ) plasma concentrations of lumefantrine than when co-artemether was administered alone . Even if important , this decrease in lumefantrine exposure was considered unlikely to impact clinical efficacy given the wide therapeutic index of co-artemether and the usual high variability in lumefantrine plasma levels , mostly and more importantly influenced by food intake . However , patients should be encouraged to eat at dosing times to compensate for this decreased bioavailability . The pharmacokinetics of artemether , DHA or mefloquine were not affected . Artemether concentrations significantly decreased over doses , independently of mefloquine co-administration , while DHA concentrations slightly ( not significantly ) increased . Therefore , no clinical ly relevant risks due to pharmacokinetic drug-drug interaction are expected at the enzymatic level following co-administration of co-artemether with CYP3A4 substrates with similar affinity to that of mefloquine The efficacy of the six-dose regimen of artemether-lumefantrine was compared with the combination of artesunate and mefloquine in a r and omised , comparative trial in Luang Namtha Province , Northern Laos . Of 1033 screened patients , 201 were positive for Plasmodium falciparum ; 108 patients of all age groups ( 2 - 66 years ) with acute , uncomplicated P. falciparum malaria were enrolled in the study , 100 of whom were followed-up for 42 days . Fifty-three patients received artemether-lumefantrine and 55 received artesunante-mefloquine . Both drug combinations induced rapid clearance of parasites and malaria symptoms ; there was no significant difference in the initial therapeutic response parameters . Both regimes were well tolerated . After 42 days , cure rates were 93.6 % ( 95 % CI = 82.5 - 98.7 % ; 44 of 47 patients ) for artemether-lumefantrine and 100 % ( 95 % CI = 93.3 - 100.0 % ; 53 of 53 patients ) for artesunate-mefloquine . The results show the excellent efficacy and tolerability of both artemether-lumefantrine and artesunate-mefloquine in Northern Laos ABSTRACT Artemether-lumefantrine ( AL ) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy . Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic ( PK ) properties in this vulnerable group . The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome . Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL ( 80/480 mg ) twice daily for 3 days . All patients provided five venous plasma sample s for drug quantification at r and om times over 7 days . Inter- and intraindividual variability was assessed , and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach ( NONMEM ) . A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether ( AM ) and lumefantrine ( LF ) and their metabolites . Pregnancy status and diarrhea showed a significant influence on LF PK . The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were , respectively , 34 % lower and 78 % higher in pregnant women than in nonpregnant patients . The overall PCR-uncorrected treatment failure rates were 18 % in pregnant women and 5 % in nonpregnant women ( odds ratio [ OR ] = 4.04 ; P value of 0.22 ) . A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response ( P = 0.03 ) . The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group , mostly due to lower posttreatment prophylaxis . Hence , a modified treatment regimen of malaria in pregnancy should be considered |
10,860 | 29,174,966 | CONCLUSIONS PTX-3 significantly predicts disease severity and mortality in sepsis | OBJECTIVES Pentraxin-3 ( PTX-3 ) is a multi-functional pattern recognition molecule produced by various cell types of peripheral tissues in different infections .
It is raised in sepsis , but its values in predicting disease severity or mortality outcomes have been controversial .
Therefore , we conducted a systematic review and meta- analysis of these associations . | The long pentraxin-3 ( PTX3 ) is a key component of the humoral arm of the innate immune system . PTX3 is produced locally in response to pro-inflammatory stimuli . To investigate PTX3 levels and its use as a biomarker in patients with systemic inflammation , we developed a solid-phase enzyme-linked immunosorbent assay based on novel anti-PTX3 monoclonal antibodies detecting PTX3 with high sensitivity . The assay was applied on 261 consecutive patients admitted to an intensive care unit prospect ively monitored with the systemic inflammatory response syndrome ( SIRS ) . 100 blood donors were included as controls . PTX3 levels were elevated in patients ( median = 71.3 ng/ml ) compared with the controls ( median = 0 ng/ml ) ( Mann-Whitney , p<0.0001 ) . ROC analysis showed that PTX3 levels were significantly specific ( 85.0 % ) and sensitive ( 89.1 % ) to discriminate between healthy controls and patients ( area under the curve ( AUC ) 0.922 ( 95 % CI 0.892 to 0.946 , p<0.0001 ) ) . Higher levels of PTX3 were associated with the development of sepsis , severe sepsis and septic shock ( p = 0.0001 ) . The serum levels of PTX3 correlated significantly with SAPS2 score ( Spearman 's rho 0.28 , p<0.0001 ) . Patients with high levels of PTX3 at admission did have a higher 90 day mortality rate than patients with the 25 % lowest levels ( Cox regression analysis , hazard ratio 3.0 , p = 0.0009 ) . In conclusion , we have established a highly sensitive and robust assay for measurement of PTX3 and found that its serum concentrations correlated with disease severity and mortality in patients with SIRS and sepsis Background New biomarkers are needed to assess the severity of necrotizing soft tissue infection ( NSTI ) at an early stage and to individualize treatment strategies . We assessed pentraxin-3 ( PTX3 ) as a marker of disease severity and risk of death in patients with NSTI . Methods We conducted a prospect i ve , observational study in the intensive care unit at Copenhagen University Hospital , where treatment of NSTI is central ized at a national level . We compared PTX3 , procalcitonin and C-reactive protein in septic shock versus nonshock patients and in amputated versus nonamputated patients using the Mann-Whitney U test . The prognostic value of the markers for 180-day mortality was assessed using Cox regression analyses . Results Patients with NSTI ( n = 135 ) were included over 25 months with up to 2.5-year follow-up ; 71 % had septic shock , amputation was undertaken in 20 % and the 180-day mortality was 27 % . Baseline plasma PTX3 level was significantly higher in patients with septic shock ( 67.3 versus 24.6 ng/mL , p < 0.0001 ) and in patients who underwent amputation ( 118.6 versus 43.6 ng/mL , p = 0.019 ) . No significant differences in baseline procalcitonin or C-reactive protein levels were found according to amputation ( 25.2 versus 7.0 μg/L , p = 0.060 and 202 versus 225 mg/L , p = 0.123 ) , respectively . Baseline PTX3 level above the median was associated with death ( p = 0.009 , log-rank test ) and the univariate Cox regression analysis revealed a significant association between PTX3 level upon admission and 180-day mortality ( hazard ratio 2.60 ( 95 % confidence interval 1.28–5.29 ) , p = 0.008 ) . When adjusted for age , sex , chronic disease and Simplified Acute Physiology Score II , no significant association was found . Conclusions High PTX3 level is associated with septic shock , amputation and risk of death in patients with NSTI , but it is not an independent predictor of 180-day mortality in this patient group . Trial registration Clinical Trials.gov Identifier : NCT02180906 . Date of registration : June 29 , 2014 Purpose Pentraxin 3 ( PTX3 ) is an inflammatory mediator produced by neutrophils , macrophages , myeloid dendritic and endothelial cells . During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur . PTX3 , as a mediator of inflammation , may represent an early marker of severity and outcome in sepsis . Methods This study is based on a prospect i ve trial regarding the impact of glycemic control on coagulation in sepsis . Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed . At enrollment , we recorded sepsis signs , disease severity , coagulation activation [ prothrombin fragments 1 + 2 ( F1 + 2 ) ] and fibrinolysis inhibition [ plasminogen activator inhibitor-1 ( PAI-1 ) ] . We measured plasma PTX3 levels at enrollment , everyday until day 7 , then at days 9 , 11 , 13 , 18 , 23 and 28 . Mortality was recorded at day 90 . Results Although not different on day 1 , PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days ( p = 0.002 by general linear model ) . On day 1 , PTX3 levels were higher in septic shock than in severely septic patients ( p = 0.029 ) . Day 1 PTX3 was significantly correlated with platelet count ( p < 0.001 ) , SAPS II score ( p = 0.006 ) and SOFA score ( p < 0.001 ) . Day 1 PTX3 was correlated with F1 + 2 concentration and with PAI-1 activity and concentration ( p < 0.05 for all ) . Conclusions Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality . PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction Abstract Objectives : To determine the diagnostic values of plasma C-reactive protein ( CRP ) , procalcitonin ( PCT ) , and interleukin-6 ( IL-6 ) using an electrochemiluminescence immunoassay ( ECLIA ) method ( Roche Diagnostics GmbH , Mannheim , Germany ) to identify severe sepsis in an emergency room ( ER ) setting . Methods : This was a single-centre prospect i ve follow-up study of 539 consecutive adult patients admitted to the ER with suspected infection . Blood sample s were taken concurrently with blood cultures at admission . Patients were divided into 5 groups on the basis of systemic inflammatory response syndrome ( SIRS ) criteria , documentation of bacterial infection , and organ dysfunction . Fifty-nine patients with no SIRS or bacterial infection , 68 patients with bacterial infection but no SIRS , 54 patients with SIRS but no bacterial infection , 309 patients with sepsis ( SIRS and bacterial infection ) , and 49 patients with severe sepsis ( sepsis and organ failure ) were evaluated . Results : In a logistic regression model , the odds ratio ( OR ) for PCT was 1.58 ( 95 % confidence interval ( CI ) 1.37–1.82 , p < 0.0001 ) , for IL-6 was 1.54 ( 95 % CI 1.32–1.80 , p < 0.0001 ) , and for CRP was 1.33 ( 95 % CI 1.01–1.75 , p = 0.045 ) . The area under the curve ( AUC ) was 0.77 ( 95 % CI 0.71–0.84 ) for PCT , 0.72 ( 95 % CI 0.64–0.80 ) for IL-6 , and 0.60 ( 95 % CI 0.51–0.69 ) for CRP . PCT emerged as the best marker for severe sepsis , but the difference in AUC was not significant between PCT and IL-6 . In multivariate logistic regression analysis , after adjusting for confounders , PCT and IL-6 remained significant independent predictors of severe sepsis . Conclusions : PCT and IL-6 proved superior to CRP in detecting patients with severe sepsis . The findings thus support the use of either PCT or IL-6 as an early tool to diagnose severe sepsis . The automatic ECLIA method allows even night-shift measurements Background : Useful biomarkers that can serve as prognostic predictors are of great value in clinical practice because of the complex individual response to sepsis . Pentraxin 3 ( PTX3 ) , as a multifunctional pattern‐recognition molecule , has been reported to be closely associated with the severity of infectious diseases in intensive care units ( ICU ) . The aim of this study was to investigate whether PTX3 could serve as a potential prognostic biomarker in patients with septic shock . Material s and Methods : This single‐center prospect i ve observational study was conducted during May 2012‐May 2015 in the ICU of Taizhou People 's Hospital . We compared the clinical data and laboratory tests in surviving and deceased patients with septic shock within 28 days from admission . Potential independent prognostic factors for septic shock were analyzed by using univariate and multiple Cox proportional hazards regression analyses . Results : A total of 112 patients admitted to the ICU with septic shock were enrolled in our study with an overall 28‐day mortality of 25.9 % ( 29 of 112 patients ) . PTX3 level was the only independent risk factor for the 28‐day mortality by univariate and multivariate Cox analysis ( hazard ratio = 3.87 ; 95 % CI : 1.66‐8.81 , P = 0.004 ) . The deceased patients had significant higher levels of PTX3 at the 4 different points ( baseline , day 1 , day 2 and day 3 ) versus the survivors ( P < 0.001 ) . Results from Kaplan‐Meier curves and log‐rank test revealed that high PTX3 level ( above the median value ) was statistically associated with a lower 28‐day survival rate ( P = 0.014 ) . Conclusions : The baseline PTX3 level was an independent predictor for 28‐day mortality in patients with septic shock OBJECTIVES The aim was to assess the diagnostic and prognostic value of measuring pentraxin 3 ( PTX3 ) together with C-reactive protein ( CRP ) in patients with ventilator-associated pneumonia ( VAP ) . BACKGROUND The PTX3 values increase rapidly during multiple inflammatory conditions , but little is known about its characteristics in VAP . METHODS Measurement of PTX3 and CRP levels in plasma from 136 consecutive patients receiving mechanical ventilation > 48 h in a prospect i ve single center study . RESULTS A PTX3 threshold of > 16.43 ng/ml provided a specificity of 74.0 % and a sensitivity of 68.6 % for the diagnosis of VAP . PTX3 correlated with severity of sepsis and peaked earlier than CRP in patients with confirmed VAP . Multivariate Cox regression analysis showed PTX3 was the independent predictor for mortality of VAP . CONCLUSIONS PTX3 was not superior to CRP as a biomarker to diagnose VAP , but it was an early indicator of inflammation and had better prognostic value to predict mortality than CRP OBJECTIVE To estimate the diagnostic value of serum PCT , CRP , leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients . DESIGN AND SETTING Prospect i ve , observational study in a four bed Burn Intensive Care Unit . PATIENTS Forty-three patients admitted in a Burn ICU were included in our study . MEASUREMENTS AND RESULTS Serum PCT , CRP concentrations , WCC ( white cell count ) , neutrophils and temperature were measured within the first 24h after-burn and daily thereafter . Severity of organ failure was estimated by sequential organ failure assessment ( SOFA ) score . Every day we classified all patients in one of the following three categories : non-systemic inflammatory condition ( non-SIRS ) , SIRS non-infected and SIRS 2 infected or sepsis . Patients with infected SIRS differ significantly from non-infected SIRS in PCT ( 11.8+/-15.8 versus 0.63+/-0.0.43 , respectively , p < 0.001 ) . On the other h and , WCC , temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS . CRP was elevated in all three groups but did n't differ significantly between SIRS non-infected and septic patients . Area under receiver operating curves was 0.975 and showed reasonable discriminative power ( p = 0.002 , 95 % CI , 0.91 - 1.035 ) in predicting of sepsis only for PCT . CONCLUSIONS Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury BACKGROUND The long pentraxin PTX3 is a key component of the humoral arm of innate immunity related to sepsis severity and mortality . We evaluated the clinical and prognostic significance of circulating PTX3 in the largest cohort ever reported of patients with severe sepsis or septic shock . MATERIAL S AND METHODS Plasma PTX3 was measured on days 1 , 2 and 7 after r and omization of 958 patients to albumin or crystalloids for fluid resuscitation in the multicentre Albumin Italian Outcome Sepsis ( ALBIOS ) trial . We tested the association of PTX3 and its changes over time with clinical severity , prevalent and incident organ dysfunctions , 90-day mortality and treatment . RESULTS PTX3 was high at baseline ( 72 [ 33 - 186 ] ng/mL ) and rose with the severity and number of organ dysfunctions ( P < 0·001 ) and the incidence of subsequent new failures . The PTX3 concentration dropped from day 1 to 7 , but this decrease was less pronounced in patients with septic shock ( P = 0·0004 ) . Higher concentrations of PTX3 on day 1 predicted incident organ dysfunctions . Albumin supplementation was associated with lower levels of PTX3 in patients with septic shock ( P = 0·005 ) but not in those without shock . In a fully adjusted multivariable model , PTX3 on day 7 predicted 90-day mortality . Smaller drops in PTX3 predicted higher 90-day mortality . CONCLUSIONS In severe sepsis and septic shock , early high PTX3 predict subsequent new organ failures , while a smaller drop in circulating PTX3 over time predicts an increased risk of death . Patients with septic shock show lower levels of PTX3 when assigned to albumin than to crystalloids |
10,861 | 25,297,823 | The efficacy of a rehabilitation intervention was assessed using accelerometry by three studies : in two studies both accelerometry and clinical test scores detected a post-treatment difference but in one study accelerometry data did not change despite clinical test scores showing motor and functional improvements . | The aim of this review was to identify and summarise publications , which have reported clinical applications of upper limb accelerometry for stroke within free-living environments and make recommendations for future studies . | The authors examined sources of variance in self-reported physical activity in a cohort of healthy adults ( n = 580 ) from Worcester , Massachusetts ( the Seasonal Variation of Blood Cholesterol Study , 1994 - 1998 ) . Fifteen 24-hour physical activity recalls of total , occupational , and nonoccupational activity ( metabolic equivalent-hours/day ) were obtained over 12 months . R and om effects models were employed to estimate variance components for subject , season , day of the week , and residual error , from which the number of days of assessment required to achieve 80 % reliability was estimated . The largest proportional source of variance in total and nonoccupational activity was within-subject variance ( 50 - 60 % of the total ) . Differences between subjects accounted for 20 - 30 % of the overall variance in total activity , and seasonal and day-of-the-week effects accounted for 6 % and 15 % , respectively . For total activity , 7 - 10 days of assessment in men and 14 - 21 days of assessment in women were required to achieve 80 % reliability . For nonoccupational activity , 21 - 28 days of assessment were required . This study is among the first to have examined the sources of variance in daily physical activity levels in a large population of adults using 24-hour physical activity recall . These findings provide insight for underst and ing the strengths and limitations of short term and long term physical activity assessment s employed in epidemiologic studies Background and Purpose — More than 70 % of individuals who have a stroke experience upper limb deficits that impact daily activities . Increased amount of upper limb therapy has positive effects ; however , practical and inexpensive methods of therapy are needed to deliver this increase in therapy . Methods — This was a multi-site single blind r and omized controlled trial to determine the effectiveness of a 4-week self-administered grade d repetitive upper limb supplementary program ( GRASP ) on arm recovery in stroke . 103 in patients with stroke were r and omized to the experimental group ( GRASP group , n=53 ) or the control group ( education protocol , n=50 ) . The primary outcome measure was the Chedoke Arm and H and Activity Inventory ( CAHAI ) , a measure of upper limb function in activities of daily living . Secondary measures were used to evaluate grip strength and paretic upper limb use outside of therapy time . Intention-to-treat analysis was performed . Group differences were tested using analysis of covariance . Results — At the end of the 4-week intervention ( approximately 7 weeks poststroke ) , the GRASP group showed greater improvement in upper limb function ( CAHAI ) compared to the control group ( mean difference 6.2 ; 95 % CI : 3.4 to 9.0 ; P<0.001 ) . The GRASP group maintained this significant gain at 5 months poststroke . Significant differences were also found in favor of the GRASP protocol for grip strength and paretic upper limb use . No serious adverse effects were experienced . Conclusion — A self-administered homework exercise program provides a cost- , time- , and treatment-effective delivery model for improving upper limb recovery in subacute stroke Objective : To compare the outcome of robot-assisted therapy with dose-matched active control therapy by using accelerometers to study functional recovery in chronic stroke patients . Design : Prospect i ve , r and omized , controlled trial . Setting : Stroke units in three medical centres . Subjects : Twenty patients post stroke for a mean of 22 months . Intervention : Robot-assisted therapy ( n = 10 ) or dose-matched active control therapy ( n = 10 ) . All patients received either of these two therapies for 90–105 minutes each day , 5 days per week , for four weeks . Main measures : Outcome measures included arm activity ratio ( the ratio of mean activity between the impaired and unimpaired arm ) and scores on the Fugl-Meyer Assessment Scale , Functional Independence Measure , Motor Activity Log and ABILH AND question naire . Results : The robot-assisted therapy group significantly increased motor function , hemiplegic arm activity and bilateral arm coordination ( Fugl-Meyer Assessment Scale : 51.20 ± 8.82 , P = 0.002 ; mean arm activity ratio : 0.76 ± 0.10 , P = 0.026 ; ABILH AND question naire : 1.24 ± 0.28 , P = 0.043 ) compared with the dose-matched active control group ( Fugl-Meyer Assessment Scale : 40.90 ± 13.14 ; mean arm movement ratio : 0.69 ± 0.11 ; ABILH AND question naire : 0.95 ± 0.43 ) . Conclusions : Symmetrical and bilateral robotic practice , combined with functional task training , can significantly improve motor function , arm activity , and self-perceived bilateral arm ability in patients late after stroke OBJECTIVE To examine the psychometric properties of an objective method for assessing real-world arm activity in a large sample with subacute stroke . DESIGN Validation study . SETTING Community . PARTICIPANTS Persons 3 to 9 months poststroke ( N=169 ) with mild to moderate motor impairment of their hemiparetic arm enrolled in a multisite , r and omized clinical trial of constraint-induced movement therapy . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants wore an accelerometer on each arm outside the laboratory for 3 days before and after treatment or an equivalent no-treatment period . They also completed the Actual Amount of Use Test ( AAUT ) , which is an observational measure of spontaneous more-impaired arm use , and the Motor Activity Log ( MAL ) , which is an interview assessing more-impaired arm use in daily life . RESULTS Low-pass-filtered accelerometer recordings were reliable ( r range , > .8 ) and stable ( P range , > .48 ) . Their validity was also supported . Correlations calculated across all participants at baseline between the ratio of more-impaired to less-impaired arm accelerometer recordings and AAUT and MAL scores were .60 and .52 , respectively . CONCLUSIONS Accelerometry provides an objective , real-world index of more-impaired arm activity with good psychometric properties Aim : The aim of the present study was the evaluation of actigraphy as a tool to objectify the recovery process after motor paresis due to stroke . Methods : The motor activity of both arms of patients suffering from stroke was actigraphically recorded at four different time points during the course of rehabilitation : 24–36 h , 5–7 days , 3 months , and 6 months after stroke . Results : Motor activity monitored by wrist-worn actigraphs located at the impaired side revealed an increase in activity between the first two time points and the subsequent ones . Additionally , actigraphic recordings showed lower total motor activity at the impaired side as compared to the nonimpaired side . A significant positive correlation was found between the actigraphically recorded motor activity and the results of the Sc and inavian Stroke scale , the Barthel Index , the Rankin Scale Score and with the Motoricity Index during the 1st week , which corresponds to the time when neurological deficits were most pronounced . Conclusion : Our results suggest that actigraphy is a useful tool in the objective evaluation of motor activity after stroke . Moreover , actigraphy covers additional aspects that are not reflected by the usual stroke scales in a clinical situation |
10,862 | 21,223,353 | The remaining studies involved Nd : YAG laser , Er : YAG laser and CO2 laser , and all showed that the three types of lasers were superior to topical desensitising agents , but the superiority was slight .
A systematic review of the literature indicates the likelihood that laser therapy has a slight clinical advantage over topical medicaments in the treatment of dentine hypersensitivity . | The aim of this systematic review was to compare the effectiveness of laser therapy with that of topical desensitising agents in treating dentine hypersensitivity .
A secondary objective was to determine the safety of laser application according to the relevant studies . | INTRODUCTION Various methods and material s are used in the treatment of dentin hypersensitivity . The aim of this r and omized prospect i ve controlled clinical trial was to evaluate and compare the desensitizing effects of the neodymium-doped yttrium aluminium garnet ( Nd : YAG ) laser and fluoride varnish by considering the degree of pre- and posttreatment pain , discomfort , and functional complications . METHODS Twenty patients with clinical ly diagnosed cervical dentin hypersensitive teeth were included and r and omly allocated to either the application of fluoride varnish ( group fluoride ) or Nd : YAG laser ( 100 mJ , 20 Hz ; group Nd : YAG ) . The assessment of pain and discomfort was performed by a visual analog scale after an air blast at baseline , immediately after treatment , and at patient visits on weeks 1 , 2 , 3 , and 4 . RESULTS Laser treatment result ed in significant improvements of discomfort immediately after treatment and after 1 week . At the 2- , 3- , and 4-week examination , the discomfort in group fluoride decreased up to nearly 75 % to 85 % of baseline scores , whereas the effect of the laser stayed nearly unchanged . The visual analog scale scores for pain at 4 weeks examination were significantly lower in the fluoride group compared with those in the laser group ( p < 0.05 ) . CONCLUSIONS Nd : YAG laser is a suitable tool for the immediately successful reduction of dentinal hypersensitivity and has better patient satisfaction and shorter treatment time Sixty adult patients were examined for dentin hypersensitivity prior to periodontal surgery . Stimuli used included mechanical , cold water and compressed air blasts . A subjective assessment of the degree of hypersensitivity for each stimulus was recorded . This presurgical examination revealed 249 hypersensitive areas among 60 subjects . Following surgery there was over a 100 % increase in the pain ( hypersensitivity ) score . Desensitization with a 10 % strontium chloride hexahydrate dentifrice was begun 1 week after surgical treatment . After 7 weeks of dentifrice use the pain score was reduced 75.5 % in the test group . This was a reduction to a point below the preoperative level . The placebo group showed a reduction of 34.2 % which was still above the preoperative level . These results agree with other clinical studies that have demonstrated a desensitizing effect of strontium chloride OBJECTIVE The aim of the present study was to evaluate and compare the efficacy of CO(2 ) and Er : YAG lasers alone and in combination with topical sodium fluoride ( NaF ) in the management of dentine hypersensitivity . MATERIAL S AND METHODS A group of 50 patients presenting with a total of 420 hypersensitive teeth were r and omly allocated into five groups . Group 1 was treated with 2 % NaF , groups 2 and 3 were lased by a CO(2 ) ( 1 W , continuous wave mode , for 10 sec ) or Er : YAG ( 30 Hz , 60 mJ for 10 sec , without water/air spray ) laser , and groups 4 and 5 received NaF plus the CO(2 ) and the Er : YAG laser , respectively . The scanning speed of the laser was 0.8 mm/sec . The degree of thermal sensitivity was determined with an evaporative stimulus consisting of a 1-sec air blast at a distance of 2 mm from each site tested . Quantification of the degree of discomfort was determined according to a four-point pain scale before treatment and 1 wk , 1 mo , and 6 mo after treatment . RESULTS All treatment forms result ed in significant improvement of discomfort . At 1 wk , 1 mo , and 6 mo , cold air blast scores were significantly reduced compared to baseline scores , except for the NaF group . In the NaF group , there was a statistically significant increase in mean degree of discomfort at 6 mo compared with 1 wk ( p + /- 0.01 ) and 1 mo ( p + /- 0.001 ) . Comparison of the other treatment regimens revealed that cold air blast scores were significantly lower for the other four treatments than for NaF gel alone ( p + /- 0.001 ) . No superiority was found for desensitization among the CO(2 ) , Er : YAG , CO(2 ) + NaF , and Er : YAG + NaF groups . CONCLUSIONS We concluded that both the CO(2 ) and Er : YAG lasers have promising potential for the treatment of dentine hypersensitivity . Lasers in combination with NaF gel appear to show better efficacy compared to either treatment modality alone OBJECTIVE To compare the clinical efficacy of the GaAlAs laser and dentin bonding agent in treating dentin hypersensitivity . METHODS One hundred and forty teeth from 70 patients diagnosed with dentin hypersensitivity , were divided into two groups : In group I , teeth were irradiated with 30 mW GaAlAs laser for 1 min and in group II , teeth were applied with dentin bonding agent . Sensitivity was assessed by tactile and thermal tests , measured with the criteria proposed by Uchida at baseline and after treatment ; immediately , at 15 and at 30 days . RESULTS The reduction of dentin hypersensitivity was observed in both treatments using the GaAlAs laser and dentin bonding agent . However , a greater reduction was observed over time up to day 15 and no significant change was observed between days 15 and 30 . Statistically significant differences in the level of dentin hypersensitivity between bonding agent and the GaAlAs laser were found at each observation period ( p < 0.05 ) . CONCLUSION The GaAlAs laser had less desensitizing efficacy compared with dentin bonding agent . However , the desensitizing effect of the GaAlAs laser still could be considered an effective therapy for treating dentin hypersensitivity Our previous in vitro study indicated that Nd : YAG laser irradiation on dentin could melt normal dentin surface and close the exposed dentinal tubule orifices without creating surface cracks . This study evaluated the morphologic changes of hypersensitive dentin after Nd : YAG laser irradiation . Thirty patients with clinical ly diagnosed cervical dentin hypersensitive teeth were treated with a Nd : YAG laser of 30 mJ intensity at 10 pulses per second for 2 min . An impression of the sensitive area was taken before and after laser treatment and then examined with a scanning electron microscope . The impression of the dentin surface after Nd : YAG laser treatment showed no protrusive rods , in contrast with the presence of numerous rods before laser irradiation . Because protrusive rods are a measure of open dentinal tubules , we interpret these data to support the hypothesis that Nd : YAG laser irradiation at specifications of 30 mJ , 10 pulses per second , and 2 min can be used to seal the exposed dentinal tubules Clinical trials on dentine hypersensitivity have been numerous and protocol s varied . To date there is little consensus as to the conduct of studies on this poorly-understood yet common and painful dental condition . A committee of interested persons from academia and industry was convened to discuss the subject of clinical trials on dentine hypersensitivity and a consensus report is presented . A double-blind r and omized parallel groups design is recommended , although cross-over design s may be used for the preliminary screening of agents . Subjects may have multiple sites scored . Sample size will be determined by estimating the variability in the study population , the effect to be detected and the power of the statistical test to be used . Subject selection is based on a clinical diagnosis of dentine hypersensitivity , excluding those with conflicting characteristics such as currently-active medical or dental therapy . The vestibular surfaces of incisors , cuspids and bicuspids are preferred as sites to be tested . A range of sensitivity levels should be included . Tactile , cold and evaporative air stimuli should be applied . Negative and benchmark controls should be incorporated . Most trials should last 8 weeks . Sensitivity may be assessed either in terms of the stimulus intensity required to evoke pain or the subjective evaluation of pain produced by a stimulus using a visual analog or other appropriate scale . The subject 's overall assessment may be determined by question naire . Outcomes should be expressed in terms of clinical ly significant changes in symptoms . Follow-up evaluation is required to determine the persistence of changes . At least 2 independent trials should be conducted before a product receives approval Various methods and material s used in the treatment of dentin hypersensitivity are thought to achieve a therapeutic benefit by tubule occlusion . The aim of the present study was to evaluate the combined occluding effect of sodium fluoride varnish and Nd : YAG laser irradiation on human dentinal tubules . Thirty-six dentin specimens with exposed dentinal tubule orifices were used in this study . The sample s were r and omly divided into four groups . Groups A , B , and C were varnished by sodium fluoride , whereas group D served as a control . Then , group C was lased by 30 mJ of Nd : YAG laser , 10 pulses/s for 2 min by light painting . Three hours later , groups B and C were brushed by an electrical toothbrush for 30 min . Under SEM observation , the control group showed numerous exposed dentinal tubule orifices , and the sodium fluoride varnished specimens showed closure of exposed dentinal tubule orifices . After electrical toothbrushing , most of the sodium fluoride varnish was brushed away , except in the specimens that were irradiated by Nd : YAG laser . Over 90 % of the dentinal tubule orifices were occluded by sodium fluoride varnish combined with Nd : YAG laser irradiation OBJECTIVES This study evaluated the immediate and 3 month clinical effects of a low-level gallium-aluminum-arsenide ( GaAlAs ) laser and a 3 % potassium oxalate gel for the treatment of dentinal hypersensitivity . MATERIAL S AND METHODS A total of 164 teeth from 30 patients with clinical diagnoses of dentinal hypersensitivity were selected for this r and omized , placebo-controlled , double-blind clinical study . The teeth were r and omized to three groups : GaAlAs laser , oxalate gel , and placebo gel . The treatment sessions were performed at 7 d intervals for four consecutive weeks . The degree of sensitivity in response to an air blast and tactile stimuli was assessed according to a visual analogue scale at baseline , immediately after the fourth application , and then 3 months after the fourth application . The reductions in dentinal hypersensitivity from baseline at the two follow-up assessment s were evaluated as the main outcome . RESULTS In both the active and control groups , there were statistically significant reductions in dentinal hypersensitivity immediately after and 3 months after the treatments , when compared with the hypersensitivity at baseline . No significant differences among the three groups could be detected in their efficacy at either the immediate or 3 month evaluations irrespective of the stimulus . CONCLUSIONS The treatments under study were effective for reducing dentinal hypersensitivity , and longer observational periods could enhance the ability of studies to detect differences between active and placebo groups Dentine hypersensitivity has of long been known to be a common clinical problem in dental practice s. Lasers have recently come to play a prominent role in the treatment of this disorder . They might , however , cause dental pulp damage . This study was conducted to evaluate the effect of Nd : yttrium – aluminum – garnet ( YAG ) laser on partial oxygen saturation of pulpal blood in sensitive anterior teeth . In this clinical trial , 65 hypersensitive teeth were selected and r and omly allocated to two groups . The study group involved Nd : YAG laser treatment , while no treatment was employed for the control group . Using a pulse oximetry system , evaluations were preformed of the partial oxygen saturation in the pulpal blood before , immediately after , 1 week after , and 1 month after the treatment . The results were analyzed using the SPSS software and repeated- measures analysis of variance and paired- sample s t tests . The mean partial oxygen saturation of the blood was found to be 85.4 % in the study group , which was not significantly different from that of the control group . No significant differences were observed in the control group between the means obtained from pretreatment and post-treatment intervals ( P > 0.05 ) . The Post-treatment partial oxygen saturation mean rose to 89.3 % ( P = 0.001 ) and remained constant throughout the following week after it . However , no significant differences were found between the pretreatment partial oxygen saturation mean and the same measurement 1 month after treatment ( P = 0.702 ) . Nd : YAG laser therapy for dentine desensitization of anterior teeth caused no persistent changes in the partial oxygen saturation of pulpal blood . It may , therefore , be concluded that the diffusion of heat induced by the Nd : YAG laser into the pulp within the limit of the desensitization parameters cause no irreversible damages in the dental pulp BACKGROUND , AIMS Promising results using Nd : YAG laser against dentin hypersensitivity have been reported . The aim of this double-blind , controlled , split-mouth design ed clinical trial was to assess the effect of a single Nd : YAG laser application on alleviating hypersensitivity . METHODS / RESULTS Seventeen subjects participated in the study . Each of them had two teeth treated ; one with the laser activated and one with nonactivated ( placebo ) , for 2 min The assessment of pain was performed by a VAS , after an air blast at baseline immediately after treatment , at 1 week , 4 weeks and 16 weeks . Mean values of VAS for test and control teeth were compared by paired t-test ( alpha = 0.05 ) . The results showed mean baseline VAS values of 6.59 ( + /- 1.65 ) and 6.14(+/- 1.95 ) for test and control teeth , respectively . Immediately after treatment , these values decreased to 4.09(+/- 2.28 ) and 3.89(+/- 2.11 ) , respectively . After 1 week , 4 weeks and 16 weeks the mean values for test and control teeth were 3.85 + /- 2.36 , 4.03 + /- 1.95 , 3.60 + /- 2.66 , and 4.44 + /- 2.56 , 3.41 + /- 2.30 , 3.42 + /- 2.30 , respectively . There were no statistically significant differences between test and control at any time . However , both groups improved significantly ( P < 0.05 ) from baseline to immediately after application , and at 1 week , 4 weeks and 16 weeks , respectively . The changes that occurred between immediately after application and 1 week , 4 weeks and 16 weeks , respectively , were not statistically significant . CONCLUSION It is concluded that the effect of treatment of hypersensitive teeth with Nd : YAG laser is not different from placebo . The observed effects seem to last for at least 16 weeks Dentin hypersensitivity ( DH ) is one of the most common complications that affect patients after periodontal therapy . So far , many investigators have successfully used different types of laser on DH treatment . The aim of this study was to evaluate the comparative effect of Nd : YAG laser and Er : YAG laser on human teeth desensitization . A group of nine patients with a total of 63 chronic hypersensitive teeth were selected . Each one of them should at least have three hypersensitive teeth . These teeth were r and omly allocated into three groups . Group 1 , Nd : YAG laser ( 1 W , 15 Hz , 60 s , two times ) ; group 2 , Er : YAG laser ( 100 mJ , 3 Hz , 60 s , two times ) ; and group 3 serves as control group without any treatment . Assessment of pain was performed by a visual analysing scale ( VAS ) after stimulation of sensitive tooth by using the sharp tip of an explorer . This test was performed before treatment , immediately after that and at 1- , 3- and 6-month intervals after treatment by one blinded examiner . Analysis of VAS score between the three groups at the time of treatment did not show any significant difference ( p = 0.506 ) . However , by using repeated-measurement analysis of variance test , significant differences were seen in the three groups between before-treatment VAS score and after treatment ( p < 0.0005 ) . This statistically significant difference in the control group demonstrated a placebo effect . However , the effect of using Nd : YAG and Er : YAG lasers was stronger than this placebo effect , so that after removing the effect of the placebo , differences immediately after , 1 , 3 and 6 months post treatment between all three groups still were statistically highly significant ( p < 0.0005 ) . Compared to the Er : YAG laser group , using Nd : YAG laser result ed in a significant reduction of VAS score at each follow-up examination ( p < 0.0005 ) . Although using Nd : YAG and Er : YAG laser in desensitization of hypersensitive teeth showed a placebo effect limited to a short time , results of this study demonstrated that both of these lasers have an acceptable therapeutic effect . The observed effects seemed to last for at least 6 months . It was concluded that Nd : YAG laser is more effective than Er : YAG laser in reduction of patients ’ pain BACKGROUND AND AIM Several dentifrices have shown to be effective in reducing dentine hypersensitivity ( DH ) , but more effective products are needed . The aim of the study was to evaluate the desensitizing efficacy of a new dentifrice based on zinc-carbonate hydroxyapatite ( CHA ) nanocrystals . METHODS AND MATERIAL S Using a double-blind , r and omized design , the new dentifrice was compared with potassium nitrate/fluoride dentifrice ( active control ) . The participant 's DH was evaluated at baseline and after 4 and 8 weeks using airblast ( primary outcome ) , tactile , cold water and subjective tests ( secondary outcomes ) . RESULTS The final sample consisted of 70 subjects with baseline DH ; 36 received the new dentifrice and 34 the control one . Both dentifrices were largely effective ; the percentage of score reduction from baseline to 8 weeks was greater than 28 % for all tests ( and greater than 55 % for the cold water test ) in both groups . As compared with controls , experimental subjects had a significantly greater improvement in the airblast test score ( mean percentage of reduction of 46.0%versus 29.4 % in controls ) and the subjective test score ( 47.5%versus 28.1 % , respectively ) , with both differences already being significant after 4 weeks . In contrast , there was no significant difference between groups for either the tactile or cold water tests at any time point and with any outcome . CONCLUSIONS This study documented that the new dentifrice containing zinc-CHA nanocrystals significantly reduced dentinal hypersensitivity after 4 and 8 weeks , supporting its utility in clinical practice PURPOSE To compare the clinical effect over 3 months of two commercially available desensitizing agents on the level of discomfort of patients with complaints of dentin sensitivity . MATERIAL S AND METHODS An oxalate-containing pre-polymerized resin suspension ( Pain-Free ) , a 0.7 % fluoride solution ( DentinBloc ) , and a distilled water placebo were compared in a clinical setting . Ten volunteer patients exhibiting three or more teeth that were sensitive to touch and to a stream of forced air were enrolled in the study ( 52 teeth total ) . Each patient 's level of sensitivity to tactile stimuli and to a forced air stream was recorded using a visual analog scale ( VAS ) . The tactile stimulus was a metal probe rubbed across the exposed dentin with a constant pressure of 40 grams . A 1-second blast of air from a dental unit air syringe was used to generate the air stream . The desensitizing agents were applied according to manufacturers ' guidelines . Sensitivity measurements were recorded at baseline , immediately after treatment , at 1 week , 1 month , and at 3 months . VAS pain scores were analyzed using a repeated measures ANOVA ( alpha = 0.05 ) . RESULTS The pre-polymerized resin suspension ( Pain-Free ) , the fluoride-containing solution ( DentinBloc ) , and the placebo all decreased dentin sensitivity . No significant difference was found among the desensitizing agents at any time period ( P > 0.05 ) BACKGROUND The aim of the present study was to evaluate clinical ly and under scanning electron microscopy ( SEM ) the efficacy of Nd : YAG laser irradiation alone and in combination with 5 % sodium fluoride varnish in the management of dentin hypersensitivity . METHODS The study was conducted on 40 patients divided into four groups who had at least one tooth of Grade III mobility with clinical ly elicitable dentin hypersensitivity . Following the pretreatment assessment of hypersensitivity using the visual analog scale ( VAS ) and cold air blast test , the selected tooth in all the groups received 1 % citric acid treatment for 1 minute . Group 1 patients received no further treatment ; group 2 , 3 , and 4 patients received additional treatment with 5 % sodium fluoride varnish , Nd : YAG laser for 2 minutes , and a combination of 5 % sodium fluoride varnish and Nd : YAG laser , respectively . Two hours following treatment , hypersensitivity was again assessed , and the teeth were extracted , sectioned , and scanned using scanning electron microscopy ( SEM ) . RESULTS The mean VAS score in group 1 showed a 27 % increase from baseline , but groups 2 , 3 , and 4 showed a decrease of 33 % , 44 % , and 62 % , respectively . The mean cold air blast score showed a 22 % increase in group 1 , but values decreased by 43 % , 50 % , and 83 % in groups 2 , 3 , and 4 , respectively . The number of patent tubules also progressively decreased from group 1 through group 4 . CONCLUSIONS The combination of Nd : YAG laser and 5 % sodium fluoride varnish seems to show an impressive efficacy , when compared to either treatment alone , in treating dentin hypersensitivity . The SEM findings seem to relate to the clinical findings in that reduction in number/patency of tubules was associated with improvement in treatment efficacy BACKGROUND To evaluate the immediate efficacy in the reduction of dentine hypersensitivity ( DH ) when applying an 810 nm diode laser ( DL ) , and a 10 % potassium nitrate bioadhesive gel ( NK10 % ) . MATERIAL AND METHODS Forty-five consecutive periodontal maintenance patients of both sexes , with a DH > or= 2 on the verbal rating scale ( VRS ) in one or more teeth , were r and omly allocated into three equal groups : 15 patients received DL and placebo gel ; 15 patients were tested with a placebo laser and NK10 % ; and the remaining 15 received a placebo laser and placebo gel . The DH was evaluated at the start of the study , 15 and 30 min . after the laser application , and on days 2 , 4 , 7 , 14 , 30 and 60 by a blind examiner . RESULTS After 15 min . , observations showed a reduction in DH after an evaporative stimulus ( ES ) of 36.9 % ( 0.86 ) , three times greater than that of the control group ( 0.23 ) ( p=0.008 ) . After 14 days , this effect was even greater [ DL 71.7 % (1.67)/NK10 % 36.3 % (1.73)/control 28.1 % ( 0.73 ) ; p=0.004 ] , and lasted until day 60 [ 65.7 % (1.53)/30.4 % (0.73)/25.8 % ( 0.67 ) ; p=0.01 ] . CONCLUSIONS The DL and NK10 % gel were proven effective in the treatment of DH . A significantly greater immediate response was observed with DL The pulsed Nd : YAG laser is advocated as an alternative means of providing analgesia during routine dental procedures . Since the evidence to support this cl aim is mainly anecdotal , a clinical trial was carried out using an electric pulp tester ( EPT ) to measure the extent and duration of any analgesic effect induced by pulsed Nd : YAG laser treatment . A double-blind crossover experiment involving laser and sham treatments was used on 21 subjects . A small ( 3.6 arbitrary units ) but statistically significant increase was observed in the mean responses measured 5 min after laser treatment with 113 mJ pulses at 15 pulses s-1 ( pps ) for 3 min . The pain thresholds returned to baseline values after 60 min . No statistically significant changes in threshold were found with the sham treatment . The order in which laser and sham treatment was received made no difference to the results AIM A r and omised clinical trial was design ed to compare the immediate efficacy ( 48 - 96 h ) of two treatments with bioadhesive gels with different concentrations of potassium nitrate ( NK 5 % versus NK 10 % ) on dentine hypersensitivity ( DH ) . We evaluated DH by means of the use of the evaporative stimulus ( ES ) , as the main outcome , using a placebo control group as reference . PATIENTS AND METHODS Forty-five consecutive patients who , after stimulation with a blast of air , had at least one tooth with DH > or = 2 according to the verbal ratings scale ( VRS ) scale were selected . They were r and omly treated with a bioadhesive gel with 5 % NK , 10 % NK or a placebo gel without NK . The DH was evaluated at baseline , days 2 , 4 , 7 and 14 by an examiner blind to the procedure . The response to the ES with a blast of air , to the tactile stimulation with a probe and the subjective evaluation of the patient measured on the VRS scale were recorded . Statistical analysis was made using the Kruskal-Wallis test . RESULTS A greater reduction of DH after ES was observed after 48 h of treatment in the NK10 % group ( 35.8 % ) compared to the NK5 % group and placebo group ( 11.8 % and 13.4 % , respectively ) . This difference increased significantly at 96 h ( p=0.003 ) . No significant differences were observed for the other variables . These preliminary results may support the usefulness of an NK 10 % gel to reduce the DH after stimulation with a blast of air during the first 4 days of its appearance AIM The aim of the present study was to evaluate and compare the desensitizing effects of an Er : YAG laser ( KEY II(R ) , KaVo , Germany ) and Dentin Protector ( Vivadent , Germany ) on cervically exposed hypersensitive dentine . METHOD A group of 30 patients showing a total of 104 contralateral pairs of hypersensitive and caries-free teeth was selected and r and omly allocated in a split-mouth design to either ( 1 ) Er : YAG laser ( 80 mJ/pulse , 3 Hz ) , or ( 2 ) the application of Dentin Protector ( polyurethane-isocyanate 22.5 % ; methylenechloride 77.5 % ) whereat one pair served as an untreated control in each patient . The degree of sensitivity to a thermal stimulus was determined qualitatively with an evaporative stimulus defined as a 3-s air blast at a distance of 2 mm from each site to be tested . A qualitative registration of the degree of discomfort was determined according to an arbitrary pain scale in 4 degrees . Recordings were assessed before treatment , immediately after , 1 week , 2 and 6 months after treatment by 1 blinded examiner . RESULTS Both treatment forms result ed in significant improvements of discomfort immediately after and 1 week post treatment . After 2 months , the discomfort in the Dentin Protector(R ) group increased up to 65 % of the baseline score and even up to 90 % after 6 months , whereas the effect of the laser remained at the same level that was achieved immediately after treatment . The differences immediately after , 1 week , 2 and 6 months post treatment between both groups were statistically high significant ( p < or = 0.001 ; respectively ) . Compared to the untreated control group , both treatment forms result ed in a significant reduction of discomfort at each follow-up examination . CONCLUSION It was concluded that desensitizing of hypersensitive dentine with an Er : YAG laser is effective and the maintenance of the positive result was more prolonged than with Dentin Protector The aim of this study was to evaluate in vivo the use of low-level galium-aluminium-arsenide ( GaAlAs ) ( BDP 600 ) laser and sodium fluoride varnish ( Duraphat ) in the treatment of cervical dentine hypersensitivity . Twelve patients , with at least two sensitive teeth were selected . A total of 60 teeth were included in the trial . Prior to desensitizing treatment , dentine hypersensitivity was assessed by a thermal stimulus and patients ' response to the examination was considered to be a control . The GaAlAs laser ( 15 mW , 4 J/cm2 ) was irradiated on contact mode and fluoride varnish was applied at cervical region . The efficiency of the treatments was assessed at three examination periods : immediately after first application , 15 and 30 days after the first application . The degree of sensitivity was determined following predefined criteria . Data were su bmi tted to analysis and no statistically significant difference was observed between fluoride varnish and laser . Considering the treatments separately , there was no significant difference for the fluoride varnish at the three examination periods , and for laser therapy , significant difference ( P < 0.05 ) was found solely between the values obtained before the treatment and 30 days after the first application . It may be concluded that both treatments may be effective in decreasing cervical dentinal hypersensitivity . Moreover , the low-level GaAlAs laser showed improved results for treating teeth with higher degree of sensitivity OBJECTIVES In two clinical trials of 8 weeks duration , the ability of a new dentifrice , containing potassium nitrate , stannous fluoride and sodium fluoride to reduce dentine hypersensitivity was compared with either a non-desensitising fluoride dentifrice or a commercially available desensitising dentifrice ( Sensodyne F ) to reduce dentine hypersensitivity . METHOD In both studies , the participants had to have at least two sensitive root surfaces . Subjects were stratified by baseline tactile and air blast sensitivity scores and the number of sensitive teeth and r and omly allocated to 2 balanced groups . In the first study ( N=81 ) the new dentifrice was compared with a fluoride dentifrice and in the second study ( N=105 ) with Sensodyne F. Participants were requested to brush with their assigned dentifrice twice a day for one minute . At 4 and 8 weeks the sensitive teeth were again examined and their tactile and air blast sensitivity scores recorded . RESULTS In study 1 , the group using the new dentifrice tolerated greater pressure after 4 ( 34.9 g ) and 8 weeks ( 38.4 g ) than the group using the fluoride dentifrice ( 22.9 g and 19.0 g , respectively ) . These differences were statistically significant ( p<0.001 ) . At 4 and 8 weeks , the mean air blast scores for the group using the new dentifrice ( 1.39 and 0.83 ) were lower than for the group using fluoride dentifrice ( 1.78 and 1.76 ) and were significantly different at 8 weeks ( p<0.001 ) . In study 2 the group using the new dentifrice tolerated greater pressure after 4 ( 40.5 g ) and 8 weeks ( 43.7 g ) than the group using Sensodyne F ( 27.8 g and 33.2 g , respectively ) . These differences were statistically significant ( p<0.001 ) . At 4 and 8 weeks , the mean air blast scores for the group using the new dentifrice ( 1.10 and 0.67 ) were significantly lower than the group using Sensodyne F ( 1.90 and 1.57 ) ( p<0.001 ) . CONCLUSIONS These studies demonstrate that the new dentifrice , containing potassium nitrate , stannous fluoride and sodium fluoride is significantly better at reducing dentine hypersensitivity than both the dentifrice containing sodium fluoride and the one containing potassium chloride , triclosan and sodium fluoride ( Sensodyne F ) |
10,863 | 28,213,052 | n‐3 fatty acids were associated with better global cognition and some specific cognitive domains though some results were conflicting .
Adherence to the MedDiet was also significantly associated with better cognitive performance and less cognitive decline .
Finally , better cognitive performance was observed in men compared to women and mixed results were also found for the influence of APOE4 genotype on the association between n‐3 fatty acids or MedDiet and cognition .
Conclusions : Studies suggest that n‐3 fatty acids in the diet and adherence to the MedDiet are beneficial in slowing age‐related cognitive decline .
Highlightsn‐3 fatty acids were associated with better cognitive performance in the older population .Greater adherence to the Mediterranean diet was related with better cognitive performance .
Greater adherence to the Mediterranean diet was associated with less cognitive decline | Background : Intake of n‐3 fatty acids and adherence to the Mediterranean diet ( MedDiet ) have been shown to slow the progression of age‐related cognitive decline , but the results are mixed .
We summarized and evaluated the effect of n‐3 fatty acids and MedDiet on cognitive outcomes in a cognitively healthy aged population . | BACKGROUND Dietary intake of fish and the omega-3 fatty acids have been associated with lower risk of Alzheimer disease and stroke . OBJECTIVE To examine whether intakes of fish and the omega-3 fatty acids protect against age-related cognitive decline . DESIGN Prospect i ve cohort study . SETTING Geographically defined Chicago , Ill , community . PARTICIPANTS Residents , 65 years and older , who participated in the Chicago Health and Aging Project . MAIN OUTCOME MEASURE Change in a global cognitive score estimated from mixed models . The global score was computed by summing scores of 4 st and ardized tests . In-home cognitive assessment s were performed 3 times over 6 years of follow-up . RESULTS Cognitive scores declined on average at a rate of 0.04 st and ardized units per year ( SU/y ) . Fish intake was associated with a slower rate of cognitive decline in mixed models adjusted for age , sex , race , education , cognitive activity , physical activity , alcohol consumption , and total energy intake . Compared with a decline rate in score of -0.100 SU/y among persons who consumed fish less than weekly , the rate was 10 % slower ( -0.090 SU/y ) among persons who consumed 1 fish meal per week and 13 % slower ( -0.088 SU/y ) among persons who consumed 2 or more fish meals per week . The fish association was not accounted for by cardiovascular-related conditions or fruit and vegetable consumption but was modified after adjustment for intakes of saturated , polyunsaturated , and trans fats . There was little evidence that the omega-3 polyunsaturated fatty acids were associated with cognitive change . CONCLUSIONS Fish consumption may be associated with slower cognitive decline with age . Further study is needed to determine whether fat composition is the relevant dietary constituent Tissue levels of n-3 fatty acids reflect dietary intake , but quantitative data about rate of incorporation and levels as a function of intake are scarce . We fed 58 men 0 , 3 , 6 , or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters , erythrocytes , and subcutaneous fat during and after supplementation . Eicosapentaenoic acid ( EPA ) in cholesteryl esters plateaued after 4 - 8 weeks ; the incorporation half-life was 4.8 days . Steady-state levels increased by 3.9 + /- 0.3 mass % points ( + /- SE ) for each extra gram of EPA eaten per day . Incorporation of docosahexaenoic acid ( DHA ) was erratic ; plateau values were 1.1 + /- 0.1 mass % higher for every g/d ingested . Incorporation of EPA into erythrocyte membranes showed a half-life of 28 days ; a steady state was reached after 180 days . Each g/d increased levels by 2.1 + /- 0.1 mass % . C22:5n-3 levels increased markedly . Changes in DHA were erratic and smaller . EPA levels in adipose tissue rose also ; the change after 6 months was 67 % of that after 12 months in gluteal and 75 % in abdominal fat . After 12 months each gram per day caused an 0.11 + /- 0.01 mass % rise in gluteal fat for EPA , 0.53 + /- 0.07 for C22:5n-3 , and 0.14 + /- 0.03 for DHA . Thus , different ( n-3 ) fatty acids were incorporated with different efficiencies , possibly because of interconversions or different affinities of the enzymatic pathways involved . EPA levels in cholesteryl esters reflect intake over the past week or two , erythrocytes over the past month or two , and adipose tissue over a period of years . These findings may help in assessing the intake of ( n-3 ) fatty acids in epidemiological studies BACKGROUND Plasma fatty acids may affect the risk of cognitive decline in older adults . OBJECTIVES We prospect ively studied the association between plasma fatty acids and cognitive decline in adults aged 50 - 65 y at baseline and conducted a subgroup analysis . DESIGN From 1987 through 1989 , the Atherosclerosis Risk in Communities ( ARIC ) Study analyzed plasma fatty acids in cholesteryl esters and phospholipids in whites residing in Minneapolis , MN . From 1990 through 1992 and from 1996 through 1998 , 3 neuropsychological tests in the domains of delayed word recall , psychomotor speed , and verbal fluency were administered . We selected cutoffs for statistically reliable cognitive decline in each of these domains and a measure of global cognitive change computed by principal-components analysis . Multivariate logistic regression was conducted . Focusing on n-3 highly unsaturated fatty acids ( HUFAs ) , a subgroup analysis assessed differential association across potential effect modifiers implicated in oxidative stress and increased risk of neurodegenerative disease . RESULTS In the 2251 study subjects , the risk of global cognitive decline increased with elevated palmitic acid in both fractions and with high arachidonic acid and low linoleic acid in cholesteryl esters . Higher n-3 HUFAs reduced the risk of decline in verbal fluency , particularly in hypertensive and dyslipidemic subjects . No significant findings were shown for psychomotor speed or delayed word recall . CONCLUSIONS Promoting higher intakes of n-3 HUFAs in the diet of hypertensive and dyslipidemic persons may have substantial benefits in reducing their risk of cognitive decline in the area of verbal fluency . However , clinical trials are needed to confirm this finding BACKGROUND Very-long-chain n-3 polyunsaturated fatty acids ( n-3 PUFAs ) are suggested to be related to cognitive performance in older adults . However , limited data exist on the association between n-3 PUFAs and performance in specific cognitive domains . OBJECTIVE We evaluated the association between plasma n-3 PUFA proportions and cognitive performance in 5 cognitive domains and determined whether plasma n-3 PUFA proportions predict cognitive change over 3 y. DESIGN We used data from the FACIT trial , in which participants received folic acid or placebo capsules for 3 y. Fatty acid proportions in plasma cholesteryl esters at baseline were measured in 807 men and women aged 50 - 70 y. Cognitive performance for memory , sensorimotor speed , complex speed , information-processing speed , and word fluency was assessed at baseline and after 3 y. The cross-sectional analyses were based on all 807 participants ; the longitudinal analyses were based only on 404 participants in the placebo group . RESULTS Higher plasma n-3 PUFA proportions predicted less decline in sensorimotor speed ( multiple linear regression coefficient , z score = 0.31 ; 95 % CI : 0.06 , 0.57 ) and complex speed ( 0.40 ; 95 % CI : 0.10 , 0.70 ) over 3 y. Plasma n-3 PUFA proportions did not predict 3-y changes in memory , information-processing speed , or word fluency . The cross-sectional analyses showed no association between plasma n-3 PUFA proportions and performance in any of the 5 cognitive domains . CONCLUSIONS In this population , plasma n-3 PUFA proportions were associated with less decline in the speed-related cognitive domains over 3 y. These results need to be confirmed in r and omized controlled trials CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases , but its association with cognitive decline is unclear . OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1410 adults ( > or = 65 years ) from Bordeaux , France , included in the Three-City cohort in 2001 - 2002 and reexamined at least once over 5 years . Adherence to a Mediterranean diet ( scored as 0 to 9 ) was computed from a food frequency question naire and 24-hour recall . MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests : the Mini-Mental State Examination ( MMSE ) , Isaacs Set Test ( IST ) , Benton Visual Retention Test ( BVRT ) , and Free and Cued Selective Reminding Test ( FCSRT ) . Incident cases of dementia ( n = 99 ) were vali date d by an independent expert committee of neurologists . RESULTS Adjusting for age , sex , education , marital status , energy intake , physical activity , depressive symptomatology , taking 5 medications/d or more , apolipoprotein E genotype , cardiovascular risk factors , and stroke , higher Mediterranean diet score was associated with fewer MMSE errors ( beta = -0.006 ; 95 % confidence interval [ CI ] , -0.01 to -0.0003 ; P = .04 for 1 point of the Mediterranean diet score ) . Performance on the IST , BVRT , or FCSRT over time was not significantly associated with Mediterranean diet adherence . Greater adherence as a categorical variable ( score 6 - 9 ) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort , but among individuals who remained free from dementia over 5 years , the association for the highest compared with the lowest group was significant ( adjusted for all factors , for MMSE : beta = -0.03 ; 95 % CI , -0.05 to -0.001 ; P = .04 ; for FCSRT : beta = 0.21 ; 95 % CI , 0.008 to 0.41 ; P = .04 ) . Mediterranean diet adherence was not associated with the risk for incident dementia ( fully adjusted model : hazard ratio , 1.12 ; 95 % CI , 0.60 to 2.10 ; P = .72 ) , although power to detect a difference was limited . CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests . Higher adherence was not associated with risk for incident dementia IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline , a strong risk factor for development of dementia . Epidemiologic studies suggest that a Mediterranean diet , an antioxidant-rich cardioprotective dietary pattern , delays cognitive decline , but clinical trial evidence is lacking . OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet . DESIGN , SETTING , AND PARTICIPANTS Parallel-group r and omized clinical trial of 447 cognitively healthy volunteers from Barcelona , Spain ( 233 women [ 52.1 % ] ; mean age , 66.9 years ) , at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1 , 2003 , through December 31 , 2009 . All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study . INTERVENTIONS Participants were r and omly assigned to a Mediterranean diet supplemented with extravirgin olive oil ( 1 L/wk ) , a Mediterranean diet supplemented with mixed nuts ( 30 g/d ) , or a control diet ( advice to reduce dietary fat ) . MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery : Mini-Mental State Examination , Rey Auditory Verbal Learning Test ( RAVLT ) , Animals Semantic Fluency , Digit Span subtest from the Wechsler Adult Intelligence Scale , Verbal Paired Associates from the Wechsler Memory Scale , and the Color Trail Test . We used mean z scores of change in each test to construct 3 cognitive composites : memory , frontal ( attention and executive function ) , and global . RESULTS Follow-up cognitive tests were available in 334 participants after intervention ( median , 4.1 years ) . In multivariate analyses adjusted for confounders , participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049 ) and Color Trail Test part 2 ( P = .04 ) compared with controls ; no between-group differences were observed for the other cognitive tests . Similarly adjusted cognitive composites ( mean z scores with 95 % CIs ) for changes above baseline of the memory composite were 0.04 ( -0.09 to 0.18 ) for the Mediterranean diet plus olive oil , 0.09 ( -0.05 to 0.23 ; P = .04 vs controls ) for the Mediterranean diet plus nuts , and -0.17 ( -0.32 to -0.01 ) for the control diet . Respective changes from baseline of the frontal cognition composite were 0.23 ( 0.03 to 0.43 ; P = .003 vs controls ) , 0.03 ( -0.25 to 0.31 ) , and -0.33 ( -0.57 to -0.09 ) . Changes from baseline of the global cognition composite were 0.05 ( -0.11 to 0.21 ; P = .005 vs controls ) for the Mediterranean diet plus olive oil , -0.05 ( -0.27 to 0.18 ) for the Mediterranean diet plus nuts , and -0.38 ( -0.57 to -0.18 ) for the control diet . All cognitive composites significantly ( P < .05 ) decreased from baseline in controls . CONCLUSIONS AND RELEVANCE In an older population , a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N35739639 Capturing the dynamics of gray matter ( GM ) atrophy in relation to the conversion from mild cognitive impairment ( MCI ) to clinical ly probable Alzheimer 's disease ( AD ) would be of considerable interest . In this prospect i ve study we have used a novel longitudinal voxel-based method to map the progression of GM loss in MCI patients over time and compared converters to non-converters . Eighteen amnestic MCI patients were followed-up for a predefined fixed period of 18 months and conversion was judged according to NINCDS-ADRDA criteria for probable AD . Each patient underwent a high-resolution T1-weighted volume MRI scan both at entry in the study and 18 months later . We used an optimal VBM protocol to compare baseline imaging data of converters to those of non-converters . Moreover , to map GM loss from baseline to follow-up assessment , we used a modified voxel-based morphometry ( VBM ) procedure specially design ed for longitudinal studies . At the end of the follow-up period , seven patients had converted to probable AD . Areas of lower baseline GM value in converters mainly included the hippocampus , parahippocampal cortex , and lingual and fusiform gyri . Regions of significant GM loss over the 18-month follow-up period common to both converters and non-converters included the temporal neocortex , parahippocampal cortex , orbitofrontal and inferior parietal areas , and the left thalamus . However , there was significantly greater GM loss in converters relative to non-converters in the hippocampal area , inferior and middle temporal gyrus , posterior cingulate , and precuneus . This accelerated atrophy may result from both neurofibrillary tangles accumulation and parallel pathological processes such as functional alteration in the posterior cingulate . The ability to longitudinally assess GM changes in MCI offers new perspectives to better underst and the pathological processes underlying AD and to monitor the effects of treatment on brain structure BACKGROUND Docosahexaenoic acid ( DHA ) is an abundant fatty acid in the brain . In the diet , DHA is found mostly in fatty fish . The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia . OBJECTIVE To determine whether plasma phosphatidylcholine ( PC ) DHA content is associated with the risk of developing dementia . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve follow-up study in 899 men and women who were free of dementia at baseline , had a median age of 76.0 years , and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease . MAIN OUTCOME MEASURES Plasma PC fatty acid levels were measured at baseline . Cox proportional regression analysis was used to assess relative risks of all-cause dementia and Alzheimer disease according to baseline plasma levels . RESULTS Ninety-nine new cases of dementia ( including 71 of Alzheimer disease ) occurred during the follow-up . After adjustment for age , sex , apolipoprotein E epsilon4 allele , plasma homocysteine concentration , and education level , subjects in the upper quartile of baseline plasma PC DHA levels , compared with subjects in the lower 3 quartiles , had a relative risk of 0.53 of developing all-cause dementia ( 95 % confidence interval , 0.29 - 0.97 ; P=.04 ) and 0.61 of developing Alzheimer disease ( 95 % confidence interval , 0.31 - 1.18 ; P=.14 ) . Subjects in the upper quartile of plasma PC DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week ( P<.001 ) in a subset of 488 participants . We found no other significant associations . CONCLUSION The top quartile of plasma PC DHA level was associated with a significant 47 % reduction in the risk of developing all-cause dementia in the Framingham Heart Study To examine the association between dietary habits , cognitive functioning and brain volumes in older individuals , data from 194 cognitively healthy individuals who participated in the Prospect i ve Investigation of the Vasculature in Uppsala Seniors cohort were used . At age 70 , participants kept diaries of their food intake for 1week . These records were used to calculate a Mediterranean diet ( MeDi ) score ( comprising dietary habits traditionally found in Mediterranean countries , e.g. high intake of fruits and low intake of meat ) , with higher scores indicating more pronounced MeDi-like dietary habits . Five years later , participants ' cognitive capabilities were examined by the seven minute screening ( 7MS ) ( a cognitive test battery used by clinicians to screen for dementia ) , and their brain volumes were measured by volumetric magnetic resonance imaging . Multivariate linear regression analyses were constructed to examine the association between the total MeDi score and cognitive functioning and brain volumes . In addition , possible associations between MeDi 's eight dietary features and cognitive functioning and brain volumes were investigated . From the eight dietary features included in the MeDi score , pertaining to a low consumption of meat and meat products was linked to a better performance on the 7MS test ( P=0.001 ) and greater total brain volume ( i.e. the sum of white and gray matter , P=0.03 ) when controlling for potential confounders ( e.g. BMI ) in the analysis . Integrating all dietary features into the total MeDi score explained less variance in cognitive functioning and brain volumes than its single dietary component meat intake . These observational findings suggest that keeping to a low meat intake could prove to be an impact-driven public health policy to support healthy cognitive aging , when confirmed by longitudinal studies . Further , they suggest that the MeDi score is a construct that may mask possible associations of single MeDi features with brain health domains in elderly population In the present study , we tested whether elderly with a high dietary intake of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) would have higher cognitive test scores and greater brain volume than those with low dietary intake of these fatty acids . Data were obtained from the Prospect i ve Investigation of the Vasculature in Uppsala Seniors ( PIVUS ) cohort . The dietary intake of EPA and DHA was determined by a 7-day food protocol in 252 cognitively healthy elderly ( 122 females ) at the age of 70 years . At age 75 , participants ' global cognitive function was examined , and their brain volumes were measured by magnetic resonance imaging ( MRI ) . Three different multivariate linear regression models were applied to test our hypothesis : model A ( adjusted for gender and age ) , model B ( additionally controlled for lifestyle factors , e.g. , education ) , and model C ( further controlled for cardiometabolic factors , e.g. , systolic blood pressure ) . We found that the self-reported 7-day dietary intake of EPA and DHA at the age of 70 years was positively associated with global gray matter volume ( P < 0.05 , except for model C ) and increased global cognitive performance score ( P < 0.05 ) . However , no significant associations were observed between the dietary intake of EPA and DHA and global white matter , total brain volume , and regional gray matter , respectively . Further , no effects were observed when examining cognitively impaired ( n = 27 ) elderly as separate analyses . These cross-sectional findings suggest that dietary intake of EPA and DHA may be linked to improved cognitive health in late life but must be confirmed in patient studies Objective XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets ( MedDiet ) . Design XXXr and omized trial after 6.5 years of nutritional intervention . Setting Eight primary care centers affiliated to the University of Navarra . Participants A r and om sub sample of 285 participants ( 95 r and omly allocated to each of 3 groups ) of the PREDIMED-NAVARRA trial . All of them were at high vascular risk ( 44.8 % men , 74.1± 5.7 years at cognitive evaluation ) . Interventions Nutritional intervention comparing two MedDiets ( supplemented with extra-virgin olive oil [ EVOO ] or mixed nuts ) versus a low-fat control diet . Participants received intensive education to increase adherence to the intended intervention . Participants allocated to the MedDiet groups received EVOO ( 1 l/week ) or 30 g/day of mixed nuts . Dietary habits were evaluated using a vali date d 137-item food frequency question naire ( FFQ ) . Additionally , adherence to MedDiet was appraised using a 14-item question naire both at baseline and yearly thereafter . Measurements XXXcognitive performance as a main outcome and cognitive status ( normal , mild cognitive impairment [ MCI ] or dementia ) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention . Results Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group . After adjustment for sex , age , education , apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , this group also showed lower MCI ( OR=0.34 95 % CI : 0.12–0.97 ) compared with control group . Participants assigned to MedDiet+Nuts group did not differ from controls . Conclusion A long-term intervention with an EVOO-rich MedDiet result ed in a better cognitive function in comparison with a control diet . However , non-significant differences were found for most cognitive domains . Participants allocated to an EVOO-rich MedDiet had less MCI than controls Background We aim ed to investigate if overweight and obese adults " close " to Mediterranean diet present better insulin , lipids profile and better pressure levels , compared to individuals close to a more Westernized diet . Methods The ATTICA study is a population -based cohort that has r and omly enrolled 3042 adult men and women , stratified by age – gender , from the greater area of Athens , during 2001–2002 . Of them , in this work were have studied 1762 participants with excess body weight , meaning overweight ( BMI : 25–29.9 kg/m2 ) and obese ( BMI > 30 kg/m2 ) . 1064 were men and 698 women ( 20–89 years old ) . Adherence to Mediterranean diet was assessed through a diet-score that was based on a vali date d food-frequency question naire . Blood pressure was measured and also fasting glucose , insulin and blood lipids . Insulin sensitivity was also assessed by the homeostasis model assessment ( HOMA ) approach ( glucose × insulin/22.5 ) . Results Individuals with excess bodyweight in the highest tertile of diet score , were more insulin sensitive than those in the lowest tertile ( 11.4 % lower HOMA , p = 0.06 ) , had 13 % lower levels of total cholesterol ( p = 0.001 ) and 3 mmHg decrease of systolic blood pressure levels ( p < 0.001 ) , when adjusted for age , sex and BMI . Multivariate analysis after taking into account several confounders demonstrated that insulin sensitivity , total cholesterol and systolic blood pressure were independently but only modestly correlated with Mediterranean diet in people with excess bodyweight . Conclusion Adherence to Mediterranean diet is modeslty associated with a better insulin sensitivity , lower levels of total cholesterol and lower levels of systolic blood pressure in overweight and obese subjects . This may suggest that compared to general population , the beneficial effect of this diet in cardiovascular system of excess body weight people is limited Background Krill oil , rich in n-3 ( omega-3 ) polyunsaturated fatty acids ( PUFAs ) incorporated in phosphatidylcholine , has been reported to have many effects on physiological function . However , there are few studies using psychophysiological methods published that describe the effects of krill oil on brain function . We investigated the influence of ingestion of krill oil on cognitive function in elderly subjects by using near-infrared spectroscopy and electroencephalography . Methods A r and omized , double-blind , parallel-group comparative study design was adopted . Forty-five healthy elderly males aged 61–72 years were assigned to receive 12 weeks of treatment with : medium-chain triglycerides as placebo ; krill oil , which is rich in n-3 PUFAs incorporated in phosphatidylcholine ; or sardine oil , which is abundant in n-3 PUFAs incorporated in triglycerides . Changes in oxyhemoglobin concentrations in the cerebral cortex during memory and calculation tasks were measured . The P300 component of event-related potentials was also measured during a working memory task . Results During the working memory task , changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups were significantly greater than those in the medium-chain triglyceride group at week 12 . The differential value for P300 latency in the krill oil group was significantly lower than that in the medium-chain triglyceride group at week 12 . With regard to the calculation task , changes in oxyhemoglobin concentrations in the krill oil group were significantly greater than those in the medium-chain triglyceride group at week 12 . Conclusion This study provides evidence that n-3 PUFAs activate cognitive function in the elderly . This is especially the case with krill oil , in which the majority of n-3 PUFAs are incorporated into phosphatidylcholine , causing it to be more effective than sardine oil , in which n-3 PUFAs are present as triglycerides Objective Previous observational studies reported beneficial effects of the Mediterranean diet ( MedDiet ) on cognitive function , but results were inconsistent . We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet . Methods We assessed 522 participants at high vascular risk ( 44.6 % men , age 74.6 ± 5.7 years at cognitive evaluation ) enrolled in a multicentre , r and omised , primary prevention trial ( PREDIMED ) , after a nutritional intervention comparing two MedDiets ( supplemented with either extra-virgin olive oil ( EVOO ) or mixed nuts ) versus a low-fat control diet . Global cognitive performance was examined by Mini-Mental State Examination ( MMSE ) and Clock Drawing Test ( CDT ) after 6.5 years of nutritional intervention . Research ers who assessed the outcome were blinded to group assignment . We used general linear models to control for potential confounding . Results After adjustment for sex , age , education , Apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control ( adjusted differences : + 0.62 95 % CI + 0.18 to + 1.05 , p=0.005 for MMSE , and + 0.51 95 % CI + 0.20 to + 0.82 , p=0.001 for CDT ) . The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control ( adjusted differences : + 0.57 ( 95 % CI + 0.11 to + 1.03 ) , p=0.015 for MMSE and + 0.33 ( 95 % CI + 0.003 to + 0.67 ) , p=0.048 for CDT ) . These results did not differ after controlling for incident depression . Conclusions An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet . IS RCT BACKGROUND Healthy dietary patterns may protect against age-related cognitive decline , but results of studies have been inconsistent . OBJECTIVE We examined associations between Dietary Approaches to Stop Hypertension (DASH)- and Mediterranean-style dietary patterns and age-related cognitive change in a prospect i ve , population -based study . DESIGN Participants included 3831 men and women ≥65 y of age who were residents of Cache County , UT , in 1995 . Cognitive function was assessed by using the Modified Mini-Mental State Examination ( 3MS ) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score . Mixed-effects repeated- measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score . RESULTS The range of rank-order DASH and Mediterranean diet scores was 1661 - 25,596 and 2407 - 26,947 , respectively . Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores . People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 ( P = 0.001 ) . The corresponding difference for Mediterranean quintiles was 0.94 ( P = 0.001 ) . These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [ mean quintile 5 compared with 1 differences : 1.19 ( P < 0.001 ) , 1.22 ( P < 0.001 ) , respectively ] . CONCLUSIONS Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period . Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant-centered diets around the globe BACKGROUND Increased consumption of n-3 ( omega-3 ) long-chain polyunsaturated fatty acids ( LC PUFAs ) , especially eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , may maintain cognitive function in later life . OBJECTIVE We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people . DESIGN At total of 867 cognitively healthy adults , aged 70 - 79 y , from 20 general practice s in Engl and and Wales were r and omly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo . Treatment-allocation codes were obtained from a central computerized r and omization service . Trained research nurses administered a battery of cognitive tests , including the primary outcome , the California Verbal Learning Test ( CVLT ) , at baseline and 24 mo . Intention-to-treat analysis of covariance , with adjustment for baseline cognitive scores , age , sex , and age at leaving full-time education , included 748 ( 86 % ) individuals who completed the study . RESULTS The mean age of participants was 75 y ; 55 % of the participants were men . Withdrawals and deaths were similar in active ( n = 49 and n = 9 , respectively ) and placebo ( n = 53 and n = 8 , respectively ) arms . Mean ( + /-SD ) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo ( 49.9 + /- 2.7 mg EPA/L in the active arm compared with 39.1 + /- 3.1 mg EPA/L in the placebo arm ; 95.6 + /- 3.1 mg DHA/L in the active arm compared with 70.7 + /- 2.9 mg DHA/L in the placebo arm ) . There was no change in cognitive function scores over 24 mo , and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome . CONCLUSIONS Cognitive function did not decline in either study arm over 24 mo . The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study . The Older People And n-3 Long-chain polyunsaturated fatty acids ( OPAL ) Study was registered at www.controlled-trials.com as IS RCT N 72331636 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 IMPORTANCE Cognitive decline is a major cause of disability in stroke survivors . The magnitude of survivors ' cognitive changes after stroke is uncertain . OBJECTIVE To measure changes in cognitive function among survivors of incident stroke , controlling for their prestroke cognitive trajectories . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study of 23,572 participants 45 years or older without baseline cognitive impairment from the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) cohort , residing in the continental United States , enrolled 2003 - 2007 and followed up through March 31 , 2013 . Over a median follow-up of 6.1 years ( interquartile range , 5.0 - 7.1 years ) , 515 participants survived expert-adjudicated incident stroke and 23,057 remained stroke free . EXPOSURE Time-dependent incident stroke . MAIN OUTCOMES AND MEASURES The primary outcome was change in global cognition ( Six-Item Screener [ SIS ] , range , 0 - 6 ) . Secondary outcomes were change in new learning ( Consortium to Establish a Registry for Alzheimer Disease Word-List Learning ; range , 0 - 30 ) , verbal memory ( Word-List Delayed Recall ; range , 0 - 10 ) , and executive function ( Animal Fluency Test ; range , ≥0 ) , and cognitive impairment ( SIS score < 5 [ impaired ] vs ≥5 [ unimpaired ] ) . For all tests , higher scores indicate better performance . RESULTS Stroke was associated with acute decline in global cognition ( 0.10 points [ 95 % CI , 0.04 to 0.17 ] ) , new learning ( 1.80 points [ 95 % CI , 0.73 to 2.86 ] ) , and verbal memory ( 0.60 points [ 95 % CI , 0.13 to 1.07 ] ) . Participants with stroke , compared with those without stroke , demonstrated faster declines in global cognition ( 0.06 points per year faster [ 95 % CI , 0.03 to 0.08 ] ) and executive function ( 0.63 points per year faster [ 95 % CI , 0.12 to 1.15 ] ) , but not in new learning and verbal memory , compared with prestroke slopes . Among survivors , the difference in risk of cognitive impairment acutely after stroke , compared with immediately before stroke , was not statistically significant ( odds ratio , 1.32 [ 95 % CI , 0.95 to 1.83 ] ; P = .10 ) ; however , there was a significantly faster poststroke rate of incident cognitive impairment compared with the prestroke rate ( odds ratio , 1.23 per year [ 95 % CI , 1.10 to 1.38 ] ; P < .001 ) . For a 70-year-old black woman with average values for all covariates at baseline , stroke at year 3 was associated with greater incident cognitive impairment : absolute difference of 4.0 % ( 95 % CI , -1.2 % to 9.2 % ) at year 3 and 12.4 % ( 95 % CI , 7.7 % to 17.1 % ) at year 6 . CONCLUSIONS AND RELEVANCE Incident stroke was associated with an acute decline in cognitive function and also accelerated and persistent cognitive decline over 6 years In this large-scale prospect i ve epidemiological study , we examined associations of long-term adherence to the Mediterranean diet ( MeDi ) and subsequent cognitive function and decline . We included 16,058 women from the Nurses ' Health Study , aged ≥70 y , who underwent cognitive testing by telephone 4 times during 6 y , beginning in 1995 - 2001 , and provided repeated information on diet between 1984 and the first cognitive exam . Primary outcomes were the Telephone Interview for Cognitive Status ( TICS ) and composite scores of verbal memory and global cognition . MeDi adherence was based on intakes of : vegetables , fruits , legumes , whole grains , nuts , fish , red and processed meats , moderate alcohol , and the ratio of monounsaturated : saturated fat . Long-term MeDi exposure was estimated by averaging all repeated measures of diet ( > 13 y , on average ) . In primary analyses of cognitive change , the MeDi was not associated with decline in global cognition or verbal memory . In a secondary approach examining cognitive status in older age , determined by averaging all 4 repeated measures of cognition , each higher quintile of long-term MeDi score was linearly associated with better multivariable-adjusted mean cognitive scores [ differences in mean Z-scores between extreme quintiles of MeDi = 0.06 ( 95 % CI : 0.01 , 0.11 ) ; = 0.05 ( 95 % CI : 0.01 , 0.08 ) ; and = 0.06 ( 95 % CI : 0.03 , 0.10 ) st and ard units ; P-trends = 0.004 , 0.002 , and < 0.001 for TICS , global cognition , and verbal memory , respectively ] . These associations were similar to those observed in women 1 - 1.5 y apart in age . In summary , long-term MeDi adherence was related to moderately better cognition but not with cognitive change in this very large cohort of older women |
10,864 | 16,254,759 | There was strong evidence that work disability duration is significantly reduced by work accommodation offers and contact between healthcare provider and workplace ; and moderate evidence that it is reduced by interventions which include early contact with worker by workplace , ergonomic work site visits , and presence of a RTW coordinator .
For these five intervention components , there was moderate evidence that they reduce costs associated with work disability duration .
Conclusions : Our systematic review provides the evidence base supporting that workplace-based RTW interventions can reduce work disability duration and associated costs , however the evidence regarding their impact on quality -of-life outcomes was much weaker | Introduction : A systematic review was conducted to review the effectiveness of workplace-based return-to-work ( RTW ) interventions . | This study evaluated a two-year multidisciplinary early intervention pilot programme for back-injured nurses employed at a large teaching hospital , using a pre- versus post-programme analysis . The purpose was to ascertain whether this programme could reduce the incidence , morbidity , time lost and cost due to back injuries in the 250 nurses employed on ten targeted high-risk wards . Injuries in the remaining 1395 nurses employed on the other 45 wards were monitored concurrently for comparison . The programme consisted of prompt assessment , treatment and rehabilitation through modified work . Evaluative data were gathered by one research nurse on st and ardized forms at the time of injury , weekly until return to work , and at a six-month follow-up . Time lost and cost data for up to one-year post-injury were derived from workers ' compensation statements . Compared to the two years prior to introduction of the programme , the rates of back injuries and lost-time back injuries decreased by 23 % and 43 % , respectively , on the targeted wards , while these increased on the control wards . Combined expenditure was 32 % lower per injury and 34 % lower per lost-time injury for those in the targeted group who consented to take part in the programme compared to their counterparts on the control wards , as the increased assessment and treatment costs per case attributable to the programme were more than offset by the savings in lower compensation ( wage loss ) costs . This programme thus reduced the incidence and time lost due to back injuries and was cost-beneficial OBJECTIVE Musculoskeletal soft tissue injuries consume considerable re sources in personal suffering , medical care , work absenteeism , and compensation benefits . Our aim was to determine specific clinical and behavioral factors that prognostically influence return to work following musculoskeletal work related injuries . METHODS A longitudinal cohort study was conducted on 148 r and omly selected workers who had not returned to work in 3 months following musculoskeletal soft tissue injury . The cohort was identified from the files of the Workers ' Compensation Board of Ontario , Canada . The workers were interviewed and assessed at 3 , 9 , 15 , and 21 months after injury . The WHO Classification of Impairment , Disabilities and H and icap was used as the conceptual framework . The analysis employed a proportional hazards regression model with allowance for time dependent covariates . RESULTS The rate of return to work for men was 1.5 times that for women , and 20 % less for every 10 year increase in age . Controlling for sex and age , psychological distress and functional disability were associated with a slower rate of return to work . The rate of return to work for workers who were provided with modified jobs was 2 times higher than for those with no such accommodation in employment . CONCLUSION The negative effect of psychological distress and functional disability on return to work rates must be considered in the design and delivery of rehabilitation programming for workers with musculoskeletal soft tissue injuries . The employer 's provision of a " modified job " is important in the prevention of continued disability Study Design . R and omized controlled trial . Objectives . To investigate the effectiveness and costs of a mini-intervention , provided in addition to the usual care , and the incremental effect of a work site visit for patients with subacute disabling low back pain . Summary of Background Data . There is lack of data on cost-effectiveness of brief interventions for patients with prolonged low back pain . Methods . A total of 164 patients with subacute low back pain were r and omized to a mini-intervention group ( A ) , a work site visit group ( B ) , or a usual care group ( C ) . Groups A ( n = 56 ) and B ( n = 51 ) underwent one assessment by a physician plus a physiotherapist . Group B received a work site visit in addition . Group C served as controls ( n = 57 ) and was treated in municipal primary health care . All patients received a leaflet on back pain . Pain , disability , specific and generic health-related quality of life , satisfaction with care , days on sick leave , and use and costs of health care consumption were measured at 3- , 6- , and 12-month follow-ups . Results . During follow-up , fewer subjects had daily pain in Groups A and B than in Group C ( Group A vs. Group C , P = 0.002 ; Group B vs. Group C , P = 0.030 ) . In Group A , pain was less bothersome ( Group A vs. Group C , P = 0.032 ) and interfered less with daily life ( Group A vs. Group C , P = 0.040 ) than among controls . Average days on sick leave were 19 in Group A , 28 in Group B , and 41 in Group C ( Group A vs. Group C , P = 0.019 ) . Treatment satisfaction was better in the intervention groups than among the controls , and costs were lowest in the mini-intervention group . Conclusions . Mini-intervention reduced daily back pain symptoms and sickness absence , improved adaptation to pain and patient satisfaction among patients with subacute low back pain , without increasing health care costs . A work site visit did not increase effectiveness Aims : To develop a model of prognosis for time receiving workers ’ compensation wage replacement benefits in the first year . Methods : A prospect i ve cohort of 907 injured workers off work because of soft tissue injuries was followed for one year through structured telephone interviews and administrative data sources . Workers were recruited at workers ’ compensation cl aim registration . Only those still off work at four weeks post- registration were included in the analysis . Data from several domains ( demographics , clinical factors , workplace factors , recovery expectations ) were collected at approximately two weeks and a subset again at four weeks . Outcome was duration on total temporary wage replacement benefits . Variable selection was carried out in two steps using content experts and backward elimination with the Cox model . Results : Body region specific functional status , change in pain , workplace offers of arrangements for return to work , and recovery expectations were independently predictive of time on benefits . Change in pain and workplace offers interacted , so the largest mutual association occurred for those whose pain was getting worse — that is , reduction in median duration from 112.5 to 32.5 days . Across observed values , widely different recovery profiles of groups of workers result ed ; for example , at four months , only one third of the highest risk group had gone off benefits while over 95 % of the lowest risk group had done so . Conclusions : Focus on a relatively small set of prognostic factors should enable occupational health practitioners to triage injured workers within the first month and concentrate on those requiring additional assistance to return to work This paper describes a participatory ergonomics program aim ed at early return to regular work of workers suffering from subacute occupational back pain and assesses the perceptions of the participants on the implementation of ergonomic solutions in the workplace . The participatory ergonomics program was used in the rehabilitation of workers suffering from subacute back pain for more than 6 weeks , a program that was associated with an increased rate of return to work . The perceptions of the participatory ergonomics participants were assessed 6 months after completion of the ergonomic intervention through a question naire sent to employer representatives , union representatives and injured workers of participating workplaces . About half of the ergonomic solutions were implemented according to the perception of the participants , with a substantial agreement between respondents Study Design . Population ‐based r and omized clinical trial . Objectives . To develop and test a model of management of subacute back pain , to prevent prolonged disability . Summary of Background Data . The present management of back pain seems inadequate , and development of innovative models has been urged . Methods . A model for the treatment of subacute work‐related back pain has been developed and evaluated in a population ‐based r and omized clinical trial . Workers ( n = 130 ) from eligible workplaces in the Sherbrooke area ( N = 31 ) , who had been absent from work for more than 4 weeks for back pain , were r and omized , based on their workplace , in one of four treatment groups : usual care , clinical intervention , occupational intervention , and full intervention ( a combination of the last two ) . The duration of absence from regular work and from any work was evaluated using survival analysis . Functional status and pain were compared at study entry and after 1 year of follow‐up . Results . The full intervention group returned to regular work 2.41 times faster than the usual care intervention group ( 95 % confidence interval 1.19‐4.89 ; P = 0.01 ) . The specific effect of the occupational intervention accounted for the most important part of this result , with a rate ratio of return to regular work of 1.91 ( 95 % confidence interval = 1.18‐3.10 ; P < 0.01 ) . Pain and disability scales demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups , compared with the trend in the usual care intervention group . Conclusions . Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain Two years of prospect i ve data on 416 back injuries were gathered at a 1100-bed acute and tertiary care hospital to assist target prevention efforts . The rate of injury among 1645 nurses was found to be highest for those working on orthopaedic , medicine , neurology , spinal and surgery wards , indicating priorities for prevention . In fact , 51 % of the orthopaedic nurses sustained at least one back injury during the two-year period . Gender did not significantly affect the risk of back injury ; however , injuries were slightly more common in nurses with less seniority and younger nurses were found to be at significantly increased risk of back injury . Almost 63 % of the back injuries which occurred in nurses working 8 h shifts on the high-risk wards occurred during the first two hours of the shift . Lifting and transferring patients with assistance were the two most common mechanisms for back injury ( 22.6 % and 23.3 % , respectively ) . In total , injured nurses attributed 52.3 % of their injuries to inadequate training ; inadequate staffing was given as the primary reason for 13.8 % of the injuries . The results suggest that training in the indications for and use of mechanical devices for lifting/transferring patients requires intensification , and a ' warm-up ' period should also be considered in the face of injuries occurring early in the shift if work activities can not be evenly planned Aims : To test the long term cost-benefit and cost-effectiveness of the Sherbrooke model of management of subacute occupational back pain , combining an occupational and a clinical rehabilitation intervention . Methods : A r and omised trial design with four arms was used : st and ard care , occupational arm , clinical arm , and Sherbrooke model arm ( combined occupational and clinical interventions ) . From the Quebec WCB perspective , a cost-benefit ( amount of consequence of disease costs saved ) and cost-effectiveness analysis ( amount of dollars spent for each saved day on full benefits ) were calculated for each experimental arm of the study , compared to st and ard care . Results : At the mean follow up of 6.4 years , all experimental study arms showed a trend towards cost benefit and cost effectiveness . These results were owing to a small number of very costly cases . The largest number of days saved from benefits was in the Sherbrooke model arm . Conclusions : A fully integrated disability prevention model for occupational back pain appeared to be cost beneficial for the workers ’ compensation board and to save more days on benefits than usual care or partial interventions . A limited number of cases were responsible for most of the long term disability costs , in accordance with occupational back pain epidemiology . However , further studies with larger sample s will be necessary to confirm these results STUDY DESIGN Cluster r and omized controlled trial . OBJECTIVE To evaluate the effectiveness of two strategies to improve the use of active sick leave ( ASL ) for patients with low back pain . SUMMARY OF BACKGROUND DATA ASL is a public sickness benefit scheme offered to promote early return to modified work for temporarily disabled workers . It was poorly used , and the authors design ed two community interventions to strengthen the implementation of ASL based on the results of a study of barriers to use among back pain patients , employers , general practitioners ( GPs ) , and local National Insurance Administration staff . METHODS Sixty-five municipalities in three counties in Norway , r and omly assigned to a passive intervention , a proactive intervention , or a control group . The interventions were targeted at patients on sick leave for low back pain for more than 16 days ( n = 6176 ) , their GPs , employers , and local insurance officers . The passive intervention included reminders about ASL on the sick leave form that GPs must complete , a st and ard agreement to facilitate ASL , targeted information , and a desktop summary for GPs of clinical practice guidelines for low back pain , emphasizing the importance of advice to stay active . The proactive intervention included these elements plus a re source person to facilitate the use of ASL and a continuing education workshop for GPs . The main outcome measure reported here is the proportion of eligible patients that used ASL . RESULTS ASL was used significantly more in the proactive intervention municipalities ( 17.7 % ) compared with the passive intervention and control municipalities ( 11.5 % , P = 0.018 ) . CONCLUSIONS A passive intervention that addressed identified barriers to the use of ASL did not increase its use . Although modest , a proactive intervention did increase its use . The main impact of the intervention was through direct contact and motivating telephone calls to patients . To the extent that GPs ' practice was changed , it was either patient mediated or by patients bypassing their GP Background The causes of prolonged disability due to back pain are multiply determined , involving medical , social , and environmental factors . Possible solutions to the problem of prolonged back pain disability have emerged from recent research but few efforts have been made to transfer evidence -based programs to large community setting s. Objective This article describes three phases of the process of transfer of evidence from rehabilitation research to community practice in the province of Quebec . Methods and Results Phase A : Based on literature review and expert knowledge , the Sherbrooke model was developed and assessed through a population -based , r and omized clinical trial . Results at 1-year follow-up showed quicker return to regular work and improvement of quality of life ; the 6-year follow-up showed the cost-effectiveness of the method .Phase B : Based on the Sherbrooke model experience and recent evidence , a new program addressing the disability paradigm was developed and implemented in the province of Quebec ( Canada ) . Results at 1- and 3-year follow-ups showed that only 24 % of workers were not working owing to their musculoskeletal disorder . The program is presently being tested through a population -based , r and omized clinical trial in a population of construction workers . Phase C : To implement the program at a provincial level , a network for management , research and education in work rehabilitation was developed . An external assessment is presently planned to evaluate return to work and economic outcomes and quality of implementation of the program in various setting STUDY DESIGN A 2-year prospect i ve inception cohort study of back injury in nurses . OBJECTIVES To determine the extent to which characteristics of nurses , of the injury , and of the workplace predict occurrence and duration of time loss from work after back injury . SUMMARY OF BACKGROUND DATA During 2 years , 320 nurses incurred 416 back injuries at a large teaching hospital in Winnipeg , Canada . Nurses injured on preselected wards were targeted for early intervention , including provision of modified work , whereas nurses injured on other wards received the usual care . METHODS Time loss attributable to the back injury during the 6 months after injury was analyzed . Three statistical models were used to examine occurrence of time loss ( logistic regression ) , duration of time loss ( Tobit regression ) , and duration of time loss once an injury incurring time loss had been documented ( least-squares regression ) . RESULTS In 218 of the 416 injuries , the injured nurse consented to interview . Whereas perceived disability was related to whether a time loss injury would ensue , self-reported pain was strongly related to the duration of time loss once an injury had become a time loss injury . Duration of time loss was reduced by participation in the return-to-work program . Mechanism of injury , specifically injury occurring while lifting patients , result ed in greater time loss . CONCLUSIONS Focusing on reducing the perception of disability at the time of injury is critical to preventing time loss , but once time loss has occurred , offer of modified work and attention to pain reduction are warranted . The findings add to the evidence that workplace-based intervention programs can be effective in reducing the morbidity result ing from back injury Studies linking medical costs to behavioral risk and risk-lowering often use means for comparisons , although cl aims data are highly skewed . The result overestimates and obscures the case for work-site health promotion . In this study , high-cost analysis is illustrated in a sample of university employees . Five risk factors were examined : cholesterol , blood pressure , cardiovascular fitness , body fat , and smoking status . Screened employees who released their cl aims ( n = 367 ) were examined against a r and om sample of employees ( n = 587 ) . Linear regression was used to determine the risk of having high cl aims costs within four gender-specific age groups . A formula was then applied to determine that more than 43 % of the cost of medical cl aims was associated with elevated risk . High-cost analysis accounts for the skewness in cl aims data and presents a clear case for work-site health promotion Althoughdoctors are increasingly evaluated on the basis of return-to-work ( RTW ) outcomes , the effect of doctor – patient communication about the workplace and RTW after an occupational injury has received little research attention . The effect of patient-reported doctor communication on duration of disabilitywas examined retrospectively in a 3-year cohort of 325 cl aim ants with alost-time low back injury . Although doctor proactive communication wasassociated with a greater likelihood of RTW during the acute phase ( < 30days of disability ) , this effect disappeared when injury and workloadcharacteristics were taken into account . A positive RTW recommendation wasassociated with about a 60 % higher RTW rate during the subacute/chronic phase(>30 days of disability ) only . Prospect i ve studies are needed to confirmthis effect . The impact of physician communication on RTW is largelyconfounded by injury and workplacefactors Sickness absenteeism caused by musculoskeletal disorders ( MSDs ) is a persistent and costly occupational health challenge . In a prospect i ve controlled trial , we compared the effects on sickness absenteeism of a more proactive role for insurance case managers as well as workplace ergonomic interventions with that of traditional case management . Patients with physician-diagnosed MSDs were r and omized either to the intervention group or the reference group offered the traditional case management routines . Participants filled out a comprehensive question naire at the initiation of the study and after 6 months . In addition , administrative data were collected at 0 , 6 , and 12 months after the initiation of the project . For the entire 12-month period , the total mean number of sick days for the intervention group was 144.9 ( SEM 11.8 ) days/person as compared to 197.9 ( 14.0 ) days in the reference group ( P < 0.01 ) . Compared with the reference group , employees in the intervention group significantly more often received a complete rehabilitation investigation ( 84 % versus 27 % ) . The time for doing this was reduced by half ( 59.4 ( 5.2 ) days versus 126.8 ( 19.2 ) , P < .01 ) . The odds ratio for returning to work in the intervention group was 2.5 ( 95 % confidence interval 1.2–5.1 ) as compared with the reference group . The direct cost savings were USD 1195 per case , yielding a direct benefit-to-cost ratio of 6.8 . It is suggested that the management of MSDs should to a greater degree focus on early return to work and building on functional capacity and employee ability . Allowing the case managers a more active role as well as involving an ergonomist in workplace adaptation meetings might also be beneficial OBJECTIVES --The aim was to combat occurrence of chronic occupational back pain . METHODS --A multidisciplinary model to manage back pain that includes both clinical and ergonomic approaches has been developed . Early detection , early clinical and ergonomic evaluations , and early active treatment make up the cornerstone of management . Detection of cases starts after four weeks of absence from work . An ergonomic intervention is implemented at six weeks . A medical specialist is involved at eight weeks . If return to work is not possible after 12 weeks , a functional recovery therapy followed by a therapeutic return to work is implemented . A multidisciplinary team decides if return to original or modified work is possible or if vocational rehabilitation is necessary . This model has been implemented by the investigators in the Sherbrooke ( Quebec , Canada ) area , and is presently being evaluated through a r and omised trial in 31 industrial settlements ( about 20,000 workers ) . A cluster r and omisation of industries and workers will allow separate testing of ergonomic and clinical interventions . RESULTS --One year after implementation , 31 of 35 of the eligible industrial sites participated in the study and 79 of 88 of the eligible workers affected by recent back pain had agreed to participate . Ergonomic and clinical interventions have been implemented as planned . Only three workers dropped out . Hence this global clinical and ergonomic management programme has been shown to be feasible in a general population . CONCLUSION --A global management programme of back pain joining ergonomic and clinical intervention with a multidisciplinary approach has not been tested yet . Linking these two strategies in a same multidisciplinary team represents a systemic approach to this multifactorial ailment . During the first year of this trial we did not find any conflict between these two interventions from the employer 's or worker 's point of view Study Design . R and omized controlled trial . Objectives . To Investigate the long-term effectiveness , costs , and effect modifiers of a mini-intervention , provided in addition to the usual care , and the incremental effect of a worksite visit for patients with subacute disabling low back pain ( LBP ) . Summary of Background Data . A mini-intervention was earlier proved to be an effective treatment for subacute LBP . Whether the beneficial effect is sustained is not known . Furthermore , modifiers of a treatment effect are largely unknown . Methods . A total of 164 patients with subacute LBP r and omized into a mini-intervention ( A , n = 56 ) , a mini-intervention plus a worksite visit ( B , n = 51 ) , or the usual care ( C , n = 57 ) . Mini-intervention consisted of a detailed assessment of the patients ’ history , beliefs , and physical findings by a physician and a physiotherapist , followed by recommendations and advice . The usual care patients received the conventional care . Pain , disability , health-related quality of life , satisfaction with care , days on sick leave , and health care consumption and costs were measured during a 24-month follow-up . Thirteen c and i date modifiers were tested for each outcome . Results . There were no differences between the three treatment arms regarding the intensity of pain , the perceived disability , or the health-related quality of life . However , mini-intervention decreased occurrence of daily ( A vs. , C , P = 0.01 ) and bothersome ( A vs. C , P < 0.05 ) pain and increased treatment satisfaction . Costs result ing from LBP were lower in the intervention groups ( A 4670 Euros , B 5990 Euros ) than in C ( C 9510 Euros ) ( A vs. C , P = 0.04 ; and B vs. C , not significant ) . The average number of days on sick leave was 30 in A , 45 in B , and 62 in C ( A vs. C , P = 0.03 ; B vs. C , not significant ) . The perceived risk for not recovering was the strongest modifier of treatment effect . Mental and mental-physical workers in A and B were less often on sick leave than those in C. Conclusions . Mini-intervention is an effective treatment for subacute LBP . Despite lack of a significant effect on intensity of low back pain and perceived disability , mini-intervention , including proper recommendations and advice , according to the “ active approach , ” is able to reduce LBP-related costs . The perceived risk of not recovering was the strongest modifier of treatment effect . In alleviating pain , the intervention was most effective among the patients with a high perceived risk of not recovering Study Design . A pre‐ versus postintervention with concurrent control group design was used to investigate the effect of a workplace‐based early intervention program on perception of disability in nurses with low back injury . Objectives . This report examines changes over time in the components of the Oswestry Low Back Pain and Disability Question naire in two groups of back‐injured nurses‐those who received the early intervention program ( study ) and those who were not offered the program ( control ) . Summary of Background Data . Early intervention programs can decrease morbidity , time lost from work , and compensation costs . Although perception of disability decreases , some residual disability remains , the nature of which is not clear . Methods . The Oswestry Low Back Pain and Disability Question naire scores of 40 study nurses and 118 control nurses at time of injury and at 6 months after injury were examined . Analysis of variance was used to compare changes in mean overall scores over time . The proportion of nurses reporting disability on individual components of the Oswestry Low Back Pain and Disability Question naire at each time period was compared with the results of a chi‐square test . Results . Overall Oswestry Low Back Pain and Disability Question naire scores were similar between study and control nurses at time of injury , but were significantly lower in study nurses at 6 months after injury . However , scores of individual Oswestry Low Back Pain and Disability Question naire components that related to job dem and s increased over time ; this was most apparent in lifting , particularly in study nurses . Conclusions . Although overall perception of disability decreased 6 months after injury , particularly in study nurses , disability in job‐related activities persisted . Residual disability after back injury should be addressed in workplace‐based prevention programs Objectives . This pilot study explored a broad range of work-related outcomes for occupational low back injuries . Methods . A model of occupational outcomes and a survey instrument were developed on the basis of interviews , expert opinion , and literature review s. New Hampshire workers who had an occupational back injury a year before the study were sample d from first reports of injury and sent a mailed survey about their postinjury experiences and related factors . Results . Of 251 r and omly selected cases , a valid address could be identified for 121 , and 99 patients responded . Almost 60 % of the respondents had lost 1 week of work or more . At 1 year after injury , half of the respondents had returned to their preinjury job and employer , and 20 % were unemployed , half of them because of the injury . Most working respondents reported no decrease in their work capacity . However , 68 % still had pain exacerbated by work , and 47 % worried that their condition would worsen with continued work . Reinjury occurred in 42 % of the respondents . The work-related outcome measures were largely independent of each other . Exploratory multivariate analyses demonstrated unique patterns of factors associated with each outcome . Reinjury risk was significantly greater in respondents whose employers offered accommodations or whose postinjury jobs had greater ergonomic risk . The small sample size limited the ability to achieve statistically significant results in multivariate analyses . Conclusions . Simply measuring return to work did not appear to capture the full range of job-related consequences from occupational back injuries in this pilot evaluation . Timing of return to work , occupational ergonomic risks , and appropriate job modifications appeared to be particularly important in a safe return to the job after an occupational low back injury . Results suggest opportunities to address risk factors that may improve work outcomes Study Design . A r and omized controlled trial in occupational health practice was conducted . Objective . To study the efficacy of early management of workers with low back pain by occupational physicians , as compared with management by the supervisor only . Summary of Background data . Health care and university workers with back pain and on sick leave for less than 1 month were included in the study . Methods . Patients with low back pain for at least 10 days on sick leave were r and omly assigned to early management by the occupational physician ( n = 61 ) or to a reference group with management by the worker ’s supervisor during the first 3 months of sick leave ( n = 59 ) . The patients were observed for 1 year and compared in terms of time until return to work , pain intensity , functional disability , and general health perception . The occupational physicians were provided with management guidelines . Results . No significant differences were found after 3 and 12 months of follow-up evaluation in terms of time until return to work ( hazard ratio , 1.3 ; 95 % CI , 0.90–1.90 ) or in terms of other health outcomes . Recurrences , however , occurred more frequently in the intervention group , but the total duration of sick leave in 1 year did not differ between the groups . Conclusions . The findings do not show a significant positive effect of an early intervention by occupational physicians on workers with low back pain . This might reflect the early phase of disability or the low intensity of the intervention result ing from overestimation of the physicians ’ compliance with the guidelines |
10,865 | 26,276,278 | Conclusions Agreement between investigators in assessing participants ’ answers is satisfactory .
The results indicate that conducting a full-scale trial is feasible . | Background Evidence suggests that systematic review s are used infrequently by physicians in clinical decision-making .
One proposed solution is to create filtered re sources so that information is vali date d and refined in order to be read quickly .
Two shortened systematic review formats were developed to enhance their use in clinical decision-making .
Methods To prepare for a full-scale trial , we conducted a pilot study to test methods and procedures in order to refine the processes . | Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as " feasibility " or " vanguard " studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format This is a prospect i ve study of clinical questions generated in primary care consultations and a comparison of two approaches to answering those clinical questions . Twenty-one doctors in a university-based primary care clinic su bmi tted 78 clinical questions arising from patient consultations during 24 clinic days ( 0.01 question per patient encounter ) . These doctors subsequently found answers to 40 % of their questions but were satisfied with only 67 % of these answers . The investigators were able to provide answers for 95 % of the questions asked and the doctors rated these answers as satisfactory in 86 % of instances . Answers obtained by investigators had significantly higher satisfaction score than those obtained by doctors ' search ( p = 0.002 ) . The two main findings of this study are ( 1 ) almost all questions arising in clinic setting could be answered by intensive search ; ( 2 ) answers found by intensive search es were judged to be more satisfactory than those found routinely by doctors . Provision of an information retrieval service in addition to training in the search ing and appraisal of medical literature are possible solutions to the information needs of busy clinicians OBJECTIVE To evaluate the quality of evidence reporting , breadth of coverage , and timeliness of content updating of 10 selected online medical texts . STUDY DESIGN AND SETTING Each text was assessed for quality based on an 11-item scale , which included items related to editorial policy and updating , appraisal , and transparent incorporation of newly published clinical research and evidence -based guidelines . Breadth of coverage was determined by the percentage of 60 r and omly selected International Classification of Diseases 10 ( ICD-10 ) codes covered by each of the texts . The same 60 ICD-10 codes were used to obtain a sample of topic chapters for the assessment of timeliness of up date s. RESULTS Quality scores ranged from a high of 9 of 11 points ( Clinical Evidence ) to a low of 0 of 11 points ( PEPID ) , with a mean score of 6.7 . Breadth of coverage ranged from 83 % of r and omly selected topics covered ( UpTo Date ) to 25 % ( Clinical Evidence ) , with 6 of 10 texts covering 60 % or more ; average coverage across all texts was 57 % . Variability was also observed with regard to average time since last content up date , ranging from 3.5 ( DynaMed ) to 29 months ( First Consult ) , with an average time since up date of 12.4 months . CONCLUSION No single re source was ideal and those seeking answers to clinical questions are well-advised not to rely solely on a single point-of-care product OBJECTIVE Usage of computer re sources at the point of care has a positive effect on physician decision making . Pediatricians ' information-seeking behaviors are not well characterized . The goal of this study was to characterize quantitatively the information-seeking behaviors of general pediatricians and specifically compare their use of computers , including digital libraries , before and after an educational intervention . METHODS General pediatric residents and faculty at a US Midwest children 's hospital participated . A control ( year 1 ) versus intervention group ( year 2 ) research design was implemented . Eligible pediatrician pools overlapped , such that some participated first in the control group and later as part of the intervention . The intervention group received a 10-minute individual training session and h and out on how to use a pediatric digital library to answer professional questions . A general medical digital library was also available . Pediatricians in both the control and the intervention groups were surveyed using the critical incident technique during 2 6-month time periods . Both groups were telephoned for 1- to 2-minute interviews and were asked , " What pediatric question ( s ) did you have that you needed additional information to answer ? " The main outcome measures were the differences between the proportion of pediatricians who use computers and digital libraries and a comparison of the number of times that pediatricians use these re sources before and after intervention . RESULTS A total of 58 pediatricians were eligible , and 52 participated ( 89.6 % ) . Participant demographics between control ( N = 41 ; 89.1 % ) and intervention ( N = 31 ; 70.4 % ) were not statistically different . Twenty pediatricians were in both groups . Pediatricians were slightly less likely to pursue answers after the intervention ( 94.7 % vs 89.2 % ) ; the primary reason cited for both groups was a lack of time . The pediatricians were as successful in finding answers in each group ( 95.7 % vs 92.7 % ) , but the intervention group took significantly less time ( 8.3 minutes vs 19.6 minutes ) . After the intervention , pediatricians used computers and digital libraries more to answer their questions and spent less time using them . CONCLUSION This study showed higher rates of physician questions pursued and answered and higher rates of computer use at baseline and after intervention compared with previous studies . Pediatricians who seek answers at the point of care therefore should begin to shift their information-seeking behaviors toward computer re sources , as they are as effective but more time-efficient BACKGROUND Clinicians often rely on review material rather than analysis of primary research to guide therapy . Systematic review s use methods to insure thoroughness and to minimize bias , but many clinicians are not familiar with systematic review s and continue to rely on narrative review s. OBJECTIVES To determine whether a traditional narrative review or a systematic review is perceived to be more useful . METHODS A clinical scenario ( patient with chronic Crohn 's disease considered for azathioprine therapy ) was circulated to gastroenterologists , along with a narrative review of therapy ( including azathioprine ) for inflammatory bowel disease written by an acknowledged expert , or with a systematic Cochrane review of the use of azathioprine for this disease . Whether knowledge of authors hip and journal source influences the perception of usefulness of a narrative review was investigated . RESULTS The Cochrane review was rated significantly more highly than the narrative review on a 100 mm visual analogue scale ( 21.3 mm ; 95 % CI 14.5 to 28 mm ) . The proportion of respondents who considered the review to be a useful guide was also higher in the group that received the Cochrane review ( 91 % ) than in the group that received the narrative review , with author and journal concealed ( 62 % ) or identified ( 70 % ) ( P<0.001 for both comparisons ) . Ratings from the two groups that received the narrative review were not significantly different . CONCLUSIONS The focused systematic review was perceived to be more useful than a traditional broad narrative review as a guide to making a decision concerning the use of specific therapy . The possible strengths of systematic review s should be more fully investigated . If there is additional evidence supporting their greater value to clinicians , they should be made more widely available to clinicians and their strengths should be publicized OBJECTIVE To measure the effects of a summary -of- findings ( SoF ) table on user satisfaction , underst and ing , and time spent finding key results in a Cochrane review . STUDY DESIGN AND SETTING We r and omized participants in an evidence -based practice workshop ( r and omized controlled trial [ RCT ] I ) and a Cochrane Collaboration entities meeting ( RCT II ) to receive a Cochrane review with or without an SoF table . In RCT I , we measured user satisfaction . In RCT II , we measured correct comprehension and time spent finding key results . RESULTS RCT I : Participants with the SoF table ( n=47 ) were more likely to " agree " or " strongly agree " that it was easy to find results for important outcomes than ( n=25 ) participants without the SoF table-68 % vs. 40 % ( P=0.021 ) . RCT II : Participants with the SoF table ( n=18 ) were more likely to correctly answer two questions regarding results than ( n=15 ) those without the SoF table : 93 % vs. 44 % ( P=0.003 ) and 87 % vs. 11 % ( P<0.001 ) . Participants with the SoF table spent an average of 90 seconds to find key information compared with 4 minutes for participants without the SoF table ( P=0.002 ) . CONCLUSION In two small trials , we found that inclusion of an SoF table in a review improved underst and ing and rapid retrieval of key findings compared with review s with no SoF table R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community |
10,866 | 23,032,138 | Low- quality evidence did not show any statistically significant effect of coffee consumption on BP or the risk of hypertension .
Given the quality of the currently available evidence , no recommendation can be made for or against coffee consumption as it relates to BP and hypertension | CONTEXT Coffee is one of the most widely consumed beverages worldwide and is known to acutely raise blood pressure ( BP ) , but the effects of chronic consumption on BP is unclear .
OBJECTIVES To conduct a systematic review and meta- analysis of available r and omized controlled trials ( RCTs ) and cohort studies to assess the effect of chronic coffee consumption on BP and the development of hypertension . | This study assessed the effects of regular coffee drinking on 24-hour ambulatory blood pressure ( ABP ) in normotensive and hypertensive older men and women . Twenty-two normotensive and 26 hypertensive , nonsmoking men and women , with a mean age of 72.1 years ( range , 54 to 89 years ) , took part in the study . After 2 weeks of a caffeine-free diet , subjects were r and omized to continue with the caffeine-free diet and abstain from caffeine-containing drinks or drink instant coffee ( 5 cups per day , equivalent to 300 mg caffeine per day ) in addition to the caffeine-free diet for a further 2 weeks . Change in systolic and diastolic blood pressures ( SBP , DBP ) determined by 24-hour ambulatory BP monitoring showed significant interactions between coffee drinking and hypertension status . In the hypertensive group , rise in mean 24-hour SBP was greater by 4.8 ( SEM , 1.3 ) mm Hg ( P=0.031 ) and increase in mean 24-hour DBP was higher by 3.0 ( 1.0 ) mm Hg ( P=0.010 ) in coffee drinkers than in abstainers . There were no significant differences between abstainers and coffee drinkers in the normotensive group for 24-hour , daytime , or nighttime SBP or DBP . In older men and women with treated or untreated hypertension , ABP increased in coffee drinkers and decreased in abstainers . Restriction of coffee intake may be beneficial in older hypertensive individuals CONTEXT Caffeine acutely increases blood pressure , but the association between habitual consumption of caffeinated beverages and incident hypertension is uncertain . OBJECTIVE To examine the association between caffeine intake and incident hypertension in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study conducted in the Nurses ' Health Studies ( NHSs ) I and II of 155,594 US women free from physician-diagnosed hypertension followed up over 12 years ( 1990 - 1991 to 2002 - 2003 question naires ) . Caffeine intake and possible confounders were ascertained from regularly administered question naires . We also tested the associations with types of caffeinated beverages . MAIN OUTCOME MEASURE Incident physician-diagnosed hypertension . RESULTS During follow-up , 19,541 incident cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in NHS II . In both cohorts , no linear association between caffeine consumption and risk of incident hypertension was observed after multivariate adjustment ( NHS I , P for trend = .29 ; NHS II , P for trend = .53 ) . Using categorical analysis , an inverse U-shaped association between caffeine consumption and incident hypertension was found . Compared with participants in the lowest quintile of caffeine consumption , those in the third quintile had a 13 % and 12 % increased risk of hypertension , respectively ( 95 % confidence interval in NHS I , 8%-18 % ; in NHS II , 6%-18 % ) . When study ing individual classes of caffeinated beverages , habitual coffee consumption was not associated with increased risk of hypertension . By contrast , consumption of cola beverages was associated with an increased risk of hypertension , independent of whether it was sugared or diet cola ( P for trend < .001 ) . CONCLUSION No linear association between caffeine consumption and incident hypertension was found . Even though habitual coffee consumption was not associated with an increased risk of hypertension , consumption of sugared or diet cola was associated with it . Further research to eluci date the role of cola beverages in hypertension is warranted Coffee consumption has been associated with elevated plasma cholesterol . One hundred eighty-one men consumed a st and ard caffeinated coffee for 2 mo followed by r and omization to continue caffeinated coffee ( control ) , change to decaffeinated coffee or no coffee for 2 mo . Plasma low-density-lipoprotein ( LDL ) cholesterol and apolipoprotein B concentrations increased significantly ( 0.12 + /- 0.65 mmol/L , P less than 0.025 ; 0.06 + /- 0.12 g/L , P less than 0.0004 , respectively ) in the group that changed to decaffeinated coffee . In a subgroup ( n = 51 ) , post-heparin lipoprotein lipase decreased significantly more ( -270 mmol free fatty acids . L-1.h-1 , P less than 0.003 ) in the decaffeinated-coffee group . Resting heart rate and blood pressure did not change significantly . Change from caffeinated to decaffeinated coffee increased plasma LDL cholesterol and apolipoprotein B whereas discontinuation of caffeinated coffee revealed no change . This finding suggests that a coffee component other than caffeine is responsible for the LDL cholesterol , apolipoprotein B , and lipase activity changes reported in this investigation BACKGROUND Only 2 prospect i ve studies have previously investigated the association between coffee consumption and incident hypertension , and the findings are equivocal . OBJECTIVE The objective was to determine the relation between coffee consumption and the incidence of antihypertensive drug treatment . DESIGN We prospect ively followed 24 710 Finnish subjects aged 25 - 64 y without a history of antihypertensive drug treatment , coronary heart disease , or stroke at baseline . Daily coffee consumption was assessed by question naires . RESULTS During a mean follow-up period of 13.2 y , 2505 participants started antihypertensive drug treatment . The multivariate-adjusted ( age , sex , study year , education , leisure-time physical activity , smoking , body mass index , high total cholesterol , history of diabetes , and alcohol , tea , fruit , vegetable , sausage , and bread consumption ) hazard ratios for antihypertensive drug treatment associated with the amount of coffee consumed daily ( 0 - 1 , 2 - 3 , 4 - 5 , 6 - 7 , or > or=8 cups ) were 1.00 , 1.29 ( 95 % CI : 1.09 , 1.54 ) , 1.26 ( 95 % CI : 1.06 , 1.49 ) , 1.24 ( 95 % CI : 1.04 , 1.48 ) , and 1.14 ( 95 % CI : 0.94 , 1.37 ) ( P for trend = 0.024 ) , respectively . This trend became marginally significant after additional adjustment for baseline systolic blood pressure ( P for trend = 0.077 ) . CONCLUSIONS The results indicate that coffee drinking seems to increase the risk of antihypertensive drug treatment , and this risk was higher in subjects with low-to-moderate coffee intakes ; however , there was no significantly increased trend in drinkers of approximately 1 cup ( 100 mL)/d or > or=8 cups/d BACKGROUND AND AIM Coffee is rich in chlorogenic acids ( CGA ) , whose metabolites may have beneficial effects such as anti-hypertensive effects . However , trial results concerning the effects of coffee on blood pressure ( BP ) are not consistent . A recent study suggested that hydroxyhydroquinone ( HHQ ) , produced by the roasting of green coffee beans , inhibits the effect of CGA . In the present study , the dose-response for CGA in HHQ-free coffee on BP were investigated in mildly hypertensive men and women . METHODS AND RESULTS The trial design was a double-blind , r and omized controlled trial , with five study groups including , control , zero-dose , low-dose , middle-dose and high-dose . The control beverage was identical to ordinary coffee . The others contained reduced HHQ levels , compared to ordinary coffee , and the CGA were adjusted in target concentration . A total of 203 subjects were r and omly allocated . Each subject drank one cup of coffee per day . The study involved a screening and a baseline observation period of 6 weeks and an intervention period of 4 weeks . BP response showed CGA has an anti-hypertensive effect in a dose-dependent manner in HHQ-free coffee , and ordinary coffee showed almost no effect . As a result , a significant correlation between BP change and the three dose-response patterns was observed ( p<0.001 ) . CONCLUSIONS This study demonstrates a dose-dependent decrease in BP for CGA in HHQ-free coffee The effects of coffee on blood pressure and heart-rate and the mediating effect of two common brewing methods , were studied in a r and omized trial in 107 young , normotensive adults . After a three-week run-in period , subjects were r and omly assigned to one of three groups , receiving either ( 1 ) 4 - 6 cups filtered coffee per day , ( 2 ) 4 - 6 cups boiled coffee per day , or ( 3 ) no coffee at all for a period of nine weeks . Because all participants consumed filtered coffee before the trial , the group continuing on filtered coffee was considered as the reference group . Both systolic ( SBP ) and diastolic blood pressure ( DBP ) decreased in the abstinence group . Compared to the filter group , only the fall in SBP after 9 weeks was statistically significant , -6.1 mmHg ( 95 % confidence limits -10.8 , -1.4 ) . After adjustment for SBP at baseline and body weight change during the study , the observed reduction decreased , to -3.4 mmHg ( -7.1 , 0.3 ) . The patterns for SBP and DBP were remarkably similar in the groups using either filtered coffee or boiled coffee . After 9 weeks of boiled coffee , mean changes from baseline for SBP and DBP were 0.4 mmHg ( -3.7 , 4.5 ) and -0.1 mmHg ( -3.4 , 3.2 ) , compared to the filter group . The heart rate showed a slight , non-significant decrease in the abstinence group . In conclusion , these findings suggest that abstinence from coffee for a period of several weeks may slightly reduce blood pressure in young normotensive subjects In a double-blind crossover trial , the effect of 4 week daily ingestion of eight cups of regular coffee ( corresponding to 504 mg caffeine ) vs eight cups of decaffeinated coffee was studied . Blood pressure , heart rate and urinary catecholamines were measured in eight healthy , young volunteers . In both groups , regular coffee immediately led to a significant increase in mean blood pressure ( + 3 and + 5 mm Hg respectively ) . The difference between both groups , however , existed only in the first 3 to 5 days of ingestion of regular coffee . On day 5 after ingestion of regular coffee , and thereafter in weekly intervals , no significant increase in catecholamine excretion was observed . The data suggest that long-term consumption of large amounts of coffee leads to only a small and transient rise in mean blood pressure . This may be due to an adaptation phenomenon . Therefore , continuous heavy coffee ingestion ( eight cups/day for 4 weeks ) by young persons does not appear to involve a risk of the development of hypertension Objective : Earlier studies and trials have shown a serum cholesterol raising effect of unfiltered coffee , which is reduced by about 80 % in filtered coffee . Recent cross-sectional studies and trials , however , have indicated that filtered coffee may have a more pronounced serum cholesterol raising effect than previously anticipated . The objective of this controlled study was to assess the effects of the intake and abstention of filtered brewed coffee on blood lipids . Design : A prospect i ve , controlled study with four consecutive trial periods . The first and third periods were 3 weeks of total coffee abstention . The second and fourth periods consisted of 4 weeks with the subjects consuming 600 ml filter brewed coffee/day . Setting : Free-living population . Volunteers . Subjects : A total of 121 healthy , nonsmoking men and women aged 29–65 y. Interventions : Not applicable . Main outcome measures : Serum total cholesterol , serum HDL cholesterol , serum triglycerides , serum lipoprotein ( a ) ( Lp(a ) ) , blood pressure and heart rate . Results : The two coffee abstention periods were associated with a decline in serum cholesterol of 0.22 mmol/l ( 95 % CI −0.31 , −0.13 ) and 0.36 mmol/l ( 95 % CI −0.46 , −0.26 ) , respectively . Filtered coffee/day 600 ml increased serum cholesterol by 0.25 mmol/l ( 95 % CI 0.15 , 0.36 ) and 0.15 mmol/l ( 95 % CI 0.04 , 0.26 ) during the two coffee drinking periods . Conclusions : Coffee abstention for 3 weeks decreased total serum cholesterol by 0.22–0.36 mmol/l . A volume of 600 ml ( about four cups ) of filtered coffee/day during 4 weeks raised total serum cholesterol by 0.15–0.25 mmol/l . Sponsorship : None Background . The longitudinal relationship between coffee use and hypertension is not well known . Aim . We did a prospect i ve study to investigate if there is a temporal relationship between coffee consumption and development of sustained hypertension . Method . We assessed 1107 white subjects with elevated blood pressure who were followed up for 6.4 years . Coffee intake and other life‐style factors were ascertained from regularly administered question naires . Incident physician‐diagnosed hypertension was the outcome measure . Results . During the follow‐up , 561 subjects developed sustained hypertension , whereas 546 subjects did not meet the criteria for treatment . Coffee drinkers developed sustained hypertension more frequently than abstainers ( 53.1 % versus 43.9 % , P = 0.007 ) . The incidence of hypertension did not differ between moderate and heavy coffee drinkers . Kaplan‐Meier analysis confirmed that sustained hypertension was developed more frequently by coffee drinkers compared with nondrinkers ( P<0.001 ) . The adjusted relative risk of hypertension was greater in both categories of coffee drinking than in abstainers ( hazard ratio , 95 % confidence limit ( CL ) = 1.24 , 1.06–1.44 ) . The risk of hypertension associated with coffee drinking increased gradually with increasing level of alcohol use ( adjusted P for interaction = 0.005 ) . Conclusions . In subjects screened for stage 1 hypertension a nonlinear association was found between coffee consumption and development of sustained hypertension BACKGROUND Whether the increase in blood pressure with coffee drinking seen in clinical trials persists over time and translates into an increased incidence of hypertension is not known . METHODS We assessed coffee intake in a cohort of 1017 white male former medical students ( mean age , 26 years ) in graduating classes from 1948 to 1964 up to 11 times over a median follow-up of 33 years . Blood pressure and incidence of hypertension were determined annually by self-report , demonstrated to be accurate in this cohort . RESULTS Consumption of 1 cup of coffee a day raised systolic blood pressure by 0.19 mm Hg ( 95 % confidence interval , 0.02 - 0.35 ) and diastolic pressure by 0.27 mm Hg ( 95 % confidence interval , 0.15 - 0.39 ) after adjustment for parental incidence of hypertension and time-dependent body mass index , cigarette smoking , alcohol drinking , and physical activity in analyses using generalized estimating equations . Compared with nondrinkers at baseline , coffee drinkers had a greater incidence of hypertension during follow-up ( 18.8 % vs. 28.3 % ; P = .03 ) . Relative risk ( 95 % confidence interval ) of hypertension associated with drinking 5 or more cups a day was 1.35 ( 0.87 - 2.08 ) for baseline intake and 1.60 ( 1.06 - 2.40 ) for intake over follow-up . After adjustment for the variables listed above , however , these associations were not statistically significant . CONCLUSION Over many years of follow-up , coffee drinking is associated with small increases in blood pressure , but appears to play a small role in the development of hypertension Recent studies suggest that chlorogenic acids , which are the main components of the polyphenol class in coffee , decrease blood pressure , and that hydroxyhydroquinone ( HHQ ) , which is generated by roasting coffee beans , inhibits the antihypertensive effect of chlorogenic acids in brewed coffee . Here , we examined the vasoreactivity and antihypertensive effects of HHQ-reduced coffee in mild hypertension . The study design was a double blind , r and omized , placebo-controlled intervention study , with a 4-week run-in period , followed by an 8-week test beverage ingestion period . The subjects were Japanese men and women with mild hypertension and vascular failure , who were not taking any antihypertensive drugs . During the test beverage ingestion period , the subjects ingested either active or placebo HHQ-reduced coffee ( chlorogenic acids per 184 ml of coffee : active , 300 mg ; and placebo , 0 mg ) daily . Subjects were r and omly divided into two groups : active group ( n=9 ) and placebo group ( n=12 ) . In the active beverage group , endothelium-dependent , flow-mediated vasodilation impairment was significantly ameliorated and systolic blood pressure was significantly decreased from the baseline , but not in the placebo group . There were no test beverage consumption-related changes in other parameters that may influence blood pressure , such as pulse , cardiac output , body weight or 24-h urine volume . Ingestion of the active beverage significantly decreased urinary isoprostane levels , suggesting a reduced oxidative stress . These findings indicate that HHQ-reduced coffee decreased blood pressure in subjects with mild hypertension . The decreased blood pressure was associated with improved vascular endothelial function In order to evaluate the effects of ' espresso ' Italian coffee on resting flow , blood pressure , and peripheral resistance , 15 non-coffee drinking healthy volunteers received 2 cups of regular coffee , 200 mg purified caffeine or placebo in a latin square double-blind crossover protocol . Before and 30 , 60 , 90 and 120 min after ingestion , segmental resting flow and BP were measured and peripheral resistance was calculated . An echocardiogram was also performed before and 60 and 120 min after caffeine intake . Both regular coffee and caffeine produced a significant decrease in resting flow and a significant increase in resistance ; both systolic and diastolic BP also increased , although not significantly . No variation was observed in heart rate and in cardiac contractility . Placebo ( highly decaffeinated coffee for regular coffee and china bitter extract for caffeine ) did not produce any haemodynamic effect . In five other healthy volunteers used to drinking more than 5 cups of coffee a day , coffee administration had no effect . These data demonstrate that the caffeine contained in espresso Italian coffee is a vasoconstrictor agent whose effects however are completely blunted in usual coffee drinkers as a consequence of adaptation Our previous study revealed the antihypertensive effects of green coffee bean extract ( GCE ) ingestion in spontaneously hypertensive rats . We suggested that this antihypertensive action was due to the fact that GCE contains chlorogenic acid ( CQA ) as a major phenolic compound , and CQA in turn contains ferulic acid as a metabolic component that acts on nitric oxide ( NO ) derived from the vascular endothelium . In this study , the effects of GCE on blood vessels were evaluated in healthy males . The subjects were 20 healthy males with reduced vasodilation responses measured by strain gauge plethysmograms ( SPG ) to ischemic reactive hyperemia . Of the 20 subjects , 10 ( mean age , 37.2 years ) ingested a test drink containing GCE ( CQA : 140 mg/day ) , and the other 10 ( mean age , 34.8 years ) ingested a placebo drink for 4 months . During the ingestion period , SPG , pulse wave velocity ( PWV ) , and serum biochemical parameters were measured , and acceleration plethysmograms ( APG ) were taken . The reactive hyperemia ratio ( RHR ) in the test drink group began to increase after ingestion for 1 month and was significantly higher ( p < 0.05 ) than that in the placebo group after ingestion for 3 months and 4 months . In addition , after ingestion for 4 months , the test drink group showed a significant decrease ( p < 0.01 ) in the plasma total homocysteine level compared with the pre-ingestion level . However , there were no significant differences in PWV or APG between the test drink group and the placebo drink group . The improvement in RHR after ingestion of a drink containing GCE suggested an improvement in vasoreactivity by this component OBJECTIVE To examine the effect of moderate coffee consumption on blood pressure over a prolonged period of time . Previous work in this area has used primarily purified caffeine . DESIGN A prospect i ve , r and omized , crossover clinical trial . SETTING A hypertension specialty outpatient clinic at the University of Tennessee , Memphis . PATIENTS Healthy , young , white men who were moderate coffee drinkers ( less than 6 cups/day ) were recruited . Twenty-four subjects were r and omized and 21 ( average age 35.5 years ) completed the trial . INTERVENTIONS Subjects were r and omized to one of two groups : Group A drank three or more cups of coffee/day for two months , then crossed over to abstaining from coffee for two months ; group B abstained from coffee first , then crossed over to drinking coffee . Only filter-brewed coffee was used . Subjects were seen at monthly intervals for blood pressure measurements . MEASUREMENTS AND MAIN RESULTS The average coffee consumption was 3.6 cups/day during the coffee-drinking phases . There was no difference between the coffee-drinking phase and the abstention phase in either systolic blood pressure ( 110.1 mmHg vs. 108.0 mmHg , respectively ; 95 % CI of difference -7.3 , 2.5 ) or diastolic blood pressure ( 67.2 mmHg vs. 69.6 mmHg , respectively ; 95 % CI of difference -2.2 , 6.4 ) . CONCLUSIONS Moderate daily consumption of coffee does not elevate blood pressure The question of whether long-term elimination of coffee from the diet lowers blood pressure has not been settled . Consumption of Sc and inavian-style “ boiled coffee ” is associated with coronary heart disease . However , little is known about the effect of brewing method on the blood pressure-raising potential of coffee . We have studied the effects on blood pressure and heart rate of total elimination of coffee and tea in comparison with drinking boiled coffee consumed as such , or boiled coffee consumed after filtration through paper filter . Thirty-one women and 33 men first consumed 6 cups/day of boiled and filtered coffee for 17 days . Then they were r and omly divided into three groups , which for the next 79 days received either unfiltered boiled coffee ( caffeine content 860 mg/1 ) , boiled- and -filtered coffee ( 887 mg caffeine/1 ) , or no coffee , the latter being replaced by fruit juice and mineral water . Total elimination of coffee did not significantly affect blood pressure or heart rate relative to boiled- and -filtered coffee . In subjects who drank boiled coffee , mean ambulant systolic blood pressure rose significantly relative to those who consumed boiled- and -filtered coffee ( mean difference ±SEM , 3.1±1.1 mm Hg , p=0.006 ) . This response showed a tendency to be stronger for women ( 4.5±1.8 mm Hg ) than for men ( 1.7±1.2 mm Hg ) . We conclude that elimination of filtered coffee has no substantial long-term effect on blood pressure , but consumption of unfiltered boiled coffee may cause a slight but significant rise in systolic blood pressure Many cross-sectional epidemiological studies have revealed that alcohol consumption is closely related to an increase in blood pressure , which is known to be associated with an elevated serum γ-glutamyltransferase ( GGT ) level , rather than to the volume of alcohol consumed . Since recent studies showed that coffee intake is inversely related to serum GGT , we investigated the effect of coffee on blood pressure in habitual alcohol drinkers . A total of 42 male hypertensive or prehypertensive volunteers who consumed alcohol and coffee daily completed this r and omized controlled crossover trial . After a 2-week baseline period , these participants were r and omly assigned to either a coffee-drinking group or a non-coffee-drinking group for the first 4 weeks . The situation was then reversed for the next 4 weeks . All participants continued their usual alcohol consumption . Blood pressure was measured once a week and compared between the two groups . After 1 week of coffee intake of more than 3 cups per day , the systolic and diastolic blood pressure began to fall slowly , and cessation of coffee intake raised the blood pressure . Systolic blood pressure was lowered by 7–10 mmHg , and diastolic pressure by 3–7 mmHg in 4 weeks . Alcohol consumption of more than 60 ml per day was maintained and there were no lifestyle changes in the participants of either group throughout the study period . Analyses of urine electrolytes and urea nitrogen indicated that there were no significant dietary changes . In conclusion , coffee intake of more than 3 cups per day in hypertensive and prehypertensive men who regularly consume alcohol lowers blood pressure A r and omized controlled trial was conducted to examine the effects of coffee ( as commonly drunk in Britain ) on blood pressure and plasma lipids in healthy subjects . Fifty-four subjects followed three regimens successively , the order being r and omized according to a Latin square design : five or more cups of coffee daily for 4 weeks ; five or more cups of decaffeinated coffee daily for 4 weeks but no ordinary coffee ; no coffee for 4 weeks . Coffee appeared to cause a small rise ( of 3 mm Hg ) in recumbent systolic blood pressure ; this effect was less than , and obscured by , changes induced by posture and mild stress . No consistent changes attributable to coffee were found in diastolic blood pressure or pulse rate . Small changes in the expected directions occurred in plasma high density lipoprotein ( HDL ) cholesterol and apolipoprotein AI ( decrease ) , and in total cholesterol , non-HDL cholesterol and apolipoprotein B ( increase ) , but none of these were statistically significant . The effect of coffee on risk of heart disease in Britain is probably small To assess the validity of self-reported illnesses , medical records were review ed for participants reporting major illnesses on the biennial follow-up question naires used in a prospect i ve cohort study which began in 1976 . In over 90 % of cases of cancer of the breast , skin , large bowel , and thyroid , histopathology reports confirmed the subjects ' self-report . Lower levels of confirmation were obtained for cancers of the lung , ovary , and uterus . Application of strict diagnostic criteria also gave lower levels of confirmation for myocardial infa rct ion ( 68 % ) and stroke ( 66 % ) . Among r and om sample s of women reporting fractures and hypertension all records obtained confirmed self-reports . For self-reported elevated cholesterol levels 85.7 % of self-reports were confirmed . Self-report is a valuable epidemiologic tool but may require additional documentation when the disease is diagnostically complex Objectives The longitudinal relationship between coffee use and hypertension is still controversial . Cytochrome P450 1A2 ( CYP1A2 ) is the main responsible enzyme for the metabolism of caffeine . The aim of the present study was to investigate the effect of coffee intake on the risk of developing hypertension needing antihypertensive treatment in individuals stratified by CYP1A2 genotype . Design We assessed prospect ively 553 young White individuals screened for stage 1 hypertension . Coffee intake was ascertained from regularly administered question naires . Incident physician-diagnosed hypertension was the outcome measure . Genotyping of CYP1A2 SNP was performed by real time PCR . Results During a median follow-up of 8.2 years , 323 individuals developed hypertension . For carriers of the slow * 1F allele ( 59 % ) , hazard ratios of hypertension from multivariable Cox analysis were 1.00 in abstainers ( reference ) , 1.72 ( 95%CI , 1.21–2.44 ) in moderate coffee drinkers ( P = 0.03 ) , and 3.00 ( 1.53–5.90 ) in heavy drinkers ( P = 0.001 ) . In contrast , hazard ratios for coffee drinkers with the rapid * 1A/*1A genotype were 0.80 ( 0.52–1.23 , P = 0.29 ) for moderate drinkers and 0.36 ( 0.14–0.89 , P = 0.026 ) for heavy drinkers . In a two-way ANCOVA , a gene × coffee interactive effect was found on follow-up changes in systolic ( P = 0.000 ) and diastolic ( P = 0.007 ) blood pressure . Urinary epinephrine was higher in coffee drinkers than abstainers but only among individuals with slow * 1F allele ( P = 0.001 ) . Conclusion These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype . Carriers of slow * 1F allele are at increased risk and should thus abstain from coffee , whereas individuals with * 1A/*1A genotype can safely drink coffee OBJECTIVE --To determine the effects on blood pressure of modifying dietary caffeine intake in patients with mild and borderline hypertension by monitoring ambulatory and clinic blood pressure . DESIGN --Four way , r and omised , crossover trial of four consecutive two week dietary regimens : normal diet , caffeine free diet alone , caffeine free diet with decaffeinated instant coffee , caffeine free diet with caffeinated instant coffee ( instant coffee phases conducted double blind ) . SETTING --Hospital hypertension clinic , Scotl and . PATIENTS --52 patients ( 23 men ; aged 26 - 67 years ) with untreated borderline or mild hypertension ( diastolic blood pressure 90 - 105 mm Hg ) who normally drank a minimum of three cups of coffee daily . MAIN OUTCOME MEASURES --Mean ambulatory blood pressure over 24 hours ; mean morning , daytime , and night time ambulatory blood pressure ; sitting clinic blood pressure at 1700 ; plasma caffeine concentration at 1700 on the last day of each regimen . RESULTS --Mean 24 hour ambulatory blood pressure was not different between regimens . There was no difference in blood pressure variability between regimens . During the caffeine free diet alone morning ambulatory diastolic blood pressure was higher ( 2.8 mm Hg ) than during the caffeine free diet with caffeinated coffee . Mean sitting clinic systolic blood pressure was higher at 1700 ( 4.7 mm Hg ) with a caffeine free diet than with the caffeine free diet with caffeinated coffee ( p less than 0.05 ) . Dietary compliance as assessed by plasma caffeine concentration was excellent . There was no significant correlation between plasma caffeine concentration and blood pressure . CONCLUSIONS --Drinking caffeinated instant coffee over a two week period does not adversely influence blood pressure in patients with borderline or mild hypertension ; abstinence is of no benefit |
10,867 | 30,973,527 | Conclusion : This review revealed that people with Parkinson 's disease viewed physical activity as an enjoyable and positive experience , which aided with control of their symptoms and enhanced their wellbeing and quality of life .
Aligned with evidence from older adults and those with long-term conditions , this review identified disease presentation , intrapersonal characteristics , program design , external support and the social and physical environment as contributory factors which influenced the ability of people with Parkinson 's disease to sustain engagement in physical activity .
The unique contribution and weighting of these factors will affect an individual 's participation in physical activity .
These qualitative findings give healthcare providers an insight into the views and experiences of people with Parkinson 's disease and are useful , alongside quantitative evidence of effectiveness , for the design of physical activity programs that are meaningful for this population .
However , a limitation of this review is that it does not address the views and experiences of people with Parkinson 's disease who are inactive | Objective : The objective of the review was to synthesize the best available qualitative evidence on the experiences and preferences of people with Parkinson 's disease for physical activity , their perceived motivators and barriers to engagement , as well as their views on support mechanisms and behavior change interventions design ed to sustain participation .
Introduction : National and international guidelines recommend regular physical activity to improve health and wellbeing and to prevent disease .
Research on Parkinson 's disease indicates that physical activity programs can be beneficial in addressing both physical symptoms and overall wellbeing .
However , despite recommendations , sustained engagement in regular physical activity among people with Parkinson 's disease is limited .
To promote physical activity it is important to underst and their perspectives on this topic . | A previous r and omized , controlled trial of tai chi showed improvements in objective ly measured balance and other motor-related outcomes in patients with Parkinson 's disease . This study evaluated whether patient-reported outcomes could be improved through exercise interventions and whether improvements were associated with clinical outcomes and exercise adherence . In a secondary analysis of the tai chi trial , patient-reported and clinical outcomes and exercise adherence measures were compared between tai chi and resistance training and between tai chi and stretching exercise . Patient-reported outcome measures were perceptions of health-related benefits result ing from participation , assessed by the Parkinson 's Disease Question naire ( PDQ-8 ) and Vitality Plus Scale ( VPS ) . Clinical outcome measures included motor symptoms , assessed by a modified Unified Parkinson 's Disease Rating Scale – Motor Examination ( UPDRS-ME ) and a 50-foot speed walk . Information on continuing exercise after the structured interventions were terminated was obtained at a 3-month postintervention follow-up . Tai chi participants reported significantly better improvement in the PDQ-8 ( −5.77 points , P = 0.014 ) than did resistance training participants and in PDQ-8 ( −9.56 points , P < 0.001 ) and VPS ( 2.80 points , P = 0.003 ) than did stretching participants . For tai chi , patient-reported improvement in the PDQ-8 and VPS was significantly correlated with their clinical outcomes of UPDRS-ME and a 50-foot walk , but these correlations were not statistically different from those shown for resistance training or stretching . However , patient-reported outcomes from tai chi training were associated with greater probability of continued exercise behavior than were either clinical outcomes or patient-reported outcomes from resistance training or stretching . Tai chi improved patient-reported perceptions of health-related benefits , which were found to be associated with a greater probability of exercise adherence . The findings indicate the potential of patient perceptions to drive exercise behavior after structured exercise programs are completed and the value of strengthening such perceptions in any behavioral intervention Objective The short-term benefits of exercise for persons with Parkinson disease ( PD ) are well established , but long-term adherence is limited . The aim of this study was to explore the feasibility , acceptability , and preliminary evidence of the effectiveness of a virtual exercise coach to promote daily walking in community-dwelling persons with Parkinson disease . Design Twenty subjects with Parkinson disease participated in this phase 1 , single-group , nonr and omized clinical trial . The subjects were instructed to interact with the virtual exercise coach for 5 mins , wear a pedometer , and walk daily for 1 mo . Retention rate , satisfaction , and interaction history were assessed at 1 mo . Six-minute walk and gait speed were assessed at baseline and after the intervention . Results Fifty-five percent of the participants were women , and the mean age was 65.6 yrs . At the study completion , there was 100 % retention rate . The subjects had a mean satisfaction score of 5.6/7 ( with 7 indicating maximal satisfaction ) with the virtual exercise coach . Interaction history revealed that the participants logged in for a mean ( SD ) of 25.4 ( 7 ) days of the recommended 30 days . The mean adherence to daily walking was 85 % . Both gait speed and the 6-min walk test significantly improved ( P < 0.05 ) . No adverse events were reported . Conclusions Sedentary persons with Parkinson disease successfully used a computer and interacted with a virtual exercise coach . Retention , satisfaction , and adherence to daily walking were high for 1 mo , and significant improvements were seen in mobility This study was carried out to evaluate progression in Parkinson 's disease ( PD ) by analyzing time taken to transit from one Hoehn and Yahr ( H&Y ) stage to the next stage and to investigate the variables that would be associated with H&Y transition times using a large PD data base that contained prospect ively collected information . Data were obtained from the movement disorder data base of the National Neuroscience Institute in Singapore . Kaplan-Meier ( KM ) survival analysis was adopted to investigate the time taken to progress through various H&Y stages . Cox regression analysis was used to examine the association between the baseline variables at the entry point of each H&Y stage and the progression to the next stage . A total of 695 patients ( mean age : 65.2 , male : 57.3 % ) were studied . Using KM analysis , the median time taken to transit from H&Y stage 1 to 2 , 2 to 2.5 , 2.5 to 3 were 20 , 62 , and 25 months , respectively ; whereas the median time taken to progress from stage 3 to 4 and 4 to 5 were 24 and 26 months , respectively . Cox regression analysis revealed that older age-at-diagnosis , longer PD duration , and higher Unified Parkinson 's Disease Rating Scale ( UPDRS ) motor scores at baseline were associated with a significantly faster progression through various H&Y stages . Gender and ethnicity were not associated with disease progression . In conclusion , H&Y transition time is a useful measure of disease progression in PD and may be utilized in clinical studies evaluating therapeutic interventions and prognostic factors in PD OBJECTIVES We recently completed the ParkFit study , a two-year r and omized controlled trial including 586 sedentary Parkinson 's disease ( PD ) patients , that evaluated a multifaceted intervention ( ParkFit program ) to promote physical activity . The results showed that the ParkFit program enables PD patients to become physically more active , suggesting that this intervention should now be further implemented into clinical practice . To facilitate this process , we here evaluate the implementation of the ParkFit program . METHODS The ParkFit program was evaluated in three ways : ( a ) experiences of patients and physiotherapists , as investigated using interviews and question naires ; ( b ) factors associated with changed activity levels ; and ( c ) subgroup analyses to identify differential effects in subgroups of patients based on baseline physical activity level , age , gender , disease severity , disease duration , and mobility . RESULTS The ParkFit program was well received : 73 % of patients indicated they would recommend the program to other patients , and 90 % of physiotherapists indicated they wanted to use the ParkFit program in other patients . Multiple forward regression analysis result ed in a model with two variables : less baseline physical activity , and better mobility were associated with larger changes in levels of physical activity ( R(2)=38 % ) . The program was effective in almost all subgroups . In women , most sedentary patients and patients with higher disease severity , the estimated effect size was largest . CONCLUSION We conclude that the ParkFit program was effective in almost all specific subgroups . Therapists and patients experienced no major hurdles . Suggestions for improvement are : ( 1 ) improve education for therapists with respect to theories about behavioral change ; ( 2 ) formulate concrete and specific examples of exercise goals ; and ( 3 ) pay more specific attention to patients with co morbidities , cognitive dysfunction and a lack of motivation during education OBJECTIVE The expected emotional consequences of future actions are thought to play an important role in health behavior change . This research examined whether anticipated affective consequences of success and failure vary across stages of physical activity change and differentially predict physical activity adoption as compared to maintenance . DESIGN Using a prospect i ve design over a 3-month period , a community sample of 329 healthy , middle-aged adults were assessed at 2 time points . MAIN OUTCOME MEASURES Anticipated positive and negative emotions , stage of behavior change ( precontemplation [ PC ] , contemplation [ C ] , preparation [ P ] , action [ A ] , maintenance [ M ] ) , and level of physical activity . RESULTS At baseline , anticipated positive emotions were greater in C versus PC , whereas anticipated negative emotions were greater in M versus A and in M versus P. Higher anticipated positive but not negative emotions predicted physical activity adoption and maintenance after 3 months . CONCLUSION Although the expected affective consequences of future success and failure differentiated among individuals in the early and later stages of physical activity change , respectively ; only the anticipated affective consequences of success predicted future behavior AIM This study aim ed to evaluate the feasibility and cultural considerations of a minimally supervised , home-based exercise program in Jordan . METHODS Quantitative and qualitative approaches were used . Thirty participants were r and omly allocated to either an 8-week intervention group ( n = 16 ) , or a st and ard care group ( n = 14 ) . The intervention incorporated the home use of an exercise DVD , walking program and initial instructional sessions and weekly phone calls provided by a physiotherapist . Interviews were used to explore feasibility . Unified Parkinson 's disease rating scale ( UPDRS-III ) ; balance and walking speed were assessed . RESULTS The retention rate was 86.7 % and mean adherence rate was 77 % . Personal and sociocultural barriers of adherence to the exercise program were identified . UPDRS-III at follow-up was lower in the intervention group . CONCLUSION A home exercise program was feasible . Sociocultural barriers specific to Arabic culture may affect the uptake of such an intervention in Parkinson 's disease in these countries |
10,868 | 31,069,997 | For post-diagnosis statin uses , there is no difference in ACM when stratified by KRAS gene ( KRAS ) mutation status .
Our meta- analysis demonstrates that both pre-diagnosis and post-diagnosis statin uses are associated with reduced ACM and CSM for CRC patients | BACKGROUND Colorectal cancer ( CRC ) remains one of the most common types of cancer and a leading cause of death worldwide .
Previous studies indicated that statins may have a potential protective effect on CRC .
METHODS We conducted this meta- analysis to systematic ally assess the overall and cancer-specific survival benefit of statin uses on CRC patients . | Summary Purpose Pre clinical data has demonstrated the potential of simvastatin to overcome cetuximab resistance in KRAS mutant CRC patients . Therefore , we design ed a study using simvastatin/cetuximab/irinotecan for KRAS mutant CRC patients who are refractory to irinotecan and oxaliplatin-based chemotherapy . Patients and methods In this phase II study , patients received 500 mg/m2 cetuximab , 150–180 mg/m2 ( day 1 ) , and 80 mg simvastatin ( once daily , days 1–14 , every 2 weeks ) . The primary endpoint was the objective response rate ( ORR ) . Secondary endpoints were progression-free survival ( PFS ) , overall survival ( OS ) , the disease control rate ( DCR ) , and safety . We also analyzed the relationship between the RAS gene expression signature score and treatment response to simvastatin/cetuximab/irinotecan . Results Fifty-two KRAS mutant CRC patients were enrolled . The ORR ( complete response [ CR ] , 0 ; partial response [ PR ] , 1 ) was 1.9 % ( 95 % confidence interval [ CI ] , −1.8–5.6 ) . The DCR ( CR , 0 ; PR , 1 ; stable disease , 33 ) was 65.4 % ( 95 % CI , 52.5–78.3 ) . The median PFS and OS from the time of study drug administration were 7·6 months ( 95 % CI , 4.4–10.8 ) and 12.8 months ( 95 % CI , 9.5–16.2 ) , respectively . The most common grade 3/4 adverse events were anemia ( 28.8 % ) , neutropenia ( 13.5 % ) , and diarrhea ( 7.7 % ) . The RAS signature score was significantly correlated with the maximal change in target lesions from baseline ( r = 0.57 , P = 0.014 ) . Conclusion The simvastatin/cetuximab/irinotecan regimen showed promising efficacy and safety in KRAS mutant CRC patients who failed irinotecan and oxaliplatin-based chemotherapy . The RAS signature may be a novel predictor of treatment response to cetuximab-combined chemotherapy in CRC patients BACKGROUND & AIMS Statin use has been associated with a reduced incidence of colorectal cancer and might also affect survival of patients diagnosed with colon cancer . Statins are believed to inhibit Ras signaling and may also activate the bone morphogenetic protein ( BMP ) signaling pathway in colorectal cancer cells . We investigated the effects of statins on overall survival of patients with a diagnosis of colon cancer , and whether their effects were associated with changes in KRAS or the BMP signaling pathways . METHODS Data were derived from the PHARMO data base network ( Netherl and s ) and linked to patients diagnosed with colon cancer from 2002 through 2007 , listed in the Eindhoven Cancer Registry . We obtained information on causes of death from statistics Netherl and s. We constructed a tissue microarray of 999 colon cancer specimens from patients who underwent surgical resection from 2002 through 2008 . Survival was analyzed with statin user status after diagnosis as a time-dependent covariate . Multivariable Poisson regression survival models and Cox analyses were used to study the effect of statins on survival . Tumor tissues were analyzed by immunohistochemistry for levels of SMAD4 , BMPR1A , BMPR1B , and BMPR2 proteins . Tumor tissues were considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A , BMPR1B , or BMPR2 . DNA was isolated from tumor tissues and analyzed by quantitative polymerase chain reaction to detect mutations in KRAS . The primary outcome measures were overall mortality and cancer-specific mortality . RESULTS In this cohort , 21.0 % of the patients ( 210/999 ) were defined as statin users after diagnosis of colon cancer . Statin use after diagnosis was significantly associated with reduced risk of death from any cause ( adjusted relative risk [ RR ] , 0.67 ; 95 % confidence interval [ CI ] , 0.51 - 0.87 ; P = .003 ) and death from cancer ( adjusted RR , 0.66 ; 95 % CI , 0.49 - 0.89 ; P = .007 ) . Statin use after diagnosis was associated with reduced risk of death from any cause or from cancer for patients whose tumors had intact BMP signaling ( adjusted RR , 0.39 ; 95 % CI , 0.22 - 0.68 ; P = .001 ) , but not for patients whose tumors did not have BMP signaling ( adjusted RR , 0.81 ; 95 % CI , 0.55 - 1.21 ; P = .106 ; P < .0001 for the interaction ) . Statin use after diagnosis was not associated with reduced risk of death from any cause or from cancer for patients whose tumors did not contain KRAS mutations ( adjusted RR , 0.81 ; 95 % CI , 0.56 - 1.18 ; P = .273 ) or whose tumors did have KRAS mutations ( adjusted RR , 0.59 ; 95 % CI 0.35 - 1.03 ; P = .062 ; P = .90 for the interaction ) . CONCLUSIONS In an analysis of 999 patients with a diagnosis of colon cancer , we associated statin with reduced risk of death from any cause or from cancer . The benefit of statin use is greater for patients whose tumors have intact BMP signaling , independent of KRAS mutation status . R and omized controlled trials are required to confirm these results BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . BACKGROUND Although pre clinical and epidemiological data suggest that statins may have antineoplastic properties , the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown . METHODS We conducted a prospect i ve observational study of 842 patients with stage III colon cancer enrolled in a r and omized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival . Disease-free survival ( DFS ) , recurrence-free survival ( RFS ) , and overall survival ( OS ) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status ( n = 394 ) , and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables . All statistical tests were two-sided . RESULTS Among 842 patients , 134 ( 15.9 % ) reported statin use after completing adjuvant chemotherapy . DFS among statin users and nonusers was similar ( hazard ratio [ HR ] of cancer recurrence or death = 1.04 , 95 % confidence interval [ CI ] = 0.73 to 1.49 ) . RFS and OS were also similar between statin users and nonusers ( adjusted HR of cancer recurrence = 1.14 , 95 % CI = 0.77 to 1.69 ; adjusted HR of death = 1.15 , 95 % CI = 0.77 to 1.71 ) . Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis ( P(trend ) = .63 , .63 , and .59 for DFS , RFS , and OS , respectively ) . The impact of statin use did not differ by tumor KRAS mutation status , with similar DFS , RFS , and OS for statin use among mutant and wild-type subgroups ( P(interaction ) = .84 , .67 , and .98 for DFS , RFS , and OS , respectively ) . CONCLUSION Statin use during and after adjuvant chemotherapy was not associated with improved DFS , RFS , or OS in patients with stage III colon cancer , regardless of KRAS mutation status BACKGROUND : Achieving a pathologic complete response to neoadjuvant chemoradiation improves prognosis in rectal cancer . Statin therapy has been shown to enhance the impact of treatment in several malignancies , but little is known regarding the impact on rectal cancer response to neoadjuvant chemoradiation . OBJECTIVE : The purpose of this study was to determine whether statin use during neoadjuvant chemoradiation improves pathologic response in rectal cancer . DESIGN : This was a retrospective cohort study based on data from a prospect ively maintained colorectal cancer data base . The 2 cohorts were defined by statin use during neoadjuvant chemoradiation . SETTING : This study was performed at a single tertiary referral center . PATIENTS : Four hundred seven patients with primary rectal adenocarcinoma who underwent neoadjuvant therapy then proctectomy between 2000 and 2012 were included . Ninety-nine patients ( 24.3 % ) took a statin throughout the entire course of neoadjuvant therapy . MAIN OUTCOME MEASURES : The primary outcome measure was pathologic response to neoadjuvant chemoradiotherapy as defined by the American Joint Committee on Cancer tumor regression grading system , grade s 0 to 3 . RESULTS : Patients in the statin cohort had a lower median regression grade ( 1 vs 2 , p = 0.01 ) and were more likely to have a better response ( grade s 0–1 vs 2–3 ) than those not taking a statin ( 65.7 % vs 48.7 % , p = 0.004 ) . Statin use remained a significant predictor of an American Joint Committee on Cancer grade 0 to 1 ( OR , 2.25 ; 95 % CI , 1.33–3.82 ) in multivariate analyses . Although statin use itself did not significantly improve oncologic outcomes , an American Joint Committee on Cancer grade 0 to 1 response was associated with statistically significant improvements in overall survival , disease-free survival , cancer-specific mortality , and local recurrence . LIMITATIONS : This was a retrospective study and subject to nonr and omization of patients and incorporated patients on variable statin agents and doses . CONCLUSIONS : Statin therapy is associated with an improved response of rectal cancer to neoadjuvant chemoradiation . These data provide the foundation for a prospect i ve clinical trial |
10,869 | 31,289,914 | Despite the decrease in IBL with a tourniquet , no difference was found in TBL .
In conclusion , not using a tourniquet or only using it during the cementation of implants was preferable based on the faster functional recovery , lower rate of DVTs and complications compared with using a tourniquet throughout the TKA procedure . | Although a tourniquet can effectively control intraoperative blood loss and offer clear surgical field in total knee arthroplasty ( TKA ) , its optimal usage has been controversial .
The aim of this research was to perform a systematic review and meta- analysis to compare and explore the best application of a tourniquet in TKA . | The purpose of our study is to estimate the effect of tourniquet release and cementing in perioperative blood loss associated with total knee arthroplasty . Eighty patients were r and omly allocated into two equal groups concerning the timing of tourniquet release . Group A : patients with tourniquet release and haemostasis before wound closure and group B : patients with tourniquet release after skin closure and compressive b and aging . These groups were further subdivided in two subgroups ( + and - ) depending on cementing or not of the tibial tray only . The total blood loss averaged 961 ml in group A and 692 ml in group B , while it was estimated 763 ml in the cemented group and 890 ml in the non-cemented group . The total blood loss within subgroups was Group A+ 904 ml , Group A- 1017 ml , Group B+ 622 ml and Group B- 762 ml . The mean number of blood units transfused per patient was 4.7 in Group A and 4.0 in Group B , while the mean operating time was 79 min and 66 min , respectively . Complications such as deep vein thrombosis , haematomata and minor wound complications occurred in patients of Group A and Group B , 0 and 2 , 0 and 2 , 8 and 11 , respectively . Intraoperative tourniquet release seems to be related with significantly greater blood loss ( P<0.001 ) and dem and s in blood transfusion P<0.05 as well as a longer operating time ( P<0.001 ) . Cementing of total knee replacements has a better haemostatic role compared to non-cemented prosthesis ( P<0.05 ) . Even though complications were more in postoperative tourniquet release group , no statistically significant difference was found between group A and B. Postoperative tourniquet release seems to offer better conditions of haemostasis probably due to the better controlled fibrolytic activity Background In patients undergoing total knee arthroplasty , intraoperative pulmonary embolic events are rare , and most occur following tourniquet deflation . This embolization can be observed using transesophageal echocardiography . However , the authors have encountered sudden decreases in arterial oxygen partial pressure while a tourniquet is still inflated . Therefore , the current investigation was design ed to detect emboli during the tourniquet inflation phase and to identify the composition of the echogenic material . Methods Forty-six patients were r and omly assigned to undergo total knee arthroplasty without ( control , n = 24 ) or with a tourniquet ( n = 22 ) . Hemodynamic monitoring , blood gas analysis , and continuous transesophageal echocardiography were performed during the total knee arthroplasty procedure . Right jugular blood specimens were collected whenever echogenic material was seen in the atrium . Results In the tourniquet group , embolic events occurred in 27 % of patients during femoral reaming and in 100 % after tourniquet deflation . In the control group , emboli were detected in 54 % of patients during femoral reaming . Most of the patients exhibited cardiopulmonary impairment after severe echogenic embolism , even while the tourniquet was inflated ( two patients ) . None of the blood sample s aspirated from the central catheters contained detectable material . Conclusions This prospect i ve study showed that embolic events occurred during total knee arthroplasty , even while a tourniquet was inflated . An inflated tourniquet does not completely prevent pulmonary emboli BACKGROUND Total knee arthroplasty ( TKA ) is commonly performed using a tourniquet . However , some studies have reported that several complications were associated with the use of a tourniquet in TKA . In this study we investigate whether the limited use of a tourniquet in TKA would reduce complications and facilitate postoperative recovery . METHODS Sixty patients were r and omly divided into two groups ( 30 cases/group ) : group A using the tourniquet throughout the surgical procedure , and group B using the tourniquet starting from the cementation to the completion of the procedure . Operation time , total measured blood loss , and incidence of complications were all recorded . RESULTS There was no significant difference in operation time , total measured blood loss , and hemoglobin concentration between the two groups . Incidence of postoperative complications in group B was significantly decreased in comparison to that in group A. The limb circumference at 10 cm above the superior patellar pole or below the inferior patellar pole and the pain score in group B were significantly decreased compared with that in group A at any time point . Range of motion in group B was significantly increased at three and 5 days postoperatively in comparison to that in group A. CONCLUSIONS The limited use of a tourniquet in TKA provides the benefit of decreased limb swelling and knee joint pain while not compromising the operation time or blood loss and recovery . LEVEL OF EVIDENCE Level I ( Therapeutic ) . TRIAL REGISTRATION NUMBER NCT02102581 In surgical practice , hemostasis is used to minimize postoperative bleeding in total knee arthroplasty . We performed a prospect i ve r and omized study to determine the influence of tourniquet use and the timing of its release on amount of bleeding . Eighty four patients ( 96 knees ) were scheduled for total knee arthroplasty and r and omly divided into three groups . Posterior cruciate retaining bicompartmental total knee prostheses were used in all . In group I , no tourniquet was used . In group II , a tourniquet was used and was deflated for hemostasis once all components had been inserted . In group III , the tourniquet was deflated after wound closure and application of a compressive dressing . Mean blood drainage , mean volume of blood transfusion , hemoglobin ( Hb ) and hematocrit ( Hct ) values and operative time were compared between the three groups . Mean blood drainage was 810 mL ( 300 - 1300 ) in groups I 720 mL ( 240 - 1200 ) in group II and 705 mL ( 250 - 1150 ) in group III ( p = 0.062 ) . The Hb and Hct values , tourniquet time ( for groups II and III ) and volume of blood transfusion were similar . The operative time was significantly longer for first group ( p = 0.012 ) . Using tourniquet and its intraoperative release with hemostasis , does not reduce blood loss in total knee arthroplasty , but using tourniquet reduces operation time significantly Introduction A tourniquet is used during the total knee replacement surgery to improve the visibility , to reduce the blood loss and for better cementation . Indirectly it decreases the duration of surgery and enhances the recovery of the patient . Their use however is controversial due to some side effects associated with the use of tourniquet . They may increase the risk of deep vein thrombosis and pulmonary embolism by causing venous stasis , endothelial damage and increased platelet adhesion secondary to distal limb ischemia . Material and Methods We conducted a r and omized controlled trial ( RCT ) to examine the benefits and risks associated with the use of long duration over short duration tourniquets during TKA . The study was a prospect i ve r and omised control trial with a total of 80 knees ( 40 knees in each group ) included in the study . The knees selected for surgery were r and omly allocated to one of the two groups : Group A - long duration tourniquet ( LT-group ) or Group B - short duration tourniquet ( ST-group ) . Result The average operating time in Group A ( 43.53±3.11 minutes ) was statistically less significant than that of Group B ( 51.7±2.56 minutes ) . Intra-operative blood loss in Group B , was significantly more than that of Group A. Post-operative blood loss in the drain was more in long duration tourniquet group . Total blood loss ( intra-operative + post-operative ) was more in short duration tourniquet group . Pain score ( using VAS scale ) was comparable in both the groups at the end of the second and sixth week . At sixth weeks there was no significant difference in the range of motion in both the groups . The KSS score was not significantly different in both the groups in post operative period at first , second , and six weeks . There were no events of thrombo-embolism and deep vein thrombosis in either groups . In 11 patients ( 27.5 % ) of long duration tourniquet group , swelling , and redness of knee was seen post operatively as compared to three patients ( 7.5 % ) of short duration tourniquet group . Conclusion The use of a short duration tourniquet during TKA gives better symptomatic pain relief in the early postoperative period as compared to long duration use of tourniquet . However , this is associated with increased blood loss , more operating time and not having a clear operative field . We suggest that a rational thinking and reconsidering the practice of routine use of long duration tourniquet in each and every case of TKA is required Background Total knee arthroplasty with the use of a tourniquet during the entire operation has not been shown to improve the performance of the operation and may increase the risk of complications . Questions / purpose sWe asked whether the limited use of a tourniquet for cementation only would affect ( 1 ) surgical time ; ( 2 ) postoperative pain and motion of the knee ; ( 3 ) blood loss ; or ( 4 ) complications such as risk of nerve injuries , quadriceps dysfunction , and drainage compared with use of a tourniquet throughout the procedure . Methods Seventy-one patients ( 79 knees ) were r and omized to either use of a tourniquet from the incision through cementation of the implants and deflated for closure ( operative tourniquet group ) or tourniquet use only during cementation ( cementation tourniquet group ) . The initial study population was a minimum of 30 knees in each group as suggested for r and omized studies by American Society for Testing and Material s st and ards ; termination of the study was determined by power analysis performed after 40 knees in each group showed any statistical solution to our questions would require a minimum of 260 more cases . Patients were excluded who were considered in previous r and omized studies as high risk for complications , which might be attributed to the tourniquet . Results There were no differences in terms of surgical time , pain scores , pain medicine requirements , range of motion , hemoglobin change , or total blood loss . One major complication ( compartmental syndrome ) occurred in a patient with tourniquet inflation until closure . No other complications were attributed to the use of a tourniquet . Conclusions With the numbers available , our results suggest that there are no important clinical differences between patients who had a tourniquet inflated throughout the procedure compared with those who had it inflated only during cementation . Tourniquet inflation for cementation only provides the benefit of bloodless bone for fixation and may eliminate the risks associated with prolonged tourniquet use . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence AIM To reduce blood loss in total knee arthroplasty various physical measures including the use of a tourniquet are recommended . The question of an early tourniquet release is still unsettled . PATIENTS AND METHOD To confirm our theory that blood loss and need of blood transfusions might be reduced while removing the tourniquet for meticulous hemostasis before wound closure we analysed 70 ( 41 male , 29 female ) consecutive patients with total knee arthroplasty for osteoarthritis performed by a single surgeon in a prospect ive-r and omized study between 1/1996 to 6/1998 . In group I the tourniquet was released before , in group II after wound closure . RESULTS We could n't find any significant differences in the estimated blood loss , the decrease of hemoglobin and hematocrit level , and the transfusion need . In Group II we observed two cases of deep vein thrombosis . This difference was not significant . CONCLUSION We conclude that tourniquet release for hemostasis is not an effective tool in reducing blood loss or transfusion need in total knee arthroplasty Today the use of pneumatic tourniquet is commonly accepted in total knee arthroplasty ( TKA ) to reduce perioperative blood loss . There are a few prospect i ve r and omised and nonr and omised studies that compare the effect of tourniquet release timing in cementless or cemented unilateral TKA . However , many of these studies show an inadequate reporting and methodology . This r and omized prospect i ve study was design ed to investigate the efficiency of tourniquet release timing in preventing perioperative blood loss in a simultaneous bilateral TKA study design . To our knowledge , this is the first study of its kind , in which the effect of tourniquet release timing on perioperative blood loss was investigated in simultaneous bilateral cemented TKA to compare both techniques intraindividually . In 20 patients ( 40 knees ) one knee was operated with tourniquet release and hemostasis before wound closure , and the other knee with tourniquet release after wound closure and pressure dressing . We found no significant difference in total blood loss between both techniques ( p=0.930 ) , but a significant difference in operating time ( p=0.035 ) . There were no postoperative complications at a follow-up of 6 month . Other studies report an increase the blood loss in early tourniquet release and an increase the risk of early postoperative complications in deflation of tourniquet after wound closure . In this study we found no significant difference in perioperative blood loss and no increase of postoperative complications . Therefore , we recommend a tourniquet release after wound closure to reduce the duration of TKA procedure and to avoid possible risks of extended anaesthesia We included 46 total knee arthroplasties ( 43 patients ) in a prospect i ve , r and omised study , dividing them into two groups : group A ( 23 knees , 21 patients ) in which the ischaemia was released prior to wound closure allowing control of bleeding and group B ( 23 knees , 22 patients ) releasing the tourniquet after suturing and b and aging . We compared the haemoglobin before surgery and at 24 and 48 h postoperatively , the total blood loss and the transfusions that were needed . Student 's t-test was used to analyse the data . The results we obtained were as follows : preoperative haemoglobin in group A was 14.21 g/dl and group B 14.28 g/dl ; haemoglobin at 24/48 h for group A was 10.04/10.1 g/dl and group B 10.28/10.3 g/dl ; total blood loss was 743.2 cc for group A and 692.5 cc for group B ; the mean number of blood units transfused were 2 in group A and 1.8 in group B. No statistical differences were found in the data analysed , but one of the complications in group B was major blood loss right after surgery that needed reintervention . We assume that this could have been avoided if the tourniquet had been released beforeh and . We conclude that releasing ischaemia prior to wound closure does not demonstrate a statistical difference , but like other authors , we found clinical advantages suggesting the need of further study of this situation . RésuméNous avons inclus 46 prothèses totales du genou ( 43 patients ) dans une étude prospect i ve r and omisée avec deux groupes de patients . Un premier groupe : groupe A , 23 genoux , 21 patients avec lâchage du garrot avant la fermeture avec contrôle du saignement et un groupe B , 23 genoux , 22 patients , avec lâchage du garrot après la suture et le pansement . Ont été comparés le taux d’hémoglobine préopératoire à 24 et 48 heures postopératoires , les pertes totales sanguines et la nécessité de transfusion . Les résultats obtenus ont été les suivants . En préopératoire dans le groupe A , le taux d’hémoglobine était à 14.21 g/dl et dans le groupe B de 14.28 g/dl ; l’hémoglobine à 24/48 heures pour le groupe A était à 10.04 et 10.01 g/dl respectivement et dans le groupe B 10.28 et 10.3 g/dl respectivement ; les pertes sanguines étaient de 743.2 cc pour le groupe A et de 692.5 cc pour le groupe B et le nombre d’unités transfusées était de 2 dans le groupe A et de 1.8 dans le groupe B. Il n’y a pas de différences significatives entre les deux séries , en dehors d’une complication dans le groupe B , un saignement majeur nécessitant une réintervention . Nous pouvons avoir l’assurance que cette complication aurait été évitée si le garrot avait été levé avant la fermeture . Nous pouvons conclure que le relâchement du garrot après la fermeture ne permet pas d’avoir une différence significative entre les deux séries , néanmoins , nous pensons , ainsi que d’autres auteurs , qu’il est plus avantageux sur le plan clinique de relâcher le garrot avant la fermeture The effects of using a tourniquet during total knee arthroplasty were studied in 80 patients r and omly allocated to two groups , either with or without a tourniquet . The groups were similar in mean age , gender , preoperative knee score and radiographic grading and the patients were all operated on by the same surgeon using one type of prosthesis . There was no significant difference between the two groups in operating time or total blood loss but postoperative pain was less in the patients in whom a tourniquet had not been used . They achieved straight-leg raising and knee flexion earlier and had fewer superficial wound infections and deep-vein thromboses . Total knee arthroplasty can be safely performed without the use of the tourniquet with the benefit that several adverse effects associated with its use can be avoided Purpose The optimal timing of pneumatic lower limb tourniquet application during primary elective total knee arthroplasty surgery ( TKA ) is a matter of debate . Most previous reports have failed to show significant differences between different tourniquet timings . The aim of the work was to determine how three strategies of lower limb pneumatic tourniquet application affect the outcome for TKA patients . Methods Forty-three patients who undergo TKA were r and omized into one of the three groups , and 36 of these patients completed the study . The tourniquet was inflated just before incision and deflated after the hardening of the cement for twelve patients ( Group 1 ) , it was inflated just before cement application and deflated after its hardening for another twelve patients ( Group 2 ) , and it was inflated before incision and deflated after the last suture of the skin for a further twelve patients ( Group 3 ) . Fit-to-discharge criteria and six methods for calculating estimated blood loss were used . Results The estimated blood loss in Group 1 was lower than in Group 2 , as determined by six methods of calculation ( p < 0.05 ) . Estimated blood loss in Group 3 was lower than in Group 2 , as determined by one method ( p = 0.050 ) . The mobilization performance in Group 1 was better than in Group 2 ( p = 0.023 ) and in Group 3 ( p = 0.033 ) . Group 1 was better fit to discharge than Group 3 ( p = 0.030 ) . Conclusions Inflation of an automatic pneumatic lower limb tourniquet before skin incision and its deflation after hardening of cement tends to give better outcomes in TKA patients during six postoperative days . The estimated blood loss was highest when the tourniquet was inflated just before cement application and deflated after its hardening . Level of evidence II Thigh pain following tourniquet application is a common patient complaint in the early postoperative period following total knee arthroplasty . Postoperative thigh pain was evaluated in 28 consecutive simultaneous bilateral total knee arthroplasty patients between April 1996 and October 1996 . A prospect i ve , double-blind , r and omized clinical trial was performed . Tourniquet pressure of 350 mmHg was used on 1 thigh ( thigh 1 ) and 100 mmHg plus systolic blood pressure on the other ( thigh 2 ) . A scale of pain ( no pain , mild , moderate , or severe ) was applied on the first , second , and third days , as well as 2 and 6 weeks after surgery . There were 16 men and 12 women with a mean age of 72 years ( range , 55 - 85 years ) . The mean tourniquet time was similar in both groups ( thigh 1 = 23 minutes , thigh 2 = 22 minutes ) . The mean tourniquet pressure in thigh 2 was 230 mmHg ( range , 212 - 260 mmHg ) . There was a statistically significant difference in thigh pain on the first ( P = .01 ) , second ( P = .01 ) , and third ( P = .001 ) postoperative days between both groups , with more thigh pain on the 350 mmHg side . At 6 weeks after surgery , the difference in thigh pain was gone . For total knee arthroplasty , using the tourniquet at a pressure of 100 mmHg above the systolic blood pressure is recommended . This is adequate to provide a bloodless field and will result in a less unpleasant postoperative period Background and purpose — Tourniquet application is still a common practice in total knee arthroplasty ( TKA ) surgery despite being associated with several adverse effects . We evaluated the effects of tourniquet use on functional and clinical outcome and on knee range of motion ( ROM ) . Patients and methods — 70 patients who underwent TKA were r and omized into a tourniquet group ( n = 35 ) and a non-tourniquet group ( n = 35 ) . All operations were performed by the same surgeon and follow-up was for 1 year . Primary outcomes were functional and clinical outcomes , as evaluated by KOOS and knee ROM . Secondary outcomes were intraoperative blood loss , surgical time and visibility , postoperative pain , analgesic consumption , and transfusion requirements . Results — Patients in the non-tourniquet group showed a better outcome in all KOOS subscores and better early knee ROM from surgery to week 8 . No difference was detected at the 6- and 12-month follow-ups . Postoperative pain and analgesic consumption were less when a tourniquet was not used . Surgical time and visibility were similar between groups . Intraoperative blood loss was greater when not using a tourniquet , but no postoperative transfusions were required . Interpretation— This study shows that TKA without the use of a tourniquet results in faster recovery in terms of better functional outcome and improved knee ROM . Furthermore , reduced pain and analgesic use were registered and no intraoperative difficulties were encountered Background and purpose Although a tourniquet may reduce bleeding during total knee replacement ( TKA ) , and thereby possibly improve fixation , it might also cause complications . Migration as measured by radiostereometric analysis ( RSA ) can predict future loosening . We investigated whether the use of a tourniquet influences prosthesis fixation measured with RSA . This has not been investigated previously to our knowledge . Methods 50 patients with osteoarthritis of the knee were r and omized to cemented TKA with or without tourniquet . RSA was performed postoperatively and at 6 months , 1 year , and 2 years . Pain during hospital stay was registered with a visual analog scale ( VAS ) and morphine consumption was measured . Overt bleeding and blood transfusions were registered , and total bleeding was estimated by the hemoglobin dilution method . Range of motion was measured up to 2 years . Results RSA maximal total point motion ( MTPM ) differed by 0.01 mm ( 95 % CI –0.13 to 0.15 ) . Patients in the tourniquet group had less overt bleeding ( 317 mL vs. 615 mL ) , but the total bleeding estimated by hemoglobin dilution at day 4 was only slightly less ( 1,184 mL vs. 1,236 mL ) with a mean difference of –54 mL ( 95 % CI –256 to 152 ) . Pain VAS measurements were lower in the non-tourniquet group ( p = 0.01 ) . There was no significant difference in morphine consumption . Range of motion was 11 ° more in the non-tourniquet group ( p = 0.001 at 2 years ) . Interpretation Tourniquet use did not improve fixation but it may cause more postoperative pain and less range of motion Objectives To evaluate the risk of bias tool , introduced by the Cochrane Collaboration for assessing the internal validity of r and omised trials , for inter-rater agreement , concurrent validity compared with the Jadad scale and Schulz approach to allocation concealment , and the relation between risk of bias and effect estimates . Design Cross sectional study . Study sample 163 trials in children . Main outcome measures Inter-rater agreement between review ers assessing trials using the risk of bias tool ( weighted κ ) , time to apply the risk of bias tool compared with other approaches to quality assessment ( paired t test ) , degree of correlation for overall risk compared with overall quality scores ( Kendall ’s τ statistic ) , and magnitude of effect estimates for studies classified as being at high , unclear , or low risk of bias ( metaregression ) . Results Inter-rater agreement on individual domains of the risk of bias tool ranged from slight ( κ=0.13 ) to substantial ( κ=0.74 ) . The mean time to complete the risk of bias tool was significantly longer than for the Jadad scale and Schulz approach , individually or combined ( 8.8 minutes ( SD 2.2 ) per study v 2.0 ( SD 0.8 ) , P<0.001 ) . There was low correlation between risk of bias overall compared with the Jadad scores ( P=0.395 ) and Schulz approach ( P=0.064 ) . Effect sizes differed between studies assessed as being at high or unclear risk of bias ( 0.52 ) compared with those at low risk ( 0.23 ) . Conclusions Inter-rater agreement varied across domains of the risk of bias tool . Generally , agreement was poorer for those items that required more judgment . There was low correlation between assessment s of overall risk of bias and two common approaches to quality assessment : the Jadad scale and Schulz approach to allocation concealment . Overall risk of bias as assessed by the risk of bias tool differentiated effect estimates , with more conservative estimates for studies at low risk Purpose A pneumatic tourniquet is commonly used in total knee arthroplasty ( TKA ) to improve surgical field visualisation but may result in quadriceps muscle ischaemia . We performed this study to analyse the effect of the tourniquet on recovery following TKA . Material s and Methods A prospect i ve r and omised single-blinded trial was undertaken to examine the effect of the tourniquet on post-operative pain , swelling , blood loss , quadriceps function and outcome following TKA . Twenty patients with osteoarthritis of the knee were r and omised to tourniquet or no tourniquet groups . Quadriceps function was assessed using surface electromyography ( EMG ) during active knee extension . Results The no tourniquet group had significantly less pain in the early post-operative period compared to the tourniquet group . There was no difference in Oxford knee score , range of motion , or thigh and knee swelling up to 12 months post-operatively . Quadriceps function , measured by surface EMG , was compromised for the first six months post-surgery by tourniquet use . The radiological cement mantle at the bone prosthesis interface at 12-month follow-up was not affected by the absence of a tourniquet . Conclusions We believe that it is safe and beneficial for our patients to routinely perform TKA without a tourniquet Purpose The aim of this study was to explore the influence of a half-course tourniquet strategy on the peri-operative blood loss and early functional recovery in primary total knee arthroplasty . Methods A prospect i ve clinical r and omised controlled study was carried out in which 64 patients were equally divided into two groups : half-course group and whole-course group . A series of indicators were observed and recorded . These included operation time , peri-operative blood loss , visual analogue scale ( VAS ) score of the thigh or knee , limb swelling index , rehabilitation progress and occurrence of deep venous thrombosis cases . Results There was no significant difference in operation time between the two groups . The intra-operative blood loss was slightly more in the half-course group , while the difference was not significant . The post-operative blood loss and calculated blood loss were less in the half-course group and the difference was significant . The thigh VAS score , limb swelling and time intervals required for patients to achieve straight leg raises and 90 ° of knee flexion in the half-course group were better than in the whole-course group . No case of symptomatic deep venous thrombosis happened in this study , while occult incidence of deep venous thrombosis happened in both groups , but no significant difference between the groups was confirmed . Conclusions The half-course tourniquet strategy could decrease the total peri-operative blood loss in primary total knee arthroplasty . It was beneficial in helping patients to achieve earlier functional recovery by improving the pain experience and limb swelling early in the post-operative period BACKGROUND There has been controversy regarding the incidence of deep vein thrombosis ( DVT ) after total knee arthroplasty ( TKA ) with or without the use of a tourniquet . The aim of this r and omized , prospect i ve study was to clarify the effects of tourniquet use on DVT in TKA . METHODS The subjects were 109 patients scheduled to undergo TKA from April 2008 to March 2009 before the establishment of the American Association of Orthopedic Surgeons ( AAOS ) practice guidelines . They were r and omized into two groups : 51 patients in the tourniquet group ( group T ) and 52 patients in the control group without a tourniquet ( group C ) . We investigated the thrombotic presence using ultrasonography one week after surgery and compared both groups . RESULTS There was no difference in the rate of proximal DVTs ( P=0.63 ) . However , the risk of distal DVT was significantly higher in group T than in group C ( 52.9 % vs. 23.1 % ; P=0.002 ) . CONCLUSIONS Use of the tourniquet in TKA increased the risk of distal DVT One hundred consecutive primary total knee arthroplasties performed by a single surgeon were prospect ively r and omized into two groups to study the effect of tourniquet release for hemostasis on postoperative blood loss and transfusion requirements . The two groups were comparable . Variables such as antiinflammatory drug use ; anesthetic ; soft-tissue release ; and component fixation were analyzed . There was no significant difference between the groups in terms of perioperative blood loss , decrease in hemoglobin or hematocrit level , transfusion need , or incidence of wound or thromboembolic complications . Tourniquet release for hemostasis is not an effective means of limiting postoperative blood loss or reducing transfusion need after primary total knee arthroplasty We performed a prospect i ve , r and omized study on 76 patients ( 82 knees ) scheduled for total knee arthroplasty to determine the effect of tourniquet release and hemostasis on the peri- and postoperative blood loss . Patients were r and omly divided in two groups . Posterior cruciate retaining tricompartmental total knee prostheses were used in all . In group 1 , the tourniquet was deflated intraoperatively after the prosthetic components were settled and hemostasis was done . In group 2 , the tourniquet was released after the wound was closed and a compressive b and age was applied . Mean blood drainage was 880.85 ml ( 320–1,315 ) in group 1 and 745.36 ml ( 220–1,175 ) in group 2 ( p=0.03 ) . The mean number of blood transfusions given , hemoglobin and hematocrit values , operation time , and tourniquet time were similar in both groups . Intraoperative tourniquet release and hemostasis does not reduce total blood loss in total knee arthroplasty . RésuméNous avons exécuté une étude prospect i ve et r and omisée sur 76 malades ( 82 genoux ) programmé pour arthroplastie du genou total pour déterminer l’effet de la levée de garrot- hémostase sur le perte de sang per — et postopératoire . Une prothèse tricompartmentale du genou , avec conservation du croisé postérieur totale a été utilisée dans tous les cas . Les malades étaient r and omisés et divisés en deux groupes . Dans le groupe 1 le garrot a été dégonflé en intraopératoire après que les composants prothétiques aient été posés et l’hémostase a , alors été faite . Dans le groupe 2 le garrot a été retiré après la fermeture et la mise en place d’un pansement compressif . La perte moyenne de sang par drainage était 880.85 ml ( 320–1315 ) dans le groupe 1 et 745.36 ml ( 220–1175 ) dans le groupe 2 ( p=0.03 ) . Le nombre moyen de transfusions du sang effectuées , les valeurs de l’hémoglobine et de l’hématocrite , la durée opératoire et la durée du garrot étaient semblables dans les deux groupes . La levée du garrot pendant l’opération avec hémostase ne réduit pas la perte totale du sang dans l’arthroplastie du genou We studied the effects of the timing of tourniquet release in 88 patients r and omly allocated for release after wound closure and b and aging ( group A ) , or before the quadriceps layer had been closed allowing control of bleeding before suture ( group B ) . The groups were similar in mean age , weight , gender , preoperative knee score , radiographic grading , and prosthesis implanted . Patients in group B had less postoperative pain , achieved earlier straight-leg raising , and had fewer wound complications . Five patients in group A had to return to theatre , three for manipulation under anaesthesia , one for secondary closure of wound dehiscence , and one for drainage of a haematoma . The last patient later developed a deep infection , which was treated by a two-stage revision . There were no significant differences between the two groups in operating time , or the decrease in haemoglobin concentration at 48 hours postoperatively . Some of the adverse effects of the use of a tourniquet for knee surgery can be significantly reduced by early tourniquet release , with haemostasis before the quadriceps mechanism and the wound are closed Abstract Introduction . To investigate whether the occurrence of pulmonary embolism ( PE ) and /or deep vein thrombosis ( DVT ) are influenced by use of a tourniquet or not in the patients who underwent total knee arthroplasty for rheumatoid arthritis ( RA ) . Patients and methods . The patients were r and omly divided into a with-tourniquet group ( 19 patients ) and a without-tourniquet group ( 18 patients ) . In the first group , snowstorm-like echogenic particles were observed after deflation of the tourniquet in all patients according to the transesophageal echocardiography . Results . In addition , the PaO2 level was significantly decreased . Also , one had a PE , and DVT was confirmed in two patients . In the without-tourniquet group , none of these conditions was noted . Conclusion . These results suggest that the use of a tourniquet will promote the risk of developing postoperative PE and /or DVT after total knee arthroplasty BACKGROUND Although tourniquets are widely used in total knee arthroplasty , their effectiveness in reducing blood loss and their influence on the postoperative course remain unclear . Tourniquet-related soft-tissue damage is a related concern . We performed a prospect i ve , r and omized , controlled trial to clarify the effect of tourniquets in total knee arthroplasty . METHODS Seventy-two patients undergoing total knee arthroplasty were r and omly allocated to a tourniquet or non-tourniquet group . Blood loss and changes in C-reactive protein , creatine phosphokinase , and other indicators of soft-tissue damage were monitored preoperatively and postoperatively on Days 1 , 2 , and 4 . Thigh pain , knee pain , limb swelling , rehabilitation progress , and hospital stays were also recorded for comparison . RESULTS Patients in the tourniquet group showed smaller decreases in hemoglobin ( mean and st and ard deviation , 2.6 ± 0.9 versus 3.7 ± 1.3 g/dL ) and hematocrit ( 7.6 % ± 2.8 % versus 10.4 % ± 4.0 % ) , less calculated blood loss ( 303 ± 119 versus 423 ± 197 mL ) , and smaller increases in C-reactive protein ( peak value , 175 ± 55 versus 139 ± 75 mg/dL ) and creatine phosphokinase ( peak value , 214 ± 89 versus 162 ± 104 U/L ) compared with those in the non-tourniquet group . There was slightly less postoperative pain in the non-tourniquet group . There were no significant differences between the groups in terms of swelling , rehabilitation progress , or hospital stays . CONCLUSIONS The use of a tourniquet during total knee arthroplasty was effective for reducing blood loss and avoiding excessive postoperative inflammation and muscle damage . The use of a tourniquet was related to slightly more postoperative pain but did not affect postoperative recovery Purpose The purpose of the study was whether the use of a tourniquet increases cement mantle thickness in primary total knee arthroplasty and influences the calculated blood loss and postoperative pain . Methods Ninety patients with a primary total knee arthroplasty ( TKA ) were enroled in this prospect i ve r and omised trial and divided into a group with ( n = 45 ) and without tourniquet ( n = 45 ) . The radiological tibial cement mantle thickness was evaluated postoperatively in four zones on anteroposterior and two zones on lateral radiographs , and values were cumulated . Additionally , the calculated blood loss and postoperative pain levels were recorded . Results There was a median cumulative cement mantle thickness of 13 mm ( range 8–19 mm ) without tourniquet and of 14.2 mm ( range 9–18 mm ) with tourniquet ( p = 0.009 ) . The median calculated blood loss was 0.6 L ( range 0.2–2.0 L ) without and 0.9 L ( range 0.3–1.5 L ) ( p = 0.02 ) with tourniquet . Patient-reported postoperative pain levels were significantly higher in the tourniquet group during mobilisation ( p = 0.01 ) and at rest ( p = 0.001 ) . Conclusions The use of a tourniquet in primary TKA increased the tibial cement mantle thickness but also increased the postoperative calculated blood loss and postoperative pain . Surgeons might take this into consideration for decision-making whether to use a tourniquet during TKA.Level of evidence II OBJECTIVE To determine the value of the use of a pneumatic tourniquet in total knee arthroplasty . METHODS Sixty patients were prospect ively r and omized into 2 groups , one group underwent total knee replacement with a tourniquet ( n = 30 ) and one without ( n = 30 ) . Operating time , blood loss , postoperative mean morphine requirement , swelling , ecchymosis , earlier straight-leg raising and postoperative knee flexion were measured in both groups . RESULTS There was no significant difference in the total blood loss between the 2 groups although the intraoperative blood loss was significantly greater in those without a tourniquet . The mean morphine requirement , postoperative swelling , scope of ecchymosis , earlier straight-leg raising and postoperative knee flexion in the patients that had surgery without a tourniquet were significantly better than those with a tourniquet . CONCLUSION Knee arthroplasty operation with the use of a tourniquet has only small benefits on the total blood loss , but hinder in patients ' early postoperative rehabilitation exercises Purpose Tourniquets are still widely used in total knee arthroplasty ( TKA ) , although they may be associated with several adverse effects . An observer-blinded , r and omized , controlled trial was performed to evaluate the effects of tourniquet use in TKA . Methods Fifty participants who underwent staged bilateral TKA were recruited for this study . The first-side TKA was r and omly allocated to either long- duration tourniquet use or short- duration tourniquet use followed by a 3-month washout period and crossover to the other tourniquet strategy for the opposite-side TKA . Blood loss was monitored perioperatively . The operating time , allogeneic blood transfusion rate , thigh pain , knee pain , limb swelling , clinical outcome as measured by the Likert-type Western Ontario and McMaster University ( WOMAC ) score , straight leg raising and knee active range of motion ( ROM ) were also recorded . Results The long- duration tourniquet group exhibited reduced total blood loss [ −99.1 ml , 95 % confidence interval ( CI ) −168.1 to −30.1 , P = 0.0411 ] and intraoperative blood loss ( −225.2 ml , 95 % CI −369.5 to −80.9 , P = 0.0071 ) compared with the short- duration tourniquet group . However , there were greater postoperative blood loss ( 69.6 ml , 95 % CI 21.1 to 118.2 , P = 0.0282 ) and hidden blood loss ( 52.8 ml , 95 % CI 10.5 to 95.1 , P = 0.0332 ) in the long- duration tourniquet group . The short- duration tourniquet group showed better outcomes for thigh and knee pain , limb swelling , WOMAC score at 6-week follow-up , straight leg raising and knee ROM . Similar allogeneic blood transfusion rates were observed for both groups . Conclusion Total and intraoperative blood losses were reduced with the long- duration tourniquet use , whereas the short- duration tourniquet use would reduce postoperative and hidden blood losses without increasing the allogeneic blood transfusion rate . In addition , short- duration tourniquet use would result in faster recovery and less pain during the early rehabilitation period following TKA.Level of evidence BACKGROUND Thigh tourniquet is commonly used in total knee arthroplasty ( TKA ) but may contribute to pain and muscle damage . Consequently , the reduction in knee-extension strength after TKA may be caused by quadriceps muscle ischaemia underneath the cuff . AIM To examine if not using a thigh tourniquet during surgery was more effective than using a thigh tourniquet in preserving knee-extension strength 48 h after fast-track TKA . METHODS A total of 64 patients undergoing TKA were r and omized ( 1:1 ) to the use of tourniquet ( T-group ) or no tourniquet ( NT-group ) . In the T-group the tourniquet cuff pressure was based on the patient 's systolic pressure and a margin of 100 mm Hg . It was inflated immediately before surgery and deflated as soon as surgery ended . The primary outcome was the change in knee-extension strength from pre-surgery to 48 h after surgery ( primary end point ) . Secondary outcomes were pain , nausea , length of hospital stay ( LOS ) and periarticular swelling . RESULTS Knee-extension strength 48 h after surgery was substantially reduced by about 90 % in both groups , with no statistically significant difference between groups ( mean difference 1.5 N/kg , 95 % CI 1.3 - 1.6 ) . Among the secondary outcomes , the T-group had less bleeding during surgery ( 56 vs. 182 mL , P<0.01 ) compared with the NT-group . There was no difference in postoperative haemoglobin levels , pain , nausea , LOS or periarticular swelling between the groups . CONCLUSION Not using a thigh tourniquet during surgery was not superior in preserving knee-extension strength at the primary endpoint 48 h after fast-track TKA , compared to using a tourniquet Background : Tourniquet use during primary total knee arthroplasty is thought to reduce intraoperative blood loss and improve visibility . Our goal was to investigate whether tourniquet use is necessary for controlling intraoperative blood loss when alternatives such as tranexamic acid ( TXA ) are available . Methods : One hundred and fifty patients were equally r and omized to 3 groups . Group A was treated with a tourniquet as well as multiple doses of intravenous TXA ( 20 mg/kg 5 to 10 minutes before the skin incision and 10 mg/kg 3 , 6 , 12 , and 24 hours later ) along with 1 g of topical TXA , Group B was treated the same as Group A but without the tourniquet , and Group C was treated with the tourniquet only . Results : The amount of intraoperative blood loss was similar for the 3 groups . Group B had significantly less hidden blood loss than Group A ( p = 0.018 ) and Group C ( p < 0.001 ) . No significant differences ( p > 0.05 ) were observed between Group A and Group B with regard to total blood loss , drainage volume , intraoperative blood loss , transfusion rate , or maximum change in the hemoglobin ( Hb ) level . We also found significantly more benefits for Group B compared with Groups A and C with regard to postoperative swelling ratio , levels of inflammatory biomarkers , visual analog scale ( VAS ) pain scores , range of motion at discharge , Hospital for Special Surgery ( HSS ) score , and patient satisfaction . There were no significant differences ( p > 0.05 ) in the deep venous thrombosis or pulmonary embolus rates among the 3 groups . More wound secretion was observed in the groups in which a tourniquet was used . Conclusions : Patients treated with multiple doses of intravenous and topical TXA without a tourniquet had less hidden blood loss , a lower ratio of postoperative knee swelling , less postoperative knee pain , lower levels of inflammatory biomarkers , better early knee function , and even better early satisfaction than those treated with a tourniquet . Long-term follow-up should be performed to evaluate the effects on prosthetic fixation and long-term survival of total knee arthroplasty performed without a tourniquet . Level of Evidence : Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence STUDY OBJECTIVE To determine the perioperative frequency of deep vein thrombosis ( DVT ) after lower limb joint prosthesis surgery using Doppler ultrasonography ( US ) . DESIGN Prospect i ve cohort study . SETTING Operating room and hospital ward . PATIENTS 144 consecutive ASA physical status 1 and 2 patients who underwent elective total hip arthroplasty ( THA ; n=64 ) or total knee arthroplasty ( TKA ; n= 80 ) . INTERVENTIONS Patients were allocated to two groups , those who developed DVT ( DVT group ) postoperatively and those who did not ( no-DVT group ) . To examine the perioperative risk factors for DVT after THA or TKA , comparative analysis of the two groups was done . MEASUREMENTS Doppler US was performed on all patients from the bilateral femoral to lower limb to detect the existence of DVT postoperatively . MAIN RESULTS DVT was detected in 61 patients ( 42 % ) , including three proximal DVT patients ( 2 % ) . Preoperative elevated plasma D-dimer value [ P = 0.0131 , odds ratio ( OR ) 1.54 , 95 % CI 1.10 - 2.17 ] and history of hyperlipidemia ( P = 0.0453 , OR 6.92 , 95 % CI 1.04 - 46.00 ] were significant risk factors for the onset of DVT . A preoperative plasma D-dimer cutoff value as a diagnostic test was obtained as 0.85 μg/mL. CONCLUSIONS A high preoperative plasma D-dimer value and /or history of hyperlipidemia were risk factors for DVT after THA or TKA OBJECTIVE In lower-extremity surgery there are significant risks associated with the use of tourniquets . This prospect i ve study was done to assess to what extent these risks may be offset by the potential advantages of tourniquets , namely reductions in blood loss , length of hospital stay and complication rates . DESIGN A prospect i ve case study . SETTING A major urban hospital . PATIENTS Sixty-three consecutive patients scheduled for primary cemented total knee arthroplasty ( TKA ) were blindly r and omized into tourniqet ( n = 33 ) and non-tourniquet ( n = 30 ) groups . INTERVENTION TKA during which a pneumatic tourniquet was applied or not applied to control blood loss . MAIN OUTCOME MEASURES Perioperative blood loss , operating time , complication rates , hospital stay and transfusion needs . RESULTS Differences in the total measured blood loss , intraoperative blood loss and the Hemovac drainage blood loss between the 2 groups were not significantly different ( p > 0.25 ) . The calculated total blood loss was actually lower in the non-tourniquet group ( p = 0.02 ) . Between the groups there were no statistical differences in surgical time , length of hospital stay , transfusion requirements or rate of complications ( although there was a trend to more complications in the tourniquet group ( p = 0.06 ) ) . CONCLUSION The effectiveness of a pneumatic tourniquet to control blood loss in TKA is question able The purpose of this study is to examine the effect of a postoperative blood salvage drain and timing of tourniquet release on the maximal hematocrit drop after total knee arthroplasty . Thirty-seven total knees were prospect ively r and omized into either an early or late tourniquet release group . Hematocrit drop and drainage amounts were recorded . We found no significant difference in maximal hematocrit drop , drainage amounts , or total surgical time between the groups . We conclude that the use of a blood salvage drain should not influence the surgeon 's preference on timing of tourniquet release in total knee arthroplasty The control of perioperative blood loss is a major concern in cementless knee arthroplasty surgery . We r and omized retrospectively 55 patients ( 60 knees in total ) who had undergone cementless total knee arthroplasty and determined the efficacy of tourniquet release either " before " ( 30 knees ) or " after " ( 30 knees ) wound closure . Measurements of total blood loss showed significant differences between the groups ( " Before " group , 906 + /- 238 mL ; " After " group , 731 + /- 332 mL ; P = .0225 ) . The levels of red blood cells , hemoglobin , and hematocrit recovered to the preoperative levels by 3 months after surgery in both groups . In summary , we recommend that the tourniquet be released after wound closure and that a compressive dressing be applied with the aim of limiting or reducing perioperative blood loss without significant effects of the transfer requirement in the 2 groups , provided that tourniquet time is kept below 60 minutes to avoid ill effects of the tourniquet We conducted a prospect i ve , r and omized study of 77 primary knee replacement operations on 75 patients ( 52 women ) , with a mean age of 71 years , to evaluate the effect of tourniquet release for hemostasis on blood loss and transfusion requirements . The operations were all done with spinal anesthesia and the use of a midline skin incision and medial parapatellar approach . In group I , the tourniquet was released for hemostasis before the wound was closed . In group 2 , the tourniquet was first released after the wound was closed and a compressive dressing had been applied . The total intra- and postoperative blood losses were , on average , 858 mL ( SD 443 ) in group I and 589 mL ( 347 ) in group 2 ( p = 0.01 ) . The median units of blood given and the postoperative decreases in hemoglobin values were similar in both groups . In a subgroup of 45 cementless prostheses , the 25 patients with prostheses allocated to group 1 lost 1022 mL ( 397 ) blood , compared to 646 mL ( 333 ) by the 20 patients with prostheses in group 2 ( p = 0.01 ) . Our findings speak against the efficacy of tourniquet release for hemostasis in knee replacement surgery We studied the effect of timing of tourniquet release on blood loss in 81 patients ( 85 knees ) who were operated on for total knee replacement . The patients were r and omly allocated to one of two groups . In one group , the tourniquet was released for hemostasis before wound closure and in the other group , the tourniquet was not released until the wound was closed and a compressive dressing applied . We found no difference in total blood loss between the two groups and conclude that intraoperative release of the tourniquet for hemostasis is not effective for reducing blood loss in total knee replacement Total knee replacement often is performed with tourniquet application . The advantages of a dry field , including fixation , are well known , but it still is debatable if tourniquet application increases deep vein thrombosis . Measurement of coagulation markers is a well accepted method of study ing thrombogenesis activation intraoperatively and postoperatively . Twenty patients undergoing total knee replacement with subarachnoid anesthesia were assigned r and omly to two groups : either with tourniquet application ( Group I ) or without tourniquet application ( Group II ) . There were no differences between patients in the two groups in terms of age , gender , diagnosis ( all had osteoarthritis ) , operative time , and total ( intraoperative and postoperative ) blood loss . Markers for thrombin generation and fibrinolysis were measured . Blood sample s were drawn at four times : baseline before the operation ; after bone cuts ; after cement fixation ( Group II ) or 2 minutes after tourniquet deflation ( Group I ) ; and 1 hour after surgery . Markers of thrombin generation and fibrinolysis showed a significant increase from baseline in all the patients . In Group II these markers started to increase during surgery , whereas in Group I the increase occurred at the end of the procedure when the tourniquet was deflated . The total amount of thrombin generation was significantly higher in Group II ( without tourniquet ) , whereas fibrinolysis was significantly greater in Group I. Total knee replacement is accompanied by a hypercoagulative state with or without the use of a tourniquet , but it seems to be higher when the tourniquet is not used . In addition , tourniquet application may increase fibrinolysis Background We aim ed to compare the effect of tourniquet use or lack of it on recovery following uncomplicated primary total knee arthroplasty ( TKA ) . Methods In a prospect i ve r and omised double-blinded study , 150 patients undergoing primary TKA were assigned to either a tourniquet or non-tourniquet group . At the early phase , 3 and 6 months after surgery , an independent observer assessed the primary outcome measure ( i.e. total blood loss ) and secondary outcome measures ( i.e. wound complications , visual analogue scale pain score and knee range of motion ) . Results The tourniquet group exhibited reduced intraoperative blood loss ( 215.7 ± 113.7 ml vs. 138.6 ± 93.9 ml , P < 0.001 ) and shorter operating time ( 77.2 ± 14.5 min vs. 82.0 ± 12.7 min , P = 0.038 ) . However , the non-tourniquet group showed less postoperative blood loss ( 180.2 ± 117.0 ml vs. 253.7 ± 144.2 ml , P = 0.001 ) and drainage volume ( 89.2 ± 66.3 ml vs. 164.5 ± 97.8 ml , P = 0.004 ) , less thigh pain ( all P < 0.001 ) in the initial 3 weeks , better knee range of motion ( ROM ) in the initial 3 days ( day 1 81.6 ± 17.1 vs. 75.95 ± 14.55 , P = 0.036 ; day 3 99.8 ± 13.7 vs. 93.95 ± 11.15 , P = 0.005 ) and fewer wound tension vesicles ( 10.3 vs. 29.2 % , P = 0.005 ) . Earlier straight-leg raising ( 4.6 ± 3.8 h vs. 6.4 ± 4.3 h , P = 0.01 ) and shorter length of stay ( 6.3 ± 1.7 days vs. 7.1 ± 1.9 days , P = 0.001 ) were found in the non-tourniquet group . Similar total blood loss and blood transfusion rate were observed for both groups . All other parameters revealed no significant differences . Conclusions Our study suggests that a non-tourniquet TKA would lead to early rehabilitation without increasing side effects . Trial registration Chinese Clinical Trials Registry , ChiCTR-IOR-16007851 , We performed a prospect i ve , r and omized , controlled trial to know whether a short duration of tourniquet application affects surgical time , post-operative swelling , pain , early rehabilitation and complications compared to st and ard use of tourniquet throughout the procedure . Sixty knees were r and omized . There were no differences in terms of surgical time and pain experienced between the two groups . Patients in the short duration tourniquet group had significantly less thigh swelling ( 3.7±1.6 versus 4.8±2.35 p<0.01 ) . There were no differences in the early rehabilitation between the groups . Soft tissue complications were higher in st and ard duration group . The use of tourniquet only during cementation of the implants reduces the thigh swelling and soft tissue complications associated with tourniquet use throughout the procedure BACKGROUND Tourniquets used during total knee arthroplasty may lead to many complications . The aim of this study was to determine perioperative blood loss and its clinical relevance in total knee replacement surgery after applying a tourniquet . METHODS From June 2009 to October 2009 , 60 consecutive patients who underwent routine total knee arthroplasty were r and omly divided into two groups and were treated with or without a tourniquet ( 30 patients /group ) . There were no significant differences in patient baseline characteristics between the two groups . We compared the two groups of patients in terms of intra- and postoperative bleeding , invisible or visible bleeding , and total blood loss . RESULTS None of the patients showed poor wound healing , lower extremity deep venous thrombosis or other complications . The amount of blood loss during surgery was lower in the tourniquet group than in the control group ( P < 0.01 ) . However , postoperative visible bleeding ( P < 0.05 ) and occult bleeding ( P < 0.05 ) were significantly greater in the tourniquet group than in the control group . There was no significant difference in the total amount of blood loss between the two groups ( P > 0.05 ) . CONCLUSIONS Tourniquet can reduce bleeding during total knee replacement surgery , but is associated with greater visible and invisible blood loss Abstract . We conducted a prospect i ve , r and omised study on primary total knee replacements to evaluate the effects of tourniquet use on total calculated blood loss using Gross formula , post-operative measured blood loss , operating time , need for blood transfusion , post-operative pain , analgesia requirement and knee flexion . Forty patients were operated on with the use of an arterial tourniquet with pressure of 350 mmHg ( group A ) , and 40 patients without the use of a tourniquet ( group B ) . Total calculated blood loss was significantly increased ( P=0.0165 ) without the use of a tourniquet . There was no significant difference in measured blood loss or operating time . The median units of blood given were similar in both groups . In spite of autologous transfusions 14 % of patients received additional homologous transfusions . At 6 h post-operatively pain was significantly less ( P=0.0458 ) in group B but was similar at 24 and 48 h. There was no significant difference in analgesia requirement . The mean change in total flexion in group B was significantly better ( P<0.001 ) at 5 days than in group A , but knee flexion was similar at 10 days and 3 months . Knee arthroplasty operations without the use of a tourniquet cause a greater blood loss but have only small benefits in the early post-operative period . Résumé . Une étude prospect i ve et r and omisée a été réalisée sur 80 arthroplasties totales du genou consécutives de première intention dans le but d'évaluer l'effet de l'utilisation du garrot pneumatique sur les pertes sanguines totales calculées selon la formule de Gross , les pertes sanguines mesurées par drainage aspiratif , la durée opératoire , la nécessité de transfusion sanguine , la douleur post-opératoire , le besoin d'antalgique et la récupération de la flexion du genou . Quarante patients ont été opérés avec un garrot pneumatique gonflé à 350 mmg ( group A ) , et quarante sans garrot pneumatique ( group B ) . Les pertes sanguines totales calculées étaient plus élevées de façon significative ( P=0.0165 ) dans le groupe B. Il n'y avait pas de différence significative entre les deux groupes sur les pertes sanguines mesurées par drainage aspiratif et la durée opératoire . Le nombre de culots globulaires nécessaire était le même dans les deux groupes . Malgré un protocol e d'autotransfusion , 14 % des patients ont eu une transfusion homologue complémentaire . La douleur post-opératoire était significativement moindre ( P=0.0458 ) à la sixième heure dans le groupe B mais était identique à 24 et 48 heures . Il n'y avait pas de différence sur la consommation d'antalgique . La flexion dans le groupe B était meilleure ( P<0.001 ) au cinquième jour que dans le groupe A , mais était identique à 10 jours et au troisième mois post-opératoire pour les deux groupes . La non-utilisation d'un garrot pneumatique apporte quelques bénéfices dans la période post-opératoire immédiate mais est responsable d'une majoration des pertes sanguines totales calculées The objective of this study was to examine the characteristics of hidden blood loss and assess the effects of using a tourniquet on postoperative hidden loss in patients undergoing primary total knee arthroplasty . Eighty patients were r and omised into two groups : one group underwent operation with a tourniquet and one without . Operating time , perioperative blood loss , hidden blood loss , free haemoglobin , swelling , ecchymosis , straight leg raising action and knee flexion were measured . There were significant differences in the hidden blood loss , free haemoglobin , postoperative swelling , extent of ecchymosis , straight leg raising and postoperative knee flexion in the early period after operation between the two groups . Our results indicate that knee arthroplasty operations with a tourniquet might promote postoperative hidden blood loss and hinder patients ’ in early postoperative rehabilitation exercises . RésuméL’objectif de l’étude est de déterminer les caractéristiques des pertes sanguines occultes et les effets de l’utilisation du garrot sur ces pertes sanguines dans les prothèses totales du genou primaires . Matériel et méthode : les patients ont été r and omisés en deux groupes , un groupe a été opéré sous garrot et un groupe sans garrot . Le temps opératoire , les pertes sanguines péri-opératoires et occultes , le taux d’hémoglobine , l’hématome , l’ecchymose , la possibilité d’extension active et de flexion du genou ont été mesurés . Résultats : il y a une différence significative sur les pertes sanguines occultes , le taux d’hémoglobine , les douleurs post-opératoires , les ecchymoses , l’élévation active de la jambe et la flexion du genou post-opératoire . En conclusion , nos résultats montrent que la prothèse totale du genou avec garrot , peut entraîner des pertes de sang occultes chez les patients notamment en cours de la rééducation post-opératoire Background : It is a r and omized study to compare cement penetration on x-rays after total knee arthroplasty ( TKA ) among 3 different ways to use tourniquets ; application during the surgery , application only with implantation prosthesis and with no tourniquet use . Methods : A total 69 knees of 59 patients were included in the study in a quasir and om manner . Each patient had physical exams and st and ard radiographic evaluations at 6 weeks after the TKA procedure . Outcome evaluations included visual analog scale ( VAS ) scores , Knee Society Scores ( KSS ) , blood transfusion , and drainage status after surgery for all groups . For radiographic review , the tibial plateau was divided into zones in the anterior – posterior and lateral views , according to the Knee Society Scoring System . Results : The average age of the patients who were eligible for the study was 65.05 ( range 46–81 ) years . All 59 patients included in the study were female patients . Group 1 consisted of 24 patients who had TKA with use of a tourniquet during the entire operation . Group 2 consisted of 20 patients who had TKA with use of tourniquet only at the time of cementing and group 3 consisted of 25 patients with no use tourniquet . There is no significant difference in early cement penetration among the groups ( group 1 2.50 mm , group 2 2.28 mm , group 3 2.27 mm ; group 1 vs 2 P = .083 , group 1 vs 3 P = .091 , group 2 vs 3 P = .073 ) . There is no significant difference for postoperative drainage among the 3 groups ( group 1 245 mL , group 2 258.76 mL , group 3 175.88 mL ; group 1 vs 2 P = .081 , group 1 vs 3 P = .072 , group 2 vs 3 P = .054 ) . There was no need to transfuse more than 1 unit in any patient . The VAS score was significantly higher ( group 1 3.58 , group 2 1.55 , group 3 1.52 ; group 1 vs 2 P = .022 , group 1 vs 3 P = .018 , group 2 vs 3 P = .062 ) and KSS was significantly lower in the tourniquet group ( group 1 63 , group 2 79 , group 3 82 ; group 1 vs 2 P = .017 , group 1 vs 3 P = .02 , group 2 vs 3 P = .082 ) . Conclusion : We do not suggest long- duration tourniquet use , which can lead higher pain scores and reduce functional recovery after total knee arthroplasty Purpose When a tourniquet is used during surgery on the extremities , the pressure applied to the muscles , nerves and blood vessels can cause neuromuscular damage that contributes to postoperative weakness . The hypothesis was that the rehabilitation-related results would be improved if total knee arthroplasty ( TKA ) is performed without the use of a tourniquet . Methods 81 patients with osteoarthritis of the knee who underwent TKA surgery were r and omized to surgery with or without tourniquet . Active flexion and extension of the knee , pain by visual analog scale ( VAS ) , swelling by knee circumference , quadriceps function by straight leg raise , and timed up and go ( TUG ) test results were measured before and up to 3 months after surgery . Results ANCOVA revealed no between-groups effect for flexion of the knee at day 3 postsurgery . Compared with the tourniquet group , the nontourniquet group experienced elevated pain at 24 h , with a mean difference of 16.6 mm , p = 0.005 . The effect on mobility ( TUG test ) at 3 months was better in the nontourniquet group , with a mean difference of -1.1 s , p = 0.029 . Conclusions The hypothesis that the rehabilitation-related results would be improved without a tourniquet is not supported by the results . When the results in this study for surgery performed with and without tourniquet are compared , no clear benefit for either procedure was observed , as the more pain exhibited by the nontourniquet group was only evident for a short period and the improved mobility in this group was not at a clinical ly relevant level . Level of evidence Inconsistent results , Level II Purpose Poor scientific evidence exists on the issue of tourniquet application during total knee arthroplasty ( TKA ) . It has been suggested that tourniquet application might improve interdigitation of the cement into the periprosthetic bones due to relatively dry surgical field . The hypothesis of the present study was that tourniquet use did not affect the periprosthetic bone cement penetration . Methods The single-centre , r and omized , controlled trial included 86 patients undergoing primary TKA ( Clinical -Trials.gov NCT02475603 ) . All patients meeting the inclusion criteria were r and omly assigned to the tourniquet ( n = 43 ) or non-tourniquet ( n = 43 ) group after obtaining a written informed consent . The cumulative bone cement penetration was radiologically measured in AP ( seven zones ) and lateral views ( three zones ) as defined by Knee Society Scoring System . Further parameters such as perioperative blood loss , soft tissue swelling , pain level/analgesic consumption , operative time , length of hospital stay ( LOS ) and complication rate were statistically compared between the groups . Results The cumulative bone cement penetration averaged 28.5 ± 1.7 mm in tourniquet versus 26.6 ± 1.6 mm in non-tourniquet groups ( n.s . ) . The mean intraoperative blood loss was 250 ml higher in the non-tourniquet group ( p = 0.0001 ) . Patient-reported pre- to 6th-day post-operative reduction of the pain level was significantly higher in the non-tourniquet group ( p = 0.003 ) . The Morphine Equivalent Dose was higher in the Tourniquet group at discharge day ( p = 0.02 ) . Parameters such as total blood loss , soft tissue swelling , surgical time , LOS , and complication rates revealed similar results between the groups . Conclusions Tourniquet application did not influence the bone cement penetration significantly . Even though the intraoperative blood loss was reduced , the total blood loss was not affected significantly by tourniquet use . There was a tendency of higher post-operative pain and opioid analgesic requirement in the tourniquet group . Level of evidence Objective compare blood loss in 40 patients underwent to unilateral total knee replacement with the release of ischemia before and after skin closure and compressive dressing . Methods in a prospect i ve r and omized study , in 40 patients underwent to total knee replacement , dividing then into two groups : group A in which the ischemia was released before skin closure , allowing bleeding control and group B where the ischemia was released after skin suture and pressure dressing . We compared the results of laboratory tests of serum hemoglobin before surgery and 48 hours postoperatively , the blood volume contained in vacuum suction drain and the transfusions that was necessary . Results As a result , the post operative serum hemoglobin levels had a mean decrease of 3.57 g/dL in group A and 4.24 g/dL in group B with an average of 0.67 g/dL difference between them , statistically insignificant . The observed mean drainage , in the vacuum drain , were 705 mL in group A and 700 mL in group B. The 5 ml difference between medians was considered statistically insignificant . The number of patients who received transfusions was four patients in both groups and all received two units of red blood cells . Conclusion the post operative serum hemoglobin levels , as well as the need of blood transfusion , in the patient underwent to total knee replacement , where the ischemia was released before wound closure , has no statistical effect in comparison with patients where the sutures and b and ages were done after the ischemia release . Level of Evidence IB - Individual r and omized controlled trial with narrow confidence interval Background The goal of this work was to investigate the effects of different methods of using pneumatic tourniquet on reducing blood loss in patients undergoing cemented total knee arthroplasty ( TKA ) . Methods One hundred and fifty patients undergoing unilateral cemented TKA were r and omly divided into three groups ( 50 patients per group ) . The tourniquet was used during the entire operation ( Group A ) , used from the beginning of operation to the completion of joint replacement ( Group B ) , and from the beginning of osteotomy to the completion of arthroplasty ( Group C ) . The following parameters were recorded : intraoperative blood loss ( IBL ) , postoperative blood loss ( PBL ) , hidden blood loss ( HBL ) , and total blood loss ( TBL ) ; operation time and tourniquet time ; incidence of postoperative complications ; and hospital for special surgery ( HSS ) score . Results IBL , HBL , and TBL in group C was significantly less than that in group B ( all P < 0.05 ) . Tourniquet time in group C was significantly less than that in groups A and B ( all P < 0.05 ) . The incidence of tourniquet-related complications in group C ( 6 % ) was relatively lower than that in group A ( 10 % ) during hospitalization ( P > 0.05 ) . Post-operative HSS scores at 2 weeks after the operation in group C was significantly higher than that in group A and group B ( all P < 0.05 ) . Conclusions Our results suggest that using a tourniquet from the beginning of osteotomy to the completion of arthroplasty could significantly reduce TBL in TKA , and decrease the incidence of complications ; thereby facilitating early post-operative functional recovery |
10,870 | 27,378,490 | No significant difference was seen in quality of life , sputum weight , exercise tolerance , lung function , or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices .
There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy .
There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy .
Five studies , with data from eight different comparators , found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference , quality of life , exercise tolerance , lung function , sputum weight , oxygen saturation , and number of pulmonary exacerbations .
Longer-term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference | BACKGROUND People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs .
Repeated infections often cause lung damage and disease .
Airway clearance therapies aim to improve mucus clearance , increase sputum production , and improve airway function .
The active cycle of breathing technique ( also known as ACBT ) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control , thoracic expansion exercises , and the forced expiration technique .
This is an up date of a previously published review .
OBJECTIVES To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis . | We studied the acute effects of 4 different chest physical therapy regimens using a r and omised cross-over design in 14 patients with cystic fibrosis . Treatment A consisted of postural drainage , percussion and vibration ; treatment B of postural drainage and periodic application of a face mask with positive expiratory pressure ( PEP ) ; treatment C of PEP in the sitting position ; treatment D of the forced expiration technique in the sitting position . In terms of sputum expectorated , treatments B and C were superior to treatment D and especially to treatment A ( p less than 0.05 ) . Skin oxygen tension , PSO2 was monitored continuously during and for 35 min after treatment . A substantial and prolonged decay in PSO2 was observed during treatment A , quite different from other patterns seen . During and even following treatment C , an increase in PSO2 was noted . PEP was well accepted by the patients , who preferred treatment C , and we suggest it is incorporated in chest physical therapy regimens if the therapeutic objective is to increase expectoration It has previously been shown that unproductive coughing in both healthy subjects and patients with airways obstruction is not effective in clearing lung secretions . This study investigates the regional mucus transport in a group of subjects with airways obstruction who failed to expectorate following instructed cough and forced expiration technique . Fourteen patients ( mean + /- SEM age : 68 + /- 2 years ) with airways obstruction ( mean + /- SEM percent predicted . FEV1 : 54 + /- 5 ; daily wet weight sputum : 9.1 + /- 2.0 g ) took part in the study which was a r and omized , three-way crossover within-patient design . Each patient underwent three treatment maneuvers : control , cough ( 30 coughs over a 10-min period ) , and forced expiration ( 30 forced expirations over a 10-min period ) . An objective radioaerosol technique was used to monitor regional mucus movement within the lungs of the patients . The lungs were divided arbitrarily into four regions of interest : tracheal , inner , intermediate , and outer . Peak expiratory flow rate during cough and forced expiration was measured at the mouth . There was no correlation between the radioaerosol clearance from all regions and ( 1 ) mean peak flow during cough and forced expiration , and ( 2 ) mean 24-h sputum production prior to the study day . There were no differences in regional radioaerosol clearance between cough and forced expiration . However , both cough and forced expiration result ed in significant clearance compared with control for all regions with the exception of the forced expiration in the outer region . To our knowledge , this study is the first to demonstrate that unproductive cough and forced expiration result in movement of secretions proximally from all regions of the lung in patients with airways obstruction Background High frequency chest wall oscillation ( HFCWO ) is st and ard treatment for airway clearance in the USA and has recently been introduced in the UK and Europe . There is little published research comparing HFCWO with airway clearance techniques ( ACTs ) frequently used in the UK and Europe . The aim of this study was to compare the short-term effects of HFCWO with usual ACTs in patients with cystic fibrosis hospitalised with an infective pulmonary exacerbation . Methods A 4-day r and omised crossover design was used . Patients received either HFCWO on days 1 and 3 and usual ACTs on days 2 and 4 or vice versa . Wet weight of sputum , spirometry and oxygen saturation were measured . Perceived efficacy , comfort , incidence of urinary leakage and preference were assessed . Data were analysed by mixed model analysis . Results 29 patients ( 72 % male ) of mean ( SD ) age 29.4 ( 8.4 ) years and mean ( SD ) forced expiratory volume in 1 s ( FEV1 ) percentage predicted ( FEV1 % ) 38 ( 16.7 ) completed the study . Significantly more sputum was expectorated during a single treatment session and over a 24 h period ( mean difference 4.4 g and 6.9 g , respectively ) with usual ACTs than with HFCWO ( p<0.001 ) . No statistically significant change in FEV1 % or oxygen saturation was observed after either HFCWO or usual ACTs compared with baseline . 17 patients ( 55 % ) expressed a preference for their usual ACT . Conclusions During both a finite treatment period and over 24 h , less sputum was cleared using HFCWO than usual ACT . HFCWO does not appear to cause any adverse physiological effects and may influence adherence The Flutter VRP1 ( Flutter ) is cl aim ed to increase the clearance of excess bronchial secretions and to improve lung function and oxygenation , but these cl aims were based on computer models , laboratory assisted experiments and uncontrolled clinical trials . A prospect i ve r and omized clinical trial was undertaken , in subjects with cystic fibrosis , using the active cycle of breathing techniques as the ' gold st and ard ' . The cl aims could not be substantiated and the possibility of sputum retention was of concern when the Flutter was used as significantly more sputum ( P < 0.001 ) was cleared with the active cycle of breathing techniques alone . There were no significant changes in lung function or oxygenation Chest physiotherapy is an essential part of the management of cystic fibrosis , yet comparatively few studies have investigated the commonly used forms of chest physiotherapy during acute respiratory exacerbations . Fifteen subjects with cystic fibrosis and predominantly mild pulmonary impairment completed a r and omised cross-over trial with 24 hours between treatments . The active cycle of breathing techniques ( ACBT ) assisted by a physiotherapist was compared with the ACBT performed independently by the patient . Measurement outcomes included pulmonary function tests , indirect calorimetry and oximetry parameters . Energy expenditure was not significantly different between the two treatment regimens , though significant improvements in pulmonary function were apparent 24 hours following the therapist-assisted ACBT . In this group of subjects , neither form of treatment proved superior in terms of energy consumption , but a reduction in airways obstruction was observed as a carry-over effect following the therapist-assisted ACBT BACKGROUND --In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance . This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique ( FET ) in patients with airways obstruction . METHODS --Nineteen patients ( 11 men and eight women ) of mean ( SE ) age , % predicted FEV1 , and daily sputum wet weight of 64 ( 2 ) years , 52 (6)% , and 37.5 ( 7.9 ) g respectively participated in the study . Mucus movement from proximal and peripheral lung regions was measured by an objective non-invasive radioaerosol technique . Each patient underwent three assessment s : control , cough , and FET . During cough and FET , maximum expiratory flow was measured at the mouth level . Apparent viscosity and elasticity of the expectorated sputum sample s were measured with a viscometer . RESULTS --Compared with the control run ( mean ( SE ) clearance : 16 (3)% ) there was an increase in clearance from the whole lung during cough ( 44 (5)% ) and FET ( 42 (5)% ) , and also an enhanced clearance of inhaled , deposited radioaerosol from the trachea , inner and intermediate regions of the lungs , but not from the outer region . There were , however , no differences in regional clearance between cough and FET . Neither regional nor total clearance correlated with maximum expiratory flow , apparent viscosity , elasticity , or daily sputum wet weight . CONCLUSIONS --These results confirm that cough and FET both promote effective clearance but suggest that , unlike in vitro studies , sputum production and viscoelasticity , as well as maximum expiratory flow , provide no guide to clearance efficacy in humans We studied the effectiveness of some of the components of a physiotherapy regimen on the removal of mucus from the lungs of 6 subjects with cystic fibrosis . On 5 r and omized study days , after inhalation of a 99mTc-human serum albumin aerosol to label primarily the large airways , the removal of lung radioactivity was measured during 40 min of ( a ) spontaneous cough while at rest ( control ) , ( b ) postural drainage , ( c ) postural drainage plus mechanical percussion , ( d ) combined maneuvers ( postural drainage , deep breathing with vibrations , and percussion ) administered by a physiotherapist , ( e ) directed vigorous cough . Measurements continued for an additional 2 h of quiet rest . Compared with the control day , all forms of intervention significantly improved the removal of mucus : cough ( p less than 0.005 ) , physiotherapy maneuvers ( 0.005 less than or equal to p less than 0.01 ) , postural drainage ( p less than 0.05 ) , and postural drainage plus percussion ( p less than 0.01 ) . However , there was no significant difference between regimented cough alone and therapist-administered combined maneuvers , nor between postural drainage alone and with mechanical percussion . We conclude that in cystic fibrosis , vigorous , regimented cough sessions may be as effective as therapist-administered physiotherapy in removing pulmonary secretions . Postural drainage , although better than the control maneuver , was not as effective as cough and was not enhanced by mechanical percussion . Frequent , vigorous self-directed cough sessions are potentially as useful as more complex measures for effective bronchial toilet Background : Chest physiotherapy is essential to the management of cystic fibrosis ( CF ) . However , respiratory muscle fatigue and oxygen desaturation during treatment have been reported . The aim of this study was to determine whether non-invasive ventilation ( NIV ) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF . Methods : Twenty six patients of mean ( SD ) age 27 ( 6 ) years and forced expiratory volume in 1 second ( FEV1 ) 34 (12)% predicted completed a r and omised crossover trial comparing st and ard treatment ( active cycle of breathing technique , ACBT ) with ACBT + NIV . Respiratory muscle strength ( PImax , PEmax ) , spirometric parameters , and dyspnoea were measured before and after treatment . Pulse oximetry ( Spo2 ) was recorded during treatment . Sputum production during treatment and 4 and 24 hours after treatment was evaluated . Results : There was a significant reduction in PImax following st and ard treatment that was correlated with baseline PImax ( r=0.73 , p<0.001 ) . PImax was maintained following NIV ( mean difference from st and ard treatment 9.04 cm H2O , 95 % confidence interval ( CI ) 4.25 to 13.83 cm H2O , p=0.006 ) . A significant increase in PEmax was observed following the NIV session ( 8.04 cm H2O , 95 % CI 0.61 to 15.46 cm H2O , p=0.02 ) . The proportion of treatment time with Spo2 ⩽90 % was correlated with FEV1 ( r=−0.65 , p<0.001 ) . NIV improved mean Spo2 ( p<0.001 ) and reduced dyspnoea ( p=0.02 ) . There were no differences in FEV1 , forced vital capacity ( FVC ) or sputum weight , but FEF25–75 increased following NIV ( p=0.006 ) . Conclusion : Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF . Addition of NIV improves inspiratory muscle function , oxygen saturation and small airway function and reduces dyspnoea The aim of the study was an estimation of effectiveness of selected autodrainage methods used in the treatment of children with cystic fibrosis and an assessment of patients ' preference in relation to investigated methods . We also estimated the patients and their families ' relation to chest physiotherapy methods , which have been used at home for many years . We studied 17 patients , aged 10 - 18 ( x 13.35 ) , who were hospitalised in the Institute of Mother and Child Paediatric Clinical Dept . We compared four autodrainage methods : 1- force expiratory technique , 2- Flutter(R ) , 3- Flutter ( R ) with relaxation , 4- PEP system . Every investigated drainage methods were tested by each patient according to a determined procedure . The following indices were measured : weight of coughed up sputum , oxygen saturation ( SaO2 ) before , during and after drainage , peak expiratory flaw ( PEF ) before and after drainage . Patients ' relation to autodrainage methods was estimated on the ground of their subjective assessment in 0 - 5-point scale . The results showed that the force expiration technique and the Flutter(R ) with relaxation are the most efficient autodrainage methods determined by their coughed up sputum weight . Patients using these methods coughed up x 1.36 g and x 1.319 g sputum . Using Flutter(R ) without relaxation , patients expectorated 1.199 g sputum . PEP system turned out the least effective . Patients using the PEP system coughed up x 0.87 g sputum . In comparison , patients using postural drainage with clapping expectorated x 0.63 g sputum . We observed that the PEF decreased during every investigated drainage methods . There were no significant differences in SaO2 values before and after drainage . Concerning the patients ' preference in relation to the investigated methods , patients appreciated the most force expiratory technique ( 68 points ) . The least appreciated was the PEP system ( 33 points ) . For comparison , postural drainage with clapping has been estimated at 48.87 points Promotion of sputum expectoration by chest physiotherapy is an essential part of cystic fibrosis management . The role of exercise in improving sputum expectoration and lung function in these patients is more contentious . We therefore investigated the effect of adding an exercise programme to conventional chest physiotherapy in eight adult subjects ( four male ) with cystic fibrosis . Subjects were treated on two non-consecutive days of the second week of a course of in-patient antibiotic therapy in a cross-over fashion . On the exercise and physiotherapy day , subjects exercised 60 min before physiotherapy . On the physiotherapy alone day , subjects rested for 60 min instead of exercising . Physiotherapy was administered on both study days ( postural drainage , percussion , deep breathing , vibrations , forced expiratory technique and coughing ) . Lung function tests were performed at baseline , after exercise or rest and again immediately and 30 min after physiotherapy . Sputum weights were measured in the 60 min of exercise or rest ( period A ) and for the 60 min physiotherapy period and 30 min after physiotherapy ( period B ) . Mean total sputum expectoration ( period A and B ) was 14 g on physiotherapy alone and 21.5 g ( 4.8 ) on exercise and physiotherapy ( mean difference 7.5 g , 95 % CI 1.4 - 13.6 g , P = 0.02 ) . Mean sputum weights during period A ( i.e. rest vs. exercise ) on physiotherapy alone and exercise and physiotherapy were 2.6 and 7 g respectively ( mean difference 4.4 g , 95 % CI-0.07 - 8.8 g , P = 0.053 ) . ( ABSTRACT TRUNCATED AT 250 WORDS We studied the effects of two chest physiotherapy regimens on whole lung and regional tracheobronchial clearance ( TBC ) in ten patients with cystic fibrosis . The regimens were given on two separate days and consisted of 20 min of ( 1 ) postural drainage and the forced expiration technique ( PD + FET ) , and ( 2 ) positive expiratory pressure ( PEP-mask ) and FET ( PEP + FET ) . A third day served as control . The study days were r and omized . Each day , the clearance of lung radioactivity was measured for 3 h by gamma camera . The number of spontaneous coughs was recorded and the sputum expectorated was sample d. We found that both PD + FET and PEP + FET improved whole lung TBC at 30 minutes and 1 h four or fivefold ( p less than 0.01 ) compared with control , whereas at 2 h and 3 h only the improvement following PEP + FET ( approximately 1.4 times ) was significant ( p less than 0.05 ) . There was no significant difference in whole lung or regional TBC between the PD + FET and PEP + FET treatments . The correlations between TBC and the radioactivity content in sputum expectorated ( rs2 = 0.76 ) and between TBC and numbers of coughs ( rs2 = 0.65 ) were better than between TBC and the weight of sputum expectorated ( Rs = 0.39 ) . We conclude that PD or PEP when combined with FET have similar effects on short-term whole lung and regional TBC in patients with cystic fibrosis . Evaluation of TBC during chest physiotherapy when only based on the weight of sputum expectorated seems inadequate The aim of this study was to compare the response of infants with acute wheezing to treatments with inhaled terbutaline when administered by nebulizer or by metered-dose inhaler and spacer device ( MDI-spacer ) . Thirty-four infants between the ages of 1 and 24 months who were seen in our emergency department for acute wheezing were studied in a double-blind , r and omized trial . The participants received two treatments of terbutaline at 20-min intervals , either by a nebulizer ( 2 mg/dose in 2.8 mL of 0.9 % saline solution ) or by an MDI-spacer device ( 0.5 mg/dose ) . The outcome measure was a clinical score , based on respiratory rate , degree of wheezing , retractions , degree of cyanosis , color , and pulse oximetry data measured before treatment , 20 min after the first treatment , and again 20 min after the second treatment . There was no difference in the rate of improvement in the clinical score between infants who received terbutaline by nebulizer and those who received it by MDI-spacer . We conclude that MDI-spacers and nebulizers are equally effective means of delivering beta-2 agonists to infants and small children with acute wheezing OBJECTIVE We report the results of a long-term comparative trial of physiotherapy by the positive expiratory pressure ( PEP ) technique with a PEP mask ( Astra Meditec ) versus conventional postural drainage and percussion ( PD&P ) . Forty patients , ages 6 to 17 years , with Shwachman scores between 52 and 93 , attending the cystic fibrosis clinic were enrolled in the study and r and omly assigned to one of two groups . Group A ( control ) continued to perform physiotherapy by using PD&P for a 1-year period , whereas patients assigned to group B performed physiotherapy with the PEP technique for the same period . Compliance with physiotherapy was closely monitored for both groups throughout the study . Clinical status and pulmonary function ( forced vital capacity [ FVC ] , FEV1 , and FEF25 - 75 ) were measured at 3-month intervals . Group B ( PEP ) demonstrated improved pulmonary function in all parameters as measured by change in percent predicted value for age , gender , and height . The changes in pulmonary function over the study period were : FVC , + 6.57 ; FEV1 , + 5.98 ; and FEF25 - 75 , + 3.32 . This improvement was significantly different from that of group A ( PD&P ) whose pulmonary function declined in all parameters ( FVC , -2.17 ; FEV1 , -2.28 ; FEF25 - 75 , -0.24 ) . The differences between treatment groups were statistically significant for the changes in FVC ( p = 0.02 ) and FEV(1 ) ( p = 0.04 ) . Our results indicate that for our patients with cystic fibrosis , pulmonary physiotherapy with the PEP technique was superior to conventional physiotherapy with the PD&P technique In Pol and the st and ard treatment of pulmonary manifestation of cystic fibrosis consists of physiotherapy techniques of postural drainage with clapping . However many studies demonstrated that various alternative airway clearance techniques performed in Europe the last few years have been more effective than postural drainage . The aim of the study was a comparative analysis of the efficiency of selected chest physiotherapy methods used in the treatment of children with cystic fibrosis . We studied 21 patients , aged 5 - 18 ( x 10.57 ) , who were hospitalised in the Paediatric Clinic of National Research Institute of Mother and Child in Warsaw , Pol and . We compared five chest physiotherapy techniques : 1 - postural drainage with clapping , 2 - postural drainage with clapping and vibration , 3 - active cycle of breathing technique , 4 - Flutter(R ) , 5 - Flutter(R ) with relaxation . Every investigated drainage method was tested by each patient according to a determined procedure . The following indices were measured : weight of coughed up sputum , oxygen saturation ( SaO2 ) before , during and after drainage , peak expiratory flaw ( PEF ) before and after drainage . The biggest quantity of sputum determined by its coughed up weight was with active cycle of breathing technique ( x 2.126 g ) . In comparison , in patients using postural drainage with clapping and clapping with vibration average sputum expectoration was 0.895 and 1.012 g. Flutter device is recommended for individual usage . Our findings demonstrate that the Flutter with relaxation effectively facilitates removal of mucus from airways ( Flutter - x 1.48 g , Flutter with relaxation - x 2.012 g ) . We observed PEF decrease ( p > 0.05 ) during postural drainage with clapping and vibration . There were no significant differences in SaO2 between the values before and after drainage in every investigated technique BACKGROUND --Autogenic drainage has been suggested as an alternative method of chest physiotherapy in patients with cystic fibrosis . In this study autogenic drainage was compared with the active cycle of breathing techniques ( ACBT ) together with postural drainage . METHODS --Eighteen patients with cystic fibrosis took part in a r and omised two-day crossover trial . There were two sessions of one method of physiotherapy on each day , either autogenic drainage or ACBT . The study days were one week apart . On each day the patients were monitored for six hours . Mucus movement was quantified by a radioaerosol technique . Airway clearance was studied qualitatively using xenon-133 scintigraphic studies at the start and end of each day . Expectorated sputum was collected during and for one hour after each session of physiotherapy . Pulmonary functions tests were performed before and after each session . Oxygen saturation ( SaO2 ) and heart rate were measured before , during , and after each session . RESULTS --Autogenic drainage cleared mucus from the lungs faster than ACBT over the whole day . Both methods improved ventilation , as assessed by the xenon-133 ventilation studies . No overall differences were found in the pulmonary function test results , but more patients had an improved forced expiratory flow from 25 % to 75 % with autogenic drainage , while more showed an improved forced vital capacity with ACBT . No differences were found in sputum weight and heart rate , nor in mean SaO2 over the series , but four patients desaturated during ACBT . CONCLUSIONS --Autogenic drainage was found to be as good as ACBT at clearing mucus in patients with cystic fibrosis and is therefore an effective method of home physiotherapy . Patients with cystic fibrosis should be assessed as to which method suits them best Chest physiotherapy ( CPT ) is recommended for the clearance of bronchial secretions in the management of patients with cystic fibrosis ( CF ) . The Flutter valve ( Sc and ipharm , Birmingham , AL ) has been introduced as an alternative method to CPT for airway mucus clearance . The objective of this study was to compare the short-term effects of CPT and the Flutter valve on pulmonary function and exercise tolerance in patients with cystic fibrosis . Twenty-three patients , 5 to 21 years of age , were r and omized to receive one of two interventions : CPT or the Flutter valve , upon admission to the hospital for a 2-week treatment of pulmonary exacerbation . Pulmonary function testing ( PFTs ) and the 6-min walk test were performed on admission , day 7 , and day 14 of hospitalization . Data analysis indicated no significant differences between the two groups on admission . Both groups showed improvement in pulmonary function test results , but the Flutter group had a higher mean forced vital capacity ( FVC ) and forced expiratory volume in 1 sec ( FEV(1 ) ) compared to the CPT group after 1 week of intervention . Both groups continued to improve during the 2-week intervention , with no significant difference in FVC or FEV(1 ) between groups by the end of 2 weeks . Mean forced expiratory flow rate between 25 - 75 % of vital capacity ( FEF(25 - 75 ) ) , 6-min walk distance , and resting arterial oxyhemoglobin saturation ( SaO(2 ) ) showed little change by day 7 , but improved significantly ( P < 0.05 ) by day 14 of hospitalization in both groups , with no significant difference between groups . This study demonstrated that patients using the Flutter device had better pulmonary function after 1 week of therapy and similar improvement in pulmonary function and exercise tolerance compared to CPT after 2 weeks of therapy , suggesting that Flutter valve therapy is an acceptable alternative to st and ard CPT during in-hospital care of patients with CF Supervised directed coughing was compared to conventional physiotherapy ( postural drainage , vibration and /or percussion and coughing ) in 38 patients with cystic fibrosis aged 9 - 18 years admitted to hospital with an exacerbation of their pulmonary symptoms . Assessment included objective measures of pulmonary function and sputum characteristics . Both treatment groups showed significant improvement at the end of the 2-week period . When the patients were grade d according to their pulmonary disease , those with mild-moderate disease demonstrated a significant improvement in both treatment groups whereas those with severe lung disease showed little improvement with either treatment . Directed coughing is as effective as conventional physiotherapy in the management of patients with cystic fibrosis admitted to hospital for treatment of an exacerbation of their pulmonary symptoms The effect of the Forced Expiration Technique ( FET ) with or without Postural Drainage ( PD ) was examined in eight adults with cystic fibrosis . On four mornings the patients followed a 30-min physiotherapy session consisting in a r and omized order of either FET in a sitting position following a night of horizontal sleep ( " FET " ) , or FET in a postural drainage position following sleep including postural drainage ( " FET/PD " ) . The lung function parameters studied did not change during either of the two treatments . Sputum yield over 22.5 h before the physiotherapy sessions and over 24 h increased with PD during sleep in patients with more than 30 g of sputum per 24 h ( p less than 0.05 ) . PD during the treatment sessions did not further increase sputum production . This study indicates that sleeping head-down improves expectoration in patients with copious sputum . PD during FET is not needed after sleeping in the head-down position The aim of this study was to determine whether repeated maximum inspiratory vital capacity manoeuvres against a fixed resistance increased effective short-term sputum clearance in adults with cystic fibrosis ( CF ) . Twenty adults with CF were r and omised to receive , on alternate days , either st and ardised physiotherapy ( SP ) for 30 min , comprising postural drainage and the active cycle of breathing technique , or a series of resistive inspiratory manoeuvres ( RIM ) at 80 % of their maximum sustained inspiratory pressure developed between residual volume and total lung capacity during the first 4 days of the treatment of an exacerbation of respiratory symptoms . Expectorated sputum was collected during and for 30 min after each treatment and weighed . Total protein , immunoreactive interleukin (IL)‐8 and human neutrophil elastase ( HNE ) concentrations , and the amount of each component expectorated , were determined . Compared with SP , RIM increased sputum weight two-fold , independent of treatment order or day . The concentrations of protein , IL-8 and HNE in sputum were similar for both treatments , while the quantity expectorated was greater with RIM treatment . In conclusion , short-term resistive inspiratory manoeuvres treatment was more effective at clearing sputum and inflammatory mediators than st and ardised physiotherapy BACKGROUND Evidence indicates that there are no statistically significant differences in effectiveness among the airway clearance techniques ( ACTs ) of active cycle of breathing , autogenic drainage , positive expiratory pressure ( PEP ) or oscillating PEP in the short-term , but are there differences in the long-term ( one year ) ? The objective of the study was to demonstrate non-inferiority in the long-term . METHODS Seventy-five people with cystic fibrosis entered the prospect i ve , r and omised controlled trial of these five different ACTs . The primary outcome measure was forced expiratory volume in one second ( FEV(1 ) ) . Secondary outcome measures included exercise capacity and health related quality of life . RESULTS Using intention to treat , data were available on 65 subjects at the end of the study period . There were no statistically significant differences among the regimens in the primary outcome measurement of FEV(1 ) ( p=0.35 ) . CONCLUSION In different countries either one or several airway clearance regimens are used . This study provides evidence in support of current practice The study was design ed to ascertain the movement of mucus from proximal and peripheral regions within the human lungs during cough and the forced expiration technique ( FET ) . Mucus movement was measured using a radioaerosol technique . Seven patients ( mean + /- SEM age : 63 + /- 3 years ) with airways obstruction ( % predicted FEV1 : 44 + /- 4 ) participated in the study . Each patient underwent three assessment s in a r and omized manner : control/cough/FET . Peak expiratory flow rate ( PEFR ) was measured at the mouth during cough and FET . None of the patients produced sputum during the assessment periods . Both cough and FET compared with control increased , on average , mucus clearance from all regions ; statistical significance was achieved only for central lung regions with cough ( P less than 0.05 ) . There was no significant correlation between PEFR during cough/FET and regional lung clearance The aim of our study was to compare the short-term efficacy of three different chest physiotherapy ( CPT ) regimens ( PD , postural drainage ; PEP , positive expiratory pressure physiotherapy ; HFCC , high-frequency chest compression physiotherapy ) on patients with cystic fibrosis ( CF ) hospitalized for an acute pulmonary exacerbation . Sixteen patients with CF , 8 males , 8 females , aged 15 - 27 years ( mean , 20.3 + /- 4 ) , met the inclusion criteria : 1 ) age over 14 years ; 2 ) mild or moderate airway obstruction ; 3 ) sputum volume > 30 mL/day ; 4 ) being proficient in PD and PEP CPT . Patients at admission had ( mean + /- SD ) forced volume in 1 second ( FEV1 ) 52.2 + /- 21.9 percent predicted ; Shwachman-Kulczycki clinical score 65.1 + /- 11 points ; Chrispin-Norman chest radiography score 18.6 + /- 4.3 points . The three CPT regimens and a control-treatment ( CONT ) were administered in a r and om sequence , each patient receiving each treatment twice a day ( in 50 minute sessions ) for 2 consecutive days . During CONT and for 30 minutes after each session only spontaneous coughing was allowed . Wet and dry weight of sputum were recorded during the 50-minute sessions and 30 minutes afterward . Lung function was measured before and 30 minutes after each session . For each treatment a score was given by the patient for efficacy , and by both the patient and the physiotherapist for tolerance . Wet and dry weights of sputum collected during the sessions were greater for all CPT regimens than for CONT ( P < 0.001 , P < 0.0001 ) . No significant differences between the three CPT regimens for both wet and dry weights were found when the number of coughs was taken into account . ( ABSTRACT TRUNCATED AT 250 WORDS High-frequency chest compressions ( HFCC ) have been suggested as an alternative to conventional chest physiotherapy to aid sputum clearance in patients with cystic fibrosis ( CF ) . We aim ed to compare the active cycle of breathing techniques ( ACBT ) with the Hayek Oscillator Cuirass , performing HFCC on secretion clearance in children with CF during an exacerbation . Ten children ( 7 males ; median age , 14 years ; range , 9 - 16 ) received either two supervised sessions using HFCC or two self-treatment ACBT sessions in r and om order on successive days . Baseline pulmonary function was similar prior to treatments . Sputum weight increased significantly with ACBT compared with HFCC during treatment ( 5.2 g vs. 1.1 g , P < 0.005 , morning ; 4.1 g vs. 0.7 g , P < 0.01 , afternoon ) . Pulmonary function improved significantly after morning ACBT ( forced vital capacity ( FVC ) : 2.67 l to 2.76 l , P < 0.03 ; forced expiratory volume in 1 sec ( FEV1 ) : 1.59 l to 1.62 l , P < 0.03 ) . Following afternoon ACBT , there was a significant increase in FVC ( 2.64 to 2.79 , P < 0.02 ) , but no significant change in FEV1 . Pulmonary function did not change at any time following HFCC . Compared with ACBT , HFCC by Hayek Cuirass is not an effective airway clearance treatment modality for children with CF during an infective exacerbation Summary Using ear oximetry , we studied the oxygen saturation in nine patients with cystic fibrosis who were undergoing chest physiotherapy . All nine subjects showed desaturation , seven to a level of less than 85 % . Supplemental oxygen failed to prevent this but did promote a more rapid return to baseline . Chest physiotherapy is not without risk . Patients receiving such therapy require close observation and may benefit from supplemental oxygen OBJECTIVE Chest physiotherapy ( CPT ) is an integral part of the treatment of patients with cystic fibrosis ( CF ) . CPT imposes additional respiratory work that may carry a risk of respiratory muscle fatigue . Inspiratory pressure support ventilation ( PSV ) is a new mode of ventilatory assistance design ed to maintain a constant preset positive airway pressure during spontaneous inspiration with the goal of decreasing the patient 's inspiratory work . The aim of our study was 1 ) to evaluate respiratory muscle fatigue and oxygen desaturation during CPT and 2 ) to determine whether noninvasive PSV can relieve these potential adverse effects of CPT . METHODS Sixteen CF patients in stable condition with a mean age of 13 + /- 4 years participated to the study . For CPT , we used the forced expiratory technique ( FET ) , which consisted of one or more slow active expirations starting near the total lung capacity ( TLC ) and ending near the residual volume . After each expiration , the child was asked to perform a slow , nonmaximal , diaphragmatic inspiration . After one to four forced breathing cycles , the child was asked to cough and to expectorate . A typical 20-minute CPT session consisted of 10 to 15 FET maneuvers separated by rest periods of 10 to 20 breathing cycles each . During the study , each patient received two CPT sessions in r and om order on two different days , at the same time of day , with the same physiotherapist . During one of these two sessions , PSV was provided throughout the session ( PSV session ) via a nasal mask using the pressure support generator ARM25 design ed for acute patients ( TAEMA , Antony , France ) . The control session was performed with no nasal mask or PSV . Both CPT sessions were performed without supplemental oxygen . Lung function and maximal inspiratory pressures ( PImax ) and expiratory pressures ( PEmax ) were recorded before and after each CPT session . RESULTS Mean lung function parameters were comparable before the PSV and the control sessions . Baseline pulse oximetry ( SpO2 ) was significantly correlated with the baseline vital capacity ( % predicted ) and forced expiratory volume in 1 second ( FEV1 ) ( % predicted ) . PSV was associated with an increase in tidal volume ( Vt ) from 0.42 + /- 0.01 liters to 1.0 + /- 0.02 liters . Respiratory rate was significantly lower during PSV . SpO2 between the FET maneuvers was significantly higher during PSV as compared with the control session . SpO2 decreases after FET were significantly larger during the control session ( nadir : 91.8 + /- 0 . 7 % ) than during the PSV session ( 93.8 + /- 0.6 % ) . Maximal pressures decreased during the control session ( from 71.9 + /- 6.1 to 60.9 + /- 5.3 cmH2O , and from 85.3 + /- 7.9 to 77.5 + /- 4.8 cmH2O , for PImax and PEmax , respectively ) and increased during the PSV session ( from 71.6 + /- 8.6 to 83.9 + /- 8.7 cmH2O , and from 80.4 + /- 7.8 to 88.0 + /- 7.4 cmH2O , for PImax and PEmax , respectively ) . The decrease in PEmax was significantly correlated with the severity of bronchial obstruction as evaluated based on baseline FEV1 ( % predicted ) . Forced expiratory flows did not change after either CPT session . The amount of sputum expectorated was similar for the two CPT sessions ( 5.3 + /- 5.3 g vs 4.6 + /- 4.8 g after the control and PSV session , respectively ; NS ) . Fifteen patients felt less tired after the PSV session . Ten patients reported that expectoration was easier with PSV , whereas 4 did not note any difference ; 2 patients did not expectorate . Nine patients expressed a marked and 5 a small preference for PSV , and 2 patients had no preference . The physiotherapists found it easier to perform CPT with PSV in 14 patients and did not perceive any difference in 2 patients . DISCUSSION Our study in CF children shows that respiratory muscle performance , as evaluated based on various parameters , decreased after CPT and that significant falls in oxygen saturation occurred after the FET maneuvers despite the quiet breathing periods between each FET cycle . These unwanted effects of CPT ABSTRACT . Twenty‐eight patients suffering from cystic fibrosis , with an age range of 8‐21 years entered a r and omised cross‐over trial to study the efficacy of the Positive Expiratory Pressure ( PEP ) mask as a method of chest physiotherapy , both on its own and in conjunction with other physiotherapy techniques . Twenty‐four of these patients completed the trial consisting of 4 treatment programmes each lasting one month and with no wash‐out period between them . Five of these patients went on to a fifth programme of Forced Expiratory Technique ( FET ) alone . At the end of the trial , no significant difference was found between the programmes as regards growth , Shwachman score , Chrispin — Norman score or pulmonary function tests . Twenty‐three patients chose to continue using the PEP mask in conjunction with FET long‐term as their chest physiotherapy programme as they felt it was an effective treatment allowing increased independence , with postural drainage being kept to a minimum Both the immediate and long-term effects of chest physical therapy administered by a parent were evaluated in eight children with cystic fibrosis . Spirometric and plethysmographic evaluations were performed pre-CPT and at 5 and 30 minutes post-CPT . The pre-CPT measurements after a three-week period with no CPT were compared with the values while receiving CPT on a regular twice daily basis . There was a significant decrease after three weeks without CPT for FVC ( P less than 0.025 ) , FEV1 ( P less than 0.005 ) , FEF25 - 75 ( P less than 0.005 ) , and Vmax60TLC ( P less than 0.025 ) . When the patients had been receiving CPT on a regular basis , the only immediate effect was an increase in PEFR after 30 minutes post-CPT ( P less than 0.05 ) . After three weeks without CPT , there were increases at 30 minutes post-CPI for FVC ( P less than 0.005 ) and Vmax60TLC ( P less than 0.05 ) . These findings indicate that although there may be little immediate functional improvement when CPT is received on a regular basis , a three-week period without CPT leads to a worsening of the functional status , which is reversed with renewal of regular CPT Because of the time and the emotional cost involved in performing daily conventional chest physiotherapy in patients with cystic fibrosis , a 3-year prospect i ve study was undertaken to compare the long-term effects of postural drainage accompanied by percussion and the forced expiratory technique with the effects of the forced expiratory technique alone . Patients who performed the forced expiratory technique alone had mean annual rates of decline that were significantly different from zero for forced expiratory volume in 1 second ( p less than 0.001 ) , forced expiratory flow between 25 % and 75 % of vital capacity ( p less than 0.001 ) , and Shwachman clinical score ( p less than 0.004 ) . In the group performing conventional physiotherapy with percussion and postural drainage , only the mean annual rate of decline for forced expiratory flow between 25 % and 75 % of vital capacity was significantly different from zero ( p less than 0.03 ) , and it was significantly different from the mean rate of decline associated with the forces expiratory technique alone ( p less than 0.04 ) . We conclude that conventional chest physiotherapy should remain a st and ard component of therapy in cystic fibrosis It has been suggested that positive expiratory pressure may assist the clearance of bronchial secretions in the treatment of cystic fibrosis . It has been compared with currently used postural drainage techniques . Three treatment regimens were compared in 18 patients with cystic fibrosis . Treatment A consisted of breathing exercises emphasising inspiration , interspersed with the forced expiration technique in gravity assisted positions ; treatment B comprised breathing exercises with positive expiratory pressure alternating with the forced expiration technique in the same gravity assisted positions ; and treatment C comprised breathing exercises with positive expiratory pressure and the forced expiration technique in the sitting position . During treatment A a significantly greater quantity of sputum was produced than during treatments B and C ( p less than 0.025 and p less than 0.001 respectively ) . Treatment B produced more sputum than treatment C ( p less than 0.005 ) . There were no significant differences in arterial oxygen saturation , FEV1 or forced vital capacity . Most adolescent and adult patients are able to carry out their treatment independently using gravity assisted positions , breathing exercises emphasising inspiration , and the forced expiration technique . Sputum clearance was less effective when positive expiratory pressure was included in the treatment regimen |
10,871 | 26,544,675 | We found no information on many of the commonly available low dose codeine combinations .
For ibuprofen plus paracetamol , adverse event rates were lower than with placebo .
The proportion of people with acute pain who get good pain relief with any of them ranges from around 70 % at best to less than 20 % at worst ; low doses of some drugs in fast acting formulations were among the best .
Adverse events were generally no different from placebo . | BACKGROUND Non-prescription ( over-the-counter , or OTC ) analgesics ( painkillers ) are used frequently .
They are available in various br and s , package sizes , formulations , and dose .
They can be used for a range of different types of pain , but this overview reports on how well they work for acute pain ( pain of short duration , usually with rapid onset ) .
Thirty-nine Cochrane review s of r and omised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain .
OBJECTIVES To examine published Cochrane review s for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain .
AUTHORS ' CONCLUSIONS There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription .
The postoperative pain model is predominantly pain after third molar extraction , which is used as the industry model for everyday pain . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely Background Previous analysis of a single data set in acute pain following third molar extraction demonstrated a strong relationship between the speed of reduction of pain intensity and overall pain relief , as well as need for additional analgesia . Methods Individual patient data analysis of a single r and omized , double-blind trial of placebo , paracetamol 1000 mg , ibuprofen sodium 400 mg and ibuprofen-poloxamer 400 mg following third molar extraction . Visual analogue scale pain intensity ( VASPI ) and other measurements were made at baseline , every 5–45 min , and at 60 , 90 , 120 , 180 , 240 , 300 and 360 min . Results Most patients produced consistent VASPI results over time . For placebo and paracetamol , few patients achieved low VASPI scores and maintained them . For both ibuprofen formulations , VASPI scores fell rapidly during the first hour and were then typically maintained until later re-medication . Analysis of all patients showed that rapid VASPI reduction in the first hour was strongly correlated with good overall pain relief ( high total pain relief over 0–6 h ) , and with lesser need for additional analgesia within 6 h. Results for this analysis were in very good agreement with a previous analysis , validating the relationship between fast initial pain intensity reduction and overall good pain relief in this setting . Conclusions In acute pain following third molar extraction , faster acting analgesic formulations provide earlier onset of pain relief , better overall pain relief and a less frequent need for additional analgesia , indicating longer lasting pain relief Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale |
10,872 | 31,897,617 | Conclusion Post-operative aTACE is safe and improves overall and disease-free survival , with the greatest benefit in MVI-positive patients . | Purpose Multiple studies have demonstrated adjuvant transcatheter arterial chemoembolization ( aTACE ) after resection improved outcomes compared to resection alone for patients with hepatocellular carcinoma ( HCC ) .
Unlike pre-operative TACE which targets a lesion , aTACE is administered in the proximal hepatic artery to destroy cancer cells within the remaining liver .
This systematic review and meta- analysis aims to quantify this survival and disease-free survival ( DFS ) benefit . | Purpose Hepatectomy is considered as the potentially curative treatment for hepatocellular carcinoma ( HCC ) and used in some selected Stage IIIA HCC , which include multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s ) ( UICC TNM staging system , sixth edition ) . Transcatheter arterial chemoembolization ( TACE ) was used in retrospective studies to improve the survival outcome of resected HCC . However , its beneficial effect on the survival outcomes of the Stage IIIA patients has not been evaluated . The present study is to evaluate if hepatectomy combining with adjuvant TACE for Stage IIIA HCC result in better long-term survival outcome when compared with hepatectomy alone . Methods From January 2001 to March 2004 , we conducted a prospect i ve r and omized trial in patients with Stage IIIA HCC ( NCT00652587 ) , recruiting 115 Stage IIIA HCC patients to undergo hepatectomy with adjuvant TACE ( HT arm ) or to undergo hepatectomy alone ( HA arm ) in our cancer center . Survival outcomes of the two arms were analyzed . Results The demographic data were well matched between the two arms . There were no significant differences in the morbidity and in-hospital mortality between the two arms of patients . The most significant toxicities associated with adjuvant TACE were nausea/vomiting ( 54.4 % ) and transient hepatic toxicity ( elevation of aminotransferase , 52.6 % ) . Although there was no significant difference in the rate of recurrence between the two arms ( 50/57 vs. 56/58 , P = 0.094 ) , HT arm seemed to have more proportion of single lesion of recurrent HCC ( χ2 = 3.719 , P = 0.054 ) and more proportion of potential curative therapy for recurrence ( χ2 = 4.456 , P = 0.035 ) . Until the time of censor , 92 patients had died . The 1- , 3- , and 5-year overall survival rates and median overall survival for HT arm were 80.7 , 33.3 , 22.8 % and 23.0 months , respectively . The corresponding overall survival rates and median overall survival for HA arm were 56.5 , 19.4 , 17.5 % and 14.0 months , respectively . The difference was significant ( stratified log-rank test , P = 0.048 ) . The 1- , 3- , and 5-year disease-free survival rates and median disease-free survival for HT arm were 29.7 , 9.3 , 9.3 % and 6.0 months , respectively ; correspondingly , for HA arm were 14.0 , 3.5 , 1.7 % and 4.0 months , respectively ( stratified log-rank test , P = 0.004 ) . Conclusions For Stage IIIA HCC , hepatectomy with adjuvant TACE efficaciously and safely improved survival outcomes when compared with hepatectomy alone OBJECTIVE To explore the effect of postoperative adjuvant transarterial chemoembolization ( TACE ) upon early recurrence of hepatocellular carcinoma ( HCC ) patients after radical resection . METHODS Between November 2000 and December 2007 , 2591 HCC patients undergoing radical resection were retrospectively recruited . Patients undergoing resection alone were selected as control group while those receiving post-operative adjuvant TACE as intervention group . The patients were further stratified into tumor < or = 5 cm with low or high risk factors for residual tumor and tumor > 5 cm with low or high risk factors for residual tumor . A low risk factor for residual tumor was defined as single tumor and without microscopic tumor thrombus while a high risk factor for residual tumor was defined as 2 - 3 nodules or with the presence of microscopic tumor thrombus . The effect of adjuvant TACE upon early ( < or = 2 years ) recurrence was evaluated . RESULTS Recurrent rates of tumor < or = 5 cm with low or high risk factors for residual tumor and tumor > 5 cm with low or high risk factors for residual tumor at Month 3 post-resection were 1.34 % , 3.17 % , 5.33 % and 8.43 % in the control group versus 4.14 % ( P = 0.002 ) , 8.15 % ( P = 0.011 ) , 12.88 % ( P = 0.002 ) and 14.29 % ( P = 0.045 ) respectively in the intervention group ; recurrence rates at Month 6 post-resection were 4.63 % , 8.73 % , 11.50 % and 19.46 % in the control group versus 6.71 % ( P = 0.133 ) , 13.48 % ( P = 0.070 ) , 21.02 % ( P = 0.052 ) and 23.94 % ( P = 0.210 ) respectively in the intervention group . For patients remaining recurrence free within the first 6 months post-resection , there were no significant differences in recurrence rates at Months 9 , 12 , 18 and 24 post-operation between each intervention group and control group . CONCLUSION Postoperative adjuvant TACE has no preventive effect upon early recurrence , but may be of benefit to detect residual tumor and early recurrence 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 / AIMS Prevention of recurrence is the most important strategy to improve long-term survival after resection of hepatocellular carcinoma ( HCC ) . This comparative study aim ed to evaluate the outcome of adjuvant transarterial chemoembolization ( TACE ) after hepatectomy . METHODOLOGY From February 1996 and September 2001 , 721 consecutive patients ( adjuvant TACE treatment vs. control group ; 145 vs. 576 ) with R0 resection for HCC were analyzed . The prospect i ve data was analyzed retrospectively . RESULTS After a median follow-up of 75 months , 89 patients ( 61.4 % ) in the adjuvant TACE group and 355 patients ( 61.6 % ) in the control group had recurrent disease . There was no significant difference in the tumor recurrence rate between the 2 groups . There was significant difference in the tumor recurrence time between the 2 groups . The 1- , 3- and 5-year overall survival rates were 96.5 % , 70.0 % and 55.9 % , respectively , for the adjuvant TACE group and 80.8 % , 49.7 % and 38.8 % , respectively , for the control group . The 1- , 3- and 5-year disease-free survival rates were 79.9 % , 54.9 % and 48.4 % , respectively , for the adjuvant TACE group and 60.2 % , 39.8 % and 31.5 % , respectively , for the control group . The differences in the disease-free survival rates and the overall survival rates between the 2 groups were significant . In subgroup analysis , there was significant survival benefit in the adjuvant TACE group in the subgroup of patients with risk factors of recurrence - large tumor size , presence of satellite tumor nodules and narrow resection margin . CONCLUSIONS Adjuvant TACE improved surgical outcome in those patients with risk factors of HCC recurrence BACKGROUND Recurrence of hepatitis B-related hepatocellular carcinoma ( HCC ) after curative resection is the leading factor influencing the prognosis of the disease . Therefore , further improvement of long-term survival may depend on the prevention and treatment of the recurrent tumor . The aim of this research was to investigate the role of antiviral therapy and postoperative transcatheter arterial chemoembolization ( TACE ) in the prevention and treatment of hepatitis B-related HCC recurrence . METHODS One hundred and twenty patients who underwent curative resection of hepatitis B-related HCC between January 2005 and June 2008 at our hospital were enrolled . Patients were divided into four groups according to the post-operative adjuvant therapy they received , i.e. , control , antiviral therapy group , TACE group , and combined group . The disease-free survival ( DFS ) and the 12- , 24- , 36-month cumulative recurrence rates were studied . RESULTS There was no significant difference between isolated postoperative antiviral therapy group and control in terms of disease-free survival ( P = 0.283 ) , while it was significantly higher in the TACE group compared to control ( P = 0.019 ) . In all patients , however , viral prophylactic therapy combined with/without TACE brought a favorable result compared to those only with/without TACE ( P < 0.001 ) . Similarly , no matter combined with or without antiviral treatment , postoperative TACE prolonged DFS ( P = 0.015 ) . Naturally , a combination of viral prophylactic therapy on the baseline TACE significantly benefited patients ' postoperative DFS ( P = 0.047 ) and vice verse ( P = 0.002 ) . The 24-month cumulative recurrence rates of combined group were significantly lower than that of isolated control group and antiviral therapy ( P < 0.001 and P = 0.011 respectively ) . However , 36-month recurrence rate was significantly different in the control group compared to the TACE group and combined group ( P = 0.040 and 0.002 respectively ) ; same as the antiviral group compared to the combined group ( P = 0.034 ) . CONCLUSIONS Post-operative TACE prevents early recurrence while antiviral therapy prevents late recurrence of HCC . Combination of antiviral therapy and TACE are suggested for prevention in HCC patients with high risk of recurrence Objective : To explore the value of postoperative transarterial chemoembolization ( TACE ) and portal vein chemotherapy ( PVC ) in patients with hepatocellular carcinoma ( HCC ) in the prevention of recurrence , and to evaluate prognostic factors in a r and omized study . Method : 131 patients with HCC were r and omly divided into 3 groups : operation only ( group A , n = 45 ) ; operation plus TACE ( group B , n = 39 ) , and operation plus TACE and PVC ( group C , n = 47 ) . Disease-free survival rates as well as prognostic factors were analyzed . Results : Most of the side effects and complications related to the operation , catheters and local chemotherapy were liver decompensation ( 16.1 % ) , catheter obstruction ( 12.9 % ) , and nausea and loss of appetite ( 25.8 % ) , respectively . The disease-free survival curves were significantly different between the 3 groups as estimated by the Kaplan-Meier method ( p < 0.05 ) . Group C had a significantly higher disease-free survival rate compared to group A ( p < 0.05 ) . But no statistical differences were found between groups A and B and groups B and C ( both p > 0.05 ) . Tumor number and treatment modalities were independent prognostic factors for HCC patients ( p < 0.05 ) . Conclusion : Postoperative TACE combined with PVC may benefit the survival of patients with HCC . In specialized medical centers , aggressive methods such as TACE and PVC should be attempted on HCC patients without contraindications Vascular invasion and intrahepatic metastasis by hepatocellular carcinoma are important factors predisposing to tumor recurrence . Recurrences of this malignancy occur frequently in residual liver , and its prevention is one of the most important factors in obtaining better surgical survival . Fifty patients who underwent hepatectomy for invasive hepatocellular carcinoma with vascular invasion and /or intrahepatic metastases were studied to evaluate the effect of adjuvant bolus hepatic arterial infusion of iodized poppyseed oil ( Lipiodol ) containing anticancer drugs in preventing recurrence and in prolonging survival . Patients were assigned to two treatment groups . Twenty-three of the fifty patients received adjuvant bolus infusion of Lipiodol containing doxorubicin and mitomycin C , whereas 27 patients received no therapy . The disease-free survival rate for the patients who received adjuvant therapy was significantly better ( p < 0.05 ) than that for those who did not when measured at 172 , 516 , 688 and 860 days after hepatectomy , and the disease-free survival curve for patients with adjuvant therapy was significantly ( p = 0.0237 ) better than that without adjuvant therapy . The cumulative survival rates and curves were not significantly different between the two groups . While adjuvant hepatic arterial infusion of Lipiodol containing anticancer drugs was effective in improving disease-free survival , the effect was not satisfactory . Further trials of adjuvant chemotherapy are required to improve the surgical survival of hepatocellular carcinoma patients From April 1990 to December 1993 , 140 patients were recruited to a r and omized study to evaluate transcatheter hepatic arterial chemoembolization ( TACE ) as an adjuvant therapy for primary liver carcinoma after hepatectomy . This study investigated the principle , techniques and results of TACE . The results showed that the intrahepatic recurrence rate was 48.9 % in the patients who underwent radical resection only , but only 21.3 % in the patients who also underwent TACE 3–4 weeks after hepatectomy ( P<0.01 ) . The 1- , 2- , 3- , and 4-year survival rates were 72.3 % , 52.7 % , 35.1 % , and 35.1 % respectively for the patients who underwent radical resection only , and were 97.9 % , 85.5 % , 69.5 % , and 56.9 % for the patients who also underwent TACE 3–4 weeks after radical resectionP<0.001 ) . The 1- , 2- , 3- , and 4-year survival rates were 38.9 % , 0 % , 0 % , and 0 % for the patients who underwent palliative resection only , and were 68.3 % , 32.3 % , 21.5 % , and 21.5 % respectively for the patients undergoing TACE 3–4 weeks after palliative hepatectomyP<0.001 ) One hundred Chinese patients who received induction cytotoxic therapy for malignant lymphoma were prospect ively studied to determine the incidence , morbidity , mortality , and predisposing factors for reactivation of hepatitis B virus replication during cytotoxic therapy . In 18 ( 67 % ) hepatitis B surface antigen-positive and 10 ( 14 % ) hepatitis B surface antigen-negative patients , hepatitis developed during cytotoxic therapy ( P less than 0.0001 ) . Hepatitis could be attributed to exacerbation or reactivation of chronic hepatitis B in 13 ( 72 % ) hepatitis B surface antigen-positive patients but in only 2 ( 20 % ) hepatitis B surface antigen-negative patients ( P less than 0.0001 ) . Sudden increase or reactivation of hepatitis B virus replication gave rise to icteric hepatitis , nonfatal hepatic failure , and death in 22.3 % , 3.7 % , and 3.7 % of patients who were positive for hepatitis B surface antigen ; in 2 % , 2 % , and 0 % of those positive for hepatitis B antibodies ; and in none of those who were seronegative . Among the hepatitis B surface antigen-positive patients , male sex was the only factor that was associated with an increased risk of reactivation of hepatitis B virus replication . We recommend that hepatitis B surface antigen-positive patients with malignancies receiving cytotoxic therapy be closely monitored AIM To assess the validity of the Milan and University of California San Francisco ( UCSF ) criteria and examine the long-term outcome of orthotopic liver transplantation ( OLT ) in patients with hepatocellular carcinoma ( HCC ) in a single-center study . METHODS This study is a retrospective review of prospect ively collected data . Between 1998 and 2009 , 56 of 356 OLTs were performed in patients with HCC . Based on pathological examination of liver explants , patients were retrospectively categorized into 3 grou-ps : Milan + ( n = 34 ) , Milan -/UCSF + ( n = 7 ) and UCSF - ( n = 14 ) . RESULTS Median follow-up period was 39.5 ( 1 - 124 ) mo . The 5-year overall survival rates in the Milan + , Milan -/UCSF + and UCSF-groups were 87.7 % , 53.6 % and 33.3 % , respectively ( P < 0.000 ) . Within these groups , tumor recurrence was determined in 5.8 % , 14.3 % and 40 % of patients , respectively ( P < 0.011 ) . Additionally , the presence of microvascular invasion within the explanted liver had a negative effect on the 5-year disease free survival ( 74.7 % vs. 46.7 % , P < 0.044 ) . CONCLUSION The Milan criteria are reliable in the selection of suitable c and i date s for OLT for the treatment of HCC . For cases of OLT involving living donors , the UCSF criteria may be applied Purpose : The survival of patients with hepatocellular carcinoma ( HCC ) recurrence after curative resection is usually poor . We sought to evaluate the safety and efficacy of adjuvant transarterial chemoembolization ( TACE ) in HBV-related HCC patients with an intermediate ( a single tumor larger than 5 cm without microvascular invasion ) or high risk ( a single tumor with microvascular invasion , or two or three tumors ) of recurrence . Experimental Design : In this r and omized phase 3 trial , 280 eligible patients were assigned to adjuvant TACE ( n = 140 ) or no adjuvant treatment ( control ; n = 140 ) groups . The primary endpoint was recurrence-free survival ( RFS ) ; secondary endpoints included overall survival ( OS ) and safety . Multivariable Cox-proportional hazards model was used to determine the independent impact of TACE on patients ' outcomes . Results : Patients who received adjuvant TACE had a significantly longer RFS than those in the control group [ 56.0 % vs. 42.1 % , P = 0.01 ; HR , 0.68 ; 95 % confidence interval ( CI ) , 0.49–0.93 ] . Patients in the adjuvant TACE group had 7.8 % higher 3-year OS rate than the control group ( 85.2 % vs. 77.4 % ; P = 0.04 ; HR , 0.59 ; 95 % CI , 0.36–0.97 ) . The impact of adjuvant TACE on RFS and OS remained significant after controlling for other known prognostic factors ( HR , 0.67 ; P = 0.01 for RFS ; and HR , 0.59 ; P = 0.04 for OS ) . There was no grade 3 or 4 toxicity after adjuvant TACE . Conclusions : For patients with HBV-related HCC who had an intermediate or high risk of recurrence after curative hepatectomy , our study showed adjuvant TACE significantly reduced tumor recurrence , improved RFS and OS , and the procedure was well tolerated . Clin Cancer Res ; 24(9 ) ; 2074–81 . © 2018 AACR BACKGROUND Microvascular invasion ( MVI ) has recently been reported to be an independent prognostic factor in patients with hepatocellular carcinoma ( HCC ) . This study compared the outcomes of adjuvant transarterial chemoembolization ( A-TACE ) after hepatic resection ( HR ) in patients with HCC involving MVI . METHODS This prospect i ve study involved 200 consecutive patients with MVI-HCC who underwent HR alone ( n = 109 ) or HR with A-TACE ( n = 91).The Kaplan-Meier method was used to compare disease-free survival ( DFS ) and overall survival ( OS ) . RESULTS The two groups showed similar DFS at 1 , 2 , and 3 years ( P = 0.077 ) . The A-TACE group showed significantly higher OS than the HR-only group ( P = 0.030 ) . Subgroup analysis showed that A-TACE was associated with significantly higher DFS and OS among patients with a tumor diameter > 5 cm or with multinodular tumors . CONCLUSIONS A-TACE may improve postoperative outcomes for MVI-HCC patients , especially those with tumor diameter > 5 cm or multinodular tumors |
10,873 | 26,680,599 | DISCUSSION Our results provide additional evidence that depressive symptoms determine an additive risk effect to the progression to dementia in subjects with MCI .
The comorbidity between depression and cognitive impairment can be an intervention target for prevention of dementia in MCI subjects . | OBJECTIVE There is a long-st and ing debate in the literature whether depressive symptoms increase the risk of dementia in older with mild cognitive impairment ( MCI ) .
We aim to conduct a meta- analysis of studies that evaluated the risk of dementia in subjects with MCI and depressive symptoms compared with subjects with MCI and no depressive symptoms . | CONTEXT Prospect i ve studies have established an association between depressive symptoms and risk of dementia , but how depressive symptoms change during the evolution of dementia is uncertain . OBJECTIVE To test the hypothesis that depressive symptoms increase during the prodromal phase of Alzheimer disease ( AD ) . DESIGN Prospect i ve cohort study . PARTICIPANTS AND SETTING For up to 13 years , 917 older Catholic nuns , priests , and monks without dementia at study onset completed annual clinical evaluations that included administration of the 10-item Center for Epidemiologic Studies Depression Scale and clinical classification of mild cognitive impairment and AD . MAIN OUTCOME MEASURE Change in depressive symptoms reported on the Center for Epidemiologic Studies Depression Scale . RESULTS At baseline , participants reported a mean ( SD ) of 1.0 ( 1.5 ) depressive symptoms . Those who developed AD ( n = 190 ) showed no increase in depressive symptoms before the diagnosis was made , and this finding was not modified by age , sex , education , memory complaints , vascular burden , or personality . There was no systematic change in depressive symptoms after the AD diagnosis , although symptoms tended to decrease in women relative to men and in those with a higher premorbid level of openness and a lower premorbid level of agreeableness . Among those without cognitive impairment at baseline , depressive symptoms did not increase in those who subsequently developed mild cognitive impairment . CONCLUSION We found no evidence of an increase in depressive symptoms during the prodromal phase of AD BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Background : Apathy is a common symptom in various neuropsychiatric diseases including mild cognitive impairment ( MCI ) and dementia . Apathy may be associated with an increased risk of cognitive decline . The objective of this study was to investigate if apathy predicts the progression from MCI to Alzheimer ’s disease ( AD ) . Methods : The Alzheimer ’s Disease Neuroimaging Initiative is a prospect i ve multicentre cohort study . At baseline , 397 patients with MCI without major depression were included . Clinical data and the Geriatric Depression Scale at baseline were used . Apathy was defined based on the 3 apathy items of the 15-item Geriatric Depression Scale . The main outcome measure was the association of apathy with progression from MCI to AD . Results : During an average follow-up of 2.7 years ( SD 1.0 ) , 166 ( 41.8 % ) patients progressed to AD . The presence of symptoms of apathy without symptoms of depressive affect increased the risk of progression from MCI to AD ( hazard ratio = 1.85 , 95 % CI = 1.09–3.15 ) . Apathy in the context of symptoms of depressive affect or symptoms of depressive affect alone , without apathy , did not increase the risk of progression to AD . Conclusions : Symptoms of apathy , but not symptoms of depressive affect , increase the risk of progression from MCI to AD . Apathy in the context of symptoms of depressive affect does not increase this risk . Symptoms of apathy and depression have differential effects on cognitive decline Studies on humans show that depressive disorder is associated with an increased risk of developing cognitive dysfunction , and animal studies suggest that antidepressants may have neuroprotective abilities . On the basis of these observations , it was hypothesized that treatment with antidepressants may decrease the risk of developing dementia in patients with depression . We investigated whether continued treatment with antidepressants is associated with a decreased rate of dementia in a population of patients discharged from psychiatric healthcare service with a diagnosis of depression . We used register data on all prescribed antidepressants in all patients discharged from psychiatric healthcare service with a diagnosis of depression and with subsequent diagnoses of dementia in Denmark from 1995 to 2005 . A total of 37 658 patients with a diagnosis of depression at their first psychiatric contact and who were exposed to antidepressants after discharge were included in the study . A total of 2007 patients ( 5.3 % ) were subsequently diagnosed with dementia of any kind . The rate of dementia decreased during periods of two or more prescriptions of older antidepressants compared with the period of only one prescription of older antidepressants [ relative risk (RR)=0.83 ( 95 % confidence interval (CI)=0.70–0.98 ) ] . This finding was replicated with Alzheimer ’s disease as the outcome [ RR=0.66 ( 95 % CI=0.47–0.94 ) ] but not with dementia of other kinds as the outcome [ RR=0.88 ( 95 % CI=0.73–1.06 ) ] . In contrast , during periods of continued use of selective serotonin reuptake inhibitors or newer nonselective serotonin reuptake inhibitors , the rate of dementia was not decreased , regardless of the subtype of dementia . It was concluded that continued long-term treatment with older antidepressants is associated with a reduced rate of dementia in patients treated in psychiatric healthcare setting s , whereas continued treatment with other kinds of antidepressants is not . Method ological reasons for these findings can not be excluded because of the nonr and omized nature of data Identification of potentially modifiable risk factors for cognitive deterioration is important . We conducted a prospect i ve study of 5,607 subjects with normal cognition and 2,500 subjects with mild cognitive impairment ( MCI ) at 30 Alzheimer 's Disease Centers in the Unites States between 2005 and 2011 . Cox regression was used to determine whether depression predicted transition from normal to MCI , or MCI to Alzheimer 's disease ( AD ) . Over an average of 3.3 visits , 15 % of normal subjects transitioned to MCI ( 62/1000 per year ) , while 38 % of MCI subjects transitioned to AD ( 146/1000 per year ) . At baseline , 22 % of participants had recent ( within the last two years ) depression defined by clinician judgment ; 9 % and 17 % were depressed using the Geriatric Depression Scale ( GDS score ≥5 ) and the Neuropsychiatric Inventory Question naire ( NPI-Q ) , respectively . At baseline , depressed subjects performed significantly worse on cognitive tests . Those always depressed throughout follow-up had an increased risk for progression from normal to MCI ( RR = 2.35 ; 95 % CI 1.93 - 3.08 ) versus never depressed . Normal subjects , identified as depressed at first visit but subsequently improved , were found to have lower risk of progression ( RR 1.40 ( 1.01 - 1.95 ) ) . The ' always depressed ' had only a modest increased risk of progression from MCI to AD ( RR = 1.21 ( 1.00 - 1.46 ) . Results were similar using time-dependent variables for depression or when defining depression via the GDS or NPI-Q. We found no effect of earlier depression ( > 2 years past ) . The effect of recent depression did not differ by antidepressant treatment , APOE4 allele status , or type of MCI . In conclusion , late-life depression is a strong risk factor for normal subjects progressing to MCI Objective : To examine risk factors for mild cognitive impairment ( MCI ) and progression to dementia in a prospect i ve community-based study of subjects aged 65 years and over . Methods : 6892 participants who were over 65 and without dementia were recruited from a population -based cohort in three French cities . Cognitive performance , clinical diagnosis of dementia , and clinical and environmental risk factors were evaluated at baseline and 2-year and 4-year follow-ups . Results : 42 % of the population were classified as having MCI at baseline . After adjustment for confounding with logistic regression models , men and women classified as having MCI were more likely to have depressive symptomatology and to be taking anticholinergic drugs . Men were also more likely to have a higher body mass index , diabetes and stroke , whereas women were more likely to have poor subjective health , to be disabled , to be socially isolated , and to suffer from insomnia . The principal adjusted risk factors for men for progression from MCI to dementia in descending order were ApoE4 allele ( OR = 3.2 , 95 % CI 1.7 to 5.7 ) , stroke ( OR = 2.8 , 95 % CI 1.2 to 6.9 ) , low level of education ( OR = 2.3 , 95 % CI 1.3 to 4.1 ) , loss of Instrumental Activities of Daily Living ( IADL ) ( OR = 2.2 , 95 % CI 1.1 to 4.5 ) and age ( OR = 1.2 , 95 % CI 1.1 to 1.2 ) . In women , progression is best predicted by IADL loss ( OR = 3.5 , 95 % CI 2.1 to 5.9 ) , ApoE4 allele ( OR = 2.3 , 95 % CI 1.4 to 4.0 ) , low level of education ( OR = 2.2 , 95 % CI 1.3 to 3.6 ) , sub clinical depression ( OR = 2.0 , 95 % CI 1.1 to 3.6 ) , use of anticholinergic drugs ( OR = 1.8 , 95 % CI 1.0 to 3.0 ) and age ( OR = 1.1 , 95 % CI 1.1 to 1.2 ) . Conclusions : Men and women have different risk profiles for both MCI and progression to dementia . Intervention programmes should focus principally on risk of stroke in men and depressive symptomatology and use of anticholinergic medication in women OBJECTIVE The authors conducted a prospect i ve cohort study to estimate the risk of incident mild cognitive impairment in cognitively normal elderly ( aged ≥70 years ) individuals with or without neuropsychiatric symptoms at baseline . The research was conducted in the setting of the population -based Mayo Clinic Study of Aging . METHOD A classification of normal cognitive aging , mild cognitive impairment , and dementia was adjudicated by an expert consensus panel based on published criteria . Hazard ratios and 95 % confidence intervals were computed using Cox proportional hazards model , with age as a time scale . Baseline Neuropsychiatric Inventory Question naire data were available for 1,587 cognitively normal persons who underwent at least one follow-up visit . RESULTS The cohort was followed to incident mild cognitive impairment ( N=365 ) or censoring variables ( N=179 ) for a median of 5 years . Agitation ( hazard ratio=3.06 , 95 % CI=1.89 - 4.93 ) , apathy ( hazard ratio=2.26 , 95 % CI=1.49 - 3.41 ) , anxiety ( hazard ratio=1.87 , 95 % CI=1.28 - 2.73 ) , irritability ( hazard ratio=1.84 , 95 % CI=1.31 - 2.58 ) , and depression ( hazard ratio=1.63 , 95 % CI=1.23 - 2.16 ) , observed initially , increased risk for later mild cognitive impairment . Delusion and hallucination did not . A secondary analysis , limited in significance by the small number of study participants , showed that euphoria , disinhibition , and nighttime behaviors were significant predictors of nonamnestic mild cognitive impairment but not amnestic mild cognitive impairment . By contrast , depression predicted amnestic mild cognitive impairment ( hazard ratio=1.74 , 95 % CI=1.22 - 2.47 ) but not nonamnestic mild cognitive impairment . CONCLUSIONS An increased incidence of mild cognitive impairment was observed in community-dwelling elderly adults who had nonpsychotic psychiatric symptoms at baseline . These baseline psychiatric symptoms were of similar or greater magnitude as biomarkers ( genetic and structural MRI ) in increasing the risk of incident mild cognitive impairment BACKGROUND Mild cognitive impairment has been regarded as a precursor to dementia of Alzheimer type , but not all patients with mild cognitive impairment develop dementia . OBJECTIVE To determine whether depression may increase the risk of developing dementia . SETTING The outpatient clinics of a community general hospital . DESIGN Prospect i ve cohort study . METHODS A cohort of 114 patients with amnestic mild cognitive impairment was followed up for a mean period of 3 years . At baseline , the patients underwent memory tests , the Spanish version of the Mini-Mental State Examination , a verbal fluency test , the Geriatric Depression Scale , and the Clinical Dementia Rating Scale for staging purpose s. Psychiatric examination for depression was based on structured interview and Diagnostic and Statistical Manual of Mental Disorder , Fourth Edition criteria . We also carried out either computed tomography or magnetic resonance imaging of the brain . MAIN OUTCOME MEASURES We carried out periodic evaluations based on the Mini-Mental State Examination , verbal fluency test , Geriatric Depression Scale , Blessed Dementia Rating Scale , and Clinical Dementia Rating Scale . The end point was the development of probable Alzheimer disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association . RESULTS Depression was observed in 41 patients ( 36 % ) at baseline . After a mean period of 3 years , 59 patients ( 51.7 % ) developed dementia of Alzheimer type , and 6 died . Of the depressed patients , 35 ( 85 % ) developed dementia in comparison with 24 ( 32 % ) of the nondepressed patients ( relative risk , 2.6 ; 95 % confidence interval , 1.8 - 3.6 ) . The survival analysis also showed that depressed patients developed dementia earlier than the nondepressed . Most patients with depression at baseline exhibited a poor response to antidepressants . CONCLUSIONS We conclude that patients with mild cognitive impairment and depression are at more than twice the risk of developing dementia of Alzheimer type as those without depression . Patients with a poor response to antidepressants are at an especially increased risk of developing dementia Objective : To investigate the population -based interaction between a biological variable ( APOE & egr;4 ) , neuropsychiatric symptoms , and the risk of incident dementia among subjects with prevalent mild cognitive impairment ( MCI ) . Methods : We prospect ively followed 332 participants with prevalent MCI ( aged 70 years and older ) enrolled in the Mayo Clinic Study of Aging for a median of 3 years . The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria , after review ing neurologic , cognitive , and other pertinent data . Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Question naire . We used Cox proportional hazards models , with age as a time scale , to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Models were adjusted for sex , education , and medical comorbidity . Results : Baseline agitation , nighttime behaviors , depression , and apathy significantly increased the risk of incident dementia . We observed additive interactions between APOE & egr;4 and depression ( joint effect HR = 2.21 ; 95 % CI = 1.24–3.91 ; test for additive interaction , p < 0.001 ) ; and between APOE & egr;4 and apathy ( joint effect HR = 1.93 ; 95 % CI = 0.93–3.98 ; test for additive interaction , p = 0.031 ) . Anxiety , irritability , and appetite/eating were not associated with increased risk of incident dementia . Conclusions : Among prevalent MCI cases , baseline agitation , nighttime behaviors , depression , and apathy elevated the risk of incident dementia . There was a synergistic interaction between depression or apathy and APOE & egr;4 in further elevating the risk of incident dementia CONTEXT Cognitive impairment in late-life depression is a core feature of the illness . OBJECTIVE To test whether donepezil hydrochloride and antidepressant therapy is superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment . DESIGN R and omized , double-blind , placebo-controlled maintenance trial . SETTING University clinic . PARTICIPANTS One hundred thirty older adults aged 65 years and older with recently remitted major depression . INTERVENTIONS R and om assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo . MAIN OUTCOME MEASURES Global neuropsychological performance , cognitive instrumental activities of daily living , and recurrent depression . RESULTS Donepezil and antidepressant therapy temporarily improved global cognition ( treatment × time interaction , F₂,₂₁₆ = 3.78 ; P = .03 ) , but effect sizes were small ( Cohen d = 0.27 , group difference at 1 year ) . A marginal benefit to cognitive instrumental activities of daily living was also observed ( treatment × time interaction , F₂,₁₃₇ = 2.94 ; P = .06 ) . The donepezil group was more likely than the placebo group to experience recurrent major depression ( 35 % [ 95 % confidence interval { CI } , 24%-46 % ] vs 19 % [ 95 % CI , 9%-29 % ] , respectively ; log-rank χ² = 3.97 ; P = .05 ; hazard ratio = 2.09 [ 95 % CI , 1.00 - 4.41 ] ) . Post hoc subgroup analyses showed that of 57 participants with mild cognitive impairment , 3 of 30 participants ( 10 % [ 95 % CI , 0%-21 % ] ) receiving donepezil and 9 of 27 participants ( 33 % [ 95 % CI , 16%-51 % ] ) receiving placebo had a conversion to dementia over 2 years ( Fisher exact test , P = .05 ) . The mild cognitive impairment subgroup had recurrence rates of major depression of 44 % with donepezil vs 12 % with placebo ( likelihood ratio = 4.91 ; P = .03 ) . The subgroup with normal cognition ( n = 73 ) showed no benefit with donepezil and no increase in recurrence of major depression . CONCLUSIONS Whether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment . In cognitively intact patients , donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00177671 BACKGROUND It remains unknown whether depression and apolipoprotein E genotype are risk factors for incident mild cognitive impairment ( MCI ) . OBJECTIVE To determine whether elderly individuals with depression ( measured by the short Geriatric Depression Scale ) are at increased risk of developing incident MCI . DESIGN Prospect i ve cohort study . SETTING Primary care clinic . PARTICIPANTS A cohort of 840 cognitively normal elderly subjects without depression at recruitment who were followed up prospect ively for a median of 3.5 years ( range , 0.4 - 12.8 years ) . Subjects who developed depression ( score of > /=6 on the short Geriatric Depression Scale ; depression cohort ) were compared with all remaining subjects ( referent cohort ) . MAIN OUTCOME MEASURES Incidence of MCI ( primary outcome ) and incidence of MCI or dementia ( composite secondary outcome ) . RESULTS Individuals in the depression cohort were at significantly increased risk of subsequent incident MCI ( hazard ratio [ HR ] , 2.2 ; 95 % confidence interval [ CI ] , 1.2 - 4.1 ) after adjusting for age ( time scale ) , sex , and education , and considering dementia as a competing outcome . The association was stronger in men but did not vary by severity of depression . We observed a synergistic interaction between apolipoprotein E genotype ( epsilon3/epsilon4 or epsilon4/epsilon4 ) and depression ( joint effect HR , 5.1 ; 95 % CI , 1.9 - 13.6 ; test for additive interaction , P = .03 ) . We found a similar association between depression and the subsequent composite outcome of incident MCI or dementia ( HR , 2.6 ; 95 % CI , 1.6 - 4.3 ) . CONCLUSIONS Cognitively normal elderly individuals who develop depression are at increased risk of subsequent MCI . We found a synergistic interaction between depression and apolipoprotein E genotype BACKGROUND studies have suggested that neuropsychiatric ( NP ) symptoms influence the development of dementia among older adults . But , the results are inconsistent and there is limited information about NP symptoms in population -based sample s. OBJECTIVE to explore the association between NP symptoms and risk of cognitive decline in Chinese older persons residing in the community . DESIGN prospect i ve study . SETTING community sample . SUBJECTS a total of 321 community-dwelling Chinese older persons aged 60 or over with mild cognitive impairment participated in the study . METHODS at baseline , each subject was assessed with Clinical Dementia Rating ( CDR ) , Mini-Mental State Examination , list learning and delayed recall , and Category Verbal Fluency Test . Severity of NP symptoms was evaluated with Neuropsychiatric Inventory ( NPI ) . Global cognitive status at the end of 2-year study period was determined by CDR . RESULTS at baseline , 40.5 % of participants exhibited one or more NP symptoms ( NPI total score ≥ 1 ) . Night-time behaviours ( 22.1 % ) , depression ( 16.8 % ) , apathy ( 14.0 % ) and anxiety ( 12.8 % ) were the most common NP symptoms . At the end of 2-year follow-up , 27.5 % of participants with depression at baseline developed dementia , compared with 14.8 % of those without depression ( χ² = 4.90 , P= 0.03 ) . Aberrant motor behaviour was also significantly associated with deterioration in cognition ( χ² = 5.84 , P= 0.02 ) , although it was an infrequent occurrence . On logistic regression analysis , only depression at baseline was shown to be a risk factor for progression to dementia ( OR= 2.40 , 95 % CI 1.05 - 5.46 , P= 0.04 ) . CONCLUSION depression in non-demented older persons may represent an independent dimension reflecting early neuronal degeneration . Further studies should be conducted to assess whether effective management of NP symptoms exerts beneficial effects on cognitive function |
10,874 | 29,608,714 | IMPLICATION S Smoking prevalence among people with mental illness , substance misuse , homelessness , or criminal justice system involvement remains high .
E-cigarettes could support cessation .
Qualitative thematic synthesis revealed barriers and facilitators mapping to each component of the COM-B ( capability , opportunity , motivation , and behavior ) model , including practical barriers ; perceived effectiveness ; design features contributing to automatic and reflective motivation ; smoking bans facilitating practical opportunity ; and social connectedness increasing social opportunity . | INTRODUCTION Smoking prevalence remains high in some vulnerable groups , including those who misuse substances , have a mental illness , are homeless , or are involved with the criminal justice system .
E-cigarette use is increasing and may support smoking cessation/reduction . | INTRODUCTION Smoking cessation pharmacotherapies tested in persons with opioid use disorder have produced low quit rates . Electronic cigarettes ( e-cigarettes ) have been used by many methadone-maintained ( MMT ) smokers , but controlled trials evaluating cessation and reduction outcomes have not been performed in this population with deleterious tobacco-related health consequences . METHODS In this open trial of NJOY e-cigarettes , MMT smokers received 6 weeks of treatment and were instructed to use only e-cigarettes . Outcomes included carbon monoxide confirmed 7-day point smoking cessation prevalence at week 7 ( end of treatment ) and self-reported change in mean cigarettes per day ( CPD ) at each 2-week assessment . The final assessment was 2 weeks after treatment ended ( week 9 ) . RESULTS The 12 participants averaged 46 years old and 50 % were male . On average , participants reported smoking 17.8 ( ±5.3 ) CPD . One person had a biochemically confirmed quit at week 7 . Participants tended to report marked reductions in mean CPD between quit day ( week 1 ) and the week 3 assessment . Relative to baseline , statistically significant reductions in mean CPD were observed at all follow-up assessment s. Mean reductions in CPD were -12.4 ( 95 % confidence interval [ CI ] : -15.0 , -9.9 ; P < .001 ) , -14.8 ( 95 % CI : -17.4 , -12.2 ; P < .001 ) , -13.9 ( 95 % CI : -16.6 , -11.2 ) , and -10.8 ( 95 % CI : -13.4 , -8.2 ; P < .01 ) at the 3- , 5- , 7- , and 9-week assessment s , respectively . Adherence to e-cigarettes was 89.1 % during the 6 treatment weeks . CONCLUSIONS E-cigarettes were associated with reductions in cigarette use . Smoking cessation rates in MMT smokers are low and whether long-term smoking reductions can persist and produce health benefits should be studied . IMPLICATION S E-cigarettes were associated with reduced tobacco use in MMT smokers . Adherence to e-cigarettes is high among methadone smokers . Week-7 smoking quit rates are similar to pharmacotherapies tested in this population Background People with mental illness have higher rates of smoking than the general population and are at greater risk of smoking-related death and disability . In smokers from the general population , electronic cigarettes ( e-cigarettes ) have been shown to have a similar effect on quit rates as nicotine replacement therapy , but little is known about their effect in smokers with mental illness . Methods Secondary analysis of data from the ASCEND trial involving 657 dependent adult smokers motivated to quit , r and omised to 16 mg nicotine e-cigarette , 21 mg nicotine patch , or 0 mg nicotine e-cigarette , with minimal behavioural support . Using self-reported medication use and the Anatomical Therapeutic Chemical Classification System , we identified 86 participants with mental illness and analysed their cessation and smoking reduction outcomes . Results For e-cigarettes alone , and all interventions pooled , there was no statistically significant difference in biochemically verified quit rates at six months between participants with and without mental illness , nor in smoking reduction , adverse events , treatment compliance , or acceptability . Rates of relapse to smoking were higher in participants with mental illness . Among this group , differences between treatments were not statistically significant for cessation ( patch 14 % [ 5/35 ] , 16 mg e-cigarette 5 % [ 2/39 ] , 0 mg e-cigarette 0 % [ 0/12 ] , p = 0.245 ) , adverse events or relapse rates . However , e-cigarette users had higher levels of smoking reduction , treatment compliance , and acceptability . Conclusions The use of e-cigarettes for quitting appears to be equally effective , safe , and acceptable for people with and without mental illness . For people with mental illness , e-cigarettes may be as effective and safe as patches , yet more acceptable , and associated with greater smoking reduction . Trial registration Australian New Zeal and Clinical trials Registry , number : ACTRN12610000866000 BACKGROUND Electronic cigarettes ( e-cigarettes ) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts . We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit . METHODS We did this pragmatic r and omised-controlled superiority trial in Auckl and , New Zeal and , between Sept 6 , 2011 , and July 5 , 2013 . Adult ( ≥18 years ) smokers wanting to quit were r and omised ( with computerised block r and omisation , block size nine , stratified by ethnicity [ Māori ; Pacific ; or non-Māori , non-Pacific ] , sex [ men or women ] , and level of nicotine dependence [ > 5 or ≤5 Fagerström test for nicotine dependence ] ) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes , nicotine patches ( 21 mg patch , one daily ) , or placebo e-cigarettes ( no nicotine ) , from 1 week before until 12 weeks after quit day , with low intensity behavioural support via voluntary telephone counselling . The primary outcome was biochemically verified continuous abstinence at 6 months ( exhaled breath carbon monoxide measurement < 10 ppm ) . Primary analysis was by intention to treat . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12610000866000 . FINDINGS 657 people were r and omised ( 289 to nicotine e-cigarettes , 295 to patches , and 73 to placebo e-cigarettes ) and were included in the intention-to-treat analysis . At 6 months , verified abstinence was 7·3 % ( 21 of 289 ) with nicotine e-cigarettes , 5·8 % ( 17 of 295 ) with patches , and 4·1 % ( three of 73 ) with placebo e-cigarettes ( risk difference for nicotine e-cigarette vs patches 1·51 [ 95 % CI -2·49 to 5·51 ] ; for nicotine e-cigarettes vs placebo e-cigarettes 3·16 [ 95 % CI -2·29 to 8·61 ] ) . Achievement of abstinence was substantially lower than we anticipated for the power calculation , thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes . We identified no significant differences in adverse events , with 137 events in the nicotine e-cigarettes group , 119 events in the patches group , and 36 events in the placebo e-cigarettes group . We noted no evidence of an association between adverse events and study product . INTERPRETATION E-cigarettes , with or without nicotine , were modestly effective at helping smokers to quit , with similar achievement of abstinence as with nicotine patches , and few adverse events . Uncertainty exists about the place of e-cigarettes in tobacco control , and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels . FUNDING Health Research Council of New Zeal and INTRODUCTION Up to 75 % of people with serious mental illness ( SMI ) smoke , and most are highly dependent on nicotine , consuming more cigarettes per day than smokers without mental illness . Even with evidence -based treatment , relapses are common , result ing in high morbidity and early mortality from tobacco-related diseases . Electronic cigarettes ( e-cigarettes ) are theoretically safer because they deliver no tar or carbon monoxide ; however , their appeal is largely untested in people with SMI . METHODS We enrolled 21 chronic smokers with SMI who had failed a quit attempt and were not engaged in cessation treatment . Research staff provided e-cigarettes and instructions on how to use them , and assessed participants weekly for 4weeks . RESULTS Of the enrolled participants , 19 completed weekly assessment s. From baseline to the final study visit , mean self-reported use of combustible tobacco declined from 192 to 67cigarettes/week ( t=3.62 , df=17 , p=0.005 ) , confirmed by reduction in breath carbon monoxide from 27ppm to 15ppm ( t=3.246 , df=18 , p=0.004 ) . Use of e-cigarettes did not escalate over the 4weeks . Temporary and mild side effects , including dry/sore throat , nausea , dizziness , and cough , were reported by 58 % of participants . End of trial ratings of enjoyment , satisfaction compared to regular cigarettes , and willingness to buy e-cigarettes were high ( ranging from 3.82 - 4.51 on a 5-point scale ) . CONCLUSIONS Results of this study suggest that people with SMI may find e-cigarettes an appealing substitute for combustible cigarettes . We found no evidence of increasing nicotine dependence . Further r and omized studies are needed to better assess e-cigarette appeal and toxicity Background : Cigarette smoking is a tough addiction to break . This dependence is the most common dual diagnosis for individuals with schizophrenia . Currently three effective drugs are approved for smoking cessation : nicotine replacement therapy ( NRT ) , varenicline and bupropion . However , some serious side effects of varenicline have been reported , including depression , suicidal thoughts , and suicide . The use of bupropion also has side effects . It should not be used by people who have epilepsy or any condition that lowers the seizure threshold , nor by people who take a specific class of drugs called monoamine oxidase inhibitors . Hence , there are pharmacodynamic reason to believe they could precipitate or exacerbate psychosis . For its capacity to deliver nicotine and provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures , electronic-cigarettes may reduce nicotine withdrawal symptoms without serious side effects . Our recent work with ECs in healthy smokers not intending to quit consistently show surprisingly high success rates . We hypothesised that these positive findings could be replicated in difficult patients with schizophrenia This tool may help smokers with schizophrenia remain abstinent during their quitting attempts or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated for this special population . Methods : In this study we monitored possible modifications in smoking habits of 14 smokers ( not intending to quit ) with schizophrenia experimenting with the “ Categoria ” e-Cigarette with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend six study visits : at baseline , week-4 , week-8 , week-12 week-24 and week 52 . Product use , number of cigarettes smoked , carbon monoxide in exhaled breath ( eCO ) and positive and negative symptoms of schizophrenia levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events were also review ed . Results : Sustained 50 % reduction in the number of cig/day at week-52 was shown in 7/14 ( 50 % ) participants ; their median of 30 cig/day decreasing significantly to 15 cig/day ( p = 0.018 ) . Sustained smoking abstinence at week-52 was observed in 2/14 ( 14.3 % ) participants . Combined sustained 50 % reduction and smoking abstinence was shown in 9/14 ( 64.3 % ) participants . Nausea was observed in 2/14 ( 14.4 % ) of participants , throat irritation in 2/14 ( 14.4 % ) of participants , headache in 2/14 ( 14.4 % ) of participants , and dry cough in 4/14 ( 28.6 % ) of participants . However , these adverse events diminished substantially by week-24 . Overall , one to two cartridges/day were used throughout the study . Positive and negative symptoms of schizophrenia are not increased after smoking reduction/cessation in patients using e-cigarettes . Conclusions : We have shown for the first time that the use of e-cigarette substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke not intending to quit . This was achieved without negative impacts on the symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales Objectives While substantial research has demonstrated the poor health status of homeless population s , the health status of vulnerably housed individuals is largely unknown . Furthermore , few longitudinal studies have assessed the impact of housing transitions on health . The health and housing in transition ( HHiT ) study is a prospect i ve cohort study that aims to track the health and housing status of a representative sample of homeless and vulnerably housed single adults in three Canadian cities ( Toronto , Ottawa , and Vancouver ) . This paper discusses the HHiT study method ological recruitment strategies and follow-up procedures , including a discussion of the limitations and challenges experienced to date . Methods Participants ( n = 1,192 ) were r and omly selected at shelters , meal programmes , community health centres , drop-in centres , rooming houses , and single-room occupancy hotels from January to December 2009 and are being re-interviewed every 12 months for a 2-year period . Results At baseline , over 85 % of participants reported having at least one chronic health condition , and over 50 % reported being diagnosed with a mental health problem . Conclusions Our findings suggest that , regardless of housing status , participants had extremely poor overall health BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application INTRODUCTION Approximately 70 % of homeless youth smoke cigarettes , but their use of alternative tobacco products ( ATPs ) is unknown . This paper reports on ATP use among past-month smokers in Los Angeles County , including whether it differs by demographic characteristics , homelessness severity , past-year quit attempts , and readiness to quit smoking . Given the growing popularity of e-cigarettes , we also report on perceptions of harm and reasons for using this product . METHODS We surveyed 292 unaccompanied homeless youth who were r and omly sample d from street sites . Participants had smoked at least 100 cigarettes during their lifetime and 1 cigarette during the past month . RESULTS Seventy-two percent of youth reported past-month ATP use ( e-cigarettes = 51 % ; little cigars/cigarillos = 46 % ; hookah = 31 % ; other smokeless tobacco product = 24 % ; chewing tobacco/moist snuff = 19 % ) . Current ATP use was unrelated to most demographic characteristics or having a past-year quit attempt . However , youth who planned to quit smoking in the next 30 days were significantly less likely to report current use of hookahs , other smokeless tobacco products , or e-cigarettes . Among lifetime e-cigarette users , the most common reasons for use included not having to go outside to smoke ( 38 % ) and being able to deal with situations or places where they can not smoke ( 36 % ) ; it was less common to report using e-cigarettes to quit smoking ( 17%-18 % ) . DISCUSSION Dual use of ATPs among homeless youth smokers is common and is more likely among those who have no immediate plans to quit smoking . Effective and easily disseminable strategies for reducing all forms of tobacco use among homeless youth are urgently needed AIMS To propose a hierarchy of method ological criteria to consider when determining whether a study provides sufficient information to answer the question of whether e-cigarettes can facilitate cigarette smoking cessation or reduction . DESIGN A PubMed search to 1 February 2017 was conducted of all studies related to e-cigarettes and smoking cessation or reduction . SETTING S Australia , Europe , Iran , Korea , New Zeal and and the United States . PARTICIPANTS AND STUDIES 91 articles . MEASUREMENTS Coders organized studies according to six proposed method ological criteria : ( 1 ) examines outcome of interest ( cigarette abstinence or reduction ) , ( 2 ) assesses e-cigarette use for cessation as exposure of interest , ( 3 ) employs appropriate control/comparison groups , ( 4 ) ensures that measurement of exposure precedes the outcome , ( 5 ) evaluates dose and duration of the exposure and ( 6 ) evaluates the type and quality of the e-cigarette used . FINDINGS Twenty-four papers did not examine the outcomes of interest . Forty did not assess the specific reason for e-cigarette use as an exposure of interest . Twenty papers did not employ prospect i ve study design s with appropriate comparison groups . The few observational studies meeting some of the criteria ( duration , type , use for cessation ) triangulated with findings from three r and omized trials to suggest that e-cigarettes can help adult smokers quit or reduce cigarette smoking . CONCLUSIONS Only a small proportion of studies seeking to address the effect of e-cigarettes on smoking cessation or reduction meet a set of proposed quality st and ards . Those that do are consistent with r and omized controlled trial evidence in suggesting that e-cigarettes can help with smoking cessation or reduction |
10,875 | 23,562,414 | Based on this systematic review and meta-analyses , a single rehabilitation service may not provide health economic benefits for all patient groups and situations .
For some patients , inpatient rehabilitation may be the most cost-effective method of providing rehabilitation ; yet , for other patients , rehabilitation in the home or community may be the most cost-effective model of care . | OBJECTIVES To report if there is a difference in costs from a societal perspective between adults receiving rehabilitation in an inpatient rehabilitation setting versus an alternative setting .
If there are cost differences , to report whether opting for the least expensive program setting adversely affects patient outcomes . | Background and Purpose — Early supported discharge ( ESD ) for stroke has been shown to yield outcomes similar to or better than those of conventional care , but there is less information on the impact on costs and on the caregiver . The purpose of this study is to estimate the costs associated with an ESD program compared with those of usual care . Methods — We conducted a r and omized controlled trial of stroke patients who required rehabilitation services and who had a caregiver at home . Results — Acute-care costs incurred before r and omization when patients were medically ready for discharge averaged $ 3251 per person . The costs for the balance of the acute-care stay , from r and omization to discharge , were $ 1383 for the home group and $ 2220 for the usual care group . The average cost of providing the 4-week home intervention service was $ 943 per person . The total cost generated by persons assigned to the home group averaged $ 7784 per person , significantly lower than the $ 11 065 per person for those assigned to usual care . A large proportion of the cost differential between the 2 groups arose from readmissions , for which the usual care group generated costs more than quadruple those of the home intervention group . Conclusions — Providing care at home was no more ( or less ) expensive for those with greater functional limitation than for those with less . Caregivers in the ESD group scored consistently lower on the Burden Index than caregivers with usual care , even caregivers of persons with major functional limitations . For persons recovering from stroke and their families , ESD provides a cost-effective alternative to usual care Self-efficacy reflects an individual 's perceptions or beliefs about how capable he or she is of performing a specific activity or task and measures self-confidence to perform that specific activity or task . This study investigated the effect of in-patient cardiac rehabilitation on self-efficacy scores for 3 categories of activities : routine physical activities , daily living tasks and levels of concentration and ability to cope . On discharge from the intensive or coronary care unit , patients without contraindications to early ambulation were r and omized to either a ward ambulation program ( n = 26 ) or a dedicated exercise center program ( n = 25 ) with all patients receiving the same st and ardized education/counseling . There were no differences between the groups in self-efficacy at baseline , at hospital discharge or 7 days later . Significant improvements in self-efficacy scores were observed by day 28 in both groups for routine physical activities and daily living tasks with no change in self-efficacy scores for concentration or ability to cope . At that time the exercise center patients had higher self-efficacy scores for walking time ( p = 0.041 ) and overall exertion ( p = 0.024 ) than the ward ambulation patients . For the majority of the self-efficacy variables considered , both in-patient exercise rehabilitation programs were equally effective in improving self-efficacy scores for physical activities and daily living tasks over the first 28 days after return to home . The lower cost associated with ward ambulation programs suggests that they are more cost-effective than developing a program in a dedicated in-patient exercise center OBJECTIVE To estimate the cost-utility and cost-effectiveness of a 3-week intensive exercise training ( IET ) program directly following hospital discharge in patients with rheumatic diseases . METHODS Patients with arthritis who were admitted to the hospital because of a disease activity flare or for elective hip or knee arthroplasty were r and omly assigned to either the IET group or usual care ( UC ) group . Followup lasted 1 year . Quality -adjusted life years ( QALYs ) were derived from Short Form 6D scores and a visual analog scale ( VAS ) rating personal health . Function-related outcome was measured using the Health Assessment Question naire , the McMaster Toronto Arthritis ( MACTAR ) Patient Preference Disability Question naire , and the Escola Paulista de Medicina Range of Motion scale ( EPMROM ) . Costs were reported from a societal perspective . Differences in costs and incremental cost-effectiveness ratios ( ICERs ) were estimated . RESULTS Data from 85 patients ( 50 IET and 35 UC ) could be used for health-economic analysis . VAS personal health-based QALYs were in favor of IET . Function-related outcome showed statistically significant improvements in favor of IET over the first 6 months , according to the MACTAR ( P < 0.05 ) and the EPMROM ( P < 0.01 ) . At 1-year followup , IET was euro718 less per patient . The ICER showed a reduction in mean total costs per QALY . In 70 % of cases the intervention was cost-saving . CONCLUSION IET results in better quality of life at lower costs after 1 year . Thus , IET is the dominant strategy compared with UC . This highlights the need for implementation of IET after hospital discharge in patients with arthritis Objective : To assess the relative cost effectiveness of clinical nurse specialist care , inpatient team care , and day patient team care . Methods : Incremental cost effectiveness analysis and cost utility analysis , alongside a prospect i ve r and omised controlled trial with two year follow up . Included were patients with rheumatoid arthritis ( RA ) with increasing difficulty in performing activities of daily living over the previous six weeks . Quality of life and utility were assessed by the Rheumatoid Arthritis Quality of Life question naire , the Short Form-6D , a transformed rating scale , and the time tradeoff . A cost-price analysis was conducted to estimate the costs of inpatient and day patient hospitalisations . Other healthcare and non-healthcare costs were estimated from cost question naires . Results : 210 patients with RA ( 75 % female , median age 59 years ) were included . Aggregated over the two year follow up period , no significant differences were found on the quality of life and utility instruments . The costs of the initial treatment were estimated at € 200 for clinical nurse specialist care , € 5000 for inpatient team care , and € 4100 for day patient team care . Other healthcare costs and non-healthcare costs were not significantly different . The total societal costs did not differ significantly between in patients and day patients , but were significantly lower for the clinical nurse specialist patients by at least € 5400 . Conclusions : Compared with inpatient and day patient team care , clinical nurse specialist care was shown to provide equivalent quality of life and utility , at lower costs . Therefore , for patients with health conditions that allow for any of the three types of care , the preferred treatment from a health-economic perspective is the care provided by the clinical nurse specialist Objective : To determine whether an early increased-intensity upper limb therapy programme following acute stroke improves outcome . Design : A r and omized controlled trial . Setting : A stroke unit which provides acute care and rehabilitation for all stroke admissions . Subjects : One hundred and twenty-three patients who had had a stroke causing upper limb impairment within the previous 10 days . Intervention : The intervention group received stroke unit care plus enhanced upper limb rehabilitation provided jointly by a physiotherapist and occupational therapist , commencing within 10 days of stroke , and available up to 30 minutes/day , five days/week for six weeks . The control group received stroke unit care . Main outcome measures : The primary outcome measure was the Action Research Arm Test ( ARAT ) three months after stroke . Secondary outcome measures : Motricity Index ; Frenchay Arm Test ; upper limb pain ; Barthel ADL Index ; Nottingham E-ADL Scale ; and costs to health and social services at three and six months after stroke . Results : There were no differences in outcomes between the intervention and control groups three and six months after stroke . During the intervention period the intervention group received a median of 29 minutes of enhanced upper limb therapy per working day as in patients . The total amount of inpatient physiotherapy and occupational therapy received by the intervention group was a median of 52 minutes per working day during the intervention period and 38 minutes per working day for the control group ( p = 0.001 ) . There were no differences in service costs . Conclusions : An early increased-intensity interdisciplinary upper limb therapy programme jointly provided by a physiotherapist and occupational therapist did not improve outcome after stroke . The actual difference in the amount of therapy received by intervention and control groups was less than planned due to a competitive therapy bias BACKGROUND AND PURPOSE In an inner-London teaching hospital , a r and omized trial of " conventional " care versus early discharge to community-based therapy found no significant differences in clinical outcomes between patient groups . This report examines the economic consequences of the alternative strategies . METHODS One hundred sixty-seven patients received the early discharge package , and 164 received conventional care . Patient utilization of health and social services was recorded over a 12-month period , and cost was determined using data from provider departments and other published sources . RESULTS Inpatient stay after r and omization was 12 days ( intervention group ) versus 18 days ( controls ) ( P=0.0001 ) . Average units of therapy per patient were as follows : physiotherapy , 22.4 ( early discharge ) versus 15.0 ( conventional ) ( P=0.0006 ) ; occupational therapy , 29.0 versus 23.8 ( P=0.002 ) ; speech therapy , 13 . 7 versus 5.8 ( P=0.0001 ) . The early discharge group had more annual hospital physician contacts ( P=0.015 ) and general practitioner clinic visits ( P=0.019 ) but fewer incidences of day hospital attendance ( P=0.04 ) . Other differences in utilization were nonsignificant . Average annual costs per patient were pound sterling 6800 ( early discharge ) and pound sterling 7432 ( conventional ) . The early discharge group had lower inpatient costs per patient ( pound sterling 4862 [ 71 % of total cost ] versus pound sterling 6343 [ 85 % ] for controls ) but higher non-inpatient costs ( pound sterling 1938 [ 29 % ] versus pound sterling 1089 [ 15 % ] ) . Further analysis demonstrated that early discharge is unlikely to lead to financial savings ; its main benefit is to release capacity for an expansion in stroke caseload . CONCLUSIONS Overall results of this trial indicate that early discharge to community rehabilitation for stroke is cost-effective . It may provide a means of addressing the predicted increase in need for stroke care within existing hospital capacity & NA ; This study reports a 9–18 month follow‐up of a r and omised controlled trial of pain management programmes for chronic , non‐malignant pain . Twenty‐two in patients , 18 out patients and 12 control subjects completed the follow‐up assessment s. Significant treatment effects were demonstrated by the inpatient group on pain ratings , the Pain Behaviour Checklist , and General Health Question naire , with similar effects demonstrated by the outpatient group on the former 2 measures . The findings were confounded by higher inpatient scores at pretreatment , in comparison with the 2 other conditions . There was a high drop‐out rate of subjects , particularly from the control condition which illustrates the limitations of controlled group design s in this area . Analgesic use , activity levels and pain ratings were also evaluated using the criteria for ‘ success ’ described by Malec et al. ( 1981 ) . Results indicated that 68 % of in patients , 61 % of out patients and 21 % of control subjects met all 3 criteria . Both treatment programmes were effective in returning patients to paid employment , whilst 3 control group patients gave up work . The cost‐benefit implication s of these changes are discussed . We conclude that pain management programmes contribute substantially to the rehabilitation of chronic pain sufferers Background and Purpose The aim of the present study was to examine re source utilization during a 12-month period after acute stroke in elderly patients r and omized to care in an acute stroke unit integrated with a care continuum compared with conventional care in general medical wards . A secondary aim was to describe costs related to the severity of stroke . Methods Two hundred forty-nine consecutive patients aged ≥70 years with acute stroke within 7 days before admission , living in their own homes in Göteborg , Sweden , without recognized need of care were r and omized to 2 groups : 166 patients were assigned to nonintensive stroke unit care with a care continuum , and 83 patients were assigned to conventional care . There was no difference in mortality or the proportion of patients living at home after 1 year . Main outcomes were costs from inpatient care , outpatient care , and informal care . Results Mean annual cost per patient was 170 000 Swedish crowns ( SEK ) ( equivalent to $ 25 373 ) and 191 000 SEK ( $ 28 507 ) in the stroke unit and the general medical ward groups , respectively ( P = NS ) . Seventy percent of the total cost was for inpatient care , and 30 % was for outpatient and informal care . For patients with mild , moderate , and severe stroke , the mean annual costs per patient were 107 000 SEK ( $ 15 970 ) , 263 000 SEK ( $ 39 254 ) , and 220 000 SEK ( $ 32 836 ) , respectively ( P < 0.001 ) . There was no statistical difference in age or nonstroke diagnosis . Conclusions The total costs the first year did not differ significantly between the treatment groups in this prospect i ve study . The total annual cost per patient showed a very large variation , which was related to stroke severity at onset and not to age or nonstroke diagnoses . Costs other than those for hospital care constituted a substantial fraction of total costs and must be taken into account when organizing the management of stroke patients . The high variability in costs necessitates a larger study to assess long-term cost effectiveness STUDY OBJECTIVE We report on the incremental costs associated with improvements in health-related quality of life ( HRQL ) following 6 months of respiratory rehabilitation compared with conventional community care . DESIGN Prospect i ve r and omized controlled trial of rehabilitation . SETTING A respiratory rehabilitation unit . PARTICIPANTS Eighty-four subjects who completed the rehabilitation trial . INTERVENTION Two months of inpatient rehabilitation followed by 4 months of outpatient supervision . MEASUREMENTS AND RESULTS All costs ( hospitalization , medical care , medications , home care , assistive devices , transportation ) were included . Simultaneous allocation was used to determine capital and direct and indirect hospitalization costs . The incremental cost of achieving improvements beyond the minimal clinical ly important difference in dyspnea , emotional function , and mastery was $ 11,597 ( Canadian ) . More than 90 % of this cost was attributable to the inpatient phase of the program . Of the nonphysician health-care professionals , nursing was identified as the largest cost center , followed by physical therapy and occupational therapy . The number of subjects needed to be treated ( NNT ) to improve one subject was 4.1 for dyspnea , 4.4 for fatigue , 3.3 for emotion , and 2.5 for mastery . CONCLUSION Cost estimates of various approaches to rehabilitation should be combined with valid , reliable , and responsive measures of outcome to enable cost-effectiveness measures to be reported . Comparison studies with the same method are necessary to determine whether the improvements in HRQL that follow inpatient rehabilitation are cheap or expensive . Such information will be important in identifying the extent to which alternative approaches to rehabilitation can influence re source allocation . A consideration of cost-effectiveness from the perspective of NNT may be useful in the evaluation of health-care programs OBJECTIVE To set a baseline for measuring the development of medical rehabilitation services and outcomes for patients after stroke and promoting rehabilitation medicine in Thail and . DESIGN Multi-centre , prospect i ve study . SUBJECTS Patients after stroke in Thai Stroke Rehabilitation Registry ( TSRR ) , aged > or = 18 years , with stable medical signs , able to follow a 1-step comm and and sit for at least 30 min . METHODS Rehabilitation services were recorded daily as units of treatment ( 1 unit = 20 min ) . Length of stay and treatment costs were calculated . RESULTS Of 327 patients enrolled in the study , 285 ( 87.2 % ) completed their treatment programme . Mean length of stay was 29.4 ( st and ard deviation 17.9 ) days . The average number of total treatment units for stroke rehabilitation was 319.5 ( range 27 - 1674 units ) , with 205 units of nursing , 40 units of physical therapy and 34 units of occupational therapy as the top 3 services provided . The mean total cost for all treatments during rehabilitation was 28,399 ( st and ard deviation 22,511 ) baht ( approximately USD 789 ) . The ratio of costs not related to rehabilitation to those related to rehabilitation was approximately 2:1 . CONCLUSION This study reports the baseline for measuring the development of rehabilitation services for patients after stroke with a mean length of stay of one month , and for estimating the reasonable costs OBJECTIVE To compare costs of function- and pain-centred inpatient treatment in patients with chronic low back pain over 3 years of follow-up . DESIGN Cost analysis of a r and omized controlled trial . PATIENTS A total of 174 patients with chronic low back pain were r and omized to function- or pain-centred inpatient treatment . METHODS Data on direct and indirect costs were gathered by question naires sent to patients , health insurance providers , employers , and the Swiss Disability Insurance Company . RESULTS There was a non-significant difference in total medical costs after 3 years ' follow-up . Total costs were 77,305 Euros in the function-centred inpatient treatment group and 83,085 Euros in the pain-centred inpatient treatment group . Likewise , indirect costs after 3 years from lost work days were non-significantly lower in the function-centred in-patient treatment group ( 6354 Euros ; 95 % confidence interval -20,892 , 8392 ) and direct medical costs were non-significantly higher in the function-centred inpatient treatment group ( 574 Euros ; 95 % confidence interval -862 , 2011 ) . CONCLUSION The total costs of function-centred and pain-centred inpatient treatment were similar over the whole 3-year follow-up Background and purpose R and omised trials indicate that organised inpatient ( stroke unit ) care has an important impact on patient outcomes with an absolute risk difference ( ARD ) of 3 % for survival and 5 % for returning home . However , it is unclear what impact this complex intervention actually has in routine practice . A comprehensive national data set was used to study the impact of stroke unit implementation . Methods The Scottish linked discharge data base was used to identify all patients admitted to hospital with an incident stroke . Analyses compared case fatality and discharge home ( adjusted for age , sex , deprivation and comorbidity ) for hospitals with or without a stroke unit during four consecutive study periods : 1986–1990 , 1991–1995 , 1996–2000 and 2001–2005 . Results During the study period , the percentage of admissions to hospitals that had a stroke unit increased from 0 % to 87 % , the 6 month case fatality decreased from 45 % to 29 % and discharges home increased from 46 % to 59 % . Adjusted ORs ( 95 % CI ) for case fatality ( stroke unit versus no unit ) in each study period were as follows : not calculable ( no units before 1991 ) , 0.83 ( 0.78–0.89 ) , 0.90 ( 0.86–0.94 ) and 0.87 ( 0.82–0.91 ) . These equate to an ARD of 3.0 % over the whole study period . Equivalent data for discharge home indicated an increased odds of discharge home : not calculable , 1.23 ( 1.15–1.31 ) , 1.15 ( 1.10–1.21 ) and 1.17 ( 1.11–1.23 ) with an overall ARD of 5 % . Conclusions These results indicate a positive impact of a policy of stroke unit care on case fatality and discharge home . The estimated impact , after adjusting for case mix , appears very similar to that calculated using clinical trial data A r and omised controlled trial comparing an accelerated rehabilitation program after proximal femoral fracture with conventional care and rehabilitation was conducted with 252 elderly patients treated at an Australian general hospital in 1989/1990 . This paper presents a cost-effectiveness analysis of the accelerated rehabilitation program . The measure of cost was all direct costs of treatment and subsequent care ( medical and non-medical ) incurred during the 4 months after fracture . Effectiveness was defined as whether the patient returned to semi-independent living ; or if moderately or severely disabled prior to the fracture to the premorbid level of physical independence . The cost for treatment up to 4 months after fracture was estimated at A$ 10,600 per accelerated rehabilitation patient and A$ 12,800 per conventional care patient ( 1990 Australian dollars , A$ ) . Thus , accelerated rehabilitation releases re sources equivalent to approximately 17 % of costs for treatment per patient . When cost effectiveness is considered , the potential cost savings rise to 38 % per recovered patient BACKGROUND Home-based rehabilitation is increasingly utilized to reduce health-care costs ; however , with a shorter hospital stay , the possibility arises for an increase in adverse clinical outcomes . We evaluated the effectiveness and cost of care of home-based compared with inpatient rehabilitation following primary total hip or knee joint replacement . METHODS We r and omized 234 patients , using block r and omization techniques , to either home-based or inpatient rehabilitation following total joint replacement . All patients followed st and ardized care pathways and were evaluated , with use of vali date d outcome measures ( Western Ontario and McMaster Universities Osteoarthritis Index [ WOMAC ] , Short Form-36 , and patient satisfaction ) , prior to surgery and at three and twelve months following surgery . The primary outcome was the WOMAC function score at three months after surgery . RESULTS The mean length of stay ( and st and ard deviation ) in the acute care hospital was 6.3 + /- 2.5 days for the group design ated for inpatient rehabilitation prior to transfer to that facility compared with 7.0 + /- 3.0 days for the home-based rehabilitation group prior to discharge home ( p = 0.06 ) . The mean length of stay in inpatient rehabilitation was 17.7 + /- 8.6 days . The mean number of postoperative home-based rehabilitation visits was eight . The prevalence of postoperative complications up to twelve months postoperatively was similar in both groups , which each had a 2 % rate of dislocation and a 3 % rate of clinical ly important deep venous thrombosis . The prevalence of infection was 0 % in the home-based group and 2 % in the inpatient group . None of these differences was clinical ly important . Both groups showed substantial improvements at three and twelve months , with no significant differences between the groups with respect to WOMAC , Short Form-36 , or patient satisfaction scores ( p > 0.05 ) . The total episode-of-care costs ( in Canadian dollars ) for the inpatient rehabilitation and home-based rehabilitation arms were $ 14,532 and $ 11,082 , respectively ( p < 0.01 ) . CONCLUSIONS Despite concerns about early hospital discharge , there was no difference in pain , functional outcomes , or patient satisfaction between the group that received home-based rehabilitation and the group that had inpatient rehabilitation . On the basis of our findings , we recommend the use of a home-based rehabilitation protocol following elective primary total hip or knee replacement as it is the more cost-effective strategy Background and Purpose — To compare a community-based multidisciplinary stroke team ( CST ) approach with hospital-based rehabilitation in terms of hospital stay , functioning , quality of life , and service use and costs . Methods — Stroke patients who met pre-agreed criteria were allocated r and omly to the CST service ( n=59 ) or to usual inpatient rehabilitation and follow-up care ( n=54 ) . Assessment s were completed at r and omization and 12 months later . Caregiver strain and satisfaction ( n=55 ) were also assessed . Cost data were collected for a sub sample of 38 patients . Results — Almost 80 % of surviving patients ( n=691 ) were discharged home and a small number ( n=55 ) were readmitted . Approximately 17 % ( 113/649 ) were r and omized . There were no statistically significant differences in hospital duration , costs , or outcome measures at baseline and 12 months except for higher satisfaction reported by CST patients . Overall , both groups recorded improvement in most domains over time . Carers reported a high level of satisfaction although the level of strain among carers is cause for concern . The community group ( n=18 ) cost less than the hospital group ( n=20 ) . Conclusions — A mixed model of hospital-based and community-based rehabilitation services is likely to lead to increased patient choice and satisfaction and a potential reduction in bed pressures for less severe stroke patients Study Design . A review of the surgical costs and results in a group of patients r and omly allocated to surgery as part of a large prospect i ve r and omized trial of patients with chronic back pain . Objective . To report the observational data from the surgical arm of a r and omized trial comparing surgery with intensive rehabilitation for chronic low back pain . Clinical and economic data are reported . Summary of Background Data . Surgery for chronic low back pain is a well established but unproven intervention . The most cost-effective technique for spinal stabilization is still not established . Methods . One hundred six patients with chronic low back pain were r and omized to the surgical group of a r and omized trial comparing spinal fusion of the lumbar with a 3 week intensive rehabilitation program . The primary outcomes were the Oswestry Disability Index ( ODI ) and the Shuttle Walking Test measured at baseline and 2 years postr and omization . Patients were stratified by preoperative diagnosis , smoking habit , and litigation . Complications were assessed and costs analyzed . Results . Of the 176 surgical patients , 56 underwent postero-lateral fusion , 57 underwent interbody fusion , and 24 underwent flexible stabilization of the spine . The mean ODI for all patients in the surgical arm of the trial improved from a baseline of 46.5 ( SD 14.6 ) to 34.2 ( SD 21 ) at 2 years . Health care costs were higher ( £ 3109 difference ) for more complex procedures , and nearly 6 times as many early complications occurred with the more complex procedures . Smoking and unemployment were associated with worse results whereas litigation did not adversely affect the outcome . Conclusion . These observational changes in the ODI after surgery are similar to those reported from other studies of spinal fusion . More complex surgery is more expensive with more complications than postero-lateral fusion Abstract Background Training care givers reduces their burden and improves psychosocial outcomes in care givers and patients at one year . However , the cost effectiveness of this approach has not been investigated . Objective To evaluate the cost effectiveness of caregiver training by examining health and social care costs , informal care costs , and quality adjusted life years in care givers . Design A single , blind , r and omised controlled trial . Setting Stroke rehabilitation unit . Subjects 300 stroke patients and their care givers . Interventions Caregiver training in basic nursing and facilitation of personal care techniques compared with no caregiver training . Main outcome measures Health and social care costs , informal care costs , and quality adjusted life years in care givers over one year after stroke . Results Total health and social care costs over one year for patients whose care givers received training were significantly lower ( mean difference -£4043 ( $ 7249 ; € , 95 % confidence interval -£6544 to -£1595 ) . Inclusion of informal care costs , which were similar between the two groups , did not alter this conclusion . The cost difference was largely due to differences in length of hospital stay . The EQ-5D did not detect changes in quality adjusted life years in care givers . Conclusion Compared with no training , caregiver training during rehabilitation of patients reduced costs of care while improving overall quality of life in care givers at one year OBJECTIVE Cost-effectiveness of a geriatric rehabilitation programme . DESIGN Economic evaluation alongside a r and omized controlled trial . METHODS A total of 741 subjects with progressively decreasing functional ability and unspecific morbidity were r and omly assigned to either an inpatient rehabilitation programme ( intervention group ) or st and ard care ( control group ) . The difference between the mean cost per person for 12 months ' care in the rehabilitation and control groups ( incremental cost ) and the ratio between incremental cost and effectiveness were calculated . Clinical outcomes were functional ability ( Functional Independence Measure ( FIM(TM ) ) ) and health-related quality of life ( 15D score ) . RESULTS The FIM(TM ) score decreased by 3.41 ( st and ard deviation 6.7 ) points in intervention group and 4.35 ( st and ard deviation 8.0 ) in control group ( p = 0.0987 ) . The decrease in the 15D was equal in both groups . The mean incremental cost of adding rehabilitation to st and ard care was 3111 euros per person . The incremental cost-effectiveness ratio for FIMTM did not show any clinical ly significant change , and the rehabilitation was more costly than st and ard care . A cost-effectiveness acceptability curve suggests that if decision-makers were willing to pay 4000 euros for a 1-point improvement in FIMTM , the rehabilitation would be cost-effective with 70 % certainty . CONCLUSION The rehabilitation programme was not cost-effective compared with st and ard care , and further development of outpatient protocol s may be advisable Background and Purpose : This study sought to evaluate early supported discharge and continued rehabilitation at home after stroke , at a minimum of 6 months after the intervention , in terms of patient outcome , re source use and health care cost . Methods : Eighty-three patients , moderately impaired 5–7 days after acute stroke , were included in a r and omized controlled trial , 42 being allocated to the intervention and 41 to routine rehabilitation . One-year follow-up of patient outcome included mortality , motor capacity , dysphasia , activities of daily living , social activities , perceived dysfunction , and self-reported falls . Re source use over 12 months included inpatient hospital care , outpatient health care , use of health-related services , informal care , and cost of health care . Results : On univariate analysis there was no difference in patient outcome . Multivariate regression analysis showed that intervention had a significant effect on independence in activities of daily living . A significant difference in inpatient hospital care , initial and recurrent , was observed , with a mean of 18 ( intervention ) versus 33 days ( control ) ( p = 0.002 ) . Further significant differences were that the control group registered more outpatient visits to hospital occupational therapists ( p = 0.02 ) , private physical therapists ( p = 0.03 ) and day-hospital attendance ( p = < 0.001 ) , while the intervention group registered more visits to nurses in primary care ( p = 0.03 ) and home rehabilitation ( p = < 0.001 ) . Other differences in outcomes or re source utilization were nonsignificant . Conclusion : In Sweden , early supported discharge with continued rehabilitation at home proved no less beneficial as a rehabilitation service , and provided care and rehabilitation for 5 moderately disabled stroke patients over 12 months after stroke onset for the cost of 4 in routine rehabilitation OBJECTIVE To investigate return to work and cost-effectiveness of the addition of cognitive-behavioral treatment to st and ard therapy compared to st and ard 3-week inpatient rehabilitation for patients with chronic low back pain . METHODS A prospect i ve economic evaluation alongside a r and omized controlled trial was performed . Outcomes included days off work due to spinal complaints , health-related quality of life , and direct and indirect disease-related costs . RESULTS A total of 409 patients with chronic low back pain , who were admitted to a 3-week inpatient rehabilitation , were r and omly assigned to usual care or usual care plus cognitive behavioral treatment . Average incremental costs for psychological treatment during rehabilitation were Euros 127 ( 95 % CI 125.6 , 130.9 ; p < 0.001 ) . Six months after rehabilitation , patients in the intervention group were absent from work an average of 5.4 ( 95 % CI -1.4 , 12.1 ; p = 0.12 ) days less than patients receiving usual treatment . Between groups , there were no significant differences in quality -adjusted life-years gained or in direct medical or nonmedical costs . The cognitive behavioral treatment showed lower indirect costs : Euros 751 ( 95 % CI -145 , 1641 ; p = 0.097 ) . CONCLUSION Adding a cognitive behavioral component to st and ard therapy may reduce work days lost and thus decrease indirect costs . From a societal perspective , the cost of the psychological treatment was compensated by lower indirect costs The economic evaluation of a patient education program " ankylosing spondylitis"-based on a r and omised controlled prospect i ve multi-center study design -compares program costs and savings in direct and indirect follow-up costs . The collection of health services and cost data was conducted by question ing staff ( education programme costs ) and patients ( follow-up costs ) . The present study results are : program costs per patient range between 117 euro ( 10 participants per course ) and 186 euro ( 6 participants per course ) . Savings in indirect costs ( unfitness to work ) amount to 2500 euro and thus overcompensate program costs . Currently patient data are verified by sickness fund data and direct follow-up costs and qualitiy of life data are analysed Twenty-six patients with rheumatoid arthritis ( RA ) participated either in a 21 day , community sponsored , in-patient multidisciplinary rehabilitation program ( N = 20 ) or ; received traditional , out-patient physiotherapy design ed by the patient 's rheumatologist ( N = 6 ) . Clinical assessment s were made ( prior to , immediately after , and 6 months after rehabilitation ) to evaluate the response to these two quite different rehabilitative measures that included : functional classification , joint score index , subjective VAS of pain , HAQ , pain disability index , Comprehensible psychopathological rating scale , hemoglobin , and CRP measurements . Economic assessment s included salary , direct and community sponsored costs , for rehabilitation and costs for sick days and production losses . No clear-cut differences between the two rehabilitation modes were detected . Both modes showed improvement in different assessment parameters ; patients with higher education and , therefore , with a less joint-disturbing work profile appeared to profit more from an extensive in-patient rehabilitation program . Patients with less education and a more manually-oriented working profile , did worse and had a higher tendency to seek medical pensioning , in spite of rehabilitative measures . As the total costs for out-patient rehabilitation only add up to 15.8 % of the total costs for in-patient rehabilitation , this study setting cautiously suggests that out-patient rehabilitation might be an acceptable alternative to individualized patient groups that might not compromise clinical and vocational outcome . Larger patient groups are needed , however , to confirm these findings The aim of this cost-effectiveness study was to compare a combined operant programme plus cognitive/relaxation programme with an operant programme plus attention-control and to compare both programmes with a waiting-list control group and with operant rehabilitation provided , as usual , by the same rehabilitation centre . One hundred and forty eight patients with chronic low back pain were r and omly assigned to the different conditions . The economic endpoints were the costs of the programme and other health care utilisation , costs for the patient , and indirect costs associated with production losses due to low back pain . The effects were measured in terms of global assessment of change and utilities , using rating scale and st and ard gamble methods . The 3-year study determined that adding a cognitive component to an operant treatment did not lead to significant differences in costs and improvement in quality of life when compared with the operant treatment alone . Compared with the common individual rehabilitation therapy it can be concluded that the same effects can be reached at the same or lower costs with a shorter , more intense st and ardised group programme . The operant treatment alone is more effective than providing no treatment in the waiting-list control group Objective : To compare hospital and home setting s for the rehabilitation of patients following hip fracture . Design : R and omized controlled trial comparing accelerated discharge and home-based rehabilitation ( n = 34 ) with conventional hospital care ( n = 32 ) for patients admitted to hospital with hip fracture . Setting : Three metropolitan hospitals in Adelaide , Australia . Subjects : Sixty-six patients with fractured hip . Interventions : Patients assigned to the home-based rehabilitation group were discharged within 48 hours of r and omization . The project team therapists made visits to the patient ’s home and negotiated a set of realistic , short-term and measurable treatment goals with both the patient and carer . Those r and omized to usual care remained in hospital for conventional rehabilitation . Main outcome measures : Physical and social dependence , balance con”dence , quality of life , carer strain , patient and carer satisfaction , use of community services and incidence of adverse events such as re-admission and falls . Results : While there was no difference between the groups for all measures of quality of life , patients in the accelerated discharge and home-based rehabilitation group recorded a greater improvement in MBI from r and omization ( p < 0.05 ) and scored higher on the Falls Ef”cacy Scale ( p < 0.05 ) at four months . There was no difference in falls rates . Patients in the home-based rehabilitation group had a shorter stay in hospital ( p < 0.05 ) but a longer stay in rehabilitation overall ( p < 0.001 ) . The groups were comparable on the rate and length of admissions after discharge , use of community services , need for carer input and contact with general practitioner ( GP ) after discharge Background : An early supported discharge service ( ESD ) appears to be a promising alternative to conventional care . The aim of this trial was to compare the use of health services and costs with traditional stroke care during a one-year follow-up . Methods : Three hundred and twenty patients were r and omly allocated either to ordinary stroke unit care or stroke unit care combined with ESD which was coordinated by a mobile team . The use of all health services was recorded prospect ively ; its costs were measured as service costs and represent a combination of calculated average costs and tariffs . Hospital expenses were measured as costs per inpatient day and adjusted for the DRG . Results : There was a reduction in average number of inpatient days at 52 weeks in favour of the ESD group ( p = 0.012 ) , and a non-significant reduction in total mean service costs in the ESD group ( EUR 18,937/EUR 21,824 ) . ESD service seems to be most cost-effective for patients with a moderate stroke . Conclusion : Acute stroke unit care combined with an ESD programme may reduce the length of institutional stay without increasing the costs of outpatient rehabilitation compared with traditional stroke care Study Design . A subgroup of 195 patients with chronic low back pain , being part of a larger study of other musculoskeletal patients , were included in a r and omized controlled prospect i ve clinical study . Objectives . To evaluate the outcome in terms of return to work and cost-effectiveness of a light multidisciplinary treatment program with an extensive multidisciplinary program and treatment as usual initiated by their general practitioner . Summary of Background Data . Light multidisciplinary programs seem to reduce sick leave in patients with subacute low back pain . There are few , if any , previous studies of the effectiveness of light versus extensive multidisciplinary treatment on return to work in patients with chronic low back pain . Methods . Patients with chronic low back pain ( n = 195 ) , on an average sick-listed for 3 months , were included . The patients were r and omized to a light multidisciplinary treatment program , an extensive multidisciplinary program , or treatment as usual by their primary physician . Full return to work was used as outcome response , and follow-up was 26 months after the end of treatment . Cost – benefit was calculated for the treatment programs . Results . In men significantly better results for full return to work were found for the light multidisciplinary treatment compared with treatment as usual , but no differences were found between extensive multidisciplinary treatment and treatment as usual . No significant differences between any of the two multidisciplinary treatment programs and the controls were found for women . Productivity gains for the society from light multidisciplinary treatment versus “ treatment as usual ” of 57 male patients with low back pain would during the first 2 years accumulate to U.S. $ 852.000 . Conclusions . The light multidisciplinary treatment model is a cost-effective treatment for men with chronic low back pain This study tested the effects of a project network technique called the Critical Path Method ( CPM ) on the costs and outcomes of inpatient team stroke rehabilitation . On admission to a large , academic , inpatient rehabilitation hospital adults who had a recent ( < 120 days ) stroke were r and omly assigned to receive rehabilitation services from a team trained in CPM ( N = 53 ) or from usual care teams ( N = 68 ) . Results showed no significant difference between groups in length of stay , hospital charges , or functional status at discharge . CPM may be effective in patient care services that are less influenced by specialization , professional issues , and external regulation and in setting s where patient outcomes are relatively fixed and predictable , and medical care is integrated across institutions CONTEXT Inpatient rehabilitation after elective hip and knee arthroplasty is often necessary for patients who can not function at home soon after surgery , but how soon after surgery inpatient rehabilitation can be initiated has not been studied . OBJECTIVE To test the hypothesis that high-risk patients undergoing elective hip and knee arthroplasty would incur less total cost and experience more rapid functional improvement if inpatient rehabilitation began on postoperative day 3 rather than day 7 , without adverse consequences to the patients . DESIGN R and omized controlled trial conducted from 1994 to 1996 . SETTING Tertiary care center . PARTICIPANTS A total of 86 patients undergoing elective hip or knee arthroplasty and who met the following criteria for being high risk : 70 years of age or older and living alone , 70 years of age or older with 2 or more comorbid conditions , or any age with 3 or more comorbid conditions . Of the 86 patients , 71 completed the study . INTERVENTIONS R and om assignment to begin inpatient rehabilitation on postoperative day 3 vs postoperative day 7 . MAIN OUTCOME MEASURES Total length of stay and cost from orthopedic and rehabilitation hospital admissions , functional performance in hospitals using a subset of the functional independence measure , and 4-month follow-up assessment using the R AND 36-item health survey I and the functional status index . RESULTS Patients who completed the study and began inpatient rehabilitation on postoperative day 3 exhibited shorter mean ( + /-SD ) total length of stay ( 11.7+/-2.3 days vs 14.5+/-1.9 , P<.001 ) , lower mean ( + /-SD ) total cost ( $ 25891+/-$3648 vs $ 27762+/-$3626 , P<.03 ) , more rapid attainment of short-term functional milestones between days 6 and 10 ( 36.2+/-14.4 m ambulated vs 21.4+/-13.3 m , P<.001 ; 4.8+/-0.8 mean transfer functional independence measure score vs 4.3+/-0.7 , P<.01 ) , and equivalent functional outcome at 4-month follow-up . CONCLUSION These data showed that high-risk individuals were able to tolerate early intensive rehabilitation , and this intervention yielded faster attainment of short-term functional milestones in fewer days using less total cost BACKGROUND R and omized trials have shown that integrating services for acute stroke care may lead to organizational improvements , higher efficiency and better patient outcomes in the acute phase . AIM To compare the costs and effects of stroke services in an experimental group of patients compared to a group of patients receiving conventional care . DESIGN Prospect i ve non-r and omized controlled trial . METHODS We compared all consecutively hospitalized stroke patients in three experimental stroke service setting s ( Delft , Haarlem and Nijmegen , n = 411 ) with concurrent patients receiving conventional stroke care ( n = 187 ) over 6 months follow-up . Main end-points were total costs per patient and total health-adjusted days per 100 patients as measured by the EuroQol-5D score during follow-up . RESULTS Mean total costs per patient were 16,000 Euro ( 95%CI 14,670 Euro-16,930 Euro ) : 13,160 Euro in Delft , 16,790 Euro in Haarlem , 20,230 Euro in Nijmegen , and 13,810 Euro in the control regions . Early discharge in Delft saved about 2500 Euro hospital costs per patient . General patient health in Delft was significantly better than in the control regions ; Haarlem and Nijmegen showed no difference in health . DISCUSSION Our study confirms the potential to improve stroke outcomes in a cost-effective way in Dutch setting s. This was seen in the group of patients in Delft , a complete and relatively simple stroke service , but not in two other regions with more complex stroke services . Important factors are reduction of hospital days and , most likely , adequate multidisciplinary rehabilitation Seventy-four patients presenting with a mixed pattern of urinary symptoms were r and omly allocated to undergo either inpatient or outpatient continence programs as initial treatment , without prior urodynamic investigation . Both programs consisted of physiotherapy , bladder retraining , fluid normalization , dietary advice and general support and advice . Nine out of 39 in the outpatient group and 8 out of the 35 of the impatient group failed to complete the study . There was a significant decrease in frequency , nocturia , number of incontinent episodes and visual analog scores for both groups . In addition the out patients had a significant reduction in loss on pad testing , and a significantly greater improvement in their visual analog score . In each group 63 % were cured or improved to the extent that they did not require further treatment . Staff costs per outpatient were half those for an inpatient . We conclude that outpatient conservative treatment as detailed above is a successful first-line treatment of urinary incontinence in women . It is as successful and possibly better than inpatient treatment , and is significantly cheaper OBJECTIVE To investigate improvement rates and medical services costs in older brain injured adults relative to younger patients . DESIGN Descriptive statistics were computed in a prospect i ve comparative study of 50 patients 55 years and older and 50 patients 18 to 54 years old matched for gender and injury severity ( number of days in coma , admission Glasgow Coma Score , intracranial pressure ) . Independent t tests were performed to examine differences between the two sample s on specific variables . SETTING Five medical centers in the federally sponsored Traumatic Brain Injury Model Systems Project that provide emergency medical services , intensive and acute medical care , inpatient rehabilitation , and a spectrum of community rehabilitation services . PARTICIPANTS Patients were selected from a national data base of 531 rehabilitation in patients admitted to acute care within 8 hours of traumatic brain injury between 1989 and 1994 . MAIN OUTCOME MEASURES Disability Rating Scale , Functional Independence Measure , Rancho Los Amigos Levels of Cognitive Functioning Scale , length of stay , acute care and rehabilitation charges , and discharge disposition . RESULTS Older persons averaged a significantly longer rehabilitation length of stay , higher total rehabilitation charges , and a lower rate of change on functional measures . No significant differences between groups were found for acute care length of stay , daily rehabilitation charges , acute care charges ( daily or total ) , or discharge disposition . CONCLUSIONS Although older persons demonstrated functional changes , the cost of change was substantially higher than for younger patients , coincident with longer lengths of stay . These higher overall charges and slower rates of change may effect changes in referral and management patterns OBJECTIVES To compare outcomes between stroke patients managed on the stroke unit , on general wards with stroke team support or at home by specialist domiciliary team and to derive prognostic variables that will identify patients most suitable for management by each strategy . To describe organisational aspects of individual strategies of stroke care and to evaluate cost-effectiveness of each strategy and its acceptability to patients , carers and professionals . DESIGN Prospect i ve single-blind r and omised controlled trial undertaken in patients recruited from a community-based stroke register . SETTING Suburban district in south-east Engl and . PARTICIPANTS Patients with disabling stroke who could be supported at home . INTERVENTIONS The stroke unit gave 24-hour care provided by specialist multidisciplinary team based on clear guidelines for acute care , prevention of complications , rehabilitation and secondary prevention . The stroke team provided management on general wards with specialist team support . The team undertook stroke assessment s and advised ward-based nursing and therapy staff on acute care , secondary prevention and rehabilitation aspects . Domiciliary care involved management at home under the supervision of a GP and stroke specialist with support from specialist team and community services . Support was provided for a maximum of 3 months . MAIN OUTCOME MEASURES The primary measure was death or institutionalisation at 1 year . Secondary measures were dependence , functional abilities , mood , quality of life , re source use , length of hospital stay , and patient , carer and professional satisfaction . RESULTS Of the 457 patients r and omised , 152 patients were allocated to the stroke unit ; 152 patients to stroke team and 153 patients to domiciliary stroke care ( average age 76 years , 48 % women ) . The groups were well matched for baseline characteristics , stroke type and severity , level of impairment and initial disability . Fifty-one ( 34 % ) patients in the domiciliary group were admitted to hospital after r and omisation . Mortality and institutionalisation at 1 year were lower on stroke unit compared with stroke team or domiciliary care . Significantly fewer patients on the stroke unit died compared with those managed by the stroke team . The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team or domiciliary care . These differences were present at 3 and 6 months after stroke . Stroke survivors managed on the stroke unit showed greater improvement on basic activities of daily living compared with other strategies . Achievement of higher levels of function was not influenced by strategy of care . Quality of life at 3 months was significantly better in stroke unit and domiciliary care patients . There was greater dissatisfaction with care on general wards compared with stroke unit or domiciliary care . Poor outcome with domiciliary care and on general wards was associated with Barthel Index < 5 , incontinence and , on general wards , age over 75 years . The total costs of stroke per patient over the 12-month period were pound 11,450 for stroke unit , pound 9527 for stroke team and pound 6840 for home care . However , the mean costs per day alive for the stroke unit were significantly less than those for the specialist stroke team patients , but no different from domiciliary care patients . Costs for the domiciliary group were significantly less than for those managed by the specialist stroke team on general wards . CONCLUSIONS Stroke units were found to be more effective than a specialist stroke team or specialist domiciliary care in reducing mortality , institutionalisation and dependence after stroke . A role for specialist domiciliary services for acute stroke is not supported by this study . Management of patients with strokes on general medical wards , even with specialist team input , is not supported by this study . The stroke unit intervention was less costly per patient day alive and more effective than the stroke team intervention . The stroke unit was more effective and of equivalent cost when compared to home care . Hence , the stroke unit is a more cost-effective intervention than either stroke team or home care . Further research is needed to underst and processes contributing to the reduction in mortality on stroke units and to determine the generalisability of these results and the factors that will influence the implementation of the findings of this study in clinical practice Clinical trials have demonstrated the superiority of coordinated interdisciplinary stroke unit care over conventional treatment of stroke patients on general medical wards . The evidence is so strong that several national bodies have recommended that stroke unit care be widely implemented . Translation of these research findings and care guidelines into clinical practice , however , represents a challenge for health care systems unaccustomed to managing stroke in a coordinated manner . This report describes the organization , operation and outcomes of the Acute Stroke Unit at the Queen Elizabeth II Health Sciences Centre in Halifax . By replicating and adapting the core characteristics identified in the r and omized trials , we have been able to demonstrate the effectiveness of stroke unit care in a routine clinical setting . Our experience may help facilitate the development of organized stroke care in Canada BACKGROUND Over the past 20 years , both inpatient units and outpatient clinics have developed programs for geriatric evaluation and management . However , the effects of these interventions on survival and functional status remain uncertain . METHODS We conducted a r and omized trial involving frail patients 65 years of age or older who were hospitalized at 11 Veterans Affairs medical centers . After their condition had been stabilized , patients were r and omly assigned , according to a two-by-two factorial design , to receive either care in an inpatient geriatric unit or usual inpatient care , followed by either care at an outpatient geriatric clinic or usual outpatient care . The interventions involved teams that provided geriatric assessment and management according to Veterans Affairs st and ards and published guidelines . The primary outcomes were survival and health-related quality of life , measured with the use of the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) , one year after r and omization . Secondary outcomes were the ability to perform activities of daily living , physical performance , utilization of health services , and costs . RESULTS A total of 1388 patients were enrolled and followed . Neither the inpatient nor the outpatient intervention had a significant effect on mortality ( 21 percent at one year overall ) , nor were there any synergistic effects between the two interventions . At discharge , patients assigned to the inpatient geriatric units had significantly greater improvements in the scores for four of the eight SF-36 subscales , activities of daily living , and physical performance than did those assigned to usual inpatient care . At one year , patients assigned to the outpatient geriatric clinics had better scores on the SF-36 mental health subscale , even after adjustment for the score at discharge , than those assigned to usual outpatient care . Total costs at one year were similar for the intervention and usual-care groups . CONCLUSIONS In this controlled trial , care provided in inpatient geriatric units and outpatient geriatric clinics had no significant effects on survival . There were significant reductions in functional decline with inpatient geriatric evaluation and management and improvements in mental health with outpatient geriatric evaluation and management , with no increase in costs We r and omly assigned frail elderly in patients with a high probability of nursing-home placement to an innovative geriatric evaluation unit intended to provide improved diagnostic assessment , therapy , rehabilitation , and placement . Patients r and omly assigned to the experimental ( n = 63 ) and control ( n = 60 ) groups were equivalent at entry . At one year , patients who had been assigned to the geriatric unit had much lower mortality than controls ( 23.8 vs. 48.3 per cent , P less than 0.005 ) and were less likely to have initially been discharged to a nursing home ( 12.7 vs. 30.0 per cent , P less than 0.05 ) or to have spent any time in nursing home during the follow-up period ( 26.9 vs. 46.7 per cent , P less than 0.05 ) . The control-group patients had substantially more acute-care hospital days , nursing-home days , and acute-care hospital readmissions . Patients in the geriatric unit were significantly more likely to have improvement in functional status and morale than controls ( P less than 0.05 ) . Direct costs for institutional care were lower for the experimental group , especially after adjustment for survival . We conclude that geriatric evaluation units can provide substantial benefits at minimal cost for appropriate groups of elderly patients , over and above the benefits of traditional hospital approaches Public opinion has become one of the primary inputs in setting priorities , rationing and allocating health re sources . The present study focuses on the priorities of the Israeli public aged 45 - 75 in allocating scarce medical re sources between prolonging survival ( the ' Rule of Rescue ' ) and preventing a severe and permanent disability ( quality of life ) . The findings indicate that the ' Rule of Rescue ' is dominant for more than a quarter of the population even when death is postponed by only one month . More than a tenth of the population are ready to adopt prioritization by lottery . Economic condition , gender and health status have no effect on priority choices . The main determinants of the choices are age and religiosity , with older individuals more likely to choose r and om prioritization and religious people tending to prefer saving life even when the opportunity costs are high OBJECTIVE --Comparison of day hospital attendance and home physiotherapy for stroke patients leaving hospital to determine which service produces greater functional and social improvement for the patient , reduces emotional stress for the care giver , and lessens the need for community support . DESIGN --Stratified , r and omised trial of stroke patients attending day hospital two days a week or receiving home treatment from a community physiotherapist . The six month assessment results are reported in this paper . SUBJECTS-- Patients over 60 years old resident within the Bradford metropolitan district discharged home after a new stroke with residual disability . SETTING --Four day hospitals in two health authorities and domiciliary work undertaken by experienced community physiotherapists . MAIN OUTCOME MEASURES --Barthel index , functional ambulatory categories , Motor Club assessment , Frenchay activities index , and Nottingham health profile were used . Carers ' stress was indicated by the general health question naire . Treatment given and community care provided were recorded . RESULTS --Of 124 patients recruited , 108 were available for re assessment at six months . Both treatment groups had significantly improved in functional abilities between discharge and six months . The improvements were significantly greater for patients treated at home ( Mann-Whitney test ; Barthel index , median difference 2 ( 95 % confidence interval 0 to 3 ) p = 0.01 ; Motor Club assessment , median difference 2 ( 1 to 5 ) , p = 0.01 ) . The home treated patients received less treatment ( median difference 16 ( 11 to 21 ) treatments , p less than 0.001 ) . More than a third of patients in both groups showed depressed mood , and a quarter of care givers were emotionally distressed . CONCLUSIONS --Home physiotherapy seems to be slightly more effective and more re source efficient than day hospital attendance and should be the preferred rehabilitation method for aftercare of stroke patients . New strategies are needed to address psychosocial function for both patients and care givers Recently , Christensen et al. reported the clinical effects of a low-cost rehabilitation program equally efficient to a relatively intensive program of individual , physiotherapist-guided exercise therapy . Yet , the low-cost approach is not fully supported as an optimal strategy until a full-scale economic evaluation , including extra-hospital effects such as service utilization in the primary health care sector and return-to-work , is conducted . The objective of this study was to conduct such evalution i.e. investigate the cost-effectiveness of ( 1 ) a low-cost rehabilitation regimen with a behavioural element and ( 2 ) a regimen of individual exercise therapy , both in comparison with usual practice , from a health economic , societal perspective . Study design was a cost-effectiveness evaluation of an RCT with a 2-year follow-up . Ninety patients having had posterolateral or circumferential fusion ( indicated by chronic low back pain and localized pathology ) were r and omized 3 months after their spinal fusion . Vali date d pain- and disability index scales were applied at baseline and at 2 years postoperative . Costs were measured in a full-scale societal perspective . The probability of the behavioural approach being cost-effective was close to 1 given pain as the prioritized effect measure , and 0.8 to 0.6 ( dependent on willingness to pay per effect unit ) given disability as the prioritized effect measure . The probability of the exercise therapy approach being cost-effective was modest due to inferior effectiveness . Results proved robust to relevant sensitivity analysis although a differentiated cost-effectiveness ratio between males and females was suspected . In conclusion , a simple behavioural extension , of setting up group meetings for patients , to a regimen with a strict physiotherapeutic focus was found cost-effective , whereas the cost-effectiveness of increasing frequency and guidance of a traditional physiotherapeutic regimen was unlikely in present trial setting Background : We conducted a prospect i ve study to assess the costs of initial hospitalization for a first hip fracture and to evaluate the excess costs attributable to the hip fracture during the one-year period following hospital discharge . Methods : This investigation was design ed as a one-year prospect i ve cohort study with matched-pair analysis . Elderly women who were receiving care for a first hip fracture at four Belgian hospitals were matched , with respect to age and residence , with women ( control subjects ) with no history of hip fracture who lived in the same neighborhood . The initial hospitalization costs were tabulated from the hospital invoices . To estimate the costs during the year after hospital discharge , health-care services utilized by the hip-fracture patients and by the control subjects were recorded . We used the official reimbursement rates to assign a cost to these services , and the results are reported in United States dollars . Results : The mean age of the 159 patients who had a hip fracture was 79.3 years , and that of the 159 control subjects was 78.7 years . The total mean cost of the initial hospitalization was $ 9534 for the hip-fracture patients . The total direct costs during the year after discharge averaged $ 13,470 for the hip-fracture patients and $ 6170 for the control subjects . Thus , the excess direct cost during the one-year period following hospital discharge averaged $ 7300 for the hip-fracture patients . The largest cost differences were attributable to nursing-home stays ( 31 % ) , rehabilitation-center stays ( 31 % ) , hospitalizations ( 16 % ) , and home physical-therapy services ( 14 % ) . Two-fifths of the excess costs were spent during the three months following hospital discharge . Moreover , we observed a shift in re source utilization after hospital discharge . Conclusions : Our one-year prospect i ve study demonstrated that the costs of treating a hip-fracture patient are about three times greater than those of caring for a patient without a fracture . This study also highlights the savings to society if a hip fracture can be avoided BACKGROUND Stroke unit is the most effective treatment method to benefit stroke patients . Our study is to evaluate the early effectiveness of a hospital stroke unit ( SU ) . METHODS Three hundred and ninety-two patients who had suffered from acute strokes and who were admitted to our hospital between December 2001 and January 2003 were recruited for this controlled study . All patients were sent at r and om to either the SU or the general ward ( GW ) for treatment . The following indices were measured by : Barthel Index ( BI ) , National Institute of Health Stroke Scale ( NIHSS ) , Oxford H and icap Scale ( OHS ) . RESULTS The mean change in BI score between the day of admission and the day of discharge was 20.00 + /- 24.36 for the SU group and 10.63 + /- 23.59 for the GW group . A difference that is statistically significant ( P = 0.000 ) . The mean change in NIHSS score was -2.01 + /- 6.61 for the SU group and 0.55 + /- 7.44 for the GW group . A difference that is also statistically significant ( P = 0.000 ) . Finally , the mean change in OHS score was -0.74 + /- 1.04 for the SU group and -0.28 + /- 0.98 for the GW group , also a statistically significant difference ( P = 0.000 ) . Among SU patients , patient satisfaction was higher ( P = 0.000 ) , the rehabilitation success rate was higher ( P = 0.000 ) , and there were fewer complications ( P = 0.000 ) . CONCLUSION Compared to GW patients , stroke patients treated in a special SU were able to return to normal daily activities earlier , with better social abilities , and have reduced neurological defects , without increasing the overall economic burden BACKGROUND Chronic knee pain is a major cause of disability in the elderly . Management guidelines recommend exercise and self-management interventions as effective treatments . The authors previously described a rehabilitation programme integrating exercise and self-management [ Enabling Self-management and Coping with Arthritic knee Pain through Exercise ( ESCAPE-knee pain ) ] that produced short-term improvements in pain and physical function , but sustaining these improvements is difficult . Moreover , the programme is untried in clinical environments , where it would ultimately be delivered . OBJECTIVES To establish the feasibility of ESCAPE-knee pain and compare its clinical effectiveness and costs with outpatient physiotherapy . DESIGN Pragmatic , r and omised controlled trial . SETTING Outpatient physiotherapy department and community centre . PARTICIPANTS Sixty-four people with chronic knee pain . INTERVENTIONS Outpatient physiotherapy compared with ESCAPE-knee pain . OUTCOMES The primary outcome was physical function assessed using the Western Ontario and McMaster Universities Osteoarthritis Index . Secondary outcomes included pain , objective functional performance , anxiety , depression , exercise-related health beliefs and healthcare utilisation . All outcomes were assessed at baseline and 12 months after completing the interventions ( primary endpoint ) . ANCOVA investigated between-group differences . RESULTS Both groups demonstrated similar improvements in clinical outcomes . Outpatient physiotherapy cost pound 130 per person and the healthcare utilisation costs of participants over 1 year were pound 583 . The ESCAPE-knee pain programme cost pound 64 per person and the healthcare utilisation costs of participants over 1 year were pound 320 . CONCLUSIONS ESCAPE-knee pain can be delivered as a community-based integrated rehabilitation programme for people with chronic knee pain . Both ESCAPE-knee pain and outpatient physiotherapy produced sustained physical and psychosocial benefits , but ESCAPE-knee pain cost less and was more cost-effective OBJECTIVE To assess whether outcomes and costs differ for elderly patients admitted to rehabilitation hospitals , subacute nursing homes , and traditional nursing homes . DESIGN Inception cohort stratified by provider type and followed prospect ively for 6 months . SETTING A total of 92 hospital-based units and freest and ing facilities from 17 states . PATIENTS A total of 518 r and omly selected patients with hip fracture and 485 stroke patients admitted from November 1991 to February 1994 . MAIN OUTCOME MEASURES At 6 months comparing community residence , recovery to premorbid levels in 5 activities of daily living ( ADLs ) , Medicare costs , and the number of therapy and physician visits . Outcomes were adjusted for premorbid residence and function , caregiver availability , comorbid illness , admission function , cognition , depression , sensory deficits , and mobility impairments . RESULTS On admission , rehabilitation hospital patients were more likely ( P<.001 ) to have caregivers and better cognitive and physical function . Hip fracture patients admitted to rehabilitation hospitals did not differ from patients admitted to nursing homes in returning to the community ( adjusted odds ratio [ OR ] , 1.3 ; 95 % confidence interval [ CI ] , 0.6 - 2.6 ) or in the number of ADLs recovered to premorbid level ( difference , 0.09 ADL ; 95 % CI , -0.27 - 0.44 ) , but stroke patients admitted to rehabilitation hospitals were more likely to return to the community ( adjusted OR , 3.3 ; 95 % CI , 1.5 - 7.2 ) and recover ADLs ( difference , 0.63 ADL ; 95 % CI , 0.20 - 1.07 ) . Subacute nursing home patients with stroke were more likely than traditional nursing home patients to return to the community ( adjusted OR , 6.8 ; 95 % CI , 2.2 - 21.4 ) , there was no difference in return to the community for patients with hip fracture ( adjusted OR , 1.6 ; 95 % CI , 0.7 - 3.6 ) , and there were no differences in recovery of ADLs for either condition . Medicare costs were greater ( P<.001 ) for rehabilitation hospital patients than for subacute nursing home patients , and the costs for subacute nursing home patients were greater ( P=.03 for stroke and .009 for hip fracture ) than for traditional nursing home patients . CONCLUSIONS Study findings are consistent with enhanced outcomes for elderly patients with stroke treated in rehabilitation hospitals but not for patients with hip fracture . Subacute nursing homes were more effective than traditional nursing homes in returning patients with stroke to the community , despite comparable functional outcomes We determined the effect of geriatric rehabilitation of hip fracture patients on mortality , length of hospital stay , and functional recovery . In a r and omized , controlled intervention study , 243 community dwelling hip fracture patients over 64 years of age were r and omly assigned to 2 rehabilitation groups . The intervention group ( n = 120 ) was referred to a geriatric ward for team rehabilitation , and the controls ( n = 123 ) to local hospital wards for st and ard care . The median length of total hospital stay after a hip fracture operation was 34 ( 95 % CI 28 - 38 ) days in the intervention group and 42 ( 95 % CI 35 - 48 ) days in the control group ( p = 0.05 ) . The intervention group recovered instrumental activities of daily living faster ( p = 0.05 ) . Direct costs of medical care during the first year did not differ remarkably This article presents the final results of a project comparing the economic effects of outpatient and inpatient rehabilitation in Mecklenburg-Vorpommern . The data analysed have been derived from the total population of applicants for orthopaedic-traumatologic rehabilitation who are suitable for outpatient rehabilitation in all criteria . The r and omized and controlled study at first verified whether the outcome parameters of the two variants of rehabilitation are approximately equal . If this condition is fulfilled the differences between amounts and periods of payments and costs incumbent on the pension insurance agency are analyzed . And in fact , the final results confirm that , in suitable patients , outpatient rehabilitation can achieve approximately the same outcomes as inpatient rehabilitation -- but at distinctly lower cost Women with active rheumatoid arthritis who were judged to be in need of hospitalization were assigned at r and om to receive inpatient therapy ( n = 35 ) or intensive outpatient therapy ( n = 36 ) . All relevant costs of treatment were measured . At 19 weeks , clinical outcomes , as summarized in a pooled index , were significantly better in the inpatient group ( pooled index units : inpatient 0.72 , outpatient 0.25 ; F[1,69 ] = 10.9 , P = 0.002 ) . Inpatient therapy produced a sustained three-fold increase in efficacy , at a 2.5-fold increase in cost to society OBJECTIVES to compare the cost effectiveness of post-acute care for older people provided in community hospitals with general hospital care . DESIGN cost-effectiveness study embedded within a r and omised controlled trial . SETTING seven community hospitals and five general hospitals at five centres in the midl and s and north of Engl and . PARTICIPANTS 490 patients needing rehabilitation following hospital admission with an acute illness . INTERVENTION multidisciplinary team care for older people in community hospitals . MEASUREMENTS EuroQol EQ-5D scores transformed into quality -adjusted life years ; health and social service costs during the 6-month period following r and omisation . RESULTS there was a non-significant difference between the community hospital and general hospital groups for changes in quality -adjusted life-year values from baseline to 6 months ( mean difference 0.048 ; 95 % confidence interval -0.028 to 0.123 ; P = 0.214 ) . Re source use was similar for both groups . The mean ( st and ard deviation ) costs per patient for health and social services re sources used were comparable for both groups : community hospital group 8,946 pounds ( 6,514 pounds ) ; general hospital group 8,226 pounds ( 7,453 pounds ) . These findings were robust to sensitivity analyses . The incremental cost-effectiveness ratio estimate was 16,324 pounds per quality -adjusted life year . A cost effectiveness acceptability curve suggests that if decision makers ' willingness to pay per quality -adjusted life year was 10,000 pounds , then community hospital care was effective in 47 % of cases , and this increased to only 50 % if the threshold willingness to pay was raised to 30,000 pounds . CONCLUSIONS the cost effectiveness of post-acute rehabilitation for older people was similar in community hospitals and general hospitals |
10,876 | 18,620,740 | The incidence of DVT in patients undergoing elective TKA appears to have declined in patients receiving warfarin thromboprophylaxis | BACKGROUND There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis ( DVT ) has decreased in patients undergoing total knee arthroplasty ( TKA ) or total hip arthroplasty ( THA ) .
OBJECTIVES To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA . | BACKGROUND Warfarin , which requires coagulation monitoring , is associated with relatively high rates of thromboembolism despite providing adequate prophylaxis . This study compared an oral direct thrombin inhibitor , ximelagatran , with warfarin in order to evaluate the safety and efficacy of the medication for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty . METHODS Following surgery , patients were r and omly assigned to fixed-dose oral ximelagatran ( 36 mg twice daily ) or warfarin ( target international normalized ratio , 2.5 ) , both administered for seven to twelve days in a double-blind , double-dummy design . Warfarin was initiated on the evening of the day of surgery , and ximelagatran , on the morning after surgery . The primary efficacy end point was the incidence of asymptomatic deep-vein thrombosis determined by bilateral venography , objective ly confirmed symptomatic deep-vein thrombosis or pulmonary embolism , and death from all causes during treatment . RESULTS Adequate venograms or confirmed symptomatic events ( efficacy population ) were obtained for 1949 patients . Venous thromboembolism and death from all causes occurred in 22.5 % ( 221 ) of 982 ximelagatran-treated patients and in 31.9 % ( 308 ) of 967 warfarin-treated patients ( p < 0.001 ) . Proximal deep-vein thrombosis and pulmonary embolism were observed in 3.1 % ( thirty ) and 0.2 % , respectively , of the patients in the ximelagatran group and in 3.4 % ( thirty-three ) and 0.4 % , respectively , of the patients in the warfarin group . The six deaths from all causes included 0.3 % ( four ) of the ximelagatran-treated patients and 0.2 % ( two ) of the warfarin-treated patients . Major bleeding was noted in 1 % ( twelve ) of the ximelagatran-treated patients and in 0.4 % ( five ) of the warfarin-treated patients ( p = 0.09 ) . CONCLUSIONS Oral ximelagatran ( 36 mg twice daily ) , administered without coagulation monitoring or dose adjustment and started the day after total knee arthroplasty , demonstrates superior efficacy compared with warfarin prophylaxis , with no wound complications and no significant difference with respect to bleeding events , although the rate of major bleeding events was greater with ximelagatran than with warfarin . LEVEL OF EVIDENCE Therapeutic Level One hundred forty-nine consecutive patients requiring lower extremity total joint arthroplasty were r and omized to either coumadin ( 52 patients ) or intermittent pneumatic compression ( 48 patients ) as prophylaxis against deep vein thrombosis ( DVT ) . Forty-nine patients were excluded . When fully ambulatory , the presence or absence of DVT was diagnosed by ascending venography ( 90 % of patients ) , nuclear venography , venous dopplers , or impedence plethysmography . The two groups were similar in average age ( 64 years ) , indication for arthroplasty ( pain because of arthritis in 90 % ) , gender ( 98 % male ) , and average number of risk factors ( 2.4 ) . Twenty-five percent of patients on coumadin and 25 % of patients on intermittent pneumatic compression ( IPC ) developed DVT . IPC was more effective than coumadin following primary total hip arthroplasties ( THAs ) ( 16 % versus 24 % incidence DVT ) ; coumadin was more effective than IPC following primary total knee arthroplasties ( TKAs ) ( 19 % versus 32 % incidence of DVT ) . DVT developed in 36 % of patients following revision arthroplasty . Seventy-five percent of all thrombi were proximal . Both IPC and coumadin were found to be safe ; there was no increased perioperative bleeding in the coumadin group . Of three postoperative deaths , one was possibly due to pulmonary embolism ( PE ) The effect of the pneumatic tourniquet on the incidence of postoperative deep venous thrombosis is uncertain . We carried out a controlled study comparing the incidence of deep venous thrombosis when a tourniquet was used with the incidence when a tourniquet was not used . Thrombosis was detected by radioisotope venography . The results of the study showed no difference in incidence and we concluded that the pneumatic tourniquet has no influence on the formation of a thrombus in a deep vein In a r and omized , prospect i ve trial of 100 patients , we have studied the safety and efficacy of warfarin sodium in comparison with that of dextran 40 in the prevention of venous thrombosis in patients at high risk for deep vein thrombosis after elective total hip or knee replacement . Warfarin was given in a new two-step regimen design ed to avoid bleeding complications while still preventing venous thrombosis . A low dose of warfarin was started ten to 14 days preoperatively , and the prothrombin time was regulated to between 1.5 and 3 seconds longer than control at the time of surgery ; immediately after surgery , the dose was increased to prolong the prothrombin time to 1.5 times control . The overall incidence of venous thrombosis as documented by venography was less in the 53 patients treated with warfarin than in the 37 treated with dextran ( 21 % v 51 % ) , as was the incidence of thrombi in the femoral or popliteal veins ( 2 % v 16 % ) . Objective measures of blood loss showed no difference between patients treated with warfarin or dextran , and excessive postoperative bleeding was infrequent and similar in both treatment groups . This study demonstrates that two-step warfarin therapy provides highly effective prophylaxis of postoperative venous thrombosis after elective hip or knee prosthetic surgery without excessive risk of perioperative bleeding The authors undertook a r and omised prospect i ve study to investigate the contribution of thigh tourniquets to the formation of intra-operative venous emboli during lower limb surgery . Patients were r and omised to have a thigh tourniquet or no tourniquet and transoesophageal echocardiography was used to detect embolic signals in the right heart during and after knee arthroscopy . Three physicians blinded to patient demographics and tourniquet status separately assessed videotapes of the echocardiograms for evidence of emboli . Of the 32 patients r and omised , 18 underwent knee arthroscopy with and 14 without tourniquet . Emboli were seen in 72 % ( 95 % CI 55 to 84 ) of patients , in 14 patients with tourniquet and in 9 patients without tourniquet . There was an estimated 13 % greater incidence of emboli in the tourniquet group compared to the non-tourniquet group , a difference which was not statistically significant ( Fisher 's Exact Test , p = 0.45 ) . No patients suffered symptoms or signs attributable to a pulmonary embolus We assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan ( Org 10172 ) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a r and omized , placebo-controlled , double-blind trial in 197 consecutive patients . The heparinoid ( 750 anti-factor Xa-units , s.c . , b.i.d . ) was administered to 97 patients and 99 patients received placebo . Study medication was started preoperatively and continued for 10 days . Efficacy was assessed by bilateral phlebography at day 10 , postoperatively . The incidence of deep-vein thrombosis was 56.6 % and 15.5 % respectively in the placebo and heparinoid treated patients ( incidence reduction : 74 % ; P less than 0.001 ) . This reduction was observed both for proximal-vein thrombosis ( 25 % to 8 % ; P less than 0.005 ) and isolated calf-vein thrombosis ( 31 % to 7 % ; P less than 0.001 ) . No major hemorrhage was observed . The number of red-cell units transfused and drain-fluid loss were comparable for the two study groups . Six patients in the heparinoid group and none in the control group developed minor wound hematomas ( P less than 0.05 ) . During an 8-week post-discharge follow-up period three patients with a normal venogram at day 10 developed clinical ly apparent venous thromboembolism , which was confirmed by objective testing . All three patients belonged to the heparinoid-treated group . We conclude that 750 anti-factor Xa units Org 10172 s.c . twice daily starting preoperatively is safe and effectively reduces early deep-vein thrombosis following elective total hip replacement . Further studies on the incidence of post-discharge thromboembolism are required The scientific community 's quest for unbiased research received a strong boost from a recent policy amendment on r and omised controlled trials ( RCTs ) in this journal . Henceforth , the status of allocation concealment will be clearly indicated in the abstract s along with that of blinding . Thus , readers will have additional information by which to judge the internal validity of trials . In this editorial I address the background and rationale for these enhancements . R and om allocation to intervention groups remains the only method of ensuring that the groups being compared are on an equivalent footing at the outset of the study , thus eliminating selection and confounding biases . This has allowed RCTs to play a key part in advancing medical science . The success of r and omisation depends on 2 interrelated processes.1 , 2 The first entails generating a sequence by which the participants in a trial are allocated to intervention groups . To ensure unpredictability of that allocation sequence , investigators should generate it by a r and om process . The second process , allocation concealment , shields those involved in a trial from knowing upcoming assignments in advance.3 , 4 Without this protection , investigators and patients have been known to change who gets the next assignment , making the comparison groups less equivalent.5 , 6 For example , suppose that an investigator creates an adequate allocation sequence using a r and om number table . However , the investigator then affixes the list of that sequence to a bulletin board , with no allocation concealment . Those responsible for admitting participants could ascertain the upcoming treatment allocations and then route participants with better prognoses to the experimental group and those with poorer prognoses to the control group , or vice versa . Bias would result . Inadequate allocation concealment also Tourniquet time and its relationship to blood loss and deep vein thrombosis were studied in 80 cases of unilateral total knee arthroplasty . These data were part of a prospect i ve multicenter double-blind study on thromboprophylaxis for knee surgery . This study reports on the cases done at one institution in which the tourniquet was used in three different ways : group 1 , no tourniquet use ; group 2 , limited tourniquet use for cementing time only ; group 3 , tourniquet use throughout the whole case . Blood loss was significantly related to tourniquet time ( P = .0001 ) . The incidence of deep vein thrombosis was not related to the tourniquet group ( P = .9 ) We performed a prospect i ve r and omized clinical study to determine whether use of a thigh tourniquet influences the incidence of deep venous thrombosis . The lower limbs of patients who were scheduled for elective surgery on the fore part of the foot were r and omized and assigned to one of three treatment categories : Group I , no tourniquet ; Group II , exsanguination by an Esmarch b and age before tourniquet application ; and Group III , exsanguination by elevation of the extremity prior to application of a tourniquet . The 117 limbs of seventy-one patients included in this study were evaluated preoperatively and twenty-four and seventy-two hours postoperatively with 125I-labeled fibrinogen , and preoperatively and seventy-two hours postoperatively with Doppler ultrasound studies and phleborheography . The findings in all of the Doppler ultrasound studies and all of the phleborheograms were normal . Two of the 125I-fibrinogen studies were positive , but subsequent contrast venography revealed that these were false-positive findings . We therefore concluded that the use of a thigh tourniquet does not increase the risk of deep venous thrombosis in patients who have had an operation on the fore part of the foot The effects of using a tourniquet during total knee arthroplasty were studied in 80 patients r and omly allocated to two groups , either with or without a tourniquet . The groups were similar in mean age , gender , preoperative knee score and radiographic grading and the patients were all operated on by the same surgeon using one type of prosthesis . There was no significant difference between the two groups in operating time or total blood loss but postoperative pain was less in the patients in whom a tourniquet had not been used . They achieved straight-leg raising and knee flexion earlier and had fewer superficial wound infections and deep-vein thromboses . Total knee arthroplasty can be safely performed without the use of the tourniquet with the benefit that several adverse effects associated with its use can be avoided OBJECTIVE To compare efficacy , safety , and feasibility of adjusted-dose oral anticoagulants ( OAC ) versus fixed-dose subcutaneous low molecular weight heparin ( LMWH ) for the prevention of deep venous thrombosis ( DVT ) in patients who have undergone elective hip or knee replacement . DESIGN Multicentre , single blind r and omised trial . OAC ( acenocoumarol , target International Normalised Ratio , 2.0 - 3.0 ) and LMWH ( nadroparine , 60 aXa IU/kg once daily ) were started preoperatively and continued for 10 days . All outcome measures were adjudicated by an independent committee unaware of treatment allocation . SUBJECTS 672 consecutive patients scheduled for elective hip or knee replacement surgery . All patients wore bilateral graduated compression stockings . MAIN OUTCOME MEASURES The endpoint for the assessment of efficacy was venography confirmed DVT or confirmed symptomatic pulmonary embolism . The endpoint for the assessment of safety was clinical ly important bleeding during study treatment or within 48 h of the end of treatment . RESULTS Among the 517 patients with interpretable venograms , 391 had a hip replacement and 126 had a knee implant . DVT was demonstrated in 50 ( 20 % ) of 257 patients allocated to OAC and 43 ( 17 % ) of 260 patients allocated to nadroparine ( p = 0.45 ) , for an absolute difference in DVT incidence of 2.9 % in favour of nadroparine ( 95 % CI , -3.7 - 9.5 ) . Clinical ly important bleeding occurred in eight ( 2.3 % ) of the 342 oral anticoagulant treated patients and in five ( 1.5 % ) of the 330 nadroparine treated patients ( p = 0.62 ) , for an absolute difference in favour of nadroparine of 0.8 % ( 95 % Cl , -1.3 - 2.9 ) . CONCLUSION Patients who undergo major orthopaedic operations have a high risk of venous thromboembolism . Once daily fixed-dose subcutaneous nadroparine is at least as efficacious and safe as daily adjusted OAC for prophylaxis against DVT after hip or knee implantation but is more simple to administer This study compares the benefits of aspirin and warfarin prophylactic agents for patients with thromboembolic disease after total joint arthroplasty . It is a prospect i ve r and omized study of 388 patients having total hip or total knee surgery . All consecutive patients having total hip or total knee surgery were entered into this study and evaluated with preoperative and postoperative ventilation perfusion scans and a postoperative venogram . The aspirin and warfarin treatment groups were compared by size and location of venographically revealed clots and changes in ventilation perfusion scans . The results showed that there was no difference in the size or location of deep venous thrombosis in the aspirin or warfarin treatment groups . The venogram was negative in 44.5 % of patients ; 28.8 % had small calf clots , 16 % had large calf clots , 3.9 % had popliteal clots , and 6.7 % had femoral clots . Patients with total knee replacement had a 2.6 times greater incidence of calf deep venous thrombosis than patients with total hip replacement . There was no difference between the aspirin and warfarin groups in the incidence of changes in ventilation perfusion scans ( 18.9 % ) . There was no difference between the 2 groups in bleeding complications . The results suggest that aspirin and warfarin are equivalent in prophylaxis against thromboembolic disease , as determined by prevention of venographic changes or changes in ventilation perfusion scans There is experimental evidence that low-molecular-weight fractions of heparin are as effective as the st and ard form but cause less bleeding . We therefore performed a double-blind , r and omized trial comparing PK10169 low-molecular-weight heparin with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery . Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days . Fifty patients in each treatment group underwent surveillance with [125I]fibrinogen leg scanning and impedance plethysmography . In the first 24 patients , venography was performed only if either surveillance test was positive . Because the rate of venous thrombosis detected in those patients was unexpectedly low , venography was requested in the remaining 76 patients , even if the screening tests were negative . In this latter group , venous thrombosis occurred in 4 patients ( 10.8 percent ) given PK10169 heparin and 20 patients ( 51.3 percent ) given placebo ( P = 0.0002 ) ; the corresponding rates for proximal-vein thrombosis were 5.4 percent and 23.1 percent , respectively ( P = 0.029 ) . In the entire group of 100 patients , venous thrombosis occurred in 12 percent of those given PK10169 heparin and 42 percent of those given placebo ( P = 0.0007 ) , and the corresponding rates for proximalvein thrombi were 4 percent and 20 percent , respectively ( P = 0.014 ) . The observed hemorrhagic rate was 4 percent in each treatment group . We conclude that prophylaxis with fixed-dose PK10169 heparin is effective and safe for patients undergoing elective hip replacement Abstract Introduction . To investigate whether the occurrence of pulmonary embolism ( PE ) and /or deep vein thrombosis ( DVT ) are influenced by use of a tourniquet or not in the patients who underwent total knee arthroplasty for rheumatoid arthritis ( RA ) . Patients and methods . The patients were r and omly divided into a with-tourniquet group ( 19 patients ) and a without-tourniquet group ( 18 patients ) . In the first group , snowstorm-like echogenic particles were observed after deflation of the tourniquet in all patients according to the transesophageal echocardiography . Results . In addition , the PaO2 level was significantly decreased . Also , one had a PE , and DVT was confirmed in two patients . In the without-tourniquet group , none of these conditions was noted . Conclusion . These results suggest that the use of a tourniquet will promote the risk of developing postoperative PE and /or DVT after total knee arthroplasty Orgaran ( danaparoid sodium injection ) is a novel antithrombotic agent . Early studies suggest that this compound may be beneficial in preventing deep vein thrombosis in predisposed patients . This multicenter , r and omized , assessor blinded , clinical trial compared subcutaneous danaparoid with warfarin for the prevention of deep vein thrombosis in patients undergoing hip replacement surgery . Bilateral venography was used to detect thrombi . Patients also underwent follow-up examinations 1 , 2 , and 3 months after discontinuation of the study to determine the after effects of treatment . Nearly 27 % of patients who received warfarin and 14.6 % of patients who received danaparoid developed deep vein thrombosis , a risk reduction of 46 % . The absolute difference in the incidence of deep vein thrombosis was 12.3 % in favor of danaparoid . The incidence of venographically documented proximal deep vein thrombosis was 1.5 % for danaparoid and 4.1 % for warfarin . These results demonstrate that danaparoid is more effective than warfarin in preventing deep vein thrombosis following hip replacement surgery . The preoperative administration of danaparoid does not increase surgical blood loss compared with warfarin We carried out an audit on the result of achieving early walking in total knee replacement after instituting a new rehabilitation protocol , and assessed its influence on the development of deep-vein thrombosis as determined by Doppler ultrasound scanning on the fifth post-operative day . Early mobilisation was defined as beginning to walk less than 24 hours after knee replacement . Between April 1997 and July 2002 , 98 patients underwent a total of 125 total knee replacements . They began walking on the second post-operative day unless there was a medical contraindication . They formed a retrospective control group . A protocol which allowed patients to start walking at less than 24 hours after surgery was instituted in August 2002 . Between August 2002 and November 2004 , 97 patients underwent a total of 122 total knee replacements . They formed the early mobilisation group , in which data were prospect ively gathered . The two groups were of similar age , gender and had similar medical comorbidities . The surgical technique and tourniquet times were similar and the same instrumentation was used in nearly all cases . All the patients received low-molecular-weight heparin thromboprophylaxis and wore compression stockings post-operatively . In the early mobilisation group 90 patients ( 92.8 % ) began walking successfully within 24 hours of their operation . The incidence of deep-vein thrombosis fell from 27.6 % in the control group to 1.0 % in the early mobilisation group ( chi-squared test , p < 0.001 ) . There was a difference in the incidence of risk factors for deep-vein thrombosis between the two groups . However , multiple logistic regression analysis showed that the institution of an early mobilisation protocol result ed in a 30-fold reduction in the risk of post-operative deep-vein thrombosis when we adjusted for other risk factors Background Oral anticoagulation is most frequently monitored using the prothrombin time , but an alternative approach is measurement of native , fully carboxylated , prothrombin antigen ( NPA ) . We have correlated results of the prothrombin time and NPA with development of venous thrombosis or bleeding complications in a clinical trial of warfarin prophylaxis following total hip arthroplasty to determine the potential value of NPA measurement for monitoring oral anticoagulation . Methods and Results Patients in one arm of a prospect i ve , r and omized trial received warfarin prophylactically beginning 10 to 14 days before total hip arthroplasty in a dose adjusted to prolong the international normalized ratio ( INR ) to 1.5 on the day of surgery and 2.5 after surgery . NPA was measured by ELISA , and the prothrombin time was measured using rabbit brain thromboplastin . Sample s were tested from 97 patients , and data from 81 patients who had adequate venography were analyzed to correlate test results with occurrence of thrombosis . The prothrombin time and INR were less sensitive than NPA to the lowest intensities of anticoagulation , with the prothrombin time index increasing from 1.0 to 1.3 and the INR increasing from 1.0 to 2.0 , whereas the NPA concentration decreased fourfold , from 200 to 50 pg/mL. There was little correlation between either the prothrombin time index or the INR and the development of thrombosis , whereas NPA concentrations were significantly higher on the day of surgery and on postoperative days 1 , 3 , 5 , and 7 in patients who developed venous thrombosis . Higher concentrations of NPA were associated with an increased risk of venous thrombosis , but there was no relation between thrombosis and the prothrombin time index or INR There was no significant correlation between surgical blood loss and prothrombin time index , INR , or NPA concentration . However , patients who received the largest number of transfusions on the day of surgery had significantly lower NPA concentrations than patients who required no transfusion . Conclusion These results indicate that the NPA concentration more accurately reflects the antithrombotic effect of warfarin than does prothrombin time and may be superior in monitoring prophylactic oral anticoagulation BACKGROUND Venous thromboembolic disease in the form of deep venous thrombosis and pulmonary embolism is a major risk after a total hip arthroplasty . Enoxaparin , a low-molecular-weight heparin , has been shown to reduce the prevalence of deep venous thrombosis after total hip arthroplasty . Warfarin , an orally administered anticoagulant , has been used historically to reduce the risk of deep venous thrombosis after total hip arthroplasty . METHODS We compared enoxaparin and adjusted-dose warfarin with respect to their safety and their efficacy in the prevention of clinical ly important venous thromboembolic disease , defined as distal or proximal deep venous thrombosis or pulmonary embolism , or both , during hospitalization after total hip arthroplasty . We also evaluated the prevalence of complications and mortality from venous thromboembolic disease within three months after discharge . RESULTS Three thous and and eleven patients at 156 centers were r and omly assigned to prophylactic treatment with injection of enoxaparin or oral administration of adjusted-dose warfarin during hospitalization . During the study , fifty-five ( 3.6 percent ) of the 1516 patients who were managed with enoxaparin and fifty-six ( 3.7 percent ) of the 1495 patients who were managed with warfarin had venous thromboembolic disease . Twenty-one patients ( 0.7 percent ) , which included four ( 0.3 percent ) of those managed with enoxaparin and seventeen ( 1.1 percent ) of those managed with warfarin ( p = 0.0083 ) , had venous thromboembolic disease during hospitalization . After discharge from the hospital , venous thromboembolic disease developed in ninety patients ( 3.0 percent ) : fifty-one ( 3.4 percent ) of those managed with enoxaparin and thirty-nine ( 2.6 percent ) of those managed with warfarin . One patient who had been managed with enoxaparin died because of a pulmonary embolism , which was confirmed at autopsy . Three additional patients ( one who had been managed with enoxaparin and two who had been managed with warfarin ) died , and the deaths were attributed to venous thromboembolic disease ; however , no autopsies were performed . Twenty-six patients ( 0.9 percent ) ( eighteen managed with enoxaparin and eight managed with warfarin ) had clinical ly important bleeding . CONCLUSIONS Inpatient programs providing treatment with either enoxaparin ( thirty milligrams every twelve hours ) or adjusted-dose warfarin for a mean of 7.3 days afforded protection against venous thromboembolic disease , with overall rates of morbidity and mortality of 3.7 and 0.6 percent , respectively , and a very low rate of major bleeding complications ( 0.9 percent ) for three months after total hip arthroplasty . During hospitalization , the patients managed with enoxaparin had a lower rate of venous thromboembolic disease than those managed with adjusted-dose warfarin ( p = 0.0083 ) . This benefit was lost after the medication was discontinued , with no difference in the prevalences of venous thromboembolic disease between the two groups at three months after discharge from the hospital CONTEXT Inpatient rehabilitation after elective hip and knee arthroplasty is often necessary for patients who can not function at home soon after surgery , but how soon after surgery inpatient rehabilitation can be initiated has not been studied . OBJECTIVE To test the hypothesis that high-risk patients undergoing elective hip and knee arthroplasty would incur less total cost and experience more rapid functional improvement if inpatient rehabilitation began on postoperative day 3 rather than day 7 , without adverse consequences to the patients . DESIGN R and omized controlled trial conducted from 1994 to 1996 . SETTING Tertiary care center . PARTICIPANTS A total of 86 patients undergoing elective hip or knee arthroplasty and who met the following criteria for being high risk : 70 years of age or older and living alone , 70 years of age or older with 2 or more comorbid conditions , or any age with 3 or more comorbid conditions . Of the 86 patients , 71 completed the study . INTERVENTIONS R and om assignment to begin inpatient rehabilitation on postoperative day 3 vs postoperative day 7 . MAIN OUTCOME MEASURES Total length of stay and cost from orthopedic and rehabilitation hospital admissions , functional performance in hospitals using a subset of the functional independence measure , and 4-month follow-up assessment using the R AND 36-item health survey I and the functional status index . RESULTS Patients who completed the study and began inpatient rehabilitation on postoperative day 3 exhibited shorter mean ( + /-SD ) total length of stay ( 11.7+/-2.3 days vs 14.5+/-1.9 , P<.001 ) , lower mean ( + /-SD ) total cost ( $ 25891+/-$3648 vs $ 27762+/-$3626 , P<.03 ) , more rapid attainment of short-term functional milestones between days 6 and 10 ( 36.2+/-14.4 m ambulated vs 21.4+/-13.3 m , P<.001 ; 4.8+/-0.8 mean transfer functional independence measure score vs 4.3+/-0.7 , P<.01 ) , and equivalent functional outcome at 4-month follow-up . CONCLUSION These data showed that high-risk individuals were able to tolerate early intensive rehabilitation , and this intervention yielded faster attainment of short-term functional milestones in fewer days using less total cost BACKGROUND In a previous study of the prevention of venous thromboembolism after total knee replacement , the efficacy of ximelagatran , an oral direct thrombin inhibitor that does not require monitoring of coagulation or dose adjustment , was found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice daily . The purpose of the present study was to determine whether a higher dose of ximelagatran is superior to warfarin . METHODS This r and omized , double-blind trial compared a regimen of 7 to 12 days of oral ximelagatran , at a dose of 24 or 36 mg twice daily , starting the morning after surgery , with warfarin therapy started the evening of the day of surgery . The composite end point of venous thromboembolism and death from all causes and the incidence of bleeding were the primary outcome measures . RESULTS Among the 1851 patients in the efficacy analysis , oral ximelagatran at a dose of 36 mg twice daily was superior to warfarin with respect to the primary composite end point of venous thromboembolism and death from all causes ( 20.3 percent vs. 27.6 percent ; P=0.003 ) . There were no significant differences between these two groups with respect to major bleeding ( incidence , 0.8 percent and 0.7 percent , respectively ) , perioperative indicators of bleeding , wound characteristics , or the composite secondary end point of proximal deep-vein thrombosis , pulmonary embolism , and death ( 2.7 percent vs. 4.1 percent ; P=0.17 ) . CONCLUSIONS The efficacy of oral ximelagatran , administered starting the morning after total knee replacement , was superior to that of warfarin for prevention of venous thromboembolism . Rates of hemorrhagic complications with the two drugs were similar Widespread use of adjusted low-dose warfarin has been limited by the inconvenience of outpatient laboratory monitoring and the perceived risk of bleeding complications . We sought to determine if the dose of warfarin could be lowered safely even further , eliminating the need for laboratory monitoring and lowering the complication rate . Two hundred forty-five Patients undergoing primary total joint arthroplasty ( n = 245 ) were r and omized prospect ively to adjusted low-dose warfarin ( international normalized ratio [ INR ] , 1.4 - 1.8 ) or fixed minidose warfarin ( 2 mg daily , regardless of INR ) before hospital discharge . Prophylaxis continued for 6 weeks , with twice-weekly laboratory monitoring . Patients were followed for bleeding , thromboembolic events , and minor reported complications of warfarin therapy . With the numbers available , the rates of thromboembolic and bleeding events were not significantly different using equivalence analysis . Of patients in the fixed group , 8 % had INRs > 3.1 , necessitating a decrease in dosage to 1 mg . Although such a fixed-dose protocol may simplify outpatient prophylaxis , intermittent monitoring still would be required because a subset of patients achieve a moderate level of anticoagulation and would be at risk for bleeding complications A prospect i ve , r and omized study of the effectiveness of intraoperative and postoperative use of intermittent pneumatic compression , alone or in combination with oral administration of either aspirin or low-dose warfarin , was done of a consecutive series of patients who had a total hip replacement and were more than thirty-nine years old . All patients began walking by the third postoperative day . One hundred and ninety-six patients who had 217 total hip arthroplasties were included . Twenty-eight per cent of the procedures were revisions of a previous total hip replacement or of an endoprosthesis , and the remainder were primary arthroplasties . Patients were r and omized as to the type of prophylaxis that they received : intermittent pneumatic compression alone , seventy-six hips ; intermittent pneumatic compression and aspirin , seventy-two hips ; or intermittent pneumatic compression and low-dose warfarin , sixty-nine hips . Before discharge from the hospital , and at an average of seven days after the operation , all patients were evaluated for the presence of proximal deep-vein thrombosis with either venography on the side of the operation or with bilateral venous ultrasonography . The relative frequency with which thrombosis occurred in a proximal vein was not significantly different in the three groups ; the over-all relative frequency was 10 per cent . Intermittent compression during and after the operation effectively reduces the rate of proximal-vein thrombosis after total hip replacement . With the number of patients in our study , the effectiveness of this technique could not be shown to be augmented by oral administration of either aspirin or low-dose warfarin Context Warfarin is associated with rates of deep venous thrombosis of 38 % to 55 % when prescribed during total knee arthroplasty and requires frequent monitoring and dose adjustment . The oral thrombin inhibitor ximelagatran has shown promise in prophylaxis of venous thromboembolism in patients undergoing hip and knee arthroplasty . Ximelagatran does not require monitoring or dose adjustment . Contribution This r and omized , controlled trial compared ximelagatran with warfarin in 680 patients undergoing total knee arthroplasty and found that ximelagatran was at least as effective as warfarin . Implication s Ximelagatran is an option for prophylaxis of venous thromboembolism in patients undergoing total knee arthroplasty , but this study had limited power to compare adverse effects . The Editors Venous thromboembolism is common after major orthopedic surgery . Meta- analysis has indicated that without prophylaxis , the incidence of deep venous thrombosis ( DVT ) is 50 % to 60 % ( 1 ) . Prophylaxis with low-molecular-weight heparin ( LMWH ) or warfarin is recommended , but the incidence of venographically confirmed DVT at the time of hospital discharge remains approximately 31 % with the former and 47 % with the latter ( 1 ) . In addition , proximal DVT is found in 7 % to 12 % of patients who receive prophylaxis with either regimen ( 1 ) . Currently , the use of LMWH and warfarin is approximately evenly divided in North America ( 2 , 3 ) . Warfarin has a slow onset of action and is inconvenient because it requires frequent coagulation monitoring and dose adjustment ( 3 , 4 ) . Low-molecular-weight heparin does not require monitoring but must be administered parenterally , which can be difficult after hospital discharge . Ximelagatran is a novel oral direct thrombin inhibitor . After administration , it is rapidly absorbed and transformed to its active form , melagatran ( 5 ) , which provides competitive , direct inhibition of both free and clot-bound thrombin . Administration of ximelagatran results in predictable plasma concentrations of melagatran that increase linearly in relation to dose in healthy volunteers ( 5 ) and surgical patients ( 6 , 7 ) . Fixed doses of ximelagatran without coagulation monitoring have been studied in phase II trials and have shown promising results in prophylaxis of venous thromboembolism after total hip or knee arthroplasty ( 8 , 9 ) . In this phase III trial , we compared the efficacy and safety of ximelagatran and warfarin for the prevention of venous thromboembolism after total knee arthroplasty . Methods Study Design We performed a r and omized , double-blind study comparing ximelagatran with warfarin for the prevention of venous thromboembolism after total knee arthroplasty . Patients were recruited from 74 hospitals in the United States and Canada . The study was performed in accordance with the Declaration of Helsinki and was approved by the institutional review board at each hospital . Patients were evaluated for eligibility 1 to 30 days before surgery and were r and omly assigned to treatment postoperatively on the day of surgery . Those that appeared to meet the inclusion criteria were approached before surgery to discuss the study and to sign consent forms if they were interested . Those who agreed to participate were reevaluated after surgery and before r and omization to ensure that they still met entry criteria . R and omization was stratified by unilateral or bilateral surgery at each center and was implemented through an interactive voice response system . Treatment was given for 7 to 12 days , and venography was performed within 12 hours of the final dose . Patients were followed clinical ly for 4 to 8 weeks after surgery . Patients Patients were eligible if they were scheduled for elective total knee arthroplasty , were at least 18 years of age , weighed 40 to 125 kg , and provided consent . Women had to be surgically sterile , postmenopausal for at least 2 years , or using reliable contraception . Criteria for exclusion were scheduled hemiarthroplasty , surface repair , or revisionary surgery ; planned external pneumatic compression prophylaxis ; immobilization for 3 or more days before surgery ; major surgery , ischemic stroke , myocardial infa rct ion , or administration of any investigational drug within 30 days before surgery ; a history of intracranial , retroperitoneal , or intraocular bleeding or any other disorder associated with increased risk for bleeding ; gastrointestinal bleeding within 90 days before surgery or endoscopically verified ulcer disease within 30 days before surgery ; uncontrolled hypertension ; cytotoxic treatment for active malignancy ; clinical ly significant liver disease ; thrombocytopenia ; drug or alcohol abuse in the past 6 months ; allergy to contrast media or iodine ; contraindication to warfarin ; severe renal impairment ( defined as estimated creatinine clearance < 0.5 mL/s [ < 30 mL/min ] ) ; or traumatic epidural or spinal puncture before surgery . Metformin was stopped before administration of contrast media for venography and was restarted after 48 hours if renal function was normal . If an epidural or spinal catheter was used , it had to be removed within 36 hours after surgery and at expected trough levels of melagatran . Treatment with thrombolytic drugs and the following anticoagulants or antiplatelet agents was not allowed within 7 days before surgery or during administration of the study drug : heparins , warfarin , dipyridamole , sulfinpyrazone , ticlopidine , clopidogrel , nonselective cyclooxygenase anti-inflammatory drugs with half-life exceeding 20 hours , at least 500 mg of aspirin per day , or dextran . Treatment Regimens Tablets containing 24 mg of ximelagatran ( AstraZeneca , Wilmington , Delaware ) or placebo were given in the morning and evening , with the first dose given on the morning after surgery and at least 12 hours after surgery . Capsules containing warfarin ( Coumadin , DuPont Pharmaceuticals , Wilmington , Delaware ) or placebo were given each evening , starting on the day of surgery after hemostasis was adequate . Warfarin was started at a minimum dose of 5 mg and was then titrated to achieve a target international normalized ratio ( INR ) of 2.5 ( range , 1.8 to 3.0 ) . Patients remained in the hospital according to local practice , usually for 3 to 4 days , after which they self-administered the medication . To guide dosing , INRs were measured locally by using a point-of-care device or a laboratory on postoperative days 1 to 3 and as needed in the interim and after discharge until the day of venography . The point-of-care devices were preprogrammed to encrypt INR values , which could be decrypted only by the central anticoagulation management center ( Omnicare Clinical Research , Lake Bluff , Illinois ) . International normalized ratios from local laboratories were reported to the Center , which then faxed real or sham INR values to the investigator . The investigator used these values to determine the next dose of warfarin or placebo . Sham INR values were generated to mimic usual values in persons receiving warfarin . Treatment adherence was assessed by counting tablets and capsules used in the hospital , dispensed at discharge , and returned at the end of the study . Efficacy Assessment s The primary efficacy variable was the incidence of DVT ( proximal or distal ) or pulmonary embolism . The secondary efficacy variable was the incidence of proximal DVT or pulmonary embolism . Both variables considered events that occurred during treatment . Deep venous thrombosis was evaluated by ascending venography on the leg or legs that had undergone surgery ( 10 , 11 ) . St and ardized film documentation contained no more than nine images per leg . The Central Adjudication Committee assessed venograms for the primary efficacy end point . The criterion for DVT was a consistent intraluminal filling defect on at least two images . Evaluable venograms required visualization of all of the deep veins except the muscular veins and the anterior tibial veins , although DVT was counted if these veins were seen and thrombus was detected . Non-evaluable venograms were defined as those that showed a lack of filling in a region of the deep system of the leg without the presence of an intraluminal filling defect elsewhere in the same region . Ultrasound diagnosis was sufficient for symptomatic proximal DVT , but venography was required for diagnosis of symptomatic distal DVT . Analysis of local interpretations of venograms was included in the statistical analysis plan before unblinding . Pulmonary embolism was diagnosed when a lung scan showed high probability , defined as one or more segmental perfusion defects seen in at least two views with corresponding normal ventilation . Pulmonary embolism was also diagnosed by pulmonary angiography showing a persistent intraluminal defect or abrupt cutoff of a vessel greater than 2.5 mm in diameter . All cases of suspected pulmonary embolism were adjudicated central ly . Patients with thrombosis were treated according to local practice . Safety Assessment s All bleeding events were recorded , including bleeding at the site of surgery , volumes of blood loss and transfusion , and wound appearance . Independent experts classified bleeding events as major if they were clinical ly overt and showed one or more of the following : critical site involvement ( intracranial , retroperitoneal , intraocular , intraspinal , or pericardial ) , bleeding index of 2.0 or greater ( calculated as the number of units of red blood cells transfused plus the difference between prebleeding hemoglobin level minus postbleeding event hemoglobin level [ g/dL ] ) , medical or surgical intervention at the operative site , or fatal bleeding . The bleeding index provides a measure of hemoglobin change as modified by transfusion and has been used in other studies of prophylaxis after orthopedic procedures ( 12 , 13 ) . Clinical ly overt bleeding with none of the other characteristics was classified as minor . The investigators also classified the overall appearance and characteristics of the surgical wound as being as BACKGROUND Oral anticoagulants and low-molecular-weight heparin are both recommended for venous thromboembolism prophylaxis after total hip replacement . To date , these regimens have not been compared by means of clinical end points in the extended prophylaxis setting . METHODS We r and omly assigned 1279 patients 3 days after total hip replacement surgery to fixed-dose subcutaneous low-molecular-weight heparin ( reviparin sodium , 4200 anti-Xa IU ) or adjusted-dose oral anticoagulant ( international normalized ratio , 2 - 3 ; acenocoumarol ) for a 6-week period . The primary end point was the failure rate , defined as the combined clinical events of a confirmed symptomatic thromboembolic event , a major hemorrhage , or death . All patients were followed up throughout the study interval . The primary objective was to compare the observed cumulative failure rate in the low-molecular-weight heparin vs oral anticoagulant group . RESULTS In the intent-to-treat population , objective ly documented symptomatic thromboembolic events occurred in 15 ( 2.3 % ) of 643 patients vs 21 ( 3.3 % ) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants , respectively ( P = .30 ; 95 % confidence interval for the difference , -0.8 % to 2.8 % ) . Major bleeding occurred in 9 ( 1.4 % ) of 643 patients vs 35 ( 5.5 % ) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants , respectively ( P = .001 ) . The failure rate was 24 ( 3.7 % ) of 643 patients compared with 53 ( 8.3 % ) of 636 patients who received low-molecular-weight heparin or oral anticoagulants ( P = .001 ) . CONCLUSIONS A significantly higher benefit-risk ratio was observed for patients undergoing elective hip replacement who received extended out-of-hospital prophylaxis with low-molecular-weight heparin vs acenocoumarol . Low-molecular-weight heparin prophylaxis was at least as effective as oral anticoagulants , but with a marked improvement in safety Despite modern surgical techniques and early patient mobilization , venous thromboembolism remains a major complication of knee arthroplasty [ 1 - 3 ] . Without prophylaxis , the reported incidences of venographically verified deep venous thrombosis and proximal venous thrombosis have ranged from 55 % to 70 % and from 10 % to 30 % , respectively [ 2 , 4 - 8 ] . Fatal pulmonary embolism , allegedly uncommon ( incidence less than 1 % [ 9 ] ) , remains an avoidable cause of perioperative death in these patients . The burden of postoperative venous thromboembolism must also be assessed in terms of the morbidity from the acute event , the risk for long-term postphlebitic complications [ 10 , 11 ] , and the effect of venous thromboembolism on the cost of health care delivery [ 12 , 13 ] . Preventing venous thromboembolism after knee arthroplasty is difficult because of the relative resistance of this type of surgery to the effects of most thromboprophylaxis options [ 6 , 14 - 18 ] , the substantial hemorrhagic risk associated with the surgical procedure [ 19 ] , and the lack of consensus on the safest and most effective method . The main hemorrhagic threat of thromboprophylaxis in knee surgery is hemarthrosis , which may require surgical drainage or may compromise the result of the reconstruction . Less intense warfarin and low-molecular-weight heparins have been evaluated as prophylaxis after knee surgery [ 8 , 20 - 24 ] . Warfarin has the advantage of oral administration , and low-molecular-weight heparins do not require laboratory monitoring . In previous studies comparing warfarin with low-molecular-weight heparins , patients having either hip or knee surgery were evaluated together [ 20 , 21 ] , interventions were unblinded [ 21 , 22 ] , or unilateral venography was done [ 21 - 23 ] . We thus conducted a double-blind , r and omized trial with bilateral venographic assessment of the effectiveness and safety of postoperative , adjusted-dose warfarin compared with those of postoperative , fixed-dose enoxaparin in patients having knee arthroplasty . Methods Patients Eight hundred sixty-five consecutive adult patients having knee arthroplasty at eight hospitals were evaluated . Sixty-eight patients were excluded for the following reasons : allergy to contrast material ( 20 patients ) ; need for oral anticoagulant or antiplatelet agents ( 18 patients ) ; bleeding diathesis ( 9 patients ) ; gastrointestinal hemorrhage within 3 months of surgery ( 7 patients ) ; renal or hepatic insufficiency ( 4 patients ) ; uncontrolled hypertension ( 3 patients ) ; illicit drug use or alcohol abuse ( 3 patients ) ; participation in the present study within the last 3 months ( 1 patient ) ; hemorrhagic stroke within 3 months of surgery ( 1 patient ) ; receipt of other investigational drugs in the past month ( 1 patient ) ; and warfarin allergy ( 1 patient ) . Of the 797 patients eligible for the study , 670 ( 84 % ) gave informed consent . Interventions The 670 eligible and consenting patients were r and omly allocated after surgery to receive either warfarin sodium ( 334 patients ) or enoxaparin ( 336 patients ) in a 1:1 ratio in blocks of four . A computer generated the r and omization schedule . We stratified r and omization by study center , history of venous thromboembolism , and use of a cemented or uncemented prosthesis . Patients in the warfarin group also received subcutaneous saline placebo every 12 hours . The treatment goal was to maintain the international normalized ratio between 2.0 and 3.0 using a prespecified nomogram . Patients in the enoxaparin group received 30 mg of enoxaparin subcutaneously every 12 hours and warfarin placebo once daily . Therapy with oral medications began on the evening of the day on which surgery was done ( day 1 ) , and therapy with subcutaneous medications began on the morning of the first day after surgery ( day 2 ) . Study medications were administered for 14 days or until hospital discharge , whichever occurred first . No other thromboprophylactic agents or antiembolic stockings were used . Patient Surveillance and Outcome Measures The primary end point was the incidence of deep venous thrombosis in patients with adequate bilateral venograms and symptomatic pulmonary embolism . Venography was done on day 14 or earlier if the patient was discharged or if patients developing clinical ly suspected deep venous thrombosis had abnormal noninvasive test results . The diagnostic criterion for thrombosis was a constant intraluminal filling defect seen on two or more views . Venograms were considered adequate if the entire deep venous system could be seen to at least the level of the common femoral vein . Bilateral compression ultrasonography of the tibioperoneal trunk , popliteal vein , superficial femoral vein in at least two sites , and common femoral vein was routinely done before venography . A positive venous ultrasound was defined as the noncompressibility of a vein segment . Patients with clinical ly suspected venous thrombosis had either compression ultrasonography or impedance plethysmography when symptoms developed . Venography was done immediately if the noninvasive test result was abnormal . Symptomatic patients with a normal noninvasive test result had repeated testing every other day until predischarge venography was done . Patients with suspected pulmonary embolism had lung scanning . Pulmonary embolism was excluded on the basis of a normal perfusion scan and was confirmed by a high-probability scan ; the latter was defined as showing one or more segmental perfusion defects with normal or near-normal ventilation . Patients with abnormal lung scans that did not show a high probability of embolism subsequently had pulmonary angiography . Patients with proven venous thromboembolism received heparin treatment followed by oral anticoagulant agents as per local practice . Patients who did not develop venous thromboembolism received no further thromboprophylaxis after hospital discharge . Secondary end points were clinical ly overt hemorrhage and postoperative blood loss . Major hemorrhage was defined as overt bleeding that 1 ) decreased the hemoglobin level by 20 g/L or more or 2 ) necessitated transfusion of 2 or more units of packed red cells , hemarthrosis requiring evacuation , discontinuation of prophylaxis , or interruption of physiotherapy for at least 24 hours . Minor hemorrhage was defined as overt bleeding that did not meet the criteria for major hemorrhage . All patients were followed for 6 months . During this interval , patients were instructed to contact the investigator if they developed symptoms suggestive of venous thromboembolism . Blinding Oral medications were monitored by an independent physician who was aware of the r and omization schedule but was not otherwise involved in the study . Dosage adjustments were based on the measured international normalized ratios in patients receiving warfarin and on phantom international normalized ratios , generated a priori , in patients receiving warfarin placebo . Patients receiving warfarin placebo also had daily blood sampling for sham measurements of the international normalized ratio . International normalized ratios were not recorded in the patients ' charts . All diagnostic tests and bleeding episodes were adjudicated by a central committee that was unaware of treatment allocation or clinical findings . Statistical Analysis The rates of deep venous thrombosis in the two treatment groups were compared using the chi-square test with Yates correction . Blood loss was analyzed using one-way analysis of variance . The rates of pulmonary embolism and the proportion of patients receiving packed red cells were analyzed using the Fisher exact test . We used the statistical package S-PLUS version 3.1 ( StatSci , Seattle , Washington ) . Estimation of Sample Size On the basis of the assumption that the incidence of deep venous thrombosis in enoxaparin recipients would be approximately 20 % [ 8 ] and with an value of 0.05 ( two-tailed ) and a value of 0.20 , we determined that 200 patients with adequate venograms per group would be required to show at least a 50 % reduction in the rate of thrombosis in the enoxaparin group compared with the warfarin group . Interim Analysis We did a preplanned interim analysis after 200 patients with adequate venograms were enrolled . An independent committee review ed the results without breaking the code . We formally used an O'Brien-Fleming stopping boundary [ 25 ] but also analyzed the overall rate of thrombosis and bleeding complications to arrive at a conclusion . We decided to continue the trial until 400 patients had adequate venograms . Study Logistics The investigators independently design ed the study and interpreted the results . The research coordinators at each site collected the data , and the sponsoring pharmaceutical firm monitored the quality of the data at each study center . Biostatisticians from the Division of Clinical Epidemiology of the Montreal General Hospital design ed the data base , and the clinical research firm Biopharmaceutical Research Consultants ( Ann Arbor , Michigan ) independently analyzed the data . Results The two treatment groups had similar important baseline characteristics ( Table 1 ) . Adequate venographic outcomes were obtained in 417 of 670 patients ( 62 % ) . Adequate venograms were not obtained in the remaining patients for the following reasons : technically inadequate venogram ( 129 patients ) , failed venous access ( 94 patients ) , refusal of the patient ( 24 patients ) , pulmonary embolism ( 3 patients ) , refusal of the treating physician ( 2 patients ) , and unavailable films ( 1 patient ) . These reasons were equally balanced between the two groups . All technically inadequate venograms result ed from incomplete opacification of the deep venous system . In many instances , radiologists were uncomfortable administering additional contrast material , particularly because the protocol required bilateral venography . An additional complicating factor was the overshadowing of the popliteal vein by the knee prosthesis , despite the protocol requirement to obtain lateral views of this area . The A r and omized trial was performed in consecutive patients undergoing total hip replacement to evaluate the effectiveness of sequential intermittent calf and thigh compression for preventing venous thrombosis compared with a control group given no prophylaxis . Both groups underwent case finding for deep vein thrombosis using combined fibrinogen I 125 leg scanning , impedance plethysmography , and venography . Deep vein thrombosis by venography was present in 77 ( 49 % ) of 158 control patients compared with 36 ( 24 % ) of 152 patients given intermittent compression . Proximal vein thrombosis was present in 42 controls ( 27 % ) compared with 22 patients ( 14 % ) given intermittent compression . Combined impedance plethysmography and leg scanning was insensitive in this patient group ( sensitivity , 46 % ) ; venography was required to detect more than half the patients with venous thrombosis . Sequential intermittent leg compression clinical ly and statistically significantly reduced the frequency of both proximal vein and calf vein thrombosis . Case finding result ed in early detection and treatment of patients with venous thrombosis Venous thrombosis rates were compared in 200 patients undergoing total hip arthroplasty and r and omized to receive either fixed mini-dose warfarin ( 1 mg daily ) or adjusted-dose warfarin to maintain an international normalized prothrombin ratio ( INR ) of 2.0 - 4.0 . Bilateral lower limb venography was performed between days 11 and 13 inclusive . Fixed mini-dose warfarin was associated with a significantly higher rate of total thrombosis ( P less than 0.05 ) . General anaesthesia was associated with a significantly higher rate of thrombosis than spinal anaesthesia ( P less than 0.05 ) . Adjusted-dose warfarin was associated with more bleeding complications than mini-dose warfarin although these were not attributable to excessive anticoagulation . A single death from pulmonary embolus occurred in the early postoperative period in a patient receiving adjusted-dose warfarin Prophylactic efficacy and safety of a low molecular weight ( LMW ) heparin against postoperative thromboembolic complications were investigated in a double-blind , r and omized study . Totally , 210 consecutive patients undergoing total hip replacement were allocated to two groups . Patients in the heparin group received 50 IU anti-Xa per kilo body weight of Logiparin once daily , and patients in the placebo group received one daily injection of saline . Additional prophylaxis in all the patients was thigh-length compression stockings beginning on the day of the operation . Deep vein thrombosis was diagnosed by bilateral ascending phlebography between Days 8 and 10 after the operation . Twenty patients were excluded from the evaluation . Thirty of 93 patients in the heparin group compared with 45 of 97 patients in the placebo group suffered a thromboembolic complication during the study ( P = 0.02 ) . The postoperative blood loss and total number of blood transfusions in the heparin group were higher than in the placebo group . However , the observed differences were of no clinical importance . Adverse effects , including bleeding complications and wound hematomas , were observed in 13 heparin patients and 7 placebo patients ( NS ) . One patient in each group died . Thrombo-prophylaxis with LMW heparin once daily was safe and more effective than the placebo in patients undergoing total hip replacement A prospect i ve r and omized trial compared the effectiveness of low-dose warfarin ( LDW ) to sequential compression devices ( SCD ) for deep venous thrombosis ( DVT ) prophylaxis in 95 patients after total hip arthroplasty ( THA ) . Patients were 39 years of age or older , with no history of previous venous disease . Bilateral lower-extremity venography was used for thrombi detection . Venous thrombi occurred in 12 patients ( all calf ) on LDW ( 26.6 % ) and 3 patients with SCDs ( one calf , two thigh ) ( 6.0 % ) . The incidence of DVT was significantly higher in the LDW group ( P less than .006 ) . In this study of average-risk patients , the use of SCDs significantly outperformed LDW as a prophylactic agent . However , the thrombi that did occur with SCDs were more critical OBJECTIVE To compare the effectiveness and safety of warfarin and external pneumatic compression ( EPC ) in prevention of venous thrombosis after total hip replacement . DESIGN Prospect i ve , r and omized trial in consecutive patients , with blinded assessment of the primary end point . SETTING University medical center and large community hospital . PATIENTS Patients over age 18 years scheduled for elective primary total hip replacement were eligible . Of 254 patients interviewed , 232 were r and omized , 220 patients had surgery and received prophylaxis , and 201 had venography . INTERVENTIONS Patients were r and omly assigned to prophylaxis with a device providing bilateral sequential EPC to both the calf and thigh or to receive warfarin in a low-intensity regimen beginning 10 to 14 days preoperatively . Prophylaxis was continued until venography . MAIN OUTCOME MEASURES Venous thrombosis was diagnosed by venography between postoperative days 6 and 8 . Bleeding was assessed by surgical blood loss , transfusion requirements , changes in hematocrit , and clinical ly identified bleeding complications . RESULTS The total incidence of venous thrombosis was virtually the same in the warfarin and EPC groups ( 31 % vs 27 % ) , but the distribution of thrombi was different . Proximal thrombosis occurred in 12 % of patients in the EPC group compared with only 3 % in the warfarin group ( P = .012 , 95 % confidence interval for difference , 2 % to 18 % ) . In contrast , calf vein thrombosis was more frequent in the warfarin group ( 21 % ) than in the EPC group ( 12 % ) ( P = .021 , 95 % confidence interval for difference , 0 % to 18 % ) . Most proximal thrombi in EPC-treated patients were located within 15 cm of the femoral head and were not continuous with thrombi in deep calf veins . The high incidence of proximal thrombosis in the EPC group result ed in termination of the study by the safety monitoring committee . Blood loss and bleeding complications were similar in the two groups . CONCLUSION Warfarin therapy is significantly more effective than EPC in preventing serious proximal vein thrombosis after total hip replacement . The greater effectiveness of warfarin therapy in preventing proximal vein thrombi and of EPC in preventing thrombosis in the calf suggests that there are differences in the pathogenesis of thrombosis in these two locations A prospect i ve , r and omized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement . Adult patients scheduled for primary or revision total knee replacement were r and omly assigned to receive either a " two-step " warfarin regimen beginning 10 - 14 days pre-operatively or , alternatively , to begin warfarin the night before surgery . Post-operatively , the dose was adjusted in both groups to achieve a target International Normalized Ratio ( INR ) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine . Bleeding was assessed by surgical blood loss , transfusion requirements , changes in hematocrit , and clinical ly identified bleeding complications . The occurrence of deep vein thrombosis was nearly the same in the two treatment groups , 39 % in patients r and omized to the two-step regimen as compared to 38 % in those beginning the night before surgery . The occurrence of proximal vein thrombosis was also similar , 5 % versus 7 % ( p = NS ) . Patients in the two-step group received 1.33 + /- 1.26 transfusions compared to 0.95 + /- 1.22 in the night before group ( p < 0.05 ) and also had a lower nadir post-operative hematocrit of 26.7 + /- 3.1 as compared to 28.5 + /- 3.2 ( p < 0.0001 ) . Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group . Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis . We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10 - 14 days pre-operatively . Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications |
10,877 | 25,061,017 | Findings demonstrate a significant prevalence of family PTSD symptoms in the months following ICU hospitalization . | Family members of intensive care unit ( ICU ) patients are at risk for symptoms of post-traumatic stress disorder ( PTSD ) following ICU discharge .
The aim of this systematic review is to examine the current literature regarding post-ICU family PTSD symptoms with an emphasis on method ological issues in conducting research on this challenging phenomenon . | Although Post-traumatic Stress Disorder ( PTSD ) is common among patients seeking care at medical clinics , little is known about the performance of screening instruments for this disorder in these setting s. Previous studies of acute trauma population s using the PTSD Checklist ( PCL ) have suggested that scores of 45 - 50 provide the best discrimination between cases and noncases . We gave the PCL to 1,225 r and omly selected women enrolled in an HMO . After interviewing a sample of 261 of these women using a structured , clinician-administered PTSD interview , we compared the results of the PCL to the clinician interviews over a range of possible cut scores using Receiver Operating Characteristic analysis . The optimum balance of sensitivity and specificity for this population was a score of 30 , yielding a sensitivity of.82 and specificity of.76 . The positive and negative likelihood ratios for this cut score were 3.40 and 0.24 , respectively . By comparison , the use of 45 as a cut score would result in very low sensitivity ( .36 ) in this setting . The lower cut score found in this study may indicate that the use of previously published cut scores of 45 - 50 may not optimize the function of the PCL as a screening tool outside of acute trauma setting s due to an unacceptably high number of false negative cases BACKGROUND Patients ' deaths in the ICU have been associated with a high burden of psychologic symptoms in families . This study identifies characteristics associated with psychologic symptoms in family members . METHODS Families of patients dying in the ICU or within 30 h of ICU discharge in 11 hospitals previously participated in a r and omized trial . In the current study , we assessed these families for symptoms of posttraumatic stress disorder ( PTSD ) and depression with follow-up surveys . Outcomes included vali date d measures of PTSD ( PTSD Checklist ) and depressive ( Patient Health Question naire ) symptoms . Predictors included family member mental-health history , involvement in decision making , and demographics . RESULTS Surveys were completed by 226 families . Response rate was 46 % in the original r and omized trial and 82 % in this study . Prevalence ( 95 % CI ) of PTSD and depressive symptoms were 14.0 % ( 9.7%-19.3 % ) and 18.4 % ( 13.5%-24.1 % ) , respectively . Family characteristics associated with increased symptoms included : female gender ( PTSD , P = .020 ; depression , P = .005 ) , knowing the patient for a shorter duration ( PTSD , P = .003 ; depression , P = .040 ) , and discordance between family members ' preferences for decision making and their actual decision-making roles ( PTSD , P = .005 ; depression , P = .049 ) . Depressive symptoms were also associated with lower educational level ( P = .002 ) . Families with psychologic symptoms were more likely to report that access to a counselor ( PTSD , P < .001 ; depression , P = .003 ) and information about spiritual services might have been helpful while the patient was in the ICU ( PTSD , P = .024 ; depression , P = .029 ) . CONCLUSIONS Families demonstrated a high prevalence of psychologic symptoms after a death in the ICU . Characteristics associated with symptoms may help target interventions to reduce these symptoms . TRIAL REGISTRATION clinical trials.gov ; Identifier : NCT00685893 Introduction : Severe traumatic brain injury ( STBI ) can cause psychological stress in proxies in the long-term . This study assessed post-traumatic stress ( PTS ) symptoms in proxies of survivors of STBI in the short-term and investigated stress-associated factors . Methods : Prospect i ve cross-sectional study , conducted at three Swiss trauma centres over 1 year . Patient and proxy demographics , trauma data including Glasgow Coma Scale ( GCS ) and management data were collected . The proxies ’ PTS symptoms were assessed by applying the Impact of Event Scale – Revised ( IES-R ) , once in the first month after the accident ( median : 11 days ) . Results : Sixty-nine proxies were included ; 52 proxies were female ( 77.8 % ) . Mean IES-R sum score for intrusions was 13.38 ( SD = 7.26 ) , for avoidance 8.91 ( SD = 5.94 ) , and for hyperarousal 9.07 ( SD = 6.75 ) . Clinical ly significant PTS symptoms were observed in 36 proxies ( 52.2 % ) ; mean IES-R sum scores were significantly higher in women . IES-R sub-scale values were inversely related with GCS at the scene of the accident and on hospital admission . Conclusions : More than half of proxies had clinical ly significant PTS symptoms shortly after their relative 's accident . More severe PTS symptoms were found in women and in proxies of patients with poorer initial GCS scores . Further research into risk groups in the short- and long-term and the long-term impact on patients of PTS syndrome in proxies is warranted OBJECTIVES To describe the occurrence of delirium in a cohort of older medical intensive care unit ( ICU ) patients and its short-term duration in the hospital and to determine the association between preexisting dementia and the occurrence of delirium . DESIGN Prospect i ve cohort study . SETTING Fourteen-bed medical ICU of an 800-bed university teaching hospital . PARTICIPANTS One hundred eighteen consecutive patients aged 65 and older admitted to the ICU . MEASUREMENTS Baseline characteristics were obtained through surrogate interviews and medical chart review . Dementia was determined using two vali date d surrogate-rated instruments . Delirium was assessed daily in the ICU using the Confusion Assessment Method ( CAM ) for the ICU ( CAM-ICU ) . After discharge from the ICU , patients were followed for up to 7 days using the CAM . RESULTS Delirium was present in 37 of 118 ( 31 % ) patients on admission . Only 45 patients had a normal mental status on admission , of whom 14 ( 31 % ) became delirious during their hospital stay . In the post-ICU period , delirium occurred in 40 % of patients . Almost half of patients with delirium in the ICU had persistent delirium in the post-ICU period . Overall , 83 of 118 ( 70 % ) had delirium during hospitalization . Stupor or coma occurred in 44 % of the patients overall , and 89 % of survivors of stupor/coma progressed to delirium . Patients with dementia were 40 % more likely to be delirious ( relative risk = 1.4 , 95 % confidence interval = 1.1 - 1.7 ) , even after controlling for comorbidity , baseline functional status , severity of illness , and invasive procedures . CONCLUSION Delirium is a frequent complication in older ICU patients and often persists beyond their ICU stay . Delirium in older ICU persons is a dynamic and complex process . Dementia is an important predisposing risk factor for the development of delirium in this population during and after the ICU stay STUDY OBJECTIVES The physical and psychological effects of caregiving have been examined in several population s. To date , no one has examined the effects of caregiving on caregivers of patients receiving long-term mechanical ventilation ( LTV ) [ patients who required > 4 days of continuous in-hospital mechanical ventilation ] who reside in a home or institutional setting after hospital discharge . The purpose of this study was to describe the characteristics and examine depression , burden , overload , and physical health in this caregiver population over a 6-month period after hospital discharge . DESIGN This was a prospect i ve longitudinal descriptive study of posthospital outcomes for patients receiving LTV and their caregivers . SETTING AND PARTICIPANTS Caregivers of 135 patients receiving LTV admitted to the ICUs of a university medical center , a Veterans Administration hospital , and small community hospital were enrolled . MEASUREMENTS AND RESULTS Interviews of caregivers were conducted at hospital discharge and 6 months later . Descriptive statistics , analysis of variance , and multiple regression analyses were used to analyze the data . Established tools were used to assess caregiver depression , burden , overload , and physical health . Caregivers reported a drop in physical health scores from hospital discharge to 6 months after discharge ( p = 0.0001 ) . Caregivers of patients residing in an institution reported higher depression ( p = 0.039 ) and overload scores ( p = 0.002 ) than did caregivers of patients residing at home 6 months after discharge ; 51.2 % of caregivers at discharge and 36.4 % at 6 months after discharge reported symptoms consistent with some degree of depression . In addition , 12.2 % of caregivers at hospital discharge and 15.6 % at 6 months after discharge were classified as having symptoms consistent with severe depression . Caregiver physical health ( p = 0.025 ) and overload ( p = 0.006 ) made statistically significant contributions to explaining caregiver depression . CONCLUSIONS Caregivers of patients receiving LTV in our sample have similar characteristics to other caregiving population s. However , our sample had higher depression scores than those reported for many other caregiver groups We examined the psychometric properties of the PTSD Checklist ( PCL ) , a self-report instrument design ed to assess symptoms of posttraumatic stress disorder . Three hundred ninety-two participants recruited in a university setting completed the PCL in addition to several well-established self-report instruments design ed to assess various forms of psychopathology ( e.g. , depression , general anxiety , PTSD ) . Ninety participants returned for readministration of selected measures . Findings provided support for psychometric properties of the PCL , including internal consistency , test – retest reliability , convergent validity , and discriminant validity . Additional strengths of the PCL are discussed CONTEXT Delirium is a common problem in the intensive care unit ( ICU ) . Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a vali date d delirium instrument for use in the ICU . OBJECTIVES To vali date a delirium assessment instrument that uses st and ardized nonverbal assessment s for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients . DESIGN AND SETTING Prospect i ve cohort study testing the Confusion Assessment Method for ICU Patients ( CAM-ICU ) in the adult medical and coronary ICUs of a US university-based medical center . PARTICIPANTS A total of 111 consecutive patients who were mechanically ventilated were enrolled from February 1 , 2000 , to July 15 , 2000 , of whom 96 ( 86.5 % ) were evaluable for the development of delirium and 15 ( 13.5 % ) were excluded because they remained comatose throughout the investigation . MAIN OUTCOME MEASURES Occurrence rate of delirium and sensitivity , specificity , and interrater reliability of delirium assessment s using the CAM-ICU , made daily by 2 critical care study nurses , compared with assessment s by delirium experts using Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS A total of 471 daily paired evaluations were completed . Compared with the reference st and ard for diagnosing delirium , 2 study nurses using the CAM-ICU had sensitivities of 100 % and 93 % , specificities of 98 % and 100 % , and high interrater reliability ( kappa = 0.96 ; 95 % confidence interval , 0.92 - 0.99 ) . Interrater reliability measures across subgroup comparisons showed kappa values of 0.92 for those aged 65 years or older , 0.99 for those with suspected dementia , or 0.94 for those with Acute Physiology and Chronic Health Evaluation II scores at or above the median value of 23 ( all P<.001 ) . Comparing sensitivity and specificity between patient subgroups according to age , suspected dementia , or severity of illness showed no significant differences . The mean ( SD ) CAM-ICU administration time was 2 ( 1 ) minutes . Reference st and ard diagnoses of delirium , stupor , and coma occurred in 25.2 % , 21.3 % , and 28.5 % of all observations , respectively . Delirium occurred in 80 ( 83.3 % ) patients during their ICU stay for a mean ( SD ) of 2.4 ( 1.6 ) days . Delirium was even present in 39.5 % of alert or easily aroused patient observations by the reference st and ard and persisted in 10.4 % of patients at hospital discharge . CONCLUSIONS Delirium , a complication not currently monitored in the ICU setting , is extremely common in mechanically ventilated patients . The CAM-ICU appears to be rapid , valid , and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purpose Objective : To describe the symptom experiences of family members of patients at high risk for dying in the intensive care unit and to assess risk factors associated with higher symptom burden . Design : Prospect i ve , cross-sectional study . Setting : Three intensive care units at a large academic medical center . Participants : A sample of 74 family members of 74 intensive care unit patients who had a grave prognosis and were judged to be at high risk for dying . Patients at high risk for dying were identified as having Acute Physiology and Chronic Health Evaluation II scores > 20 , an intensive care unit length of stay > 72 hrs , and being mechanically ventilated . Interventions : None . Measurements and Results : We assessed the degree of symptom burden approximately 4 days after the patient 's admission to the intensive care unit in the following domains : traumatic stress , anxiety , and depression . Overall , the prevalence of symptoms was high , with more than half ( 57 % ) of family members having moderate to severe levels of traumatic stress , 80 % having borderline symptoms of anxiety , and 70 % having borderline symptoms of depression . More than 80 % of family members had other physical and emotional symptoms , such as fatigue , sadness , and fear , and these were experienced at the moderate to severe levels of distress . Factors independently associated with greater severity of symptoms included younger age , female gender , and non-white race of the family member . The only patient factor significantly associated with symptom severity was younger age . Despite their symptom experience , the majority of the family members were coping at moderate to high levels and functioning at high levels during the intensive care unit experience . Conclusions : We document a high prevalence of psychological and physical symptoms among family members during an intensive care unit admission . These data complement existing data on long-term symptom burden and highlight the need to improve family centered care in intensive care units Objective To evaluate the effectiveness of the provision of information in the form of a rehabilitation program following critical illness in reducing psychological distress in the patients ’ close family . Design R and omised controlled trial , blind at follow-up with final assessment at 6 months . Setting Two district general hospitals and one teaching hospital . Patients and participants The closest family member of 104 recovering intensive care unit ( ICU ) patients . Interventions Ward visits , ICU clinic appointments at 2 and 6 months . Relatives and patients received the rehabilitation program at 1 week after ICU discharge . The program comprised a 6-week self-help manual containing information about recovery from ICU , psychological information and practical advice . Measurements and results Psychological recovery of relatives was assessed by examining the rate of depression , anxiety , and post-traumatic stress disorder (PTSD)-related symptoms by 6 months after ICU . The proportion of relatives scoring in the range > 19 on the Impact of Events Scale ( cause for concern ) was high in both groups at 49 % at 6 months . No difference was shown in the rate of depression , anxiety , or PTSD-related symptoms between the study groups . Conclusion A high incidence of psychological distress was evident in relatives . Written information concerning recovery from ICU provided to the patient and their close family did not reduce this . High levels of psychological distress in patients were found to be correlated with high levels in relatives Background : The vital role played by family caregivers in supporting dying cancer patients is well recognized , but the burden and economic impact on caregivers is poorly understood . We prospect ively examined the psychosocial , occupational and economic impact of caring for a person with a terminal illness . Methods : We studied 89 caregivers of women with advanced breast cancer receiving care at either the Ottawa or Hamilton regional cancer centres in Ontario . Patients were followed until their death or study completion at 3 years . Patients identified a principal caregiver to participate in the study . The Karnofsky Performance Status ( KPS ) index , the Medical Outcomes Study 36-item Short Form ( SF-36 ) , the Hospital Anxiety and Depression Scale , the Zarit Burden Inventory , FAMCARE and the Medical Outcomes Study Social Support Survey were administered during follow-up . Economic data were collected by means of a question naire administered by an interviewer . Assessment s were conducted every 3 months during the palliative period ( KPS score > 50 ) and every 2 weeks during the terminal period ( KPS score ≤ 50 ) . Results : Over half of the caregivers were male ( 55 % ) and the patient 's spouse or partner ( 52 % ) , with a mean age of 53 years . At the start of the palliative period , the caregivers ' mean physical functioning score was better than the patients ' ( 51.3 v. 35.1 , 95 % confidence interval [ CI ] 13.3–20.0 ) ; there were similar mean mental functioning scores ( 46.6 and 47.1 respectively ) ; similar proportions were depressed ( 11 % and 12 % ) ; and significantly more caregivers than patients were anxious ( 35 % v. 19 % , p = 0.009 ) . More caregivers were depressed ( 30 % v. 9 % , p = 0.02 ) and had a higher level of perceived burden ( 26.2 v. 19.4 , p = 0.02 ) at the start of the terminal period than at the start of the palliative period . Burden was the most important predictor of both anxiety and depression . Of employed caregivers , 69 % reported some form of adverse impact on work . In the terminal period 77 % reported missing work because of caregiving responsibilities . Prescription drugs were the most important component of financial burden . Interpretation : Caregivers ' depression and perceived burden increase as patients ' functional status declines . Strategies are needed to help reduce the psychosocial , occupational and economic burden associated with caregiving Background Family members of patients in intensive care units ( ICUs ) are at risk for mental health morbidity both during and after a patient ’s ICU stay . Objectives To determine prevalences of and factors associated with anxiety , depression , posttraumatic stress and complicated grief in family members of ICU patients . Design Prospect i ve , longitudinal cohort study . Participants Fifty family members of patients in ICUs at a large university hospital participated . Measurements We used the Control Preferences Scale to determine participants ’ role preferences for surrogate decision-making . We used the Hospital Anxiety and Depression Scale , Impact of Event Scale , and Inventory of Complicated Grief to measure anxiety and depression ( at enrollment , 1 month , 6 months ) , posttraumatic stress ( 6 months ) , and complicated grief ( 6 months ) . Results We interviewed all 50 participants at enrollment , 39 ( 78 % ) at 1 month , and 34 ( 68 % ) at 6 months . At the three time points , anxiety was present in 42 % ( 95 % CI , 29–56 % ) , 21 % ( 95 % CI , 10–35 % ) , and 15 % ( 95 % CI , 6–29 % ) of participants . Depression was present in 16 % ( 95 % CI , 8–28 % ) , 8 % ( 95 % CI , 2–19 % ) , and 6 % ( 95 % CI , 1–18 % ) . At 6 months , 35 % ( 95 % CI , 21–52 % ) of participants had posttraumatic stress . Of the 38 % who were bereaved , 46 % ( 95 % CI , 22–71 % ) had complicated grief . Posttraumatic stress was not more common in bereaved than nonbereaved participants , and neither posttraumatic stress nor complicated grief was associated with decision-making role preference or with anxiety or depression during the patient ’s ICU stay . Conclusions Symptoms of anxiety and depression diminished over time , but both bereaved and nonbereaved participants had high rates of posttraumatic stress and complicated grief . Family members should be assessed for posttraumatic stress and complicated grief & NA ; Although acting as a surrogate decision maker can be highly distressing for some family members of intensive care unit patients , little is known about whether there are modifiable risk factors for the occurrence of such difficulties . Objectives : To identify : 1 ) factors associated with lower levels of confidence among family members to function as surrogates and 2 ) whether the quality of clinician – family communication is associated with the timing of decisions to forego life support . Methods : We conducted a prospect i ve study of 230 surrogate decision makers for incapacitated , mechanically ventilated patients at high risk of death in four intensive care units at University of California San Francisco Medical Center from 2006 to 2007 . Surrogates completed a question naire addressing their perceived ability to act as a surrogate and the quality of their communication with physicians . We used clustered multivariate logistic regression to identify predictors of low levels of perceived ability to act as a surrogate and a Cox proportional hazard model to determine whether quality of communication was associated with the timing of decisions to withdraw life support . Results : There was substantial variability in family members ’ confidence to act as surrogate decision makers , with 27 % rating their perceived ability as 7 or lower on a 10-point scale . Independent predictors of lower role confidence were the lack of prior experience as a surrogate ( odds ratio 2.2 , 95 % confidence interval [ 1.04–4.46 ] , p = .04 ) , no prior discussion s with the patient about treatment preferences ( odds ratio 3.7 , 95 % confidence interval [ 1.79–7.76 ] , p < .001 ) , and poor quality of communication with the ICU physician ( odds ratio 1.2 , 95 % confidence interval [ 1.09–1.35 ] p < .001 ) . Higher quality physician – family communication was associated with a significantly shorter duration of life-sustaining treatment among patients who died ( & bgr ; = 0.11 , p = .001 ) . Conclusions : Family members without prior experience as a surrogate and those who had not engaged in advanced discussion s with the patient about treatment preferences were at higher risk to report less confidence in carrying out the surrogate role . Better- quality clinician – family communication was associated with both more confidence among family members to act as surrogates and a shorter duration of use of life support among patients who died Objective Anxiety and depression may have a major impact on a person ’s ability to make decisions . Characterization of symptoms that reflect anxiety and depression in family members visiting intensive care patients should be of major relevance to the ethics of involving family members in decision-making , particularly about end-of-life issues . Design Prospect i ve multicenter study . Setting Forty-three French intensive care units ( 37 adult and six pediatric ) ; each unit included 15 patients admitted for longer than 2 days . Patients Six hundred thirty-seven patients and 920 family members . Interventions Intensive care unit characteristics and data on the patient and family members were collected . Family members completed the Hospital Anxiety and Depression Scale to allow evaluation of the prevalence and potential factors associated with symptoms of anxiety and depression . Measurements and Main Results Of 920 Hospital Anxiety and Depression Scale question naires that were completed by family members , all items were completed in 836 question naires , which formed the basis for this study . The prevalence of symptoms of anxiety and depression in family members was 69.1 % and 35.4 % , respectively . Symptoms of anxiety or depression were present in 72.7 % of family members and 84 % of spouses . Factors associated with symptoms of anxiety in a multivariate model included patient-related factors ( absence of chronic disease ) , family-related factors ( spouse , female gender , desire for professional psychological help , help being received by general practitioner ) , and caregiver-related factors ( absence of regular physician and nurse meetings , absence of a room used only for meetings with family members ) . The multivariate model also identified three groups of factors associated with symptoms of depression : patient-related ( age ) , family-related ( spouse , female gender , not of French descent ) , and caregiver-related ( no waiting room , perceived contradictions in the information provided by caregivers ) . Conclusions More than two-thirds of family members visiting patients in the intensive care unit suffer from symptoms of anxiety or depression . Involvement of anxious or depressed family members in end-of-life decisions should be carefully discussed In some intensive care units ( ICUs ) , fewer patients who die now undergo attempts at cardiopulmonary resuscitation ( CPR ) , and many more have life support actively withdrawn prior to death than did a decade ago . To determine the frequency of withdrawal of life support , we contacted every American postgraduate training program with significant clinical exposure to critical care medicine , asking them prospect ively to classify patients who died into one of five mutually exclusive categories . We received data from 131 ICUs at 110 institutions in 38 states . There were 6,303 deaths , of which 393 patients were brain dead . Of the remaining 5,910 patients who died , 1,544 ( 23 % ) received full ICU care including failed cardiopulmonary resuscitation ( CPR ) ; 1,430 ( 22 % ) received full ICU care without CPR ; 797 ( 10 % ) had life support withheld ; and 2,139 ( 38 % ) had life support withdrawn . There was wide variation in practice among ICUs , with ranges of 4 to 79 % , 0 to 83 % , 0 to 67 % , and 0 to 79 % in these four categories , respectively . Variation was not related to ICU type , hospital type , number of admissions , or ICU mortality . We conclude that limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs . There is wide variation in end-of-life care , and efforts are needed to underst and practice patterns and to establish st and ards of care for patients dying in ICUs BACKGROUND There is a need for close communication with relatives of patients dying in the intensive care unit ( ICU ) . We evaluated a format that included a proactive end-of-life conference and a brochure to see whether it could lessen the effects of bereavement . METHODS Family members of 126 patients dying in 22 ICUs in France were r and omly assigned to the intervention format or to the customary end-of-life conference . Participants were interviewed by telephone 90 days after the death with the use of the Impact of Event Scale ( IES ; scores range from 0 , indicating no symptoms , to 75 , indicating severe symptoms related to post-traumatic stress disorder [ PTSD ] ) and the Hospital Anxiety and Depression Scale ( HADS ; subscale scores range from 0 , indicating no distress , to 21 , indicating maximum distress ) . RESULTS Participants in the intervention group had longer conferences than those in the control group ( median , 30 minutes [ interquartile range , 19 to 45 ] vs. 20 minutes [ interquartile range , 15 to 30 ] ; P<0.001 ) and spent more of the time talking ( median , 14 minutes [ interquartile range , 8 to 20 ] vs. 5 minutes [ interquartile range , 5 to 10 ] ) . On day 90 , the 56 participants in the intervention group who responded to the telephone interview had a significantly lower median IES score than the 52 participants in the control group ( 27 vs. 39 , P=0.02 ) and a lower prevalence of PTSD-related symptoms ( 45 % vs. 69 % , P=0.01 ) . The median HADS score was also lower in the intervention group ( 11 , vs. 17 in the control group ; P=0.004 ) , and symptoms of both anxiety and depression were less prevalent ( anxiety , 45 % vs. 67 % ; P=0.02 ; depression , 29 % vs. 56 % ; P=0.003 ) . CONCLUSIONS Providing relatives of patients who are dying in the ICU with a brochure on bereavement and using a proactive communication strategy that includes longer conferences and more time for family members to talk may lessen the burden of bereavement . ( Clinical Trials.gov number , NCT00331877 . Objective : To assess the impact of an intensive care unit diary on the psychological well-being of patients and relatives 3 and 12 months after intensive care unit discharge . Design : Prospect i ve single-center study with an intervention period between two control periods . Setting : Medical-surgical intensive care unit in a 460-bed tertiary hospital . Patients : Consecutive patients from May 2008 to November 2009 and their relatives . Study inclusion occurred after the fourth day in the intensive care unit . Interventions : A diary written by both the patient ’s relatives and the intensive care unit staff . Measurements and Main Results : Patients and relatives completed the Hospital Anxiety and Depression Scale and Peritraumatic Dissociative Experiences Question naire 3 months after intensive care unit discharge , and completed the Impact of Events Scale assessing posttraumatic stress – related symptoms 12 months after intensive care unit discharge . Of the 378 patients admitted during the study period , 143 were included ( 48 in the prediary period , 49 in the diary period , and 46 in the postdiary period ) . In relatives , severe posttraumatic stress – related symptoms after 12 months varied significantly across periods ( prediary 80 % , diary 31.7 % , postdiary 67.6 % ; p<.0001 ) . Similar results were obtained in the posttraumatic stress – related symptom score after 12 months in the surviving patients ( prediary 34.6 ± 15.9 , diary 21 ± 12.2 , and postdiary 29.8 ± 15.9 ; p = .02 ) . Conclusions : The intensive care unit diary significantly affected posttraumatic stress – related symptoms in relatives and surviving patients 12 months after intensive care unit discharge BACKGROUND Relatives of patients recovering from critical illness are at risk of developing posttraumatic stress disorder . OBJECTIVES To test whether providing a diary to intensive care patients and their relatives reduces the level of symptoms related to posttraumatic stress disorder in the relatives . METHODS Observational study of close family members of patients who stayed more than 72 hours in an intensive care unit , recruited in 2 centers of a 12-center r and omized controlled trial examining the effect of a diary outlining the details of the patients ' stay in the intensive care unit on the development of new-onset posttraumatic stress disorder in patients . The close family members of the patients were recruited to examine the additional effect of the provision of the patient 's diary on the family members ' symptoms related to posttraumatic stress syndrome . RESULTS Thirty-six family members were recruited , and 30 completed the study . Family members of patients who received their diary at 1 month had lower levels of symptoms related to posttraumatic stress disorder ( P = .03 ) at the 3-month follow-up than did the control family members . CONCLUSIONS Provision of a diary may help psychological recovery in patients ' families after critical illness Aims : To identify the relatives of the intensive care unit ( ICU ) patients at risk for developing symptoms of posttraumatic stress disorders . Setting : A multidisciplinary hospital ICU . Design : Prospect i ve single center observational study . Material and Methods : Relatives of patients admitted in the ICU ( May06-Nov06 ) who consented to answer the question naire participated in the study . Anxiety was assessed by using the Hospital Anxiety and Depression Scale ( HAD ) and vulnerability to posttraumatic disorder ( PTSD ) by using the Impact of Event Scale Revised ( IES-R ) which was administered on the fifth day of admission and at two months following discharge or death . Results : During admission , 48 % of the relatives had a HAD score > 11 and 72 % showed IES-R score > 26 . There was no association of HAD with gender , patient outcome , working status , age of the patient , or mode of payment of the bills . There was significant association of IES-R > 26 with trauma admission , HAD score > 11 and mode of payment with the relatives of insured being more stressed as compared to those who settled their bills personally . A total of 35 % relatives showed symptoms of posttraumatic stress reaction consistent with a high risk of PTSD after two months . Death in the hospital result ed in elevated HAD and IES-R score during admission and at the two month follow-up . Persistence of stress symptoms was more in school drop outs , working relatives , parents and those with initial anxiety score > 11 . Conclusions : HAD score greater than 11 was the only factor at admission which could statistically predict a higher PTSD score on follow-up . Adequate counseling of this group of relatives may prevent lasting psychological sequelae of an ICU admission in the relatives of critically ill |
10,878 | 26,797,158 | A greater risk reduction in CI-AKI in the statin group significantly correlated with higher estimated glomerular filtration rate ( eGFR ; p=0.003 ) CONCLUSIONS : The present trial sequential analysis provides support for statins in reducing the incidence of CI-AKI in patients undergoing CAG/PCI .
This effect appeared to be greater in patients with higher eGFR | BACKGROUND Contrast-induced acute kidney injury ( CI-AKI ) is a potential complication in coronary angiography ( CAG ) and percutaneous coronary interventions ( PCI ) .
Prior r and omized controlled trials ( RCTs ) have suggested that statins may play a role in reducing rates of CI-AKI , however it is not clear how firm the current evidence is .
OBJECTIVES The aim of this study was to conduct a meta- analysis and trial sequential analysis to determine the effects of statins in lowering CI-AKI rates in CAG and PCI . | Contrast-induced nephropathy limits the outcomes of percutaneous coronary intervention ( PCI ) . The present study compared the protective effects of different statin doses on renal function . A total of 228 patients with acute coronary syndrome undergoing selective PCI were r and omly divided into simvastatin 20-mg group ( S20 , n = 115 ) and simvastatin 80-mg group ( S80 , n = 113 ) . Serum creatinine was measured at admission , the day of PCI , and 24 and 48 hours after PCI . The creatinine clearance was calculated using the Cochcroft-Gault formula . High-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 were also measured before and after the procedure . Contrast-induced nephropathy was defined as a postprocedure increase in serum creatinine of > or = 0.5 mg/dl or > 25 % from baseline . The serum creatinine significantly increased after PCI , with the peak value occurring at 24 hours , and then began to decrease . At 48 hours , the serum creatinine had decreased to the baseline level in the S80 group , but it had failed to do so in the S20 group . At 24 and 48 hours after PCI , the serum creatinine was lower in the S80 group than in the S20 group ( p < 0.05 and p < 0.001 , respectively ) . The creatinine clearance significantly decreased after PCI , with the lowest value occurring at 24 hours , and then it began to increase . In the S80 group , the creatinine clearance recovered to baseline level at 48 hours , but it failed to do so in the S20 group . The creatinine clearance was greater at 24 and 48 hours in the S80 group than that in the S20 group . Although the procedure caused a significant increase in high-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 levels , the value was lower in the S80 group than in the S20 group ( p < 0.001 ) . In conclusion , pretreatment with simvastatin 80 mg before PCI could further decrease the occurrence of contrast-induced nephropathy compared with simvastatin 20 mg . This benefit was associated with the lowering of high-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 levels We investigated the efficacy of short-term high-dose atorvastatin in decreasing the risk of contrast-induced nephropathy ( CIN ) in patients with chronic kidney disease ( CKD ) subjected to coronary angiography and /or angioplasty . CIN occurs in up to 15 % of patients with pre-existing CKD and affects clinical outcome . The protective effect of statin therapy against CIN is still controversial . A prospect i ve , single-center study of 304 patients with baseline estimated creatinine clearance < 60 ml/min were r and omized to receive atorvastatin 80 mg/day or placebo for 48 hours before and 48 hours after contrast medium administration . All patients received intravenous saline hydration and oral N-acetylcysteine 1,200 mg 2 times/day . Iso-osmolar contrast medium was used . CIN was defined as an absolute increase of serum creatinine > or = 0.5 mg/dl within 5 days after the procedure . CIN occurred in 31 patients ( 10 % ) , 16 ( 11 % ) in the placebo group and 15 ( 10 % ) in the atorvastatin group ( p = 0.86 ) . Mean increase in creatinine was not significantly different in the 2 groups ( 0.59 + or - 0.17 in placebo group vs 0.72 + or - 0.26 mg/dl in atorvastatin group , p = 0.31 ) . Persistent kidney injury , defined as 1-month increase from baseline creatinine value > or = 25 % , was observed in 30 % in the placebo group and in 31 % in the atorvastatin group ( p = 0.58 ) . In conclusion , a short-term administration of high doses of atorvastatin before and after contrast exposure , in addition to st and ard intravenous hydration and oral N-acetylcysteine , does not decrease CIN occurrence in patients with pre-existing CKD Objectives : To investigate whether preprocedural high-dose atorvastatin decreases the incidence of contrast-induced nephropathy ( CIN ) and protects the renal function after emergency percutaneous coronary intervention ( PCI ) . Methods : Statin-naive patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) undergoing emergency PCI ( n = 161 ) r and omly received atorvastatin ( 80 mg , n = 78 , ATOR group ) or placebo [ n = 83 , control ( CON ) group ] followed by long-term atorvastatin ( 40 mg/day ) . The primary end point was incidence of CIN . Results : In the ATOR group , 2.6 % of the patients developed CIN versus 15.7 % in the CON group ( p = 0.01 ) . In the ATOR group , postprocedural serum creatinine was significantly lower ( 93.4 ± 17.1 vs. 112.6 ± 23.3 µmol/l at 48 h and 84.2 ± 14.2 vs. 95.3 ± 17.7 µmol/l at 72 h , both p < 0.0001 ) and in the CON group , peak serum cystatin C was lower ( 0.51 ± 0.14 vs. 0.61 ± 0.13 mg/l , p < 0.0001 ) . Atorvastatin pretreatment was independently associated with a decreased risk of CIN ( OR 0.084 , 95 % CI 0.015–0.462 , p = 0.004 ) . The proportion of alanine aminotransferase > 3 × upper limit of the normal value within 1 month was 3.85 versus 1.20 % ( ATOR vs. CON group , p = 0.57 ) . Conclusion : Preprocedural high-dose atorvastatin prevents CIN and protects the renal function in patients with acute STEMI undergoing emergency PCI OBJECTIVE To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy ( CIN ) in patients underwent diagnostic and therapeutic coronary intervention . METHODS All patients received atorvastatin 10 mg/d on the basis of hydrated therapy ( n = 100 ) and high dose group received additional atorvastatin 80 mg at 12 to 24 hours before procedure ( n = 50 ) . Scr , Ccr , blood beta(2)-M , urine NAG/Cr , and urine osmolality before and after the procedure were compared between the groups . RESULTS Baseline demographic characteristics and nephropathy risk factors were similar between groups . Ccr was significantly reduced while blood beta(2)-M and uric NAG/Cr were significantly increased in low dose group ( all P < 0.05 ) . Blood beta(2)-M in the high dose group was significantly lower than that in the low dose group at day 1 [ ( 2.35 + /- 0.52 ) mg/L vs. ( 2.67 + /- 0.64 ) mg/L , P = 0.008 ] , day 3 [ ( 2.49 + /- 0.55 ) mg/L vs. ( 2.80 + /- 0.64 ) mg/L , P = 0.011 ] and day 5 [ ( 2.29 + /- 0.53 ) mg/L vs. ( 2.56 + /- 0.66 ) mg/L , P = 0.026 ] post-procedure respectively;urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [ ( 1.19 + /- 0.30 ) U/mmol vs. ( 1.46 + /- 0.34 ) U/mmol , P < 0.001 ] , day 3 [ ( 1.30 + /- 0.30 ) U/mmol vs. ( 1.59 + /- 0.33 ) U/mmol , P < 0.001 ] , and day 5 [ ( 1.10 + /- 0.30 ) U/mmol vs. ( 1.34 + /- 0.35 ) U/mmol , P = 0.001 ] post-procedure respectively;Ccr in the high dose group was significantly higher than that in the low dose group at day 1 [ ( 73.69 + /- 20.99 ) ml/min vs. ( 65.19 + /- 18.72 ) ml/min , P = 0.035 ] , day 3 [ ( 64.04 + /- 15.82 ) ml/min vs. ( 56.79 + /- 14.50 ) ml/min , P = 0.019]post-procedure respectively . CONCLUSION High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction Background — The role of statins in the prevention of contrast-induced acute kidney injury ( CIAKI ) is controversial . Methods and Results — First , we investigated the in vivo effects of atorvastatin on CIAKI . Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events ( NAPLES ) II trial were r and omly assigned to ( 1 ) the atorvastatin group ( 80 mg within 24 hours before contrast media [ CM ] exposure ; n=202 ) or ( 2 ) the control group ( n=208 ) . All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution . Second , we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells . CIAKI ( ie , an increase > 10 % of serum cystatin C concentration within 24 hours after CM exposure ) occurred in 9 of 202 patients in the atorvastatin group ( 4.5 % ) and in 37 of 208 patients in the control group ( 17.8 % ) ( P=0.005 ; odds ratio=0.22 ; 95 % confidence interval , 0.07–0.69 ) . CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease ( estimated glomerular filtration rate , 31–60 mL/min per 1.73 m2 ) . In the in vitro model , pretreatment with atorvastatin ( 1 ) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and ( 2 ) restored the survival signals ( mediated by Akt and ERK pathways ) . Conclusions — A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI . This beneficial effect is observed only in patients at low to medium risk A decline in kidney function after contrast exposure is associated with a high risk of morbidity and mortality during hospitalization and over long-term periods . Several retrospective and recent prospect i ve clinical trials have shown that statin therapy might prevent contrast-induced nephropathy in patients undergoing percutaneous coronary intervention . In this study , we aim ed to assess the effects of statin therapies on renal function parameters in patients undergoing elective coronary angiography . One hundred and sixty patients undergoing elective coronary angiography were r and omized equally into two groups : atorvastatin 40 mg/day group ( statin started 3 days before coronary angiography ) and an untreated control group . An additional 80 patients were included as a chronic statin therapy group . Serum creatinine , serum cystatin C , and glomerular filtration rate ( GFR ) were measured before and 48 h after coronary angiography . Cockcroft – Gault and Modification of Diet in Renal Disease ( MDRD ) equations were used to determine GFR . After coronary angiography , serum creatinine and GFR determined by MDRD were significantly better in patients using atorvastatin than those in controls ( P = 0.002 and P = 0.004 , respectively ) . Postprocedure serum creatinine , cystatin C , and GFR determined by MDRD were also significantly better in chronic statin therapy group than those in controls ( P = 0.006 , P = 0.003 , and P = 0.004 , respectively ) . There were no differences in renal function parameters between the short-term atorvastatin group and the chronic statin therapy group . Our data demonstrate that the use of short-term atorvastatin and chronic statin therapy may have a role in protecting renal function after elective coronary angiography OBJECTIVE To evaluate the efficacy of atorvastatin in preventing contrast agent-induced nephropathy ( CIN ) in patients undergoing coronary angiography and explore the mechanism . METHODS A total of 180 patients undergoing coronary angiography or percutaneous coronary interventions ( PCI ) were r and omized into regular dose and high dose atorvastatin groups ( n=90 ) . Serum creatinine ( Scr ) , glomerular filtration rate ( GFR ) , cystatin , peripheral blood levels of myeloperoxidase ( MPO ) , malondialdehyde ( MDA ) , and superoxide dismutase ( SOD ) before and after the procedure were compared between the two groups . RESULTS The incidence of CIN was significantly lower in high-dose atorvastatin group than in the regular dose group . At 48 - 72 h after the surgery , serum Scr and cystatin levels were significantly lower and eGFR was significantly higher in the high-dose group . At 24 h after the surgery , MPO and MDA levels were significantly lower , and SOD activity was significantly higher in high-dose group than in the regular dose group . CONCLUSION High-dose atorvastatin used before angiography is more effective than the regular dose in attenuating contrast agent-induced renal dysfunction , and its mechanism is related with the inhibition of oxidative stress Contrast-induced nephropathy ( CIN ) impairs clinical outcome in patients undergoing angiographic procedures . The aim of this study was to investigate whether short-term high-dose atorvastatin load decreases the incidence of CIN after percutaneous coronary intervention ( PCI ) . Statin-naive patients with acute coronary syndrome undergoing PCI ( n = 241 ) r and omly received atorvastatin ( 80 mg 12 hours before intervention with another 40-mg preprocedure dose , n = 120 ) or placebo ( n = 121 ) . All patients had long-term atorvastatin treatment thereafter ( 40 mg/day ) . Primary end point was incidence of CIN defined as postintervention increase in serum creatinine ≥0.5 mg/dl or > 25 % from baseline . Five percent of patients in the atorvastatin arm developed CIN versus 13.2 % of those in the placebo arm ( p = 0.046 ) . In the atorvastatin group , postprocedure serum creatinine was significantly lower ( 1.06 ± 0.35 vs 1.12 ± 0.27 mg/dl in placebo , p = 0.01 ) , creatinine clearance was decreased ( 80.1 ± 32.2 vs 72.0 ± 26.6 ml/min , p = 0.034 ) , and C-reactive protein peak levels after intervention were decreased ( 8.4 ± 10.5 vs 13.1 ± 20.8 mg/l , p = 0.01 ) . Multivariable analysis showed that atorvastatin pretreatment was independently associated with a decreased risk of CIN ( odds ratios 0.34 , 95 % confidence interval 0.12 to 0.97 , p = 0.043 ) . Prevention of CIN with atorvastatin was paralleled by a shorter hospital stay ( p = 0.007 ) . In conclusion , short-term pretreatment with high-dose atorvastatin load prevents CIN and shortens hospital stay in patients with acute coronary syndrome undergoing PCI ; anti-inflammatory effects may be involved in this renal protection . These results lend further support to early use of high-dose statins as adjuvant pharmacologic therapy before percutaneous coronary revascularization Although statins have been shown to prevent contrast-induced acute kidney injury in patients with acute coronary syndromes , the benefit of statins is not known for patients at high risk for nephropathy who undergo elective coronary angiography . Two hundred twenty consecutive statin-naive patients with chronic kidney disease ( estimated glomerular filtration rate < 60 ml/min/1.73 m(2 ) ) who underwent elective coronary or peripheral angiography were r and omly assigned to receive rosuvastatin ( 40 mg on admission , followed by 20 mg/day ; n = 110 ) or no statin treatment ( control group , n = 110 ) . Contrast-induced acute kidney injury was defined by an absolute increase in serum creatinine of ≥0.5 mg/dl or a relative increase of ≥25 % measured 48 or 72 hours after the procedure . Contrast-induced acute kidney injury occurred in 15 patients ( 7.2 % ) , 9 ( 8.5 % ) in the control group and 6 ( 5.8 % ) in the rosuvastatin group ( p = 0.44 ) . The incidences of adverse cardiovascular and renal events ( death , dialysis , myocardial infa rct ion , stroke , or persistent renal damage ) were similar between the two groups at follow-up . In conclusion , rosuvastatin did not reduce the risk for contrast-induced acute kidney injury or other clinical ly relevant outcomes in at-risk patients who underwent coronary and peripheral vascular angiography BACKGROUND Contrast media cause oxidative stress , which has been suggested as one possible mechanism responsible for contrast-induced nephropathy . Statins appear to have pleiotropic effects , including antioxidant properties . We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography . METHODS We conducted a prospect i ve , r and omized , double-blind , placebo-controlled , 2-center trial , involving 247 consecutive patients with chronic renal insufficiency ( calculated creatinine clearance < or = 60 mL/min and /or serum creatinine > or = 1.1 mg/dL ) undergoing coronary angiography . Patients were r and omized to simvastatin ( n = 124 ; 160 mg total , 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure ) or placebo ( n = 123 ) . All patients received pre - and postprocedure hydration . The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients . RESULTS There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography , the primary study end point ( 0.002 + /- 0.164 vs 0.017 + /- 0.230 mg/mL respectively , P = .559 ) . The incidence of contrast-induced nephropathy , a secondary end point defined as increase of either > or = 25 % or > or = 0.5 mg/dL in serum creatinine , was 2.5 % in simvastatin-treated patients ( 3/118 ) and 3.4 % in placebo-treated patients ( 4/118 ) , a nonsignificant difference ( P = 1.00 ) . There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes . CONCLUSIONS Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography OBJECTIVES This study sought to determine if in addition to st and ard preventive measures on-admission , high-dose rosuvastatin exerts a protective effect against contrast-induced acute kidney injury ( CI-AKI ) . BACKGROUND Patients with acute coronary syndrome ( ACS ) are at high risk for CI-AKI , and the role of statin pre-treatment in preventing renal damage remains uncertain . METHODS Consecutive statin-naïve non-ST elevation ACS patients scheduled to undergo early invasive strategy were r and omly assigned to receive rosuvastatin ( 40 mg on admission , followed by 20 mg/day ; statin group n = 252 ) or no statin treatment ( control group n = 252 ) . CI-AKI was defined as an increase in creatinine concentration of ≥0.5 mg/dl or ≥25 % above baseline within 72 h after contrast administration . RESULTS The incidence of CI-AKI was significantly lower in the statin group than in controls ( 6.7 % vs. 15.1 % ; adjusted odds ratio : 0.38 ; 95 % confidence interval [ CI ] : 0.20 to 0.71 ; p = 0.003 ) . The benefits against CI-AKI were consistent , even applying different CI-AKI definition criteria and in all the pre-specified risk categories . The 30-day incidence of adverse cardiovascular and renal events ( death , dialysis , myocardial infa rct ion , stroke , or persistent renal damage ) was significantly lower in the statin group ( 3.6 % vs. 7.9 % , respectively ; p = 0.036 ) . Moreover , statin treatment given on admission was associated with a lower rate of death or nonfatal myocardial infa rct ion at 6 month follow-up ( 3.6 % vs. 7.2 % , respectively ; p = 0.07 ) . CONCLUSIONS High-dose rosuvastatin given on admission to statin-naïve patients with ACS who are scheduled for an early invasive procedure can prevent CI-AKI and improve short-term clinical outcome . ( Statin Contrast Induced Nephropathy Prevention [ PRATO-ACS ] ; NCT01185938 ) |
10,879 | 27,704,002 | Combined therapy with metronidazole is as effective and safe as carbapenem in treatment of cIAI .
Therefore , combined therapy with metronidazole offers an effective alternative to carbapenem with low risk of drug resistance | Background .
Carbapenem-resistant Enterobacteriaceae has increased dramatically in the last decade , result ing in infections that are difficult to treat and associated with high mortality rates .
To prevent further antibacterial resistance , it is necessary to use carbapenem selectively .
A combination of metronidazole with an antimicrobial agent active against aerobes is an alternative effective treatment for patients with complicated intra-abdominal infections ( cIAIs ) .
This study aim ed to compare efficacy and safety of metronidazole combination therapies and carbapenem and to provide clinical evidence regarding the optimal treatment of cIAI . | Although metronidazole ( MNZ ) has been used worldwide for more than 4 decades as a st and ard therapy for trichomoniasis , anaerobic and amebic infections , resistance to MNZ is still low . MNZ is available as oral , intravenous , and vaginal formulations , but the intravenous formulation of MNZ has not been approved in Japan . We conducted a phase 3 study to evaluate the efficacy and safety of intravenous MNZ combined with ceftriaxone ( CTRX ) in Japanese subjects with infectious peritonitis , abdominal abscess or pelvic inflammatory diseases ( PIDs ) to obtain regulatory approval . A combination of MNZ/CTRX at doses of 500 mg 3 or 4 times a day/1 or 2 g twice a day was administered intravenously to a total of 38 hospitalized subjects . MNZ/CTRX was well tolerated and exhibited excellent clinical and bacteriological efficacy with clinical efficacy rates of 100 % ( 20/20 ) in infectious peritonitis or abdominal abscess subjects and 90.0 % ( 9/10 ) in PID subjects , and the eradication rates in infectious peritonitis or abdominal abscess subjects and PID subjects were 100 % ( 16/16 ) and 100 % ( 4/4 ) , respectively , at the test of cure . MNZ/CTRX was effective in 1 subject in whom a metallo-β-lactamase-producing Bacteroides fragilis strain ( MIC of MNZ , 2 μg/ml ) was identified . The most common treatment-related adverse event was diarrhea ( 23.7 % ) , followed by nausea ( 5.3 % ) . No new safety signals were identified . MNZ/CTRX demonstrated excellent efficacy and was well tolerated in Japanese infectious peritonitis , abdominal abscess and PID subjects . This treatment regimen can be useful for anaerobic infections . Clinical registration number : NCT01473836 Tigecycline ( TGC ) has demonstrated clinical efficacy and safety , in comparison with imipenem/cilastatin in phase 3 clinical trials , for complicated intra-abdominal infection ( cIAI ) . The present study comprised a multicentre , open-label , r and omized study of TGC vs. ceftriaxone plus metronidazole ( CTX/MET ) for the treatment of patients with cIAI . Eligible subjects were r and omized ( 1:1 ) to receive either an initial dose of TGC ( 100 mg ) followed by 50 mg every 12 h or CTX ( 2 g once daily ) plus MET ( 1 - 2 g daily ) , for 4 - 14 days . The primary endpoint was the clinical response in the clinical ly evaluable ( CE ) population at the test of cure ( TOC ) assessment . Of 473 r and omized subjects , 376 were CE . Among these , clinical cure rates were 70.4 % ( 133/189 ) with TGC vs. 74.3 % ( 139/187 ) with CTX/MET ( 95 % CI -13.1 to 5.1 ; p 0.009 for non-inferiority ) . Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores > or = 10 were 56.8 % ( 21/37 ) with TGC vs. 58.3 % ( 21/36 ) with CTX/MET . The microbiologic response was similar between the two treatment arms , with microbiological eradication at TOC achieved in 68.1 % ( 94/138 ) of TGC-treated subjects and 71.5 % ( 98/137 ) of CTX/MET-treated subjects . ( The most frequently reported adverse events ( AEs ) for both treatment arms were nausea ( TGC , 38.6 % vs CTX/MET , 27.7 % ) and vomiting ( TGC , 23.3 % vs CTX/MET , 17.7 % ) . Overall discontinuation rates as a result of an AE were 8.9 % and 4.8 % in TGC- and comparator-treated subjects , respectively . The results obtained in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI BACKGROUND Appropriate antimicrobial therapy results in improved clinical outcomes in complicated intra-abdominal infections ( cIAIs ) . Recent in vitro studies have reported increasing moxifloxacin resistance of Bacteroides species , thereby caution ing empiric use in infections with these organisms . METHODS This pooled analysis of 4 r and omized clinical trials ( 2000 - 2010 ) evaluated the comparative efficacy of moxifloxacin in cIAIs , including infection with anaerobic organisms . The intent-to-treat population included 1209 patients who received moxifloxacin ( 745 microbiologically valid cases ) and 1193 patients who received comparator agents ( 741 microbiologically valid cases ) . RESULTS Overall clinical success rates in the per- protocol population were 85.6 % ( 817 of 955 patients ) for moxifloxacin and 87.8 % ( 860 of 979 patients ) for comparators . Of 642 pretherapy anaerobes from moxifloxacin-treated patients , 561 ( 87.4 % ) were susceptible at ≤2 mg/L , 34 ( 5.3 % ) were intermediate at 4 mg/L , and 47 ( 7.3 % ) were resistant at ≥8 mg/L. Moxifloxacin achieved similar clinical success rates against all anaerobes including those isolated from patients infected with Bacteroides fragilis ( 158 [ 82.7 % ] of 191 patients ) , Bacteroides thetaiotaomicron ( 74 [ 82.2 % ] of 90 patients ) and Clostridium species ( 37 [ 80.4 % ] of 46 patients ) . The overall clinical success rate for all anaerobes was 82.3 % . For all anaerobes combined , the clinical success rate was 83.1 % ( 466 of 561 patients ) for a minimum inhibitory concentration ( MIC ) of ≤2 mg/L , 91.2 % ( 31 of 34 patients ) for an MIC of 4 mg/L , 82.4 % ( 14 of 17 patients ) for an MIC of 8 mg/L , 83.3 % ( 5 of 6 patients ) for an MIC of 16 mg/L , and 66.7 % ( 16 of 24 patients ) for an MIC of ≥32 mg/L. CONCLUSIONS Moxifloxacin demonstrated clinical success for intra-abdominal infections caused by both aerobic and anaerobic isolates . More than 87 % of baseline anaerobic isolates from intra-abdominal infections were susceptible to moxifloxacin , and efficacy was maintained beyond the current susceptibility breakpoint MIC of ≤2 mg/L against major anaerobes Summary In an open , r and omised , multicentre trial , the efficacy and tolerability of empirical meropenem monotherapy ( 1 g intravenously every 8 hours ) and cefotaxime ( 2 g every 8 hours ) plus metronidazole ( 0.5 g intravenously every 8 hours ) for 5 to 10 days was compared in 94 patients with serious intra-abdominal infection who required surgery . Eighty-three patients had an evaluable clinical response . Significantly more patients in the meropenem group had a satisfactory clinical response at the end of treatment ( 41/43 [ 95.3 % ] vs 30/40 [ 75.0 % ] ; p=0.008 ) . The bacteriological response was also higher in the meropenem group ( 31/33 vs 26/32 ) . In the bacteriologically evaluable population , a satisfactory clinical response was observed in 31/33 of those who received meropenem compared to 24/32 of the cefotaxime/metronidazole recipients ( p=0.03 ) . Empirical meropenem monotherapy should prove a useful alternative to the currently st and ard combination treatment for serious intraabdominal infections . ZusammenfassungIn einer offenen , r and omisierten Multicenter-Studie wurden die Wirksamkeit und Verträglichkeit einer initialen Monotherapie mit Meropenem ( MEM , 1 g 3 × tägl . i.v . ) mit der etablierten Kombinationstherapie Cefotaxim ( CTX ) plus Metronidazol ( MTR ) ( 2 g CTX+0.5 g MTR 3 × tägl . i.v . ) verglichen . 94 Patienten mit operationspflichtigen schweren intraabdominellen Infektionen wurden einbezogen . Davon waren 83 Patienten bezüglich klinischem Ansprechen auswertbar . Die klinische Wirksamkeit war in der MEM-Gruppe signifikant höher ( 41/43 Pat.=95.3 % vs 30/40 Pat.=75 % ; p=0.008 ) . Das bakteriologische Ansprechen war in der MEM-Gruppe ebenfalls höher i m Vergleich zur Kombinationsgruppe ( 31/33 vs 26/32 ) , der Unterschied war jedoch statistisch nicht signifikant . In der bakteriologisch auswertbaren Population war das klinische Ansprechen in der MEM-Gruppe signifikant höher als i m Vergleichskollektiv ( 31/33 vs 24/32 ; p=0.03 ) . MEM erscheint somit für die initiale empirische Monotherapie bei schweren intraabdominellen Infektionen geeignet OBJECTIVES Avibactam , a novel non-β-lactam β-lactamase inhibitor , restores the in vitro activity of ceftazidime against class A , C and some class D β-lactamase-producing pathogens , including those commonly associated with complicated intra-abdominal infections ( cIAIs ) . This r and omized , active-controlled , double-blind , Phase II trial ( NCT00752219 ) aim ed to evaluate the safety and efficacy of ceftazidime/avibactam plus metronidazole compared with meropenem in hospitalized patients with cIAI . METHODS Adults with confirmed cIAI requiring surgical intervention and antibiotics were r and omized 1 : 1 to receive intravenously either ( i ) 2000 mg of ceftazidime plus 500 mg of avibactam plus a separate infusion of 500 mg of metronidazole or ( ii ) 1000 mg of meropenem plus placebo every 8 h for a minimum of 5 days and a maximum of 14 days . The primary efficacy endpoint was the clinical response in microbiologically evaluable ( ME ) patients at the test-of-cure ( TOC ) visit 2 weeks after the last dose of study therapy . RESULTS Overall , 101 patients received ceftazidime/avibactam plus metronidazole ; 102 received meropenem . The median duration of treatment was 6.0 and 6.5 days , respectively . Favourable clinical response at the TOC visit in the ME population was observed in 91.2 % ( 62/68 ) and 93.4 % ( 71/76 ) of patients in the ceftazidime/avibactam plus metronidazole and meropenem groups , respectively ( observed difference : -2.2 % ; 95 % CI : -20.4 % , 12.2 % ) . The incidence of treatment-emergent adverse events was similar for ceftazidime/avibactam plus metronidazole ( 64.4 % ) and meropenem ( 57.8 % ) . CONCLUSIONS Ceftazidime/avibactam plus metronidazole was effective and generally well tolerated in patients with cIAI , with a favourable clinical response rate in the ME population of > 90 % , similar to that of meropenem In a r and omized , double-blind clinical trial conducted at 13 medical centers , meropenem ( 1,000 mg given iv every 8 hours ) was compared with the combination of clindamycin ( 900 mg every 8 hours ) plus tobramycin ( 5 mg/[kg.d ] in three divided doses ) given iv for the treatment of intra-abdominal infections that required surgery and parenteral antibiotic therapy . At the end of treatment , efficacy data on patients who met study inclusion criteria ( intent-to-treat ) were available for 132 of 215 patients in the meropenem group and 134 of 212 patients in the clindamycin/tobramycin group ; 120 ( 91 % ) of 132 intent-to-treat patients in the meropenem group were cured , 115 ( 86 % ) of 134 intent-to-treat patients in the clindamycin/tobramycin group were cured ( P value , not significant ) . Of the patients treated with meropenem and considered evaluable according to the study protocol , 89 ( 92 % ) of 97 were cured , and 81 ( 86 % ) of 94 patients treated with clindamycin/tobramycin and considered evaluable were cured . Bacteriologic response rates for all evaluable patients ( n = 191 ) were 96 % ( 93 of 97 patients ) among those r and omized to the meropenem arm and 93 % ( 87 of 94 ) among those r and omized to the clindamycin/tobramycin arm . Adverse events occurred with similar frequency in both treatment groups ; neither seizures nor deaths related to treatment were reported for any patients in either group . The results of this trial demonstrated that meropenem , together with appropriate surgical intervention , was safe and effective in the treatment of patients who had bacterial intra-abdominal infections , most of which were secondary to complicated appendicitis OBJECTIVE To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients . DESIGN Prospect i ve , r and omized , double-blind multicenter study . SETTING University-affiliated hospitals in the United States and Canada . PATIENTS Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management . INTERVENTION Cefepime , 2 g , was administered intravenously every 12 hours ( n= 164 ) in addition to metronidazole , 500 mg ( or 7.5 mg/kg ) intravenously every 6 hours . Imipenen-cilastatin sodium , 500 mg , was administered intravenously every 6 hours ( n= 159 ) . Surgical infection management was determined by the patients ' surgeons . MAIN OUTCOME ASSESSMENT S : Clinical cure , defined as elimination of all signs and symptoms relevant to the original infection ; and treatment failure , defined as persistence , increase or worsening of signs and symptoms result ing in an antibiotic change , requirement of an additional surgical procedure to cure the infection , or a wound infection with fever . RESULTS Of the initial isolates , 84 % were susceptible to cefepime and 92 % were susceptible to imipenem-cilastatin . Among the 217 protocol -valid patients , those treated with cefepime+metronidizole were deemed clinical cures ( 88 % ) more frequently than were imipenem-cilastatin-treated patients ( 76 % ) ( P=.02 ) . Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome ( severity of presenting illness , isolation of enterococcus , type of infection , and duration of pre study hospitalization ) , there was a trend ( P=.06 ) toward a higher cure rate favoring cefepime+metronidazole . Pathogens were eradicated in significantly ( P=.01 ) more patients treated with combined cefepime and metronidazole ( 89 % ) than with imipenem-cilastatin ( 76 % ) . CONCLUSION The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections 515 patients with intra-abdominal infection participated in an open r and omized comparative multicenter trial in order to compare the efficacy , safety , and tolerance of imipenem/cilastatin with cefuroxime/metronidazole . 258 patients ( mean age 56 years ) received imipenem/cilastatin 1.5 - 2.0 g/day , and 257 patients ( mean age 54 years ) received cefuroxime 3.0 - 4.5 g/day plus metronidazole 1.0 - 1.5 g/day for at least 3 days . 130/161 evaluable patients ( 80.8 % ) receiving imipenem/cilastatin and 124/145 evaluable patients ( 85.5 % ) receiving cefuroxime/metronidazole were clinical ly cured . The microbiological response was favorable in 86.9 % in the imipenem/cilastatin group and in 90.8 % in the cefuroxime/metronidazole group . The two treatment groups were similar with respect to median time to defervescence which was 4 days . The median duration of treatment was 6 days and the median time to discharge from hospital was 9 days in both groups . Drug-related adverse reactions were observed in 14 patients receiving iminpenem/cilastatin and in 8 patients receiving cefuroxime/metronidazole . 19 patients in the imipenen/cilastatin group and 12 patients in the cefuroxime/metronidazole group died . No correlation was found between the deaths and the study drugs . The present study shows that intra-abdominal infections can be treated successfully with imipenem/cilastatin as well as with cefuroxime/metronidazole OBJECTIVE In a r and omized , double-blind , multicenter trial , ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections . A secondary objective was to demonstrate the ability to switch responding patients from intravenous ( IV ) to oral ( PO ) therapy . SUMMARY BACKGROUND DATA Intra-abdominal infections result in substantial morbidity , mortality , and cost . Antimicrobial therapy often includes a 7- to 10-day intravenous course . The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity . METHODS Patients were r and omized to either ciprofloxacin plus metronidazole intravenously ( CIP/MTZ IV ) or imipenem intravenously ( IMI IV ) throughout their treatment course , or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed ( CIP/MTZ IV/PO ) . RESULTS Among 671 patients who constituted the intent-to-treat population , overall success rates were as follows : 82 % for the group treated with CIP/MTZ IV ; 84 % for the CIP/MTZ IV/PO group ; and 82 % for the IMI IV group . For 330 valid patients , treatment success occurred in 84 % of patients treated with CIP/MTZ IV , 86 % of those treated with CIP/MTZ IV/PO , and 81 % of the patients treated with IMI IV . Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed . Of 46 CIP/MTZ IV/PO patients ( active oral arm ) , treatment success occurred in 96 % , compared with 89 % for those treated with CIP/MTZ IV and 89 % for those receiving IMI IV . Patients who received intravenous/oral therapy were treated , overall , for an average of 8.6 + /- 3.6 days , with an average of 4.0 + /- 3.0 days of oral treatment . CONCLUSIONS These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid population s. Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings Background : Presumptive antimicrobial therapy is an important aspect of the management of intra-abdominal infections . Together with surgery , antimicrobial combinations are still widely used to achieve the required spectrum of activity . The aim of this study was to evaluate the efficacy of parenteral cefepime + metronidazole vs imipenemcilastatin for the treatment of intra-abdominal infections in adult patients . Methods : Patients with a clinical ly confirmed diagnosis of intra-abdominal infection were r and omized to one of two treatment regimens : cefepime 2 g iv/12 h plus metronidazole 500 mg/8 h or imipenem-cilastatin 500 mg iv/6 h. The primary measure of clinical response was the decline of pre-treatment signs and symptoms of infection . The duration of follow-up was 30 days . Treatment failure was defined as either a lack of improvement or a worsening of pre-treatment signs and symptoms of infection . Surgical management of the infection was determined by the surgeon-in-charge . Results : Of the 122 intended-to-treat patients included in the study , 60 patients ( 33 men ) were r and omized to cefepime + metronidazole and 61 ( 27 men ) to imipenemcilastatin . Cefepime + metronidazole treatment was successful in 52 ( 87 % ) patients and imipenem-cilastatin in 44 ( 72 % ) patients ( p = 0.004 ) . Microbiological eradication was established in similar proportions in both groups ( cefepime + metronidazole , 43 ; imipenem-cilastatin , 38 ) . Conclusion : Further studies are warranted to confirm the better results with the cefepime + metronidazole regimen for the treatment of intra-abdominal infections Seventy patients admitted for abdominal surgery requiring short-term perioperative prophylaxis were r and omized to receive minocycline + gentamicin or metronidazole + gentamicin . Thirty patients were considered to be infected at the time of surgery and were treated with the same regimen . In the prophylactic cohort , one patient from each group developed postoperative fever . One patient receiving minocycline developed a wound infection . The overall infection rate was 2.6 % . In the treatment cohort , it appeared that the patients receiving metronidazole had more severe underlying diseases than those receiving minocycline . Consequently , more postoperative non-infectious complications were observed in the former . Minocycline + gentamicin appeared at least as effective than metronidazole + gentamicin in preventing postoperative infectious complications associated with abdominal surgery or in treating intra-abdominal infections A total of 192 men and 139 women aged 15 to 89 years with diagnosed intra-abdominal infection were r and omised in a 2:1 ratio to treatment with either intravenous piperacillin/tazobactam ( 3 g/375 mg every six hours ) or clindamycin ( 600 mg every six hours ) plus gentamicin ( 2.5 mg to 5.0 mg/kg every eight to 12 hours ) in a multicentre trial . Of 147 evaluable patients with microbiologically confirmed infections , 104 were treated with piperacillin/tazobactam and 43 with clindamycin plus gentamicin . The diagnoses of perforated appendicitis ( n = 79 ) , other peritonitis ( n = 32 ) , cholecystitis/cholangitis ( n = 18 ) , intraabdominal abscess ( n = 14 ) , and diverticulitis ( n = 3 ) , were distributed proportionately between the two therapeutic groups . Ninety one of 104 patients ( 88 % ) in the piperacillin/tazobactam group and 33 of 43 patients ( 77 % ) in the clindamycin plus gentamicin group were considered cured or improved ( p = 0.13 ) . In the piperacillin/tazobactam group , 80 of 88 ( 91 % ) Bacteroides fragilis group organisms and 68 of 74 ( 92 % ) E coli isolates were eradicated ; in the clindamycin plus gentamicin group , 21 of 25 ( 84 % ) Bacteroides fragilis group isolates and 23 of 30 ( 76 % ) E coli isolates were eradicated . Eleven evaluable patients in the piperacillin/tazobactam group had beta-lactamase-producing organisms that were resistant to piperacillin but susceptible to piperacillin/tazobactam ; in 10 of these patients ( 91 % ) bacteria were eradicated . We conclude that piperacillin/tazobactam is an effective antimicrobial drug for monotherapy of intra-abdominal infections , with efficacy similar to or better than st and ard aminoglycoside/anti-anaerobe combinations In an open , multicentre , r and omised study , the efficacy and safety of meropenem monotherapy as adjuvant antibiotic therapy in the surgical management of intra-abdominal infection was compared with that of the combination of cefotaxime and metronidazole . A total of 160 hospitalised adult patients with intra-abdominal infection requiring surgery were treated intravenously with either meropenem 1 g every 8 h ( by bolus injection or infusion ; n = 77 ) or cefotaxime 2 g and metronidazole 500 mg every 8 h ( n = 83 ) . Clinical and bacteriological responses to antibiotic therapy were assessed at the end of treatment and at 2 - 4 weeks ' follow-up after treatment . The clinical response rates at the end of treatment and follow-up were 91 % and 96 % , respectively , for meropenem and 100 % and 97 % , respectively , for cefotaxime plus metronidazole . The bacteriological response rates were 90 % and 93 % , respectively , for meropenem and 92 % at both time points for cefotaxime plus metronidazole . Both treatments were well tolerated . In this study , meropenem monotherapy was effective and as well tolerated as cefotaxime plus metronidazole . Meropenem monotherapy should , therefore , prove a useful alternative to st and ard combination therapy for the empirical treatment of intra-abdominal infections BACKGROUND This r and omized , open-label , multi-center trial compared tigecycline ( TGC ) , a broad-spectrum glycylcycline , with ceftriaxone-metronidazole ( CTX/MET ) for the treatment of complicated intra-abdominal infections ( cIAI ) . METHODS Eligible subjects were r and omized to receive TGC 100 mg followed by 50 mg q 12 h or CTX 2 g qd plus MET 1 - 2 g daily for 4 - 14 days . Subjects were stratified by Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ≤10 or > 10 and could not receive oral therapy . The primary endpoint was clinical response in the clinical ly evaluable ( CE ) population at the test of cure ( TOC ) assessment 8 - 44 days after the last drug dose . RESULTS Clinical responses in the CE population were 81.8 % ( 162/198 ) vs. 79.4 % ( 150/189 ) for TGC and CTX/MET , respectively ; a weighted estimate of the difference of 1.6 ( 95 % confidence interval [ CI ] -6.4 , 9.6 ) . In the microbiologically evaluable ( ME ) population , microbiological eradication rates were 82.4 % ( 98/119 ) for TGC vs. 79.6 % ( 86/108 ) for CTX/MET : a difference of 2.7 ( 95 % CI -7.9 , 13.3 ) . Common adverse events were nausea ( 21.6 % TGC vs. 21.3 % CTX/MET ) and vomiting ( 17.7 % TGC vs. 13.2 % CTX/MET ) . Discontinuation rates because of adverse events were 7.8 % for TGC and 6.4 % for CTX/MET . CONCLUSIONS Tigecycline was effective in the treatment of cIAI and was non-inferior to CTX/MET for the treatment of cIAI in hospitalized adults . Clinical Trials Identifier : NCT00230971 The efficacy and safety of intravenous ( IV ) ertapenem , 1 and 1.5 g once a day , for treatment of adults with complicated intra-abdominal infection were compared with those of IV ceftriaxone 2 g once a day plus IV metronidazole 500 mg every 8 h. After at least 3 days of IV therapy and satisfactory clinical response , patients could be switched to oral ciprofloxacin plus metronidazole . Fifty-nine patients were r and omized to receive ertapenem 1 g and 51 to receive ertapenem 1.5 g ; 55 patients were r and omized to each comparator group . At the test of cure , 4 - 6 weeks post therapy , in the 1 g cohort , 84 % ( 26/31 ) of patients treated with ertapenem and 85 % ( 35/41 ) with comparator therapy had a favourable clinical and microbiological assessment . Success rates in the 1.5 g cohort were 83 % ( 22/29 ) and 77 % ( 24/31 ) in the ertapenem and comparator groups , respectively . Drug-related adverse events were generally similar in both treatment groups . Ertapenem 1 or 1.5 g once a day followed by optional oral therapy appeared similar to combined therapy with ceftriaxone plus metronidazole with the same optional oral switch for treatment of complicated intra-abdominal infections in adults . Although not compared directly in a r and omized fashion , the efficacy and safety profiles of ertapenem 1 and 1.5 g appeared comparable . Ertapenem was generally well tolerated and had an overall safety profile similar to ceftriaxone plus metronidazole In a r and omized study the clinical and bacteriologic effectiveness of imipenem was compared with the classical combination of netilmicin with clindamycin in patients who had surgery for an intraperitoneal infection , localized or generalized , with positive bacteriologic findings of the specimen taken at surgery . Excluded were all patients who received other antibiotics before surgery , or who died within 3 days after antibiotic therapy was started . Imipenem was given at a dose of 500 mg t.i.d . , clindamycin 600 mg t.i.d . , and netilmicin according to serum levels . The diagnoses ranged from postoperative peritonitis , gallbladder empyema , perforated gastroduodenal ulcer , small bowel perforation with and without obstruction , and perforated appendicitis to perforation of the colon . The bacteriologic work-up included examination of the primary specimen ( aerobic and anaerobic ) , the urine , feces , and serologic testing for C and ida albicans once or twice a week and after the course of antibiotic therapy . In addition , pH measurements of abscesses and drainage fluids were performed . Ninety-three patients entered the study . Forty-seven patients were treated with imipenem ( test group ) , and 46 patients were treated with the combination therapy ( control group ) . The two groups did not show significant differences in age , sex , diagnostic groups , risk factors , primary bacteriology , and duration of therapy ( mean : 6.7 days ) . Thirty-eight patients ( 80.9 % ) treated with imipenem were cured , six patients ( 12.8 % ) were improved , and there were three ( 6.4 % ) failures . The respective numbers for the control group were 31 ( 67.4 % ) , 10 ( 21.7 % ) , and 5 ( 10.9 % ) . The mean duration of hospitalization was 19 days for the test group and 24.5 days for the control group . There were four wound infections in the test group and 11 wound infections in the control group . Imipenem is at least as effective in the adjuvant therapy of intra-abdominal infections as the combination of netilmicin with clindamycin We design ed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections . We included the Acute Physiology and Chronic Health Evaluation ( APACHE II ) index of severity and excluded patients without established infection . Two hundred ninety patients were enrolled , of whom 162 were evaluable . Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality , we found a significant correlation for both with APACHE II score ( p less than 0.0001 for both ) . Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients ( p = 0.043 ) . The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients ( p = 0.018 ) . This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement . Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms . For failures the maximum peak was 6.4 + /- 1.9 micrograms/mL , and time to maximum peak was 4.6 + /- 5.2 days . For successes the maximum peak was 6.1 + /- 1.7 micrograms/mL , occurring at 3.8 + /- 2.6 days . This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen ABSTRACT Ceftolozane-tazobactam ( TOL-TAZ ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens , including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae , that are associated with complicated intra-abdominal infections ( cIAIs ) . This prospect i ve , double-blind , r and omized , multicenter , phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem . Hospitalized adults with cIAIs that required surgical intervention were r and omized ( 2:1 ) to receive intravenous ( i.v . ) TOL-TAZ ( 1.5 g [ containing 1,000 mg TOL and 500 mg TAZ ] every 8 h [ q8h ] ) with or without i.v . metronidazole ( 500 mg q8h ) or i.v . meropenem ( 1 g q8h ) for 4 to 7 days . The primary endpoint was the clinical response at the test-of-cure visit in the microbiologically modified intent-to-treat ( mMITT ) and microbiologically evaluable ( ME ) population s. Secondary measures included the patients ' microbiological response and safety . In total , 82 patients received TOL-TAZ ( 90.2 % with metronidazole ) , and 39 received meropenem . For the mMITT population , clinical cure was seen in 83.6 % of the patients ( 51/61 ; 95 % confidence interval [ CI ] , 71.9 to 91.8 ) who received TOL-TAZ and 96.0 % of the patients ( 24/25 ; 95 % CI , 79.6 to 99.9 ) who received meropenem ( difference , −12.4 % ; 95 % CI , −34.9 % to 11.1 % ) ; in the ME population , clinical cure was seen in 88.7 % and 95.8 % of the patients ( difference , −7.1 % ; 95 % CI , −30.7 % to 16.9 % ) who received TOL-TAZ and meropenem , respectively . TOL-TAZ demonstrated microbiological success against Escherichia coli ( 89.5 % ) , Klebsiella pneumoniae ( 100 % ) , and P. aeruginosa ( 100 % ) . The adverse event rates were similar in the groups ( 50.0 % with TOL-TAZ and 48.8 % with meropenem ) . TOL-TAZ in combination with metronidazole was well tolerated and result ed in clinical and microbiological success rates supportive of further clinical development in patients with cIAIs . ( This study has been registered at Clinical Trials.gov under registration no. NCT01147640 . |
10,880 | 24,777,660 | Conclusions Laparoscopic incisional and ventral hernia repair is a feasible and effective alternative to the open technique .
It is associated with lower incidences of wound infection and shorter length of hospital stay .
Given the relatively short follow-up duration of trials included in the systematic review , trials with long-term follow-up are needed to compare the durability of laparoscopic and open repair | Background Laparoscopic incisional and ventral hernia repair ( LIVHR ) is an alternative approach to conventional open incisional and ventral hernia repair ( OIVHR ) .
A consensus on outcomes of LIVHR when compared with OIVHR has not been reached . | Objective : The aim of the trial was to compare laparoscopic technique with open technique regarding short-term pain , quality of life ( QoL ) , recovery , and complications . Background : Laparoscopic and open techniques for incisional hernia repair are recognized treatment options with pros and cons . Methods : Patients from 7 centers with a midline incisional hernia of a maximum width of 10 cm were r and omized to either laparoscopic ( LR ) or open sublay ( OR ) mesh repair . Primary end point was pain at 3 weeks , measured as the bodily pain subscale of Short Form-36 ( SF-36 ) . Secondary end points were complications registered by type and severity ( the Clavien-Dindo classification ) , movement restrictions , fatigue , time to full recovery , and QoL up to 8 weeks . Results : Patients were recruited between October 2005 and November 2009 . Of 157 r and omized patients , 133 received intervention : 64 LR and 69 OR . Measurements of pain did not differ , nor did movement restriction and postoperative fatigue . SF-36 subscales favored the LR group : physical function ( P < 0.001 ) , role physical ( P < 0.012 ) , mental health ( P < 0.022 ) , and physical composite score ( P < 0.009 ) . Surgical site infections were 17 in the OR group compared with 1 in the LR group ( P < 0.001 ) . The severity of complications did not differ between the groups ( P < 0.213 ) . Conclusions : Postoperative pain or recovery at 3 weeks after repair of midline incisional hernias does not differ between LR and OR , but the LR results in better physical function and less surgical site infections than the OR does . ( Clinical Trials.gov Identifier : NCT00472537 Background The laparoscopic approach has emerged in the search for a surgical technique to decrease the morbidity associated with conventional repair of ventral hernias . In this study we aim ed to compare the results of our open and laparoscopic ventral hernia repairs prospect ively . Methods Between January 2001 and October 2005 , a total of 46 patients diagnosed with ventral hernias ( primary and incisional ) who were admitted to our surgical unit and accepted to be included in this study group were examined . All patients were divided into laparoscopic repair ( n = 23 ) and open repair ( n = 23 ) subgroups in a r and omized fashion . The patients ’ demographic characteristics , operation times , body mass indices , sizes of fascial defects , hernia locations , duration s of hospital stay , presence and degrees of postoperative pain , and postoperative minor and major complications were analysed and compared . All the data were expressed as means ± SDs . Chi-square and Wilcoxon tests were used for statistical analysis , and P < 0.05 was accepted as a significant statistical value ( SPSS 11.0 for Windows ) . Results The demographic characteristics of both groups were similar . Women predominated , especially in the laparoscopy group ( P < 0.05 ) . The comparison of the results revealed that the major advantage of laparoscopy was the shortened postoperative hospital stay and the reduced incidence of mesh infection ( P < 0.05 , P < 0.05 ) . On the other h and , operation time was significantly longer in the laparoscopy group ( P < 0.05 ) . The major complications encountered in the laparoscopy group were ileus and a missed enterotomy . The most frequent minor complication was seroma , which was significantly more frequent in the laparoscopy group ( P < 0.05 ) . Postoperative pain assessment revealed similar results in both groups ( P > 0.05 ) . Conclusions The laparoscopic approach appears to be as effective as open repairs in the treatment of ventral hernias . Advanced surgical skill , laparoscopic experience and high technology are m and atory factors for successful ventral hernia repair BACKGROUND Incisional hernia is an important complication of abdominal surgery . Procedures for the repair of these hernias with sutures and with mesh have been reported , but there is no consensus about which type of procedure is best . METHODS Between March 1992 and February 1998 , we performed a multicenter trial in which we r and omly assigned to suture repair or mesh repair 200 patients who were scheduled to undergo repair of a primary hernia or a first recurrence of hernia at the site of a vertical midline incision of the abdomen of less than 6 cm in length or width . The patients were followed up by physical examination at 1 , 6 , 12 , 18 , 24 , and 36 months . Recurrence rates and potential risk factors for recurrent incisional hernia were analyzed with the use of life-table methods . RESULTS Among the 154 patients with primary hernias and the 27 patients with first-time recurrent hernias who were eligible for the study , 56 had recurrences during the follow-up period . The three-year cumulative rates of recurrence among patients who had suture repair and those who had mesh repair were 43 percent and 24 percent , respectively , with repair of a primary hernia ( P=0.02 ; difference , 19 percentage points ; 95 percent confidence interval , 3 to 35 percentage points ) . The recurrence rates were 58 percent and 20 percent with repair of a first recurrence of hernia ( P=0.10 ; difference , 38 percentage points ; 95 percent confidence interval , -1 to 78 percentage points ) . The risk factors for recurrence were suture repair , infection , prostatism ( in men ) , and previous surgery for abdominal aortic aneurysm . The size of the hernia did not affect the rate of recurrence . CONCLUSIONS Among patients with midline abdominal incisional hernias , mesh repair is superior to suture repair with regard to the recurrence of hernia , regardless of the size of the hernia IMPORTANCE Incisional hernia is the most frequent surgical complication after laparotomy . Up to 30 % of all patients undergoing laparotomy develop an incisional hernia . OBJECTIVE To compare laparoscopic vs open ventral incisional hernia repair with regard to postoperative pain and nausea , operative results , perioperative and postoperative complications , hospital admission , and recurrence rate . DESIGN Multicenter r and omized controlled trial between May 1999 and December 2006 with a mean follow-up period of 35 months . SETTING All patients were operated on in a clinical setting at 1 of the 2 participating university medical centers or at the other 8 teaching hospitals . PARTICIPANTS Two hundred six patients from 10 hospitals were r and omized equally to laparoscopic or open mesh repair . Patients with an incisional hernia larger than 3 cm and smaller than 15 cm , either primary or recurrent , were included . Patients were excluded if they had an open abdomen treatment in their medical histories . INTERVENTION Laparoscopic or open ventral incisional hernia repair . MAIN OUTCOME MEASURES The primary outcome of the trial was postoperative pain . Secondary outcomes were use of analgesics , perioperative and postoperative complications , operative time , postoperative nausea , length of hospital stay , recurrence , morbidity , and mortality . RESULTS Median blood loss during the operation was significantly less ( 10 mL vs 50 mL ; P = .05 ) as well as the number of patients receiving a wound drain ( 3 % vs. 45 % ; P < .001 ) in the laparoscopic group . Operative time for the laparoscopic group was longer ( 100 minutes vs. 76 minutes ; P = .001 ) . Perioperative complications were significantly higher after laparoscopy ( 9 % vs. 2 % ) . Visual analog scale scores for pain and nausea , completed before surgery and 3 days and 1 and 4 weeks postoperatively , showed no significant differences between the 2 groups . At a mean follow-up period of 35 months , a recurrence rate of 14 % was reported in the open group and 18 % , in the laparoscopic group ( P = .30 ) . The size of the defect was found to be an independent predictor for recurrence ( P < .001 ) . CONCLUSIONS AND RELEVANCE During the operation , there was less blood loss and less need for a wound drain in the laparoscopic group . However , operative time was longer during laparoscopy . Perioperative complications were significantly higher in the laparoscopic group . Visual analog scores for pain and nausea did not differ between groups . The incidence of a recurrence was similar in both groups . The size of the defect was found to be an independent factor for recurrence of an incisional hernia BACKGROUND Laparoscopic repair of ventral incisional hernias has not been proved to be safer than open mesh repair . DESIGN Prospect i ve r and omized trial conducted between February 1 , 2004 , to January 31 , 2007 . SETTING Four Veterans Affairs medical centers . PARTICIPANTS One hundred sixty-two patients with ventral incisional hernias . INTERVENTIONS St and ardized laparoscopic or open repair . MAIN OUTCOME MEASURES Overall complication rates at 8 weeks and the odds of complications , adjusted for study site , body mass index , and hernia type . RESULTS Of the 162 r and omized patients , 146 underwent surgery ( 73 open and 73 laparoscopic repairs ) . Complications were less common in the laparoscopic group ( 23 patients [ 31.5 % ] ) compared with the open repair group ( 35 patients [ 47.9 % ] ; adjusted odds ratio [ AOR ] , 0.45 ; 95 % confidence interval [ CI ] , 0.22 - 0.91 ; P = .03 ) . Surgical site infection through 8 weeks was less common in the laparoscopic group ( 5.6 % vs 23.3 % ; AOR , 0.2 ; 95 % CI , 0.1 - 0.6 ) . The mean worst pain score in the laparoscopic group was 15.2 mm lower on a visual analog scale at 52 weeks ( 95 % CI , 1.0 - 29.3 ; P = .04 ) . Time to resume work activities was shorter for the laparoscopic group than for the open repair group ( median , 23.0 days vs 28.5 days ) , with an adjusted hazard ratio of 0.54 ( 95 % CI , 0.28 - 1.04 ; P = .06 ) . Overall recurrence at 2 years was 12.5 % in the laparoscopic group and 8.2 % in the open repair group ( AOR , 1.6 ; 95 % CI , 0.5 - 4.7 ; adjusted P = .44 ) . CONCLUSIONS Laparoscopic repair was associated with fewer , albeit more severe , complications and improved some patient-centered outcomes . Trial Registration clinical trials.gov Identifier : NCT00240188 Background Incisional hernia is a common complication following abdominal surgery . Although the use of prosthetics has decreased recurrence rates , the st and ard open approach is still unsatisfactory . Laparoscopic techniques are an attempt to provide similar outcomes with the advantages of minimally invasive surgery . Methods Open r and omized controlled clinical trial with follow-up at 1 , 2 , 3 , 7 , and 15 days , and 1 , 3 , and 12 months from hernia repair . The study was carried out in the surgery departments of three general hospitals of the Valencia Health Agency . Objectives To compare laparoscopic with anterior open repair using health-related quality of life outcomes as main endpoints . Results Eighty-four patients with incisional hernia were r and omly allocated to an open group ( OG ) ( n = 39 ) or to a laparoscopic group ( LG ) ( n = 45 ) . Seventy-four patients completed 1-year follow up . Mean length of stay and time to oral intake were similar between groups . Operative time was 32 min longer in the LG ( p < 0.001 ) . Conversion rate was 11 % . The local complication rate was superior in the LG ( 33.3 % versus 5.2 % ) ( p < 0.001 ) . Recurrence rate at 1 year ( 7.9 % versus 9.7 % ) was similar in the two groups . There were no significant differences in the pain scores or the EQ5D tariffs between the two groups during follow-up . Conclusions Laparoscopic incisional hernia repair does not seem to be a better procedure than the open anterior technique in terms of operative time , hospitalization , complications , pain or quality of life To compare the early and intermediate results of the open and laparoscopic tension-free repair of incisional hernia , 24 patients were r and omized prospect ively to undergo laparoscopic or open repair of incisional hernia with retromuscular placement of the prosthesis using transabdominal sutures for mesh fixation . All the procedures were completed as planned . The mean duration of surgery was not significantly different between the 2 groups ( P=0.15 ) . Time to oral solid food intake was longer in the open group ( P=0.002 ) . The analgesic requirement was lower in the laparoscopic group ( P=0.05 ) . One patient after open surgery and 2 in the laparoscopic group suffered postoperative complications ( P=0.71 ) . Postoperative stay was shorter in the laparoscopic group ( P=0.006 ) . No readmission or recurrence was registered within 6 months from surgery in either group . Laparoscopic incisional hernia repair , based on the Rives-Stoppa technique , is a safe , feasible alternative to open techniques . However , larger studies and long-term follow-up are required to further evaluate the true effectiveness of this operation Background Incisional hernia is an important complication of abdominal surgery . Its repair has progressed from a primary suture repair to various mesh repairs and laparoscopic repair . Laparoscopic mesh repair is a promising alternative , and in the absence of consensus , needs prospect i ve r and omized controlled trials . Methods Between April 2003 and April 2005 , 66 patients with incisional , primary ventral and recurrent hernias were r and omized to receive either open retrorectus mesh repair or laparoscopic mesh repair . These patients were followed up at 1- , 3- , and 6-month intervals thereafter for a mean of 12.17 months ( open repair group ) and 13.73 months ( laparoscopic repair group ) . Results Lower abdominal hernias after gynecologic operations constituted the majority of the hernias ( ∼50 % ) in both groups . There was no significant injury to viscera or vessel in either group and no conversions . The defect size was 42.12 cm2 in the open ( group 1 ) and 65.66 cm2 in the laparoscopic group ( group 2 ) , and the prosthesis sizes were , respectively , 152.67 cm2 and 203.83 cm2 . The hospital stay was 3.43 days in open group and 1.47 days in laparoscopic group ( p = 0.007 ) . There was no significant difference in the pain scores between the two groups . More wound-related infectious complications occurred in the open group ( 33 % ) than in the laparoscopic group ( 6 % ) ( p = 0.013 ) . There was one recurrence in the open repair group ( 3 % ) and two recurrences in laparoscopic group ( 6 % ) ( p = 0.55 ) . Conclusions Laparoscopic repair of incisional and ventral hernias is superior to open mesh repair in terms of significantly less blood loss , fewer complications , shorter hospital stay , and excellent cosmetic outcome Five hundred and sixty‐four patients review ed 1 year after major abdominal surgery have been studied prospect ively by a single observer for 10 years to determine the incidence and significance of incisional hernia . Of 337 ( 60 per cent ) patients completing the 10 year follow‐up 37 ( 11 per cent ) developed an incisional hernia and 13 ( 35 per cent ) of these first appeared at 5 years or later . One in three hernias caused symptoms . The late appearing hernias were smaller than the early ones , and caused little trouble . Of the 18 patients who consulted their general practitioner , 11 had symptoms and of these six ( 55 per cent ) were referred for surgical opinion . Many hernias were diagnosed at routine outpatient follow‐up and were likely to receive treatment from the surgeon . Most symptomatic patients were offered surgery with the remainder usually being offered a corset . In about half our patients ( mainly those without symptoms ) surgery was refused or advised against although the patients would have accepted it . Recurrence is common after surgical repair ( 40 per cent ) but seems to be related to surgical technique . The possibility of complications occurring from an incisional hernia does not appear to be discussed with patients although obstruction occurred in 14 per cent of our patients with troublesome hernia Abstract Background : Despite being one of the most exact indications , laparoscopic treatment of eventrations and ventral hernias is barely known among the array of laparoscopic techniques . Methods : A total of 60 patients were assigned at r and om over a 3-year period to two homogeneous groups to be operated on for major ventral hernias with mesh . Half of them were operated upon laparoscopically and the rest with open surgery . Early and longer-term complications were analyzed , as were operative time and postoperative hospital stays . Results : The two groups were homogeneous in terms of demographic and clinical characteristics . The group that was operated on laparoscopically presented a lower rate of postoperative and longer-term complications ; similarly , surgery time was significantly lower ( p < 0.05 ) . Hospitalization time was also significantly lower than in the group undergoing conventional open surgery ( p < 0.05 ) . Conclusions : Laparoscopic treatment of postoperative eventration and primary ventral hernia reduces complications and relapse rates , eliminates reintervention through mesh infection , reduces operative time , and considerably shortens the hospital stay HYPOTHESIS The elective treatment of a spigelian hernia is still under discussion , fundamentally owing to its rarity . The purpose of the study is to analyze the elective surgical treatment of spigelian hernia . DESIGN A prospect i ve , r and omized controlled trial . SETTING University teaching hospital . PATIENTS AND INTERVENTIONS Two surgeons performed 11 conventional and 11 laparoscopic repairs for a spigelian hernia , alternating roles as primary surgeon and assistant . Each time the type of technique was r and omly chosen using a computerized program . MAIN OUTCOME MEASURES Epidemiological , clinical , and surgical factors are analyzed according to treatment , ie , the open or laparoscopic approach . RESULTS The statistical study shows no significant differences for epidemiological or diagnostic factors , but it does show significant advantages for laparoscopy in terms of morbidity ( P<.05 ) and hospital stay ( P<.001 ) . CONCLUSION The approach using extraperitoneal laparoscopy is the technique that offers best results in the elective treatment of spigelian hernia Laparoscopic and open techniques are both recognized treatment options for ventral hernias . We conducted a prospect i ve r and omized trial of both methods , to assess hernia recurrence , postoperative recovery and complications . Fifty‐eight patients with ventral hernias were enrolled into the trial between August 2003 and December 2005 . Of these , 31 underwent laparoscopic repair and 27 underwent open repair . Clinical parameters were documented on all patients during a median follow‐up period of 27.5 months . The demographics of the two groups were similar . There was one recurrence in each of the laparoscopic and open groups . There was an equivalent rate of operative time , length of stay , postoperative pain scores , return to normal activities , wound infection and seroma formation between the two groups . Laparoscopic and open ventral hernia repair are comparable and offer low recurrence rates |
10,881 | 23,412,217 | There were wide differences among the studies that assessed the effects of CPs on HF patients , with some contrasting clinical outcomes reported .
Secondary studies that were non-specific for CPs and included other multidisciplinary care approaches as well showed , in some cases , a shorter hospital length of stay ( LOS ) compared to usual care ; studies that focused on promoting early mobilization showed better outcomes of mortality , morbidity , function , or service utilization ; CPs mainly based on intensive occupational therapy and /or physical therapy exercises improved functional recovery and reduced LOS , with patients also discharged to a more favorable discharge destination ; CPs principally focused on early mobilization improved functional recovery .
A secondary study specifically design ed for CPs showed lower odds of experiencing common complications of hospitalization after HF . | The aim of this paper was to perform a systematic overview of secondary literature studies on care pathways ( CPs ) for hip fracture ( HF ) . | Abstract Objective : To evaluate the effect of intensive geriatric rehabilitation on demented patients with hip fracture . Design : Preplanned sub analysis of r and omised intervention study . Settting : Jyväskylä Central Hospital , Finl and . Participants : 243 independently living patients aged 65 years or older admitted to hospital with hip fracture . Intervention : After surgery patients in the intervention group ( n=120 ) were referred to the geriatric ward whereas those in the control group were discharged to local hospitals . Main outcome measures : Length of hospital stay , mortality , and place of residence three months and one year after surgery for hip fracture . Results : The median length of hospital stay of hip fracture patients with moderate dementia ( mini mental state examination score 12 - 17 ) was 47 days in the intervention group ( n=24 ) and 147 days in the control group ( n=12 , P=0.04 ) . The corresponding figures for patients with mild dementia ( score 18 - 23 ) were 29 days in the intervention group ( n=35 ) and 46.5 days in the control group ( n=42 , P=0.002 ) . Three months after the operation , in the intervention group 91 % ( 32 ) of the patients with mild dementia and 63 % ( 15 ) of the patients with moderate dementia were living independently . In the control group , the corresponding figures were 67 % ( 28 ) and 17 % ( 2 ) . There were no significant differences in mortality or in the lengths of hospital stay of severely demented patients and patients with normal mini mental state examination scores . Conclusions : Hip fracture patients with mild or moderate dementia can often return to the community if they are provided with active geriatric rehabilitation Background The incidence of hip fracture is expected to increase during the coming years , dem and ing greater re sources and improved effectiveness on this group of patients . The aim of the present study was to evaluate the effectiveness of an integrated care pathway ( ICP ) in patients with an acute fracture of the hip . Methods A nonr and omized prospect i ve study comparing a consecutive series of patients treated by the conventional pathway to a newer intervention . 112 independently living patients aged 65 years or older admitted to the hospital with a hip fracture were consecutively selected . Exclusion criteria were pathological fracture and severe cognitive impairment . An ICP was developed with the intention of creating a care path with rapid pre-operative attention , increased continuity and an accelerated training programme based on the individual patient 's prerequisites and was used as a guidance for each patient 's tailored care in the intervention group ( N = 56 ) The main outcome measure was the length of hospital stay . Secondary outcomes were the amount of time from the emergency room to the ward , to surgery and to first ambulation , as well as in-hospital complications and 30-day readmission rate . Results The intervention group had a significantly shorter length of hospital stay ( 12.2 vs. 26.3 days ; p < 0.000 ) , a shorter time to first ambulation ( 41 vs. 49 h ; p = 0.01 ) , fewer pressure wounds ( 8 vs. 19 ; p = 0.02 ) and medical complications ( 5 vs. 14 ; p = 0.003 ) than the comparison group . No readmissions occurred within 30 days post-intervention in either group . Conclusion Implementing an ICP for patients with a hip fracture was found to significantly reduce the length of hospital stay and improve the quality of care The purpose of the current study was to evaluate the effectiveness of a multidisciplinary Hip Fracture Service in the treatment of hip fractures in elderly patients . Baseline information and hospital outcomes were compared for 510 patients over the age of 65 with hip fracture treated before and after the institution of the Hip Fracture Service . Data included basic demographic data , admission laboratory results , surgical information , number of comorbidities , mortality , medical complications , discharge information , time to surgery , and length of stay in hospital . The demographics of the two groups of patients were similar . Patients treated as part of the Hip Fracture Service had fewer medical complications ( 36 % vs. 51 % ) , more often had surgery within 24 hours ( 63 % vs. 35 % ) , and had shorter hospital stays ( mean , 5.7 days vs. 8.1 days ) than patients treated before the Hip Fracture Service . These findings provide the rationale for a prospect i ve , r and omized trial of the service OBJECTIVES To evaluate the incremental cost in the year after hip fracture . DESIGN Prospect i ve cohort study . SETTING Baltimore , Maryl and . PARTICIPANTS 759 community dwelling older patients who sustained a hip fracture and participated in the Baltimore Hip Fracture Study . MEASUREMENTS Re source use for direct medical care , formal nonmedical care , and informal care in the 6 months before and the year after fracture was estimated from interviews with patients or proxy respondents . Costs in 1993 dollars were estimated by multiplying re sources times national unit cost estimates . RESULTS The annualized costs in the year before the fracture ranged between $ 18,523 and $ 20,928 . The costs in the year after the fracture equaled $ 37,250 . The incremental costs in the year after the fracture , compared with the costs in the year before the fracture , ranged between $ 16,322 and $ 18,727 . The largest cost differences were attributable to hospitalizations , nursing home stays , and rehabilitation services . CONCLUSIONS Because we compared the costs after a fracture with costs before , our estimates of the incremental cost of a hip fracture are lower than others in the literature . These results , obtained from interviews with patients enrolled in a cohort study , or their proxies , provide the best data available to date on the economic cost of hip fractures among community-dwelling older persons In recent years , intense pressures to reduce the costs of health care have led many health care organizations to seek strategies that reduce re source utilization while maintaining the quality of care [ 1 - 5 ] . Among the most popular of the methods intended to meet this challenge are critical pathways . Critical pathways are management plans that display goals for patients and provide the corresponding ideal sequence and timing of staff actions to achieve those goals with optimal efficiency [ 6 - 8 ] . Interest in critical pathways has increased tremendously during the past several years as early anecdotal reports of their cost-saving potential have been disseminated , usually outside the peer- review ed medical literature [ 7 , 9 , 10 ] . The rapid push for critical pathway implementation comes from intense competitive pressures and the persistent evidence of unexplained variation in medical practice [ 11 , 12 ] . Many managed care organizations have added their weight to this process by m and ating certain critical pathways or seeking partner hospitals that are willing to develop their own [ 7 ] . However , no controlled study has shown a critical pathway to reduce the duration of hospital stay or to decrease re source use , nor has any study shown critical pathways to improve patient satisfaction or outcomes [ 13 ] . Nevertheless , like other promising medical technologies , critical pathways are being disseminated before controlled trials have been done to evaluate their effectiveness . Despite the lack of data , an increasing number of physicians will be asked to participate in critical pathway development . Even more will find that their hospitalized patients are already on pathways that they may or may not have endorsed . To enhance the effectiveness of critical pathways and minimize the disruption to the patientphysician relationshipphysicians and other caregivers must underst and the origin , potential benefits , and potential pitfalls of this new method . Critical Pathways : A New Form of Clinical Guideline Critical pathways have varying formats and are known by many names , including critical paths , clinical pathways , and care paths . Interpreted formally , a critical pathway is the sequence of events in a process that takes the greatest length of time . Like the techniques of continuous quality improvement , critical pathway techniques were first developed for use in industry as a tool to identify and manage the rate-limiting steps in production processes [ 14 - 17 ] . First developed in the 1950s , the Critical Path Method was frequently linked with a similar approach , the Program Evaluation and Review Technique , to coordinate multiple contractors or persons in a project by identifying the key sequence of events , or critical path , the requirements of which would drive the timeline of the overall project [ 18 , 19 ] . Critical pathway techniques have subsequently been applied to projects as diverse as construction , civil engineering , town planning , marketing , ship building , product design , and equipment installation [ 6 ] . Critical pathways were first developed and applied to health care in the 1980s , when prospect i ve payment systems focused greater interest on potential methods to improve hospital efficiency [ 6 ] . Most of the first critical pathways in hospitals were developed by nurses for nursing care alone [ 20 , 21 ] , but multidisciplinary teams soon began developing pathways to encompass all aspects of care for hospitalized patients [ 22 - 24 ] . In general , efforts to develop critical pathways in health care have not incorporated the formal techniques used by industrial predecessors to identify the true critical pathway in any care process [ 18 , 25 ] . Instead , when critical pathways are used to plan medical care , the specific goals usually include the following : 1 . Selecting a best practice when practice styles vary unnecessarily . 2 . Defining st and ards for the expected duration of hospital stay and for the use of tests and treatments . 3 . Examining the interrelations among the different steps in the care process to find ways to coordinate or decrease the time spent in the rate-limiting steps . 4 . Giving all hospital staff a common game plan from which to view and underst and their various roles in the overall care process . 5 . Providing a framework for collecting data on the care process so that providers can learn how often and why patients do not follow an expected course during their hospitalization . 6 . Decreasing nursing and physician documentation burdens . 7 . Improving patient satisfaction with care by educating patients and their families about the plan of care and involving them more fully in its implementation . The general format of critical pathway guidelines is the Gantt chart , which outlines the suggested patient care process based on a time-task matrix , listing the components of care in one column and cross-aligning these entries with columns pertaining to time [ 8 ] . Figure 1 is an example of such a chart for a critical pathway for patients who have had coronary artery bypass graft surgery . Categories of multidisciplinary staff actions are listed in the first column of the pathway , with specific actions for each day of hospitalization . As indicated in Figure 1 , a patient 's diet is expected to progress successfully from ice chips to clear liquids on the first day after surgery . For all other categories of patient care , critical pathways likewise explicitly mark the transition points of patient progress and lay out a coordinated map of staff activities to achieve those transitions in the most efficient way possible . Figure 1 . The first 2 days of a simplified critical pathway for patients who have had cardiac surgery . Critical pathways differ from most clinical guidelines , protocol s , and algorithms in several key respects . First , clinical guidelines often address the appropriateness of care by delineating the indications for tests or treatments . Critical pathways , on the other h and , have almost always focused on the quality and efficiency of care after decisions have already been made to admit the patient or perform the procedure . Another way in which critical pathways differ from most clinical guidelines is that they are multidisciplinary in their development and in the scope of their implementation . Critical pathways are also design ed along specific timelines , sometimes even in hour-by-hour detail , for indicated actions , and pathways not only spell out these specific actions but also enumerate expected intermediate patient outcomes that serve as checkpoints for the performance of both the patient and the pathway . Yet another distinguishing feature of critical pathways is that their comprehensive design allows them to be used as a part of the patient record , often replacing other documentation entirely [ 6 , 24 ] . All staff interventions and intermediate clinical outcomes that occur as expected can be simply initialed on the critical pathway document . If staff actions or intermediate patient outcomes do not occur as expected , however , a variance from the pathway is said to have occurred [ 26 ] . Variances , too , can be noted on the document , along with an explanation of their cause or causes , and , if needed , a plan can be described to return the patient to the expected course of treatment and outcomes . Critical Pathway Development Topic Selection Critical pathways are typically developed for the hospital care associated with high-volume , high-cost diagnoses and procedures , particularly those for which inefficient variation in the process of care is thought to exist [ 6 ] . Surgical procedures , such as coronary artery bypass graft surgery and total hip replacement , lend themselves particularly well to critical pathways because the care process differs relatively little from patient to patient . For this same reason , obstetric procedures such as normal vaginal delivery and cesarean section have also been subjects of pathways in many institutions [ 24 ] . For most medical diagnoses , however , patient care has proved more difficult to translate successfully into critical pathways because of the greater heterogeneity among patients and problems [ 6 , 27 ] . Some institutions have reported that pathways fail when used for medical patients who have either multiple problems and therefore multiple relevant pathways or a problem that does not fit neatly within any single st and ardized pathway [ 27 - 29 ] . Despite these concerns , however , pathways have been design ed and implemented at many institutions for medical diagnoses such as myocardial infa rct ion , stroke , and deep venous thrombosis [ 23 ] . Team Composition The group that is organized to develop a critical pathway should be multidisciplinary in order to bring to the table the knowledge and perspectives that are necessary to view the care process in its entirety . Although many institutions have appointed nurses as the leaders of critical pathway teams [ 6 ] , we have found that having a physician-expert lead each team lends credibility to the pathways and builds a foundation of support among all clinicians . Each pathway team should also have a group facilitator from the hospital administration , a housestaff physician , a member of the quality management department who has expertise in critical pathway methods , and a community-based primary care physician , whose perspective on inpatient care is likely to differ from that of hospital-based physicians . The lack of active involvement by physician-experts is cited as a key reason for the failure of pathway programs ; critical pathways that are developed without physician input have ended up sequestered in a part of the medical record where physicians do not often look [ 27 , 30 ] . Simply gathering physicians , nurses , and other staff around the same table , however , may not be enough to generate the level of teamwork and communication necessary for success . It is an important challenge , especially for physicians trained in an individualistic ethic , to learn how to participate in and lead these teams OBJECTIVE To assess outcomes of using a clinical pathway for managing patients with fractured neck of femur . DESIGN Prospect i ve , pseudor and omised , controlled trial . SETTING St Vincent 's Hospital , Melbourne , Victoria ( a tertiary referral , university teaching hospital ) , 1 October 1997 to 30 November 1998 . PARTICIPANTS 111 patients ( 80 women and 31 men ; mean age , 81 years ) admitted via the emergency department with a primary diagnosis of fractured neck of femur . INTERVENTIONS Management guided by a clinical pathway ( 55 patients ) or established st and ard of care ( control group , 56 patients ) . MAIN OUTCOME MEASURES Timing of referrals and discharge planning ; total length of stay ; and complication and readmission rates within 28 days of discharge . RESULTS Patients managed according to the clinical pathway had a shorter total stay ( 6.6 versus 8.0 days ; P = 0.03 ) , even if assessment for placement by the Aged Care Assessment Service was required ( 9.5 versus 13.6 days ; P = 0.03 ) . There were no significant differences in complication and readmission rates between pathway and control patients ( complication rates , 24 % versus 36 % ; P = 0.40 ; readmission rates , 4 % versus 11 % ; P = 0.28 ) . CONCLUSION Coordinated multidisciplinary care of patients with fractured neck of femur reduces length of stay without increasing complications From November 1988 to December 1989 , all hip fracture patients in the municipality of Malmö , excluding nursing- home patients and patients who were already hospitalized at the time of the fracture , were postoperatively r and omized to rehabilitation at either the orthopedic or the geriatric department in Malmö . The study , which comprised 371 patients , compared the following end points : primary mortality ; destination at discharge ; total first- year mortality ; and the number of hip pros- theses during the first postoperative year . No significant differences were found between the two regimens . One year after the fracture , patients discharged to their previous living arrangements were invited to a control visit conducted by a physiotherapist ; no significant differences between the two groups were found in walking ability , use of walking aids , “ walking speed ” , or absence or presence of pain in the operated hip . Patients in the orthopedic group spent fewer days in the hospital , but had significantly more re- admissions , primarily due to orthopedic- related diagnoses ( p=0.003 ) . The men in the geriatric arm of the trial were on the average 5.5 years older . The types of fracture were not evenly distributed between the two regimens . More patients treated at the geriatric department received technical aids , and more had adjustments made in their homes . ( Aging Clin . Exp . Res . 7 : 11–16 , 1995 OBJECTIVE To determine whether st and ardized early rehabilitation and discharge planning increase risk-adjusted function and reduce risk-adjusted institutionalization in the first 6 months after hip fracture . DESIGN Pre-post study of 2 independent population -based inception cohorts . SETTING Two tertiary hospitals in an urban health region . PARTICIPANTS Patients with hip fracture ( N=919 ) 65 years and older . INTERVENTION Subjects were enrolled before ( control ) and after ( intervention ) implementation of st and ardized rehabilitation and discharge planning . MAIN OUTCOME MEASURES Function and institutionalization status were assessed at time of fracture and 3 and 6 months postfracture . Administrative data bases provided length of stay ( LOS ) data . RESULTS After risk-adjustment , the Barthel Index score was significantly lower 3 months postfracture in control patients with low social support compared with those with higher social support ( P<.05 ) . Social support did not affect 3-month function in the intervention cohort . Control subjects with low social support were also significantly more likely to reside in long-term care by 6 months postfracture than intervention subjects with similar social support or those with higher social support ( odds ratio=3.3 ; 95 % confidence interval , 1.4 - 7.5 ) . Total LOS did not change between cohorts . CONCLUSIONS Overall , st and ardized rehabilitation and discharge planning did not affect postoperative function or institutionalization in elderly patients with hip fracture . In intervention patients with low social support , function improved and institutionalization was reduced Two hundred and seventy-five consecutive patients over the age of 50 years admitted with a hip fracture were prospect ively studied in detail , to assess the impact of a hip fracture on their functional ability and their need for social support . One hundred and eighty-three ( 66.9 % ) patients survived to 1 year . Mortality was highest amongst those least able to perform the recorded activities . One hundred and fifty-eight ( 86 % ) of the survivors were resident in the same level of accommodation after 1 year . There was a reduction in mobility and related functions of 20 - 25 % and a reduction of 5 % in tasks not related to hip function . It is therefore estimated that in the year after a hip fracture there will be decline in functionally abilities of about 5 % unrelated to the hip fracture and about 15 - 20 % directly related to the hip fracture . There was an increase in the requirement for social support amongst survivors individually , but overall the total economic burden on social services and institutional care was not significantly changed by hip fracture The aim of this prospect i ve study was to document the functional outcome and quality of life ( QoL ) over 1 year following hip fracture in elderly women . A total of 159 unselected elderly women with a first hip fracture were matched for age and residence with an equal number of control women . Functional status was measured by completing a Rapid Disability Rating Scale version 2 ( RDRS-2 ) question naire [ score ranging from 0 ( best ) to 54 ( worse ) ] , before hospital discharge and 12 months later . To examine longitudinal change in health-related QoL , fracture subjects and controls completed the Short Form 36 ( SF-36 ) question naire . For the 134 women still alive at 1 year , the mean RDRS-2 score before hospital discharge was 16.2 ( 95 % CI : 15.0–18.0 ) and 3.5 ( 2.6–4.3 ) in patients and controls , respectively ( P<0.001 ) . During the year following hospital discharge , the mean RDRS-2 score improved to 13.0 ( 11.1–14.1 ) in hip-fracture women and worsened to 4.3 ( 3.3–5.0 ) in the control group ( differences with initial scores : P<0.001 in both groups ) . After adjustment for potential confounders ( including age and comorbidity ) , the estimated functional decline attributable to a hip fracture was 24 % in the first year . Poor functional status upon discharge was the strongest predictor of a poor functional status at 1 year . Overall , similar trends were observed when using SF-36 scores as compared with RDRS-2 scores . However , only 51 % of the study population was able to complete the SF-36 question naire at discharge and after 1 year , and these subjects were considerably younger ( P<0.001 ) , had less cognitive impairment ( P<0.001 ) , and had better functional status ( P<0.001 ) than those who were unable to complete the SF-36 . For those women able to complete the SF-36 question naires , the mean SF-36 score before hospital discharge was 56.4 ( 95 % CI : 51.9–60.9 ) and 71.1 ( 67.5–74.8 ) in patients and controls , respectively ( P<0.001 ) . During the year following hospital discharge , the mean SF-36 score improved significantly to 61.1 ( 56.5–65.7 ) in hip-fracture patients ( P=0.03 ) , but remained unchanged in the control group ( P=0.23 ) . Overall , the results of this study indicate that women who sustain a hip fracture continue to suffer from substantial functional impairment and loss in QoL at 1 year , despite a significant recovery during this 12-month period . Function upon hospital discharge is the strongest predictor of functional status 1 year later . Assessing QoL in hip fracture women through self-administered question naires is subject to considerable bias due to non-response OBJECTIVES To investigate whether a care pathway for older hip fracture patients can reduce length of stay while maintaining the quality of clinical care . DESIGN Prospect i ve study of patients admitted 12 months before and after implementation of a care pathway for the management of femoral neck fracture . Audit data for corresponding time periods from nearby orthopaedic units was used to control for secular trends . SETTING Teaching hospital . SUBJECTS Patients aged 65 years and over with a femoral neck fracture . EXCLUSION CRITERIA multiple fractures , fractures due to malignancy , re-fracture , total hip replacement , previously entered into the study , operation performed elsewhere . Three-hundred and ninety-five ( 99 % ) and 369 ( 97 % ) case records were available for full analysis . MAIN OUTCOME MEASURES primary outcome : length of stay on the orthopaedic unit . SECONDARY OUTCOMES ambulation at discharge , discharge destination , in-hospital complications , 30 day mortality , readmission within 30 days of discharge , post-operative days the patient first sat out of bed and walked . RESULTS Mean length of stay increased by 6.5 days ( 95 % confidence interval 3.5 - 9.5 days , P < 0.0005 ) in the second period with a significant improvement in ambulation on discharge ( odds ratio 1.6 , 95 % confidence interval 1.0 - 2.6 , P = 0.033 ) and a trend towards reduction in admission to long term care ( odds ratio 0.6 , 95 % confidence interval 0.3 - 1.0 , P = 0.058 ) . CONCLUSIONS This care pathway was associated with longer hospital stay and improved clinical outcomes . Care pathways for hip fracture patients can be a useful tool for raising care st and ards but may require additional re sources Background : We conducted a prospect i ve study to assess the costs of initial hospitalization for a first hip fracture and to evaluate the excess costs attributable to the hip fracture during the one-year period following hospital discharge . Methods : This investigation was design ed as a one-year prospect i ve cohort study with matched-pair analysis . Elderly women who were receiving care for a first hip fracture at four Belgian hospitals were matched , with respect to age and residence , with women ( control subjects ) with no history of hip fracture who lived in the same neighborhood . The initial hospitalization costs were tabulated from the hospital invoices . To estimate the costs during the year after hospital discharge , health-care services utilized by the hip-fracture patients and by the control subjects were recorded . We used the official reimbursement rates to assign a cost to these services , and the results are reported in United States dollars . Results : The mean age of the 159 patients who had a hip fracture was 79.3 years , and that of the 159 control subjects was 78.7 years . The total mean cost of the initial hospitalization was $ 9534 for the hip-fracture patients . The total direct costs during the year after discharge averaged $ 13,470 for the hip-fracture patients and $ 6170 for the control subjects . Thus , the excess direct cost during the one-year period following hospital discharge averaged $ 7300 for the hip-fracture patients . The largest cost differences were attributable to nursing-home stays ( 31 % ) , rehabilitation-center stays ( 31 % ) , hospitalizations ( 16 % ) , and home physical-therapy services ( 14 % ) . Two-fifths of the excess costs were spent during the three months following hospital discharge . Moreover , we observed a shift in re source utilization after hospital discharge . Conclusions : Our one-year prospect i ve study demonstrated that the costs of treating a hip-fracture patient are about three times greater than those of caring for a patient without a fracture . This study also highlights the savings to society if a hip fracture can be avoided OBJECTIVE To determine the effect of an early intervention program in an acute care setting on the length of stay in hospital of elderly patients with proximal femoral fractures . SETTING Acute orthopaedic ward of a large teaching hospital . DESIGN AND PARTICIPANTS A r and omised controlled trial comparing 38 Intervention patients with 33 St and ard Care patients . INTERVENTION Early surgery , minimal narcotic analgesia , intense daily therapy and close monitoring of patient needs via a multidisciplinary approach versus routine hospital management . MAIN OUTCOME MEASURES Length of stay ( LOS ) ; deaths ; level of independent functioning . RESULTS Mean LOS was shorter in the Intervention group than in the St and ard Care group ( 21 days v. 32.5 days ; P < 0.01 ) . After adjusting for other factors that could affect LOS ( eg , age , sex , pre-trauma functional levels , pre-trauma comorbidity and postsurgical complications ) , the Intervention program was significantly predictive of shorter LOS ( P = 0.01 ) . The Intervention group did not experience greater numbers of deaths , deterioration in function or need for social support than the St and ard Care group . CONCLUSION This early intervention program in an acute care setting results in significantly shorter length of hospital stay for elderly patients with femoral fractures A total of 709 consecutive patients admitted with a hip fracture were prospect ively studied to establish the true mortality from the fracture . At one year from injury 37 % of patients had died . For 63 ( 9 % ) of these patients the hip fracture was thought to have directly contributed to death , for 109 ( 16 % ) patients death was possibly related to the hip fracture and for 85 ( 12 % ) patients death was totally unrelated to the fracture . Analysis based on the cause of death and time from injury enables us to calculate the true mortality from proximal femoral fractures to be 15 % . The remaining deaths are due to a variety of conditions associated with ageing This r and omized controlled trial compared accelerated rehabilitation after surgical treatment of proximal femoral fracture with conventional care and was conducted in a general hospital in an outer urban area . Participating were 261 sequentially admitted patients over the age of 50 years who met predetermined inclusion criteria and all were followed up until death or 4 months after fracture . Patients who were treated with the accelerated rehabilitation programme had a 20 % reduction in length of hospital stay . Improved physical independence ( as measured by Barthel Index ) was observed after fracture in accelerated rehabilitation programme patients with limited pre-existing disability . Non-nursing-home patients receiving accelerated rehabilitation were also less likely to be discharged to nursing-home care or die in hospital . Accelerated rehabilitation led to a substantial reduction in length of hospital stay with a modest short-term improvement in level of physical independence and accommodation status after discharge We determined the effect of geriatric rehabilitation of hip fracture patients on mortality , length of hospital stay , and functional recovery . In a r and omized , controlled intervention study , 243 community dwelling hip fracture patients over 64 years of age were r and omly assigned to 2 rehabilitation groups . The intervention group ( n = 120 ) was referred to a geriatric ward for team rehabilitation , and the controls ( n = 123 ) to local hospital wards for st and ard care . The median length of total hospital stay after a hip fracture operation was 34 ( 95 % CI 28 - 38 ) days in the intervention group and 42 ( 95 % CI 35 - 48 ) days in the control group ( p = 0.05 ) . The intervention group recovered instrumental activities of daily living faster ( p = 0.05 ) . Direct costs of medical care during the first year did not differ remarkably R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community BACKGROUND Hip fractures in elderly people are associated with impaired function and ambulation and high rates of death and admission to institutions . Interventions design ed to improve the outcomes of hip fracture ( e.g. , mobility and discharge to own home ) that have incorporated interdisciplinary care have had mixed results . We compared the effectiveness of postoperative interdisciplinary care with that of usual care for elderly patients with hip fracture . METHODS The study population consisted of 279 patients at least 70 years of age from the community and from nursing homes who underwent surgical repair of hip fracture at a university-affiliated acute care hospital . The subjects were r and omly assigned to receive postoperative interdisciplinary care ( n = 141 ) or usual care ( n = 138 ) during their hospital stay . Interdisciplinary care included routine assessment and care by an internist-geriatrician , physiotherapist , occupational therapist , social worker and clinical nurse specialist , as well as twice-weekly interdisciplinary rounds to set goals for the patients and to monitor their progress . The primary outcome measure was the proportion of patients alive with no decline in ambulation or transfers in and out of a chair or bed and no change in place of residence at 6 months after surgery . RESULTS At 6 months , 56 patients ( 39.7 % ) in the interdisciplinary care group and 47 ( 34.1 % ) in the usual care group were alive and had no decline from baseline in terms of ambulation , chair and bed transfers or place of residence ( difference 5.6 % , 95 % confidence interval -5.6 % to 17.0 % ) . Multiple logistic regression analysis with adjustment for baseline factors showed no significant difference between treatment groups for the primary outcome measure at 3 months ( p = 0.44 ) or at 6 months ( p = 0.67 ) . The initial length of stay in hospital was longer for patients receiving interdisciplinary care : 29.2 ( st and ard deviation [ SD ] 22.6 ) v. 20.9 ( SD 18.8 ) days ( p < 0.001 ) . However , the mean number of days spent in an institution ( including hospital , inpatient rehabilitation and nursing home ) over the 6-month follow-up period was similar in the 2 groups ( p = 0.84 ) . A subgroup analysis suggested a trend to benefit from interdisciplinary care in patients with mild to moderate cognitive impairment . INTERPRETATION Postoperative inpatient interdisciplinary care did not result in significantly better 3- or 6-month outcomes in elderly patients with hip fracture Background It is not clear whether occupational therapy is of value for hip fracture patients . Patients and methods In a r and omized trial we studied the effects of an early , individualized , postoperative occupational training ( OT ) program on the ability of hip fracture patients to perform ADL and IADL . Secondary endpoints were self-reported fear of pain and pain when performing ADL and IADL . The need for technical aids and /or home adaptations was also investigated . 100 eligible patients ( aged ≥65 years , with independent residence ) were r and omized 50:50 to an OT or control group ( conventional care ) . During their hospital stay , members of the OT group received individual daily training which included the use of technical aids . Before discharge , the occupational therapist paid a home visit together with the patient . All patients were assessed 2–4 days after surgery , at discharge and after 2 months , using the Klein-Bell ADL scale and a modified version of the Disability Rating Index . Results At discharge , the OT group had better ability to dress , to take care of personal hygiene and bathing activities independently , and to make toilet visits . Age , sex , type of fracture or length of stay at the hospital made no significant contribution to explaining the better ADL ability on discharge . After 2 months , all patients had regained their ADL and IADL abilities . Half of the patients required technical aids and adaptations in their homes . Interpretation Individualized OT-training speed up the ability of patients to perform ADL , thus enhancing the likelihood of patients returning to independent living and reducing the need for postoperative care at home |
10,882 | 23,546,307 | DATA SYNTHESIS None of the studies showed favourable effects of the intervention on activities of daily living and none assessed social participation .
CONCLUSION There is little evidence for the effectiveness of multidisciplinary care for stroke patients being discharged home . | OBJECTIVE A systematic review of r and omized controlled trials was performed to evaluate the effectiveness of multidisciplinary care for stroke patients living in the community . | In our experience , stroke patients discharged straight to their homes sometimes showed marked deterioration . We investigated whether this negative course of events could be prevented by means of follow-up visits entailing extensive testing and result ant measures one month after discharge . The patients in our study included a selection of mild cases with a short length of hospital stay . Forty-six patients returned to the stroke unit on a follow-up visit , and 49 patients made up the control group . The groups were compared after 3 months , by means of question naires . The results did not show any definite difference between the groups . However , after 3 months we detected depressions in 13 patients in the study group and in 11 patients in the control group , most of them untreated . The study points to a need for follow-up aim ed specifically at detecting depression Background and Purpose — Functioning and disability after ischemic stroke are clinical ly meaningful and of major relevance to patients . Despite many instruments available to assess these outcomes , little is known about their interrelation and predictive factors . Methods — We prospect ively identified 4264 patients with acute ischemic stroke from 30 hospitals in Germany during a 1-year period between 1998 and 1999 and registered them in a common data bank . The patients were central ly followed up via telephone interview after 100 days and 1 year to assess various scales such as the Barthel Index ( BI ) , modified Rankin Scale ( MRS ) , extended Barthel Index ( EBI ) , Short Form-36 Physical Functioning ( SF-36 PF ) , and Center for Epidemiologic Studies –Depression short form ( CES-D ) . Results — Outcome status could be assessed in 67.2 % of patients 100 days after hospital admission . Of these , 13.9 % had died , 53.7 % had regained functional independence ( BI < 95 ) , 46.3 % had no or mild residual symptoms ( MRS ≤1 ) , and 44.6 % had no higher cognitive deficits on the EBI . Of the patients who personally answered the follow-up questions , 67 % had no major physical disability ( SF-36 PF < 60 ) , and 32.9 % reported symptoms classified as depression ( CES-D ≥10 ) . The high percentage of patients reaching the maximum score ( ceiling effect ) in the BI was less pronounced in the MRS and SF-36 PF . The predictive factors for dichotomized outcomes on each scale were similar for adverse functioning and disability but varied considerably for depression . Conclusions — To avoid ceiling effects in outcome distribution of patients treated in specialized stroke centers , the MRS and SF-36 PF instruments are preferable to the BI . Parametric use of the SF-36 PF could further improve outcome measurement by considering individual treatment effects BACKGROUND national policy recommends routine re- assessment of disabled patients and their carers at 6 months after stroke onset . The clinical and re source outcomes of this policy were investigated . DESIGN prospect i ve , single-blind , r and omised controlled trial in two centres . PARTICIPANTS a total of 265 patients with a disabling stroke and their carers . INTERVENTIONS a structured re- assessment system for patients and their carers at 6 months post-stroke or existing care . OUTCOME MEASURES primary : patient independence ( Frenchay activities index ) and carer stress ( general health question naire 28 ) . Secondary : activities of daily living , mood state , satisfaction with services , carer strain index , health and social service re source use and costs . RESULTS independence at 12 months post-stroke was similar in both groups ( Frenchay activities index , adjusted mean difference 0.64 ; 95 % confidence interval -0.74 - 2.02 ) . Emotional distress in carers was similar in both groups ( general health question naire 28 , mean difference 0.02 ; 95 % confidence interval -0.95 - 1.00 ) . Results for the secondary outcome measures and total mean costs were similar for both groups . The intervention group patients used 301 fewer hospital bed days and 1,631 fewer care home bed days . CONCLUSIONS the structured , systematic re- assessment for patients and their carers was not associated with any clinical ly significant evidence of benefit at 12 months . Health and social care re source use and mean cost per patient were broadly similar in both groups . TRIAL REGISTRATION International St and ard R and omised Controlled Trial Register ; number : IS RCT N55412871 Objective : To compare intensive with non-intensive home-based rehabilitation provision following stroke or hip fracture in old age ( 65 years ) . Design : Parallel single-blind r and omized control trial . Setting : Domiciliary provided multidisciplinary rehabilitation . Subjects : One hundred and sixty patients aged 65 or over recently discharged from hospital after suffering a stroke or hip fracture . Intervention : Patients assigned to receive six or more face-to-face contacts or three or less face-to-face contacts from members of a multidisciplinary rehabilitation team . Main measures : Patients assessed using the Barthel Index , Therapy Outcome Measure , Euroqol 5D ( EQ-5D ) , Hospital Anxiety and Depression Scale ( HADS ) and Frenchay Activities Index ( FAI ) at three months . All follow-up assessment s were conducted blind to allocation . Results : Subgroup analysis was conducted on the basis of incident condition ( stroke or hip fracture ) . Significant differences were detected for the stroke subgroup at three months [ Therapy Outcome Measure H and icap ( median difference 0.5 ( P < 0.05 ) ) and EQ-5D ( median difference 0.17 ( P < 0.05 ) ) ] and in change at three months [ Therapy Outcome Measure ( mean difference 0.52 ( SD 0.85 ) 95 % CI ( 0.16 , 0.88 ) ) and EQ-5D ( mean difference 0.15 ( SD 0.25 ) 95 % CI ( 0.05 , 0.26 ) ) ] . No significant differences were detected between the two arms of the study for the hip fracture subgroup . Conclusion : Following stroke older people who receive a more intensive communitybased multidisciplinary rehabilitation service may experience short-term benefit in relation to social participation and some aspects of health-related quality of life . A more intensive service after discharge from hospital following a hip fracture is unlikely to result in similar patient benefit OBJECTIVES To compare the effectiveness and costs of a new domiciliary rehabilitation service for elderly stroke patients with geriatric day-hospital care . DESIGN R and omized controlled trial . PARTICIPANTS Stroke patients aged 55 + who required further rehabilitation after hospital discharge or after referral to geriatricians from the community . SETTING Poole area , East Dorset , a mixed urban/rural area on the south coast of Engl and . MAIN OUTCOMES Primary -changes between hospital discharge and 6-month follow-up in physical function as measured by Barthel index . Secondary -changes over this period in Rivermead Mobility Index and mental state ( Philadelphia Geriatric Centre Morale Scale ) and differences in social activity ( Frenchay Activities Index ) and generic health status ( SF-36 ) . Health service and social service cost per patient were compared for the two groups . RESULTS 180 patients were eligible and 140 ( 78 % ) were r and omized . The groups were well balanced for age , sex , social class and initial Barthel index . We achieved follow-up in 88 % of subjects who were alive at 6 months . We detected no significant differences in patient outcomes , although there was a non-significant improvement in measures of physical function and social activity in the domiciliary group . Domiciliary patients had more physiotherapy time per session and more district nurse time , and made greater use of social service day centres and home helps . Total cost per patient did not differ significantly between the two groups , with reduced health service costs in the domiciliary arm offset by higher social service costs . CONCLUSION No significant differences were detected in the effectiveness of the two services . Neither service influenced patients ' mental state , and their social activity remained low . Total costs were similar . A mixed model of day-hospital and domiciliary care may be most cost-effective for community stroke rehabilitation , but this requires further evaluation This study compared the functional ability and perceived health status of stroke patients treated by a domiciliary rehabilitation team or by routine hospital-based services after discharge from hospital . Patients discharged from two acute and three rehabilitation hospitals in Nottingham were r and omly allocated in three strata ( Health Care of the Elderly , General Medical and Stroke Unit ) to receive domiciliary or hospital-based care after discharge . Functional recovery was assessed by the Extended Activities of Daily Living ( ADL ) scale three and six months after discharge and perceived health at six months was measured by the Nottingham Health Profile . A total of 327 eligible patients of 1119 on a register of acute stroke admissions were recruited over 16 months . Overall there were no differences between the groups in their Extended ADL scores at three or six months , or their Nottingham Health Profile scores at six months . In the Stroke Unit stratum , patients treated by the domiciliary team had higher household ( p = 0.02 ) and leisure activity ( p = 0.04 ) scores at six months than those receiving routine care . In the Health Care of the Elderly stratum , death or a move into long-term institutional care at six months occurred less frequently in patients allocated to the routine service , about half of whom attended a geriatric day hospital . Overall there was no difference in the effectiveness of the domiciliary and hospital-based services , although younger stroke unit patients appeared to do better with home therapy while some frail elderly patients might have benefited from day hospital attendance OBJECTIVE To compare a specialized interprofessional team approach to community-based stroke rehabilitation with usual home care for stroke survivors using home care services . METHODS R and omized controlled trial of 101 community-living stroke survivors ( < 18 months post-stroke ) using home care services . Subjects were r and omized to intervention ( n=52 ) or control ( n=49 ) groups . The intervention was a 12-month specialized , evidence -based rehabilitation strategy involving an interprofessional team . The primary outcome was change in health-related quality of life and functioning ( SF-36 ) from baseline to 12 months . Secondary outcomes were number of strokes during the 12-month follow-up , and changes in community reintegration ( RNLI ) , perceived social support ( PRQ85-Part 2 ) , anxiety and depressive symptoms ( Kessler-10 ) , cognitive function ( SPMSQ ) , and costs of use of health services from baseline to 12 months . RESULTS A total of 82 subjects completed the 12-month follow-up . Compared with the usual care group , stroke survivors in the intervention group showed clinical ly important ( although not statistically significant ) greater improvements from baseline in mean SF-36 physical functioning score ( 5.87 , 95 % CI -3.98 to 15.7 ; p=0.24 ) and social functioning score ( 9.03 , CI-7.50 to 25.6 ; p=0.28 ) . The groups did not differ for any of the secondary effectiveness outcomes . There was a higher total per-person costs of use of health services in the intervention group compared to usual home care although the difference was not statistically significant ( p=0.76 ) . CONCLUSIONS A 12-month specialized , interprofessional team is a feasible and acceptable approach to community-based stroke rehabilitation that produced greater improvements in quality of life compared to usual home care . Clinical trials.gov identifier : NCT00463229 BACKGROUND This r and omized controlled trial tested the effectiveness of comprehensive , interdisciplinary postdischarge care management in improving a profile of indicators of health recovery and secondary prevention ( profile of health and prevention ) in stroke and transient ischemic attack ( TIA ) patients . METHODS Ninety-six stroke/TIA patients were r and omized to usual care or intervention at discharge from our acute stroke unit . The intervention group received an in-home biopsychosocial assessment by an advanced practice nurse at 1 month . A care plan was developed by an interdisciplinary team and implemented in collaboration with the patient 's primary care physician . The profile of health and prevention , measured at 3 months , was comprised of 5 domains : ( 1 ) Neuromotor Function , ( 2 ) Severe Complications , ( 3 ) Quality of Life , ( 4 ) Management of Risk for common poststroke complications and recurrent stroke , and ( 5 ) Stroke Knowledge . A single global hypothesis test across multiple end points was used to compare the 2 groups . RESULTS The intervention significantly improved the profile of health and prevention ( P < .0001 ) . In addition , each domain showed a positive effect of the intervention . Effect sizes ( in st and ard deviation units ) of the intervention on domains were .1 for Neuromotor Function ( 90 % confidence interval [ CI ] = -.3 to .5 ) ; .4 for Severe Complications ( 90 % CI = .1 to .8 ) ; .5 for Quality of Life ( 90 % CI = .1 to .9 ) ; .6 for Management of Risk for common poststroke complications and recurrent stroke ( 90 % CI = .3 to 1 . ) ; and 1.0 for Stroke Knowledge ( 90 % CI = .6 to 1.4 ) . CONCLUSIONS This model of care management result ed in a significantly better profile of health and prevention for stroke/TIA patients 3 months postdischarge Objective : To assess the effect of three weeks of rehabilitation in the home setting for younger patients with stroke with the aim of improving activity level . Design : A r and omized controlled study with blinded evaluations at discharge , three weeks , three months and one year after discharge . Setting : Home of the patient or the ordinary day rehabilitation clinic at the university hospital . Subjects : Fifty-eight patients ( median age 53 years ) consecutively discharged from inpatient rehabilitation with a first occurrence of stroke participated in training directly after discharge . Intervention : Rehabilitation was given for 9 hours/week over three weeks . The home group received individually tailored training , based on the patient 's needs and desires , with a focus on activities in their natural context . Support and information were also given . The intervention in the day clinic group was aim ed mainly at improved functions . Main measures : The main outcome was activity , assessed with the Assessment of Motor and Process Skill ( AMPS ) . The impairment level was also evaluated . Costs were estimated . Result : There were no significant differences between the groups on any of the four assessment s. However , there seemed to be an earlier improvement on some measures ( including AMPS ) for the home group . For both groups there was a greater improvement on the activity level than on the impairment level . The costs of the home group were less than half of the costs of the day clinic group . Conclusion : With the present results , both rehabilitation programmes could be recommended , however , further studies are needed to define patients who may specifically benefit from the home rehabilitation programme . Costs should be taken into consideration OBJECTIVE We sought to evaluate whether comprehensive postdischarge care management for stroke survivors is superior to organized acute stroke department care with enhanced discharge planning in improving a profile of health and well-being . METHODS This was a r and omized trial of a comprehensive postdischarge care management intervention for patients with ischemic stroke and National Institutes of Health Stroke Scale scores greater than or equal to 1 discharged from an acute stroke department . An advanced practice nurse performed an in-home assessment for the intervention group from which an interdisciplinary team developed patient-specific care plans . The advanced practice nurse worked with the primary care physician and patient to implement the plan during the next 6 months . The intervention and usual care groups were compared using a global and closed hypothesis testing strategy . Outcomes fell into 5 domains : ( 1 ) neuromotor function , ( 2 ) institution time or death , ( 3 ) quality of life , ( 4 ) management of risk , and ( 5 ) stroke knowledge and lifestyle . RESULTS Treatment effect was near 0 SD for all except the stroke knowledge and lifestyle domain , which showed a significant effect of the intervention ( P = .0003 ) . CONCLUSIONS Postdischarge care management was not more effective than organized stroke department care with enhanced discharge planning in most domains in this population . The intervention did , however , fill a postdischarge knowledge gap OBJECTIVES to test the hypothesis as to whether persons newly discharged into the community following an acute stroke and assigned a stroke case manager would experience , compared to usual post-hospital care , better health-related quality of life ( HRQL ) , fewer emergency room visits and less non-elective hospitalisations . DESIGN a stratified , balanced , evaluator-blinded , r and omised clinical trial . SETTING five university-affiliated acute-care hospitals in Montreal , Quebec , Canada . PARTICIPANTS persons ( n = 190 ) returning home directly from the acute-care hospital following a first or recurrent stroke with a need for health care supervision post-discharge because of low function , co-morbidity , or isolation . INTERVENTION for 6 weeks following hospital discharge a nurse stroke care manager maintained contact with patients through home visits and telephone calls design ed to coordinate care with the person 's personal physician and link the stroke survivor into community-based stroke services . MEASUREMENTS the primary outcome was the Physical Component Summary ( PCS ) of the Short-Form (SF)-36 survey . A secondary outcome was utilisation of health services . Also measured was the impact of stroke on functioning . Measurements were made at hospital discharge ( baseline ) , following the 6-week intervention and at 6-months post-stroke . RESULTS the average age of the participants was 70 years . Discharge was achieved on average 12 days post-stroke and most participants had had a stroke of moderate severity . There were no differences between groups on the primary outcome measure , health services utilisation , or any of the secondary outcome measures . CONCLUSION for this population , there was no evidence that this type of passive case management inferred any added benefit in terms of improvement in health-related quality of life or reduction in health services utilisation and stroke impact , than usual post-discharge management OBJECTIVE --To determine whether the intervention of a physiotherapist improved mobility in patients seen more than one year after stroke . DESIGN --R and omised crossover trial comparing two groups offered intervention by a physiotherapist , one immediately after entry into the trial and the other after a delay of three months . The intervention consisted of identifying problems and offering advice and help to solve the problems . SETTING -- Patients ' homes in Oxfordshire . SUBJECTS-- Patients who had reduced mobility due to a stroke more than one year before entry ; 60 were recruited from a community stroke register and 34 in other ways . MAIN OUTCOME MEASURES --St and ard measures of mobility including gait speed , functional ambulation categories , the Nottingham extended activities of daily living index , and individual items from the Barthel activities of daily living index and the Frenchay activities index . Measures of manual dexterity , depression , and anxiety were used as controls . RESULTS --94 patients entered the trial and 49 were r and omised to immediate and 45 to delayed physiotherapy ; 89 were compared at the crossover point . At r and omisation the two groups were comparable . At three months the group given early therapy showed an improvement in gait speed whereas the untreated group had declined ( differences of -3.9 v 6.4 s to walk 10 m ; p less than 0.01 ) ; between three and six months the group given delayed therapy showed improvement and the previously treated group declined ( differences of 6.5 v -3.9 s to walk 10 m ; p less than 0.01 ) . A 9 % ( 95 % confidence interval 0 % to 18 % ) decrease in time taken to walk 10 m was associated with treatment and a 12 % ( 2 % to 19 % ) increase when patients were untreated . Other measures did not change significantly . CONCLUSION --Intervention of an experienced physiotherapist late after stroke specifically improves mobility , albeit by a small amount , but the effects do not seem to be maintained , perhaps because there is an underlying decline in mobility in these patients . Gait speed offers a simple and sensitive measure of outcome AIMS This paper reports a study evaluating whether exp and ing a specialist nursing role to provide outreach education and support to stroke patients and carers after discharge from hospital is effective in promoting recovery . BACKGROUND Building therapeutic relationships with patients and carers is a key component of the nursing role in stroke rehabilitation , although this is limited by the constraints of service organization . METHODS A pragmatic r and omized controlled trial was undertaken . Patients with a diagnosis of stroke were r and omized to receive continued support from a stroke nurse ( n = 87 ) or usual care and follow-up ( n = 89 ) after discharge from hospital . Patients were recruited from two hospitals in the north-west of Engl and from November 1999 to April 2001 . Patient dependence ( Barthel Index ) , general health ( Nottingham Health Profile ) , activities of living ( Frenchay Activity of Living Index ) , depression ( Beck Depression Inventory ) and carer strain ( Carer Strain Index ) were assessed at 3 and 12 months after stroke . RESULTS The continued intervention of a stroke nurse after discharge was associated with improved patient perceptions of general health at 12 months ( median difference 42.6 , P = 0.012 ) , and in particular reduced negative emotional reaction ( P = 0.037 ) and perceived social isolation ( P = 0.002 ) . In addition , the intervention reduced carer strain at 3 months ( P = 0.045 ) , and reduced deterioration in physical dependence from 3 to 12 months ( P = 0.049 ) . CONCLUSION The provision of continued intervention from a stroke nurse after discharge from hospital , focusing on education and support , has tangible benefits for patients and carers The DOMINO study compared domiciliary and hospital-based rehabilitation services for stroke patients after discharge from hospital , stratified by the hospital ward at discharge . No difference between the services had been found at 6 months , but home therapy was better than outpatient department therapy at improving household ability and leisure activity in the patients discharged from the Stroke Unit ( SU ) , and attendance at a day hospital may have been better than a domiciliary service at preventing death or institutionalization for patients discharged from Health Care of the Elderly ( HCE ) wards . We report the follow-up of the patients between 6 months and 1 year after discharge , during which time few patients received further treatment and little change in health or function occurred . Over this period the benefits of domiciliary rehabilitation in the SU group were lost , largely because the patients who had been treated in outpatient departments continued to improve . Between 6 months and 1 year the numbers of HCE patients in the two treatment groups who died or were institutionalized were similar , but the advantage of day hospital attendance was still evident at 1 year |
10,883 | 30,254,452 | Conclusion BCs , especially the Plasma-Lyte , are presumably the best choice for most critically ill patients who need fluid resuscitation .
Meanwhile , the use of H-HES was associated with an increased incidence of AKI and risk of receiving RRT . | Objective The aim of this study was to compare the effectiveness of different fluids on critically ill patients who need fluid resuscitation through a systematic review and network meta- analysis ( NMA ) . | Introduction Inadequate initial treatment and delayed hemodynamic stabilization ( HDS ) may be associated with increased risk of death in severe sepsis patients . Methods In order to compare the hemodynamic efficacy and safety of 6 % HES 130/0.4 and NaCl 0.9 % for HDS in patients with severe sepsis , we design ed a prospect i ve , multicenter , active-controlled , double-blind , r and omized study in intensive care units . Results 174 out of 196 patients reached HDS ( 88 and 86 patients for HES and NaCl , respectively ) . Significantly less HES was used to reach HDS vs. NaCl ( 1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group ( mean difference = -331± 1,033 , 95 % CI -640 to -21 , P = 0.0185 ) . Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl , respectively . Total quantity of study drug infused over four consecutive days , ICU and hospital LOS , and area under the curve of SOFA score were comparable . Acute renal failure occurred in 24 ( 24.5 % ) and 19 ( 20 % ) patients for HES and NaCl , respectively ( P = 0.454 ) . There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality , coagulation , or pruritus up to 90 days after treatment initiation . Conclusion Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups . Clinical Trials.gov To assess the effects of crystalloid and colloid resuscitation on hemodynamic response and on lung water following thermal injury , 79 patients were assigned r and omly to receive lactated Ringer 's solution or 2.5 % albumin-lactated Ringer 's solution . Crystalloid-treated patients required more fluid for successful resuscitation than did those receiving colloid solutions ( 3.81 vs. 2.98 ml/kg body weight/% body surface burn , p < 0.01 ) . In study phase 1 ( 29 patients ) , cardiac index and myocardial contractility ( ejection fraction ' and mean rate of internal fiber shortening , Vcf ) were determined by echocardiography during the first 48 hours postburn . Cardiac index was lower in the 12-to 24-hour postburn interval in the crystalloid group , but this difference between treatment groups had disappeared by 48 hours postburn . Ejection fractions were normal throughout the entire study , while Vcf was supranormal ( p < 0.01 vs. normals ) and equal in the two resuscitation groups . In study phase 2 ( SO patients ) , extravascular lung water and cardiac index were measured by a st and ard rebreathing technique at least daily for the first postburn week . Lung water remained unchanged in the crystalloid-treated patients ( p > 0.10 ) , but progressively increased in the colloid-treated patients over the seven day study ( p < 0.0001 ) . The measured lung water in each treatment group was significantly different from one another ( p < 0.001 ) . Cardiac index increased progressively and identically in both treatment groups over the study period ( p < 0.01 ) . These data refute the existence of myocardial depression during postburn resuscitation and document hypercontractile left ventricular performance . The addition of colloid to crystalloid resuscitation fluids produces no long lasting benefit on total body blood flow , and promotes accumulation of lung water when edema fluid is being reabsorbed from the burn wound Background The use of hypertonic crystalloid solutions , including sodium chloride and bicarbonate , for treating severe sepsis has been much debated in previous investigations . We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension . Methods Ninety-four severe sepsis patients with hypotension were r and omly assigned to three groups . The patients received the following injections within 15 min at initial treatment : Ns group ( n = 32 ) , 5 ml/kg normal saline ; Hs group ( n = 30 ) , with 5 ml/kg 3.5 % sodium chloride ; and Sb group ( n = 32 ) , 5 ml/kg 5 % sodium bicarbonate . Cardiac output ( CO ) , systolic blood pressure , mean arterial pressure ( MAP ) , body temperature , heart rate , respiratory rate and blood gases were measured . Results There were no differences among the three groups in CO , MAP , heart rate or respiratory rate during the 120 min trial or the 8 hour follow-up , and no significant differences in observed mortality rate after 28 days . However , improvement of MAP and CO started earlier in the Sb group than in the Ns and Hs groups . Sodium bicarbonate increased the base excess but did not alter blood pH , lactic acid or [HCO3]- values ; and neither 3.5 % hypertonic saline nor 5 % sodium bicarbonate altered the Na+ , K+ , Ca2 + or Cl- levels . Conclusion All three crystalloid solutions may be used for initial volume loading in severe sepsis , and sodium bicarbonate confers a limited benefit on humans with severe sepsis . Trial registration IS RCT N36748319 Abstract . The objective of this study was to compare the cardiac and hemodynamic responses to a rapid infusion of 1000 ml of modified fluid gelatin ( group A ) or 1000 ml of lactated Ringer 's solution ( group B ) in emergency room patients suffering from shock . This prospect i ve , r and omized , open , noncrossover study was performed at a medical center university hospital in a surgical resuscitation room in the emergency department . The subjects were 34 patients with either hypovolemic or neurogenic shock who were admitted to the emergency room . A resuscitation protocol according to Advanced Trauma Life Support ( ATLS ) with an additional central venous line or Swan-Ganz catheters for hemodynamic monitoring was used . Physical parameters and hemodynamic variables were measured at baseline and 15 minutes , 30 minutes , and 1 hour after the infusion of each fluid . In both groups the mean arterial blood pressure ( MAP ) , systolic and diastolic pressure , central venous pressure ( CVP ) , and pulmonary artery occlusion pressure ( PAOP ) increased significantly . The CVP and PAOP increased significantly more in the modified fluid gelatin resuscitation group . In patients with traumatic or neurogenic shock due to acute volume deficiency , there was significantly better hemodynamic improvement , judged by CVP and PAOP measurements using the modified fluid gelatin for volume replacement than with lactated Ringer 's solution during the first hour of resuscitation BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults , but it is not known which results in better clinical outcomes . METHODS In a pragmatic , cluster‐r and omized , multiple‐crossover trial conducted in five intensive care units at an academic center , we assigned 15,802 adults to receive saline ( 0.9 % sodium chloride ) or balanced crystalloids ( lactated Ringer 's solution or Plasma‐Lyte A ) according to the r and omization of the unit to which they were admitted . The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction ( defined as an elevation of the creatinine level to ≥200 % of baseline ) — all censored at hospital discharge or 30 days , whichever occurred first . RESULTS Among the 7942 patients in the balanced‐crystalloids group , 1139 ( 14.3 % ) had a major adverse kidney event , as compared with 1211 of 7860 patients ( 15.4 % ) in the saline group ( marginal odds ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.84 to 0.99 ; conditional odds ratio , 0.90 ; 95 % CI , 0.82 to 0.99 ; P=0.04 ) . In‐hospital mortality at 30 days was 10.3 % in the balanced‐crystalloids group and 11.1 % in the saline group ( P=0.06 ) . The incidence of new renal‐replacement therapy was 2.5 % and 2.9 % , respectively ( P=0.08 ) , and the incidence of persistent renal dysfunction was 6.4 % and 6.6 % , respectively ( P=0.60 ) . CONCLUSIONS Among critically ill adults , the use of balanced crystalloids for intravenous fluid administration result ed in a lower rate of the composite outcome of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction than the use of saline . ( Funded by the V and erbilt Institute for Clinical and Translational Research and others ; SMART‐MED and SMART‐SURG Clinical Trials.gov numbers , NCT02444988 and NCT02547779 . BACKGROUND Normal saline ( NS ) is the most commonly used crystalloid solution worldwide but contains an excess of chloride and may cause metabolic acidosis and hyperchloraemia . Such abnormalities may be attenuated by the use of a balanced solution such as Plasma-Lyte 148 ( PL-148 ) . OBJECTIVE To assess the feasibility , safety and biochemical and physiological effects of resuscitation with NS versus PL-148 in critically ill patients . DESIGN , SETTING AND PARTICIPANTS An exploratory , multicentre , doubleblind , r and omised controlled trial involving patients aged ≥ 18 years who were prescribed crystalloid fluid resuscitation by the treating clinician between 16 July and 22 October 2015 , in three multidisciplinary intensive care units in Melbourne , Victoria , Australia . METHODS R and om allocation of NS or PL-148 was concealed , and all fluids were delivered in indistinguishable bags . INTERVENTION NS or PL-148 was administered for all fluid resuscitation and for all subsequent crystalloid fluid therapy until Day 4 of ICU admission . The treating intensivist determined the rate and frequency of fluid administration . MAIN OUTCOME MEASURES Primary outcome was daily base excess ( BE ) . Relevant secondary outcomes included the incidence of acute kidney injury ( AKI ) , change in serum creatinine and serum chloride levels , and mortality . RESULTS Seventy patients were recruited , with 34 in the NS group and 33 in the PL-148 group available for analysis . Baseline characteristics of study patients were well balanced ; the mean ages were 64 and 62 years , respectively , and nearly two-thirds of the patients in each group were men . The median Acute Physiology and Chronic Health Evaluation III scores were 64 for the NS group ( interquartile range [ IQR ] , 48 - 73 ) and 55 for the PL-148 group ( IQR , 44 - 81 ) . After treatment , there was no significant difference in the worst ( most negative ) median BE between the NS and PL-148 groups ( -4 mEq/L [ IQR , -7 to -2 mEq/L ] v -3 mEq/L [ IQR , -7 to 2 mEq/L ] ; P = 0.42 ) . Chloride levels were significantly higher with NS therapy ( median , 111 mmol/L [ IQR , 108 - 116 mmol/L ] v 108 mmol/L [ IQR , 106 - 110 mmol/L ] ; P = 0.01 ) . There was no significant difference in the incidence of AKI ( P = 0.48 ) , peak creatinine levels ( P = 0.92 ) or ICU or hospital mortality between the two groups . CONCLUSIONS In our exploratory , double-blind , r and omised controlled trial , when compared with NS , PL-148 did not significantly increase BE values in critically ill patients requiring fluid resuscitation , but decreased peak chloride concentrations Introduction We sought to investigate whether the use of balanced solutions reduces the incidence of hyperchloraemic acidosis without increasing the risk for intracranial hypertension in patients with severe brain injury . Methods We conducted a single-centre , two-arm , r and omised , double-blind , pilot controlled trial in Nantes , France . Patients with severe traumatic brain injury ( Glasgow Coma Scale score ≤8 ) or subarachnoid haemorrhage ( World Federation of Neurosurgical Society grade III or higher ) who were mechanically ventilated were r and omised within the first 12 hours after brain injury to receive either isotonic balanced solutions ( crystalloid and hydroxyethyl starch ; balanced group ) or isotonic sodium chloride solutions ( crystalloid and hydroxyethyl starch ; saline group ) for 48 hours . The primary endpoint was the occurrence of hyperchloraemic metabolic acidosis within 48 hours . Results Forty-two patients were included , of whom one patient in each group was excluded ( one consent withdrawn and one use of forbidden therapy ) . Nineteen patients ( 95 % ) in the saline group and thirteen ( 65 % ) in the balanced group presented with hyperchloraemic acidosis within the first 48 hours ( hazard ratio = 0.28 , 95 % confidence interval [ CI ] = 0.11 to 0.70 ; P = 0.006 ) . In the saline group , pH ( P = .004 ) and strong ion deficit ( P = 0.047 ) were lower and chloraemia was higher ( P = 0.002 ) than in the balanced group . Intracranial pressure was not different between the study groups ( mean difference 4 mmHg [ -1;8 ] ; P = 0.088 ) . Seven patients ( 35 % ) in the saline group and eight ( 40 % ) in the balanced group developed intracranial hypertension ( P = 0.744 ) . Three patients ( 14 % ) in the saline group and five ( 25 % ) in the balanced group died ( P = 0.387 ) . Conclusions This study provides evidence that balanced solutions reduce the incidence of hyperchloraemic acidosis in brain-injured patients compared to saline solutions . Even if the study was not powered sufficiently for this endpoint , intracranial pressure did not appear different between groups . Trial registration EudraCT 2008 - 004153 - 15 and NCT00847977The work in this trial was performed at Nantes University Hospital in Nantes , France PURPOSE The aim of this study was to show that 6 % hydroxyethyl starch ( HES ) 130/0.4 achieves a better resuscitation of the microcirculation than normal saline solution ( SS ) , during early goal -directed therapy ( EGDT ) in septic patients . MATERIAL S AND METHODS Patients with severe sepsis were r and omized for EGDT with 6 % HES 130/0.4 ( n = 9 ) or SS ( n = 11 ) . Sublingual microcirculation was evaluated by sidestream dark field imaging 24 hours after the beginning of EGDT . RESULTS On admission , there were no differences in Sequential Organ Failure Assessment score , mean arterial pressure , lactate , or central venous oxygen saturation . After 24 hours , no difference arose in those parameters . Sublingual capillary density was similar in both groups ( 21 ± 8 versus 20 ± 3 vessels/mm(2 ) ) ; but capillary microvascular flow index , percent of perfused capillaries , and perfused capillary density were higher in 6 % HES 130/0.4 ( 2.5 ± 0.5 versus 1.6 ± 0.7 , 84 ± 15 versus 53 ± 26 % , and 19 ± 6 versus 11 ± 5 vessels/mm(2 ) , respectively , P < .005 ) . CONCLUSIONS Fluid resuscitation with 6 % HES 130/0.4 may have advantages over SS to improve sublingual microcirculation . A greater number of patients would be necessary to confirm these findings BACKGROUND The safety and efficacy of hydroxyethyl starch ( HES ) for fluid resuscitation have not been fully evaluated , and adverse effects of HES on survival and renal function have been reported . METHODS We r and omly assigned 7000 patients who had been admitted to an intensive care unit ( ICU ) in a 1:1 ratio to receive either 6 % HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 ( 130/0.4 , Voluven ) in 0.9 % sodium chloride or 0.9 % sodium chloride ( saline ) for all fluid resuscitation until ICU discharge , death , or 90 days after r and omization . The primary outcome was death within 90 days . Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy . RESULTS A total of 597 of 3315 patients ( 18.0 % ) in the HES group and 566 of 3336 ( 17.0 % ) in the saline group died ( relative risk in the HES group , 1.06 ; 95 % confidence interval [ CI ] , 0.96 to 1.18 ; P=0.26 ) . There was no significant difference in mortality in six predefined subgroups . Renal-replacement therapy was used in 235 of 3352 patients ( 7.0 % ) in the HES group and 196 of 3375 ( 5.8 % ) in the saline group ( relative risk , 1.21 ; 95 % CI , 1.00 to 1.45 ; P=0.04 ) . In the HES and saline groups , renal injury occurred in 34.6 % and 38.0 % of patients , respectively ( P=0.005 ) , and renal failure occurred in 10.4 % and 9.2 % of patients , respectively ( P=0.12 ) . HES was associated with significantly more adverse events ( 5.3 % vs. 2.8 % , P<0.001 ) . CONCLUSIONS In patients in the ICU , there was no significant difference in 90-day mortality between patients resuscitated with 6 % HES ( 130/0.4 ) or saline . However , more patients who received resuscitation with HES were treated with renal-replacement therapy . ( Funded by the National Health and Medical Research Council of Australia and others ; CHEST Clinical Trials.gov number , NCT00935168 . ) Background : It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome . This r and omized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarchvs normal saline in early septic shock , powered for a difference in mortality . Methods : At three Canadian and one New Zeal and academic centre , 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria , infectious source , and persistent hypotension after ≥ 1 L of crystalloid fluid were recruited . Feasibility measures were patient recruitment , blinding of the study fluids , and acceptability of the goal directed algorithms . Boluses of blinded normal saline or pentastarch ( 500 mL − maximum 3 L or 28 mL·kg−1 ) were administered within goal directed care for the first 12 hr . Results : Of 161 patients screened , 121 were excluded and 40 patients were enrolled , for a recruitment rate of 0.75 patients / site/month . Only 57 % of physicians and 54 % of nurses correctly guessed the study fluid ( P = 0.46 and P = 0.67 , respectively ) . The goal directed algorithms were acceptable to 97 % of physicians . Conclusion : The ability to recruit patients in this pilot r and omized controlled trial was below expectations . Blinding of study fluids was adequate , and resuscitation algorithms were acceptable to most physicians . Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock . Résumé Context e : Nous ne savons pas si la réanimation liquidienne avec des colloïdes ou des cristalloïdes chez les patients présentant un sepsis grave ou un choc septique est associée à un devenir clinique meilleur . Cette étude r and omisée contrôlée a déterminé la faisabilité d’une étude d’envergure testant la réanimation avec le pentastarch par rapport au sérum physiologique en début de choc septique , avec pour objectif primaire de détecter une différence dans les taux de mortalité . Method e : Quarante patients en début de choc septique , défini comme au moins deux critères du syndrome de réaction inflammatoire , une source d’infection et une hypotension persistante après ≥ 1 L de cristalloïde ont été recrutés dans trois centres universitaires canadiens et un centre néo-zél and ais . Les mesures de faisabilite étaient : le recrutement des patients , le masquage des liquides à l’étude , et I’acceptabilité des algorithmes dirigés vers des objectifs . Des bolus de normal sal in ou de pentastarch ( 500 mL — maximum 3 L ou 28 mL·kg−1 ) ont été administrés en aveugle dans le cadre de soins guidés dirigés vers des objectifs durant les 12 premieres heures . Result ats : Sur 161 patients dépistés , 121 ont été exclus et 40 patients recrutés dans le cadre de I’étude , avec un taux de recrutement de 0,75 patient/site/mois . Seulement 57 % des médecins et 54 % des infirmières ont réussi à deviner correctement le type de liquide à I’étude ( P = 0,46 etP = 0,67 , respectivement ) . Les algorithmes ont été jugés acceptables par 97 % des médecins . Conclusion : La capacité à recruter des patients pour cette étude pilote r and omisée contrôlée était moins importante qu’attendue . Le masquage des liquides était satisfaisant , et les algorithmes de réanimation ont été jugés acceptables par la majorité des médecins . Des méthodes dans le but d’améliorer le recrutement sont nécessaire pour accroître la faisabilité d’une étude multicentrique sur la réanimation liquidienne en début de choc septique BACKGROUND Hydroxyethyl starch ( HES ) [ corrected ] is widely used for fluid resuscitation in intensive care units ( ICUs ) , but its safety and efficacy have not been established in patients with severe sepsis . METHODS In this multicenter , parallel-group , blinded trial , we r and omly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6 % HES 130/0.42 ( Tetraspan ) or Ringer 's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day . The primary outcome measure was either death or end-stage kidney failure ( dependence on dialysis ) at 90 days after r and omization . RESULTS Of the 804 patients who underwent r and omization , 798 were included in the modified intention-to-treat population . The two intervention groups had similar baseline characteristics . At 90 days after r and omization , 201 of 398 patients ( 51 % ) assigned to HES 130/0.42 had died , as compared with 172 of 400 patients ( 43 % ) assigned to Ringer 's acetate ( relative risk , 1.17 ; 95 % confidence interval [ CI ] , 1.01 to 1.36 ; P=0.03 ) ; 1 patient in each group had end-stage kidney failure . In the 90-day period , 87 patients ( 22 % ) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients ( 16 % ) assigned to Ringer 's acetate ( relative risk , 1.35 ; 95 % CI , 1.01 to 1.80 ; P=0.04 ) , and 38 patients ( 10 % ) and 25 patients ( 6 % ) , respectively , had severe bleeding ( relative risk , 1.52 ; 95 % CI , 0.94 to 2.48 ; P=0.09 ) . The results were supported by multivariate analyses , with adjustment for known risk factors for death or acute kidney injury at baseline . CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy , as compared with those receiving Ringer 's acetate . ( Funded by the Danish Research Council and others ; 6S Clinical Trials.gov number , NCT00962156 . ) BACKGROUND It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units ( ICUs ) affects survival . We conducted a multicenter , r and omized , double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU . METHODS We r and omly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days . The primary outcome measure was death from any cause during the 28-day period after r and omization . RESULTS Of the 6997 patients who underwent r and omization , 3497 were assigned to receive albumin and 3500 to receive saline ; the two groups had similar baseline characteristics . There were 726 deaths in the albumin group , as compared with 729 deaths in the saline group ( relative risk of death , 0.99 ; 95 percent confidence interval , 0.91 to 1.09 ; P=0.87 ) . The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups ( P=0.85 ) . There were no significant differences between the groups in the mean ( + /-SD ) numbers of days spent in the ICU ( 6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group , P=0.44 ) , days spent in the hospital ( 15.3+/-9.6 and 15.6+/-9.6 , respectively ; P=0.30 ) , days of mechanical ventilation ( 4.5+/-6.1 and 4.3+/-5.7 , respectively ; P=0.74 ) , or days of renal-replacement therapy ( 0.5+/-2.3 and 0.4+/-2.0 , respectively ; P=0.41 ) . CONCLUSIONS In patients in the ICU , use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days Hypertonic solutions effectively improve hemodynamic parameters in patients admitted to the emergency room . However , no significant differences in outcome were observed compared with st and ard isotonic treatment in most previously published studies . This study evaluates pretreatment prognostic factors that predict a beneficial effect of hypertonic solution in patients admitted to the emergency room with hemorrhagic hypovolemia in a prospect i ve double-blind fashion . The patients ( n = 212 ) were r and omized upon admission to receive 250 mL intravenous ( i.v . ) bolus of hypertonic 7.5 % NaCl + 6 % dextran ( HSD , n = 101 ) , or isotonic 0.9 % NaCl solutions ( IS , n = 111 ) as the first treatment , followed by st and ard resuscitation . Pretreatment factors assessed were sex , age , cause of hypovolemia , revised trauma score ( RTS ) , Glasgow index , and mean arterial pressure ( MAP ) on admission . Both groups were compared for survival at 24 h and 30 days postadmission . Infused volumes were registered . HSD administration significantly increased MAP and reduced i.v . crystalloid infusions to maintain hemodynamic parameters , compared with IS . There was no difference between groups in the number of blood transfusions administered . Overall complication rates in both groups were similar ( 24 % ) . There was a significant difference ( p < .03 ) in overall ( 30 days ) survival rate between HSD ( 73 % ) and IS ( 64 % ) groups . The 24 h survival rate was significantly lower in IS ( 72 % ) compared with HSD ( 87 % ) ; p < .01 . Multivariate analyses showed that RTS and MAP were identified as independent predictors for 24 h survival in the group that received HSD . When evaluated for overall survival rate , hypertonic infusion benefited significantly only patients with MAP < 70 mmHg ( p < .01 ) BACKGROUND 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 . 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 Small volume infusions of hypertonic saline combined with dextran are very effective in resuscitating animals that have been subjected to hemorrhagic shock , and seem to be effective in resuscitating trauma patients with severe injuries . In this study , the contribution of the dextran component was investigated in a prospect i ve , three-armed , double-blind , r and omized trial . Trauma patients transported by ambulance to the hospital with a systolic blood pressure of 90 mm Hg or less were given 250 mL of ( 1 ) normal saline ( NS ) ; ( 2 ) 7.5 % NaCl ( HS , for hypertonic saline ) ; or ( 3 ) 7.5 % NaCl in 6 % dextran 70 ( HSD ) . Infusion of the study solution was followed by administration of conventional isotonic fluids as the patients ' conditions indicated . By predetermined hypothesis , the observed survival rates in the three treatment groups were compared with the predicted survival rates from the TRISS methodology . The 7.5 % NaCl solution significantly improved upon the predicted survival for the entire cohort and for high-risk patients when compared with the survival estimates from the TRISS methodology . The addition of a colloid , in the form of 6 % dextran 70 , did not offer any additional benefit , at least in this setting of rapid urban transport Background and objective To examine the kinetics of volume loading with crystalloid and colloid infusions in critically ill patients after major surgery , using the pulse contour cardiac output ( PiCCO ) monitoring technique . Methods This prospect i ve , r and omized , multicentre study of 11 ICUs involved 200 mixed postoperative hypovolaemic patients ( 50 patients per group ) in Hungary . Patients received 10 ml kg−1 of lactated Ringer 's solution , succinylated gelatin 4 % w/v , 130/0.4 hydroxyethyl starch 6 % w/v ( HES ) or human albumin 5 % w/v over 30 min . A complete haemodynamic profile was obtained at 30 , 45 , 60 , 90 and 120 min after baseline . The peak haemodynamic effects , the 120 min changes compared with baseline , the area under the curve ( AUC ) for the haemodynamic parameters over 120 min and the haemodilution effect of the solutions were analysed . The primary outcome was to compare the AUCs and the secondary outcome was to evaluate the haemodynamic changes at 120 min . Results There were significant differences in the AUCs of the haemodynamic parameters between colloids and lactated Ringer 's solution in the cardiac index and global end-diastolic volume index ( GEDVI ) ; human albumin vs. lactated Ringer 's solution in stroke volume variation ( SVV ) ; and succinylated gelatin , HES vs. lactated Ringer 's solution in the oxygen delivery index ( DO2I ) . Colloid infusions ( mainly HES and human albumin ) at 120 min caused significant changes in central venous pressure , cardiac index , GEDVI , SVV , DO2I and central venous oxygen saturation compared with baseline . The haemodilution effect was significantly greater in colloids vs. lactated Ringer 's solution . Conclusion In postoperative hypovolaemic patients , lactated Ringer 's solution can significantly improve haemodynamics at the end of volume loading , but this effect completely disappears at 120 min . Ten millilitres per kilogram of colloid bolus ( especially HES ) improved the haemodynamics at 120 min ; however , this was by only 5–25 % compared with baseline . The colloids caused significantly larger AUCs than lactated Ringer 's solution , but only in the cardiac index , GEDVI and DO2I , plus human albumin in the SVV CONTEXT Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury ( AKI ) . OBJECTIVE To assess the association of a chloride-restrictive ( vs chloride-liberal ) intravenous fluid strategy with AKI in critically ill patients . DESIGN , SETTING , AND PATIENTS Prospect i ve , open-label , sequential period pilot study of 760 patients admitted consecutively to the intensive care unit ( ICU ) during the control period ( February 18 to August 17 , 2008 ) compared with 773 patients admitted consecutively during the intervention period ( February 18 to August 17 , 2009 ) at a university-affiliated hospital in Melbourne , Australia . INTERVENTIONS During the control period , patients received st and ard intravenous fluids . After a 6-month phase-out period ( August 18 , 2008 , to February 17 , 2009 ) , any use of chloride-rich intravenous fluids ( 0.9 % saline , 4 % succinylated gelatin solution , or 4 % albumin solution ) was restricted to attending specialist approval only during the intervention period ; patients instead received a lactated solution ( Hartmann solution ) , a balanced solution ( Plasma-Lyte 148 ) , and chloride-poor 20 % albumin . MAIN OUTCOME MEASURES The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk , injury , failure , loss , end-stage ( RIFLE ) classification . Secondary post hoc analysis outcomes included the need for renal replacement therapy ( RRT ) , length of stay in ICU and hospital , and survival . RESULTS Chloride administration decreased by 144 504 mmol ( from 694 to 496 mmol/patient ) from the control period to the intervention period . Comparing the control period with the intervention period , the mean serum creatinine level increase while in the ICU was 22.6 μmol/L ( 95 % CI , 17.5 - 27.7 μmol/L ) vs 14.8 μmol/L ( 95 % CI , 9.8 - 19.9 μmol/L ) ( P = .03 ) , the incidence of injury and failure class of RIFLE-defined AKI was 14 % ( 95 % CI , 11%-16 % ; n = 105 ) vs 8.4 % ( 95 % CI , 6.4%-10 % ; n = 65 ) ( P < .001 ) , and the use of RRT was 10 % ( 95 % CI , 8.1%-12 % ; n = 78 ) vs 6.3 % ( 95 % CI , 4.6%-8.1 % ; n = 49 ) ( P = .005 ) . After adjustment for covariates , this association remained for incidence of injury and failure class of RIFLE-defined AKI ( odds ratio , 0.52 [ 95 % CI , 0.37 - 0.75 ] ; P < .001 ) and use of RRT ( odds ratio , 0.52 [ 95 % CI , 0.33 - 0.81 ] ; P = .004 ) . There were no differences in hospital mortality , hospital or ICU length of stay , or need for RRT after hospital discharge . CONCLUSION The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00885404 BACKGROUND The leading cause of late mortality after trauma is multiple organ failure syndrome , due to a dysfunctional inflammatory response early after injury . Pre clinical studies demonstrate that hypertonicity alters the activation of inflammatory cells , leading to reduction in organ injury . The purpose of this study was to evaluate the effect of hypertonicity on organ injury after blunt trauma . DESIGN Double-blind , r and omized controlled trial from October 1 , 2003 , to August 31 , 2005 . SETTING Prehospital enrollment at a single level I trauma center . PATIENTS Patients older than 17 years with blunt trauma and prehospital hypotension ( systolic blood pressure , < /= 90 mm Hg ) . INTERVENTIONS Treatment with 250 mL of 7.5 % hypertonic saline and 6 % dextran 70 ( HSD ) vs lactated Ringer solution ( LRS ) . MAIN OUTCOME MEASURES The primary end point was survival without acute respiratory distress syndrome ( ARDS ) at 28 days . Cox proportional hazards regression was used to adjust for confounding factors . A preplanned subset analysis was performed for patients requiring 10 U or more of packed red blood cells in the first 24 hours . RESULTS A total of 209 patients were enrolled ( 110 in the HSD group and 99 in the LRS group ) . The study was stopped for futility after the second interim analysis . Intent-to-treat analysis demonstrated no significant difference in ARDS-free survival ( hazard ratio , 1.01 ; 95 % confidence interval , 0.63 - 1.60 ) . There was improved ARDS-free survival in the subset ( 19 % of the population ) requiring 10 U or more of packed red blood cells ( hazard ratio , 2.18 ; 95 % confidence interval , 1.09 - 4.36 ) . CONCLUSIONS Although no significant difference in ARDS-free survival was demonstrated overall , there was benefit in the subgroup of patients requiring 10 U or more of packed red blood cells in the first 24 hours . Massive transfusion may be a better predictor of ARDS than prehospital hypotension . The use of HSD may offer maximum benefit in patients at highest risk of ARDS To evaluate the use of hypertonic saline/dextran solutions in the prehospital resuscitation of severely injured patients , we administered 250 mL of either 7.5 % sodium chloride/dextran 70 ( HSD ) ( n = 83 ) or lactated Ringer 's solution ( n = 83 ) , followed by conventional isotonic fluids , to 166 trauma patients with systolic blood pressures less than or equal to 100 mm Hg , in a prospect i ve , r and omized , double-blinded clinical trial . Patients in the sodium chloride/dextran 70 group required less fluid before hospitalization and arrived in the emergency department with higher systolic blood pressures than patients in the lactated Ringer 's solution group . The rate of survival to hospital discharge for the entire cohort was 64 % for patients in the sodium chloride/dextran 70 group vs 59 % for patients in the lactated Ringer 's solution group . The rate of survival to hospital discharge for the patients with severe head injuries was 32 % for the sodium chloride/dextran 70 group vs 16 % for the lactated Ringer 's solution group . Actuarial survival for patients with severe head injuries in the sodium chloride/dextran 70 group compared with patients with severe head injuries in the lactated Ringer 's solution group did not quite reach statistical significance . There were no adverse side effects associated with sodium chloride/dextran 70 administration . Administration of small volumes of sodium chloride/dextran 70 before hospitalization increased the blood pressure of severely injured patients more effectively than did lactated Ringer 's solution and showed tendencies toward improving survival in the patients with severe head injuries BACKGROUND / AIMS Recent studies demonstrated that extravascular lung water ( EVLW ) is a reliable and independent marker for outcome . The primary therapeutically goal in critically ill patients is to resuscitate and retain adequate organ perfusion by fluid administration , where is necessary to achieve adequate intravascular filling , but avoid initiation of pulmonary edema . METHODOLOGY Patients with severe sepsis were r and omly allocated to a group treated with 20 % Albumin 100 ml every 12 hours ( ALB ; n = 30 ) or with 6 % hydroxyethylstarch 130/0 , 4 250 ml every 6 hours ( HES ; n = 26 ) . Both treatments were completed by crystalloids or norephinephrin as necessary . We analyzed amount of developed EVLW , and relation with mortality , PaO2/FiO2 and alveolo-arterial oxygen difference . RESULTS We observed significantly greater decrease of EVLW when compared with baseline during whole monitored period of 72 hours in ALB group in contrast to HES patients ( p < 0.05 ) . Despite no significant changes of EVLW in HES group , we noted improve of PaO2/FiO2 and AaDO2 in both groups . We did not observed significant difference in mortality . CONCLUSION The present study results show can summarize that albumin reduces in a higher amount and earlier the extravascular lung water than HES , but this reduction was not associated with improvement of oxygenation functions , which was better in HES group Introduction There are limited data on the efficacy of early fluid resuscitation with third-generation hydroxyethyl starch ( HES 130 ) in burn injury . Adverse effects of HES on survival and organ function have been reported . Methods In this r and omized , controlled , double-blind trial , 48 patients with severe burn injury were assigned to receive either lactated Ringer ’s solution plus 6 % HES 130/0.4 in a ratio of 2:1 or lactated Ringer ’s solution with no colloid supplement for the first 72 hours . Primary outcome parameter was the group difference of administered total fluid from intensive care unit ( ICU ) admission up to day 3 . Secondary outcomes included kidney and lung injury and failure , length of stay , and mortality . Results Three-day totals of administered resuscitation fluid ( medians ) were 21,190 mL in the lactated Ringer ’s group and 19,535 mL in the HES group ( HES : −1,213 mL ; P = 0.39 ) . Creatinine levels from day 1 to 3 ( HES : + 0.4 μmol/L ; 95 % confidence interval ( CI ) −18.7 to 19.5 ; P = 0.97 ) and urinary outputs from day 1 to 3 ( HES : −58 mL ; 95 % CI −400 to 283 ; P = 0.90 ) were not different . Six patients in each group developed acute respiratory distress syndrome ( ARDS ) ( risk ratio 0.96 ; 95 % CI 0.35 to 2.64 ; P = 0.95 ) . Length of ICU stay ( HES vs. lactated Ringer ’s : 28 vs. 24 days ; P = 0.80 ) and length of hospital stay ( 31 vs. 29 days ; P = 0.57 ) were similar . Twenty-eight-day mortality was 4 patients in each group ( risk ratio 0.96 ; 95 % CI 0.27 to 4.45 ; P = 0.95 ) , and in-hospital mortality was 8 in the HES group vs. 5 patients in the lactated Ringer ’s group ( hazard ratio 1.86 ; 95 % CI 0.56 to 6.19 ; P = 0.31 ) . Conclusions There was no evidence that early fluid resuscitation with balanced HES 130/0.4 ( 6 % ) in addition to lactated Ringer ’s solution would lead to a volume-sparing effect in severe burn injury . Together with the findings that early renal function , incidence of ARDS , length of stay , and mortality were not negatively influenced by HES in this setting , balanced HES 130/0.4 ( 6 % ) plus lactated Ringer ’s solution could not be considered superior to lactated Ringer ’s solution alone . Trial registration Clinical Trials.gov BACKGROUND The role of fluids in trauma resuscitation is controversial . We compared resuscitation with 0.9 % saline vs hydroxyethyl starch , HES 130/0.4 , in severe trauma with respect to resuscitation , fluid volume , gastrointestinal recovery , renal function , and blood product requirements . METHODS R and omized , controlled , double-blind study of severely injured patients requiring > 3 litres of fluid resuscitation . Blunt and penetrating trauma were r and omized separately . Patients were followed up for 30 days . RESULTS A total of 115 patients were r and omized ; of which , 109 were studied . For patients with penetrating trauma ( n=67 ) , the mean ( sd ) fluid requirements were 5.1 ( 2.7 ) litres in the HES group and 7.4 ( 4.3 ) litres in the saline group ( P<0.001 ) . In blunt trauma ( n=42 ) , there was no difference in study fluid requirements , but the HES group required significantly more blood products [ packed red blood cell volumes 2943 ( 1628 ) vs 1473 ( 1071 ) ml , P=0.005 ] and was more severely injured than the saline group ( median injury severity score 29.5 vs 18 ; P=0.01 ) . Haemodynamic data were similar , but , in the penetrating group , plasma lactate concentrations were lower over the first 4 h ( P=0.029 ) and on day 1 with HES than with saline [ 2.1 ( 1.4 ) vs 3.2 ( 2.2 ) mmol litre⁻¹ ; P=0.017 ] . There was no difference between any groups in time to recovery of bowel function or mortality . In penetrating trauma , renal injury occurred more frequently in the saline group than the HES group ( 16 % vs 0 % ; P=0.018 ) . In penetrating trauma , maximum sequential organ function scores were lower with HES than with saline ( median 2.4 vs 4.5 , P=0.012 ) . No differences were seen in safety measures in the blunt trauma patients . CONCLUSIONS In penetrating trauma , HES provided significantly better lactate clearance and less renal injury than saline . No firm conclusions could be drawn for blunt trauma . STUDY REGISTRATION IS RCT N 42061860 Abstract Objective : To investigate the effect of 4 % succinylated modified fluid gelatin ( MFG ) versus mean weight , highly substituted 6 % hydroxyethyl starch ( HES ) on hemodynamic and gastric mucosal acidosis variables , in septic hypovolemic patients . Design : Prospect i ve , r and omized , clinical investigation . Setting : University hospital intensive care unit . Patients : Thirty-four septic hypovolemic ventilated and hemodynamically controlled patients . Interventions : Invasive hemodynamic and gastric tonometric measurements . Measurements and results : Hemodynamic and tonometric parameters were recorded at baseline and 60 min after infusion of 500 ml of each colloid . In all patients central venous pressure , pulmonary artery occlusion pressure , cardiac index and mean arterial pressure increased significantly with both colloids , and hemoglobin concentration decreased by the same amount while oxygen delivery remained stable . Gastric intramucosal pH increased from 7.27±0.08 to 7.31±0.07 ( p<0.001 ) with MFG and decreased non-significantly from 7.26±0.11 to 7.22±0.08 ( ns ) with HES . Carbon dioxide gastric mucosal arterial gradient decreased from 18±9 to 13±9 mmHg ( p<0.0005 ) in the MFG group and rose non-significantly from 18±11 to 21±11 mmHg with HES . Conclusions : Although MFG and 6 % HES have the same hemodynamic effects , their physicochemical properties induce different responses on gastric mucosal acidosis in septic , hypovolemic and ventilated patients . These effects of MFG and HES on gastric mucosa need to be considered in patient management Cardiac output and pulmonary wedge pressure ( PWP ) were used to evaluate the end point of fluid resuscitation in 20 patients suffering from multiple trauma and shock . Eleven patients received crystalloid resuscitation and nine patients received colloid resuscitation . Fifteen of 20 patients had an adequate cardiac output at the termination of resuscitation , but but only six of these patients had a PWP above 10 mm Hg . There was no significant correlation between left ventricular stroke work index and PWP in these patients , either at the completion of resuscitation or during the following three days . Five patients did not achieve adequate cardiac output and four of these patients died , suggesting that cardiac output was the most important criterion for adequate resuscitation . If the goal of fluid resuscitation is to achieve an adequate cardiac output , then PWP was not a reliable guide . Furthermore , using both cardiac output and PWP as a guide to fluid resuscitation of our patients , we found that the type of fluid ( crystalloid or colloid ) for resuscitation did not influence the course of respiratory distress in these patients up to three days following resuscitation Summary Objective To determine whether intravenous infusion of either human albumin or hydroxyethylstarch ( HES ) in hypo-albuminemic critically ill may lead to an increase in colloid osmotic pressure and to a better clinical outcome , i.e. lower mortality and fewer complications , compared to fluid replacement with normal saline Design Prospect i ve , r and omized controlled clinical trial during 72 hours in 61 consecutively admitted severely ill patients . R and omisation took place by sealed envelope , kept outside of the hospital . Setting Intensive care unit of the Twenteborg Hospital , Almelo , The Netherl and s . SubjectsSixty-three severely ill , hypo-albuminemic patients were selected ; 27 patients had severe sepsis and 36 were post-surgical patients with SIRS . Two patients died shortly after r and omization , 15 patients received human albumin , 15 HES 500 and 15 HES 1000 ml , and 16 saline . Interventions The patients were r and omized to receive 300 ml human albumin ( 20 % ) per day , or 1000 ml normal saline per day , or 500 ml or 1000 ml HES per day , all for 72 hours . Main outcome measures The primary outcome was plasma colloid osmotic pressure ( COP ) . Secondary end-points were fluid balance and the development of pulmonary edema . Results Administration of human albumin was effective in raising COP ( P<0.001 on day 2 and day 3 , compared to saline and HES ) . Neither fluid balances nor the development of peripheral or pulmonary edema were different between the groups . Mortality as well as length of stay at ICU were slightly higher in the group receiving human albumin although not statistically significant . Conclusion Raising colloid osmotic pressure with human albumin in hypoalbuminemic patients is not associated with improvement of the clinical Objective : To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock . Background : Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion , with a smaller volume , and modulation of the inflammatory response , to reduce subsequent organ injury . Methods : Multicenter , r and omized , blinded clinical trial , May 2006 to August 2008 , 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium . Inclusion criteria : injured patients , age ≥ 15 years with hypovolemic shock ( systolic blood pressure ⩽ 70 mm Hg or systolic blood pressure 71–90 mm Hg with heart rate ≥ 108 beats per minute ) . Initial resuscitation fluid , 250 mL of either 7.5 % saline per 6 % dextran 70 ( hypertonic saline/dextran , HSD ) , 7.5 % saline ( hypertonic saline , HS ) , or 0.9 % saline ( normal saline , NS ) administered by out-of-hospital providers . Primary outcome was 28-day survival . On the recommendation of the data and safety monitoring board , the study was stopped early ( 23 % of proposed sample size ) for futility and potential safety concern . Results : A total of 853 treated patients were enrolled , among whom 62 % were with blunt trauma , 38 % with penetrating . There was no difference in 28-day survival — HSD : 74.5 % ( 0.1 ; 95 % confidence interval [ CI ] , −7.5 to 7.8 ) ; HS : 73.0 % ( −1.4 ; 95 % CI , −8.7–6.0 ) ; and NS : 74.4 % , P = 0.91 . There was a higher mortality for the postr and omization subgroup of patients who did not receive blood transfusions in the first 24 hours , who received hypertonic fluids compared to NS [ 28-day mortality — HSD : 10 % ( 5.2 ; 95 % CI , 0.4–10.1 ) ; HS : 12.2 % ( 7.4 ; 95 % CI , 2.5–12.2 ) ; and NS : 4.8 % , P < 0.01 ] . Conclusion : Among injured patients with hypovolemic shock , initial resuscitation fluid treatment with either HS or HSD compared with NS , did not result in superior 28-day survival . However , interpretation of these findings is limited by the early stopping of the trial . Clinical Trial Registration : Clinical Trials.gov , OBJECTIVE To evaluate the use of 250 mL of a 7.5 % sodium chloride solution , both with and without added dextran 70 , for the prehospital resuscitation of hypotensive trauma patients . DESIGN Double-blind r and omized trial . SETTING Six trauma systems served by helicopter transport . PATIENTS Injured patients with systolic blood pressures less than 90 mm Hg at any time in the field or during helicopter transport . INTERVENTIONS Infusion of study solution , in the field or during transport , followed by conventional isotonic solutions as needed . Solutions studied in four cohorts were as follows : ( 1 ) lactated Ringer 's ; ( 2 ) 7.5 % sodium chloride ( hypertonic saline ) ; ( 3 ) 7.5 % sodium chloride combined with 6 % dextran 70 ; and ( 4 ) 7.5 % sodium chloride combined with 12 % dextran 70 . MAIN OUTCOME MEASURES Blood pressure response ; survival to time of hospital discharge among the treatment groups ; and survival compared with that predicted by norms from the Major Trauma Outcome Study ( MTOS ) . RESULTS The mean ( + /- SD ) change in systolic blood pressure on arrival in the emergency department was significantly higher in the hypertonic saline solution group than that in the lactated Ringer 's solution group ( 34 + /- 46 vs 11 + /- 49 mm Hg , P < .03 ) . Overall survival in the four treatment groups was 49 % , 60 % , 56 % , and 45 % ( not statistically significant ) . Survival in the hypertonic saline solution group , however , was significantly higher than that predicted by the MTOS norms ( 60 % vs 48 % , P < .001 ) . Survival to hospital discharge in patients with baseline Glasgow Coma Scale scores of 8 or less was correlated with treatment group ( P < .05 by logistic regression and P < .01 by Cox proportional-hazards analysis ; with survival in the hypertonic saline solution group [ 34 % ] vs lactated Ringer 's solution group [ 12 % ] ) . CONCLUSIONS Prehospital infusion of 250 mL of 7.5 % sodium chloride is associated with an increase in blood pressure and an increase in survival to hospital discharge compared with survival predicted by the MTOS norms . Patients with low baseline Glasgow Coma Scale scores seem to benefit the most from 7.5 % sodium chloride resuscitation . Hypertonic saline solution without added dextran 70 is as effective as the more expensive solutions that contain dextran 70 BACKGROUND Hypovolemia is a common clinical entity in critical patients , and adequate volume replacement therapy seems to be essential for maintaining tissue perfusion . However , it is still uncertain which solution is most appropriate for fluid resuscitation . OBJECTIVE The aim of this study was to investigate the effects of fluid resuscitation with 3.5 % polygeline versus 6 % hydroxyethyl starch solutions on hemodynamic functions and liver functions assessed with a noninvasive liver function monitoring system ( LIMON ) in hypovolemic patients . DESIGN This study is a prospect i ve r and omized clinical trial . MEASUREMENTS AND RESULTS Thirty hypovolemic patients ( intrathoracic blood volume index , < 850 mL/m(2 ) ) were r and omized into hydroxyethyl starch ( mean molecular weight , 130,000 Da ) and polygeline ( mean molecular weight , 30,000 Da ) groups ( 15 patients each ) . Indocyanine green plasma disappearance elimination ( ICG-PDR ) were conducted concurrently using LIMON . A dose of 0.3 mg/kg ICG was given through a cubital fossa vein as a bolus . For fluid resuscitation , 500 mL of colloid was given to the patients . Repeated hemodynamic and ICG-PDR measurements were done at baseline , after infusion , and then at 30 minutes after infusion . RESULTS Intrathoracic blood volume index and systolic , diastolic , and mean blood pressures increased significantly after infusion and remained elevated for 30 minutes after infusion , but there was no significant difference between the 2 groups . Indocyanine green plasma disappearance elimination values were similar in both groups with no significant difference between the two . CONCLUSION Increasing intrathoracic blood volume index and hemodynamic variables by fluid loading is not associated with a significant change in ICG-PDR BACKGROUND Hydroxyethylstarch used for volume restoration in brain-dead kidney donors has been associated with impaired kidney function in the transplant recipients . We undertook a multicentre r and omised study to assess the frequency of acute renal failure ( ARF ) in patients with severe sepsis or septic shock treated with hydroxyethylstarch or gelatin . METHODS Adults with severe sepsis or septic shock were enrolled prospect ively in three intensive-care units in France . They were r and omly assigned 6 % hydroxyethylstarch ( 200 kDa , 0.60 - 0.66 substitution ) or 3 % fluid-modified gelatin . The primary endpoint was ARF ( a two-fold increase in serum creatinine from baseline or need for renal replacement therapy ) . Analyses were by intention to treat . FINDINGS 129 patients were enrolled over 18 months . Severity of illness and serum creatinine ( median 143 [ IQR 88 - 203 ] vs 114 [ 91 - 175 ] micromol/L ) were similar at baseline in the hydroxyethylstarch and gelatin groups . The frequencies of ARF ( 27/65 [ 42 % ] vs 15/64 [ 23 % ] , p=0.028 ) and oliguria ( 35/62 [ 56 % ] vs 23/63 [ 37 % ] , p=0.025 ) and the peak serum creatinine concentration ( 225 [ 130 - 339 ] vs 169 [ 106 - 273 ] micromol/L , p=0.04 ) were significantly higher in the hydroxyethylstarch group than in the gelatin group . In a multivariate analysis , risk factors for acute renal failure included mechanical ventilation ( odds ratio 4.02 [ 95 % CI 1.37 - 11.8 ] , p=0.013 ) and use of hydroxyethylstarch ( 2.57 [ 1.13 - 5.83 ] , p=0.026 ) . INTERPRETATIONS The use of this preparation of hydroxyethylstarch as a plasma-volume exp and er is an independent risk factor for ARF in patients with severe sepsis or septic shock Haemaccel is widely used throughout Europe and South Africa in the resuscitation of trauma patients " . Although it is very effective when used as the sole volume exp and er , it is usually used in conjunction with a crystalloid which has been shown both experimentally and clinical ly to increase its benefits " . The colloid within Haemaccel is chemically modified bovine bone gelatine preparation . The gelatine is subjected to thermal degradation to produce a gelatine hydrolysate in the form of small polypeptides of molecular weight 12000 to 15000 . These are then cross linked to form larger molecules which have an average molecular weight of 35000 ( range 25000 - 50000 ) . In addition , the solution contains a number of other solutes including Ca2 + ( 6.2 mM ) , and exerts an oncotic pressure of 3.4 - 3.8 kaPa at 37 ° C . It is isoncotic with plasma and it has a half life in the body of approximately 5 h. Recent anecdotal reports from the Department of Surgery at the University Hospital Bloemfontein ( Orange Free State , South Africa ) suggested that trauma patients who had received Haemaccel for shock exhibited an increased bleeding tendency in the form of wound oozing , both intra and post-operatively . The aim of the present study , therefore , was to perform a controlled investigation of the effects of Hacmacccl on bleeding time in vivo in trauma victims at the Trauma Unit of Johannesburg Hospital The aim of this paper is to report the results of prospect i ve clinical trials of hypertonic saline dextran ( HSD ) in the resuscitation of hypovolaemic shock in critically injured patients . There are many types of fluids , which can be administered intravenously . Recent interest in the usage of HSD solution has confirmed that they have a place in resuscitation of a patient in shock . Heart rate and arterial pressure recovered well with HSD solution . The plasma osmolarity , sodium and potassium levels were significantly elevated in patients resuscitated with HSD . Urine output recovered rapidly and was well maintained throughout Twenty-three patients aged 20 - 58 years in a serious state of shock and suffering from major pelvic and femoral fractures sustained in traffic accidents were studied . As initial fluid management , either dextran 70 ( 1000 - 1500 ml ) together with Ringer 's acetate solution ( 2000 - 3000 ml ) , or Ringer 's acetate alone ( 5000 - 8000 ml ) , was administered on a r and om basis . Thus , 12 patients received dextran and 11 patients crystalloid treatment to counteract shock . Both groups were given whole blood . The resuscitation time -- i.e . the interval from the start of fluid therapy until a stable circulatory condition was achieved -- was significantly shorter ( P less than 0.001 ) in the dextran group ( 108 + /- 18 min ; mean + /- S.D. ) than in the Ringer group ( 170 + /- 43 min ) . During the post-resuscitative observation period of 6 days the dextran patients were given 500 ml of dextran daily , while the Ringer group did not receive any colloidal solution . To maintain a stable circulation and a urinary output above 50 ml/h the Ringer patients required significantly more ( P less than 0.001 ) crystalloid solution ( 910 + /- 300 ml ) daily than the dextran patients ( 460 + /- 400 ml ) . The frequency of adult respiratory distress syndrome ( ARDS ) was significantly lower ( P less than 0.05 ) in the dextran group ( 0 of 12 ) than in the Ringer group ( 4 of 11 ) . Thus , in the initial treatment of traumatic-haemorrhagic shock and in the post-resuscitative period dextran 70 would seem of advantage over Ringer 's acetate both in shortening the shock period and in reducing the frequency of adult respiratory distress syndrome Abstract Objective . To study the haemodynamic effects of a hypertonic saline/dextran solution compared with a normal saline solution in patients with severe sepsis . Design . Prospect i ve double blind and control-r and omised study . Setting . Adult intensive care unit in a university hospital . Patients . Twenty-nine patients with sepsis with a pulmonary artery occlusion pressure ( PAOP ) lower than 12 mmHg . Interventions . Patients were r and omised to receive 250 ml of blinded solutions of either normal saline ( SS group , n=16 ) or hypertonic saline ( NaCl 7.5%)/dextran 70 8 % ( HSS group , n=13 ) solutions . Measurements and results . Haemodynamic , blood gas , and sodium data were collected at the following time points : baseline , 30 min , 60 min , 120 min , and 180 min . PAOP was higher in the HSS group at 30 min ( 10.7±3.2 mmHg vs 6.8±3.2 mmHg ) and 60 min ( 10.3±3 mmHg vs 7.4±2.9 mmHg ) ; P<0.05 . The cardiac index increased in the HSS group and it was greater than the SS group at 30 min ( 6.5±4.7 l min–1 m–2 vs 3.8±3.4 l min–1 m–2 ) , 60 min ( 4.9±4.5 l min–1 m–2 vs 3.7±3.3 l min–1 m–2 ) , and 120 min ( 5.0±4.3 l min–1 m–2 vs 4.1±3.4 l min–1 m–2 ) ; P<0.05 . The stroke volume index followed a comparable course and it was higher at 30 min [ 53.6(39.2–62.8 ) ml m–2 vs 35.6(31.2–49.2 ) ml m–2 ] and 60 min [ 46.8(39.7–56.6 ) ml m–2 vs 33.9(32.2–47.7 ) ml m–2 ] ; P<0.05 . Systemic vascular resistance decreased in the HSS group and became significantly lower at 30 min ( 824±277 dyne s–1 cm–5 m–2 vs 1139±245 dyne s–1 cm–5 m–2 ) , 60 min ( 921±256 dyne s–1 cm–5 m–2 vs 1246±308 dyne s–1 cm–5 m–2 ) , and 120 min ( 925±226 dyne s–1 cm–5 m–2 vs 1269±494 dyne s–1 cm–5 m–2 ) . Sodium levels increased in the HSS group ( P=0.056 ) and were higher than in the SS group at 30 min ( 145±3 mEq l–1 vs 137±7 mEq l–1 ) , 60 min ( 143±4 mEq l–1 vs 136±7 mEq l–1 ) , 120 ( 142±5 mEq l–1vs 136±7 mEq l–1 ) , and 180 min ( 142±5 mEq l–1 vs 136±8 mEq l–1 ) . Conclusion . Hypertonic saline/dextran solution may improve cardiovascular performance in severe sepsis without significant side effects . The haemodynamic effect appears related mainly to a volume effect Pentastarch is a colloid that is chemically similar to Hetastarch . It has a shorter half-life ( 12 hr ) , and produces volume expansion at least 1.5 times the administered volume . We compared Pentastarch to Ringer 's lactate in 41 patients ( 21 Pentastarch , 20 Ringer 's lactate ) presenting with hemorrhagic shock . The groups were similar in age , sex , race , and type of injury . Significantly less volume of Pentastarch was required initially to resuscitate to a normal blood pressure and urine output than Ringer 's lactate ( P < 0.005 ) . Coagulation parameters ( prothrombin time , partial thromboplastin time , fibrinogen , and factor VIII ) were measured for 48 hr post-resuscitation , and no abnormalities were noted in the Pentastarch group . Serum albumin was the same in both groups throughout the study period ; however , serum colloid oncotic pressure was elevated at 1 hr post-resuscitation in the Pentastarch group ( P < 0.005 ) . There was no difference in ventilatory parameters , blood gases , pulmonary function tests , ventilator days , or hospital days between the two groups . We conclude that Pentastarch is safe and effective for the initial resuscitation from hemorrhagic shock Twenty consecutive patients with severe sepsis were r and omized to fluid challenge with 5 % albumin or 10 % low MW hydroxyethyl starch ( pentastarch ) solutions . Fluid challenge was administered iv as 250 ml of test colloid every 15 min until the pulmonary artery wedge pressure ( WP ) was greater than or equal to 15 mm Hg or a maximum dose of 2000 ml was infused . Hemodynamic , respiratory , and coagulation profiles were measured before and after fluid infusion . The amount of colloid required to achieve a WP of 15 mm Hg was comparable between groups . Both colloid infusions result ed in similar increases in cardiac output , stroke output , and stroke work . The effect of fluid infusion with pentastarch on coagulation was not significantly different from albumin , although pentastarch was associated with a 45 % decrease in factor VIII : c . We conclude that pentastarch is equivalent to albumin for fluid resuscitation of patients with severe sepsis Abstract . This study evaluates the hemodynamic effects of the administration of 10 % pentastarch solution ( PS ) during the initial treatment of hypovolemia in trauma patients . This prospect i ve r and omized phase II study included trauma patients admitted to the emergency room with hemorrhagic hypovolemia : systolic blood pressure ( SBP ) < 90 mmHg . Upon admission , the patients were r and omized to receive 10 % PS ( n= 12 ) or isotonic 0.9 % NaCl solution ( IS ) ( n= 11 ) , infused intravenously in 250-ml boluses , repeated until SBP > 100 mmHg . Blood pressure , infused volumes necessary to maintain SBP , and overall survival rates were determined and compared between groups . SBP increased significantly following either IS ( from 64.4 ± 9.2 mmHg to 111.1 ± 6.3 mmHg ) , or PS ( from 63.7 ± 10.6 mmHg to 108.1 ± 9.8 mmHg ) when compared to admission values ( p < 0.05 ) . Endovenous volumes infused were greater ( p= 0.001 ) in IS patients ( 1420 ± 298 ml ) than in PS patients ( 356 ± 64 ml ) . No blood was transfused into PS patients , compared to 370 ± 140 ml of red blood cells transfused into IS patients ( p= 0.015 ) . Mortality rates were similar in the two groups ( p= 0.725 ) . We concluded that PS is a safe , efficient method for inducing hemodynamic recovery of hypovolemic trauma patients , with a clear reduction in the intravenous volumes required for acute resuscitation INTRODUCTION Hydroxyethylstarches ( HES ) are thought to be beneficial in trauma and major surgery management , due to their volume expansion and anti-inflammatory properties . This study examined the use of 6 % ( HES ) in burn resuscitation . METHODS 26 adult patients with burns exceeding 15 % total body surface area ( TBSA ) were r and omised to either crystalloid ( Hartmann 's solution ) or a colloid-supplemented resuscitation regime , where 1/3 of the crystalloid-predicted requirement was replaced by 6 % HES . RESULTS There was no difference in age , gender or TBSA between the two groups . The median ( 95 % CI ) fluid volume/%TBSA received in the first 24 h was 307 ml and 263 ml for the crystalloid only and HES-supplemented group respectively ( p=0.0234 , Mann-Whitney ) . Body weight gain within the first 24 h after injury was significantly lower in the HES-supplemented group 2.5 kg versus 1.4 kg respectively ( p=0.0039 ) . The median ( 95 % CI ) serum C-reactive protein at 48 h after injury was 210 ( 167 - 257 ) and 128 ( 74 - 145 ) mg/L for the crystalloid only and HES-supplemented group respectively ( p=0.0001 ) . Albumin-creatinine ratio per % burn ( ACR , a marker of capillary leak ) was lower in the HES-supplemented group at 12h after burn ( p=0.0310 ) . CONCLUSIONS Patients treated with HES-supplemented resuscitation required less fluid , showed less interstitial oedema and a dampened inflammatory response compared to patients receiving isotonic crystalloid alone BACKGROUND The infusion of small volumes of hypertonic saline solution or hypertonic saline plus dextran 70 is remarkably effective in restoring adequate hemodynamic conditions after hypovolemic shock . This prospect i ve double-blind study compares the immediate hemodynamic effects of a bolus infusion of 7.5 % NaCl or 7.5 % NaCl plus 6 % dextran 70 ( both 2400 mOsm/L ) in severe hypovolemia . METHODS One hundred five adult patients admitted in hypovolemic shock ( systolic blood pressure less than 80 mm Hg ) were revived on arrival to the emergency room and administration of a 250 ml intravenous bolus of hypertonic saline solution ( n = 35 ) , hypertonic saline plus dextran ( n = 35 ) , or isotonic saline solution ( n = 35 ) . This infusion was immediately followed by st and ard crystalloid and blood replacement until systolic pressure reached 100 mm Hg . Mean arterial pressure ( MAP ) was measured every 5 minutes , and all intravenous infusions were registered . Plasma volume expansion was calculated from plasma protein concentration measurements . Patients were followed up throughout their hospital course , and results of treatment were recorded . RESULTS At the end of the infusion period , and 5 and 10 minutes after infusion , MAP was significantly higher in patients receiving either hypertonic solution , compared with the group receiving isotonic solution . All groups showed similar trends toward restoration of hemodynamic parameters thereafter . The calculated plasma volume expansion , immediately after the bolus infusion , was significantly higher ( 24.1 % + /- 1.8 % and 24.9 % + /- 1.1 % ) in the hypertonic groups , compared with isotonic groups ( 7.9 % + /- 1.3 % ) . Significantly greater volumes of fluids were required to restore systolic pressure in the patients receiving isotonic saline solution than in the groups receiving hypertonic solution . There were no significant differences between the groups receiving hypertonic solutions . The incidence of complications was low , and the mortality rate was similar in all groups . CONCLUSIONS Infusion of 250 ml hypertonic saline solution in patients with severe hypovolemia was not related to any complications , nor did it affect mortality rates ; it improved MAP significantly , acutely exp and ed plasma volume by 24 % , and reduced significantly the volumes of crystalloids and blood required in their resuscitation We evaluated the potential side effects of rapidly infusing 250 mL of either 7.5 % sodium chloride or 7.5 % sodium chloride per 6 % dextran 70 , using lactated Ringer 's as the control , to 106 critically injured patients in two prospect i ve double-blinded emergency department trials . Eight patients had a significant hyperchloremic acidemia in association with infusion of the hypertonic solutions , but all eight were moribund before infusion and many factors other than hyperchloremia could have contributed to their acidemia . Other blood chemistry changes that might have been associated with the hypertonic solutions , such as hyperosmolality or hypernatremia , were made insignificant by other factors , such as high blood alcohol levels or concomitant administration of sodium bicarbonate . There were no cases of central pontine myelinolysis ; bleeding was not potentiated . There was no difficulty with crossmatching of blood . No anaphylactoid reactions occurred . In a setting of limited volume resuscitation , the solutions are likely to have a favorable risk-to-benefit ratio Objective To compare the hemodynamic and oxygen transport responses to a rapid ( < 10-min ) infusion of 500 mL of modified fluid gelatin ( group A ) or hydroxyethyl starch ( group B ) in patients suffering from acute hypovolemia . Design Prospect i ve , r and omized , noncrossover study . Setting University hospital , general intensive care unit . Patients Twenty-eight patients with hypovolemia mechanically ventilated for concurrent acute respiratory failure . Interventions Patients were mechanically ventilated . Pulmonary and femoral artery catheters were used for hemodynamic monitoring . Measurements and Main Results Hemodynamic and oxygen transport variables were determined at baseline , 15 mins , and 30 mins after the infusion of each fluid . In both groups pulmonary artery occlusion pressure , stroke volume , and cardiac index significantly increased . In neither group did heart rate decrease . Oxygen delivery increased significantly in group A patients but not in group B patients . This result was due to greater hemodilution in group B patients . Conclusions There are no significant differences in the hemodynamic responses to hydroxyethyl starch or modified fluid gelatin . The hemodynamic and oxygen transport effects of artificial colloid solutions may not be entirely predictable and should be monitored in critically ill patients . ( Crit Care Med 1994 ; 22:600–605 Twenty-six consecutive patients in hypovolemic shock were r and omized to fluid challenge with 5 % albumin ( A ) , 6 % hetastarch ( H ) , or 0.9 % saline ( S ) solutions . Fluid challenge consisted of 250 ml of test fluid every 15 min until the pulmonary artery wedge pressure ( WP ) reached 15 mm Hg . Thereafter , WP was maintained at 15 mm Hg for an additional 24 h with infusions of the same test fluid . Vital signs , hemodynamic and respiratory variables , as well as arterial lactate and colloid osmotic pressure ( COP ) were monitored according to protocol . Chest x-rays were performed by st and ardized technique before fluid challenge and at 12 and 24 h of maintenance fluid therapy and were evaluated for evidence of pulmonary edema . Cardiac function and hemodynamic stability were restored by fluid challenge with A , H , and S. Two to 4 times the volume of S as A or H was required to achieve similar hemodynamic endpoints . COP was increased by fluid challenge with A or H but was markedly reduced by fluid challenge with S and throughout the 24-h maintenance period . Fluid challenge result ed in reductions in COP-WP gradient of 62 % in the A , 43 % in the H , and 125 % in the S groups . Resuscitation with S result ed in a significantly higher incidence of pulmonary edema ( 87.5 % ) than did resuscitation with A ( 22 % ) or H ( 22 % ) . Urine output was not different among the groups at any time during the study . We conclude that 6 % H performs as well as 5 % A as a resuscitative fluid and that resuscitation with either of these colloids is associated with a lower incidence of pulmonary edema than is resuscitation with 0.9 % Rationale : Saline is the intravenous fluid most commonly administered to critically ill adults , but it may be associated with acute kidney injury and death . Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown . Objectives : To pilot a cluster‐r and omized , multiple‐crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids . Methods : This was a cluster‐r and omized , multiple‐crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3 , 2015 to May 31 , 2015 . The intravenous crystalloid used in the unit alternated monthly between saline ( 0.9 % sodium chloride ) and balanced crystalloids ( lactated Ringer 's solution or Plasma‐Lyte A ) . Enrollment , fluid delivery , and data collection were performed using software tools within the electronic health record . The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline . The secondary outcome was major adverse kidney events within 30 days ( MAKE30 ) , a composite of death , dialysis , or persistent renal dysfunction . Measurements and Main Results : Patients assigned to saline ( n = 454 ) and balanced crystalloids ( n = 520 ) were similar at baseline and received similar volumes of crystalloid by 30 days ( median [ interquartile range ] : 1,424 ml [ 500‐3,377 ] vs. 1,617 ml [ 500‐3,628 ] ; P = 0.40 ) . Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group ( 91 % vs. 21 % ; P < 0.001 ) . MAKE30 did not differ between groups ( 24.7 % vs. 24.6 % ; P = 0.98 ) . Conclusions : An electronic health record‐embedded , cluster‐r and omized , multiple‐crossover trial comparing saline with balanced crystalloids can produce well‐balanced study groups and separation in crystalloid receipt . Clinical trial registered with www . clinical trials.gov ( NCT 02345486 ) IMPORTANCE Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear . OBJECTIVE To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit ( ICU ) with hypovolemic shock . DESIGN , SETTING , AND PARTICIPANTS A multicenter , r and omized clinical trial stratified by case mix ( sepsis , trauma , or hypovolemic shock without sepsis or trauma ) . Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill ( CRISTAL ) trial was open label but outcome assessment was blinded to treatment assignment . Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France , Belgium , North Africa , and Canada ; follow-up ended in November 2012 . INTERVENTIONS Colloids ( n = 1414 ; gelatins , dextrans , hydroxyethyl starches , or 4 % or 20 % of albumin ) or crystalloids ( n = 1443 ; isotonic or hypertonic saline or Ringer lactate solution ) for all fluid interventions other than fluid maintenance throughout the ICU stay . MAIN OUTCOMES AND MEASURES The primary outcome was death within 28 days . Secondary outcomes included 90-day mortality ; and days alive and not receiving renal replacement therapy , mechanical ventilation , or vasopressor therapy . RESULTS Within 28 days , there were 359 deaths ( 25.4 % ) in colloids group vs 390 deaths ( 27.0 % ) in crystalloids group ( relative risk [ RR ] , 0.96 [ 95 % CI , 0.88 to 1.04 ] ; P = .26 ) . Within 90 days , there were 434 deaths ( 30.7 % ) in colloids group vs 493 deaths ( 34.2 % ) in crystalloids group ( RR , 0.92 [ 95 % CI , 0.86 to 0.99 ] ; P = .03 ) . Renal replacement therapy was used in 156 ( 11.0 % ) in colloids group vs 181 ( 12.5 % ) in crystalloids group ( RR , 0.93 [ 95 % CI , 0.83 to 1.03 ] ; P = .19 ) . There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days ( mean : 2.1 vs 1.8 days , respectively ; mean difference , 0.30 [ 95 % CI , 0.09 to 0.48 ] days ; P = .01 ) and by 28 days ( mean : 14.6 vs 13.5 days ; mean difference , 1.10 [ 95 % CI , 0.14 to 2.06 ] days ; P = .01 ) and alive without vasopressor therapy by 7 days ( mean : 5.0 vs 4.7 days ; mean difference , 0.30 [ 95 % CI , -0.03 to 0.50 ] days ; P = .04 ) and by 28 days ( mean : 16.2 vs 15.2 days ; mean difference , 1.04 [ 95 % CI , -0.04 to 2.10 ] days ; P = .03 ) . CONCLUSIONS AND RELEVANCE Among ICU patients with hypovolemia , the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality . Although 90-day mortality was lower among patients receiving colloids , this finding should be considered exploratory and requires further study before reaching conclusions about efficacy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00318942 IMPORTANCE Saline ( 0.9 % sodium chloride ) is the most commonly administered intravenous fluid ; however , its use may be associated with acute kidney injury ( AKI ) and increased mortality . OBJECTIVE To determine the effect of a buffered crystalloid compared with saline on renal complications in patients admitted to the intensive care unit ( ICU ) . DESIGN AND SETTING Double-blind , cluster r and omized , double-crossover trial conducted in 4 ICUs in New Zeal and from April 2014 through October 2014 . Three ICUs were general medical and surgical ICUs ; 1 ICU had a predominance of cardiothoracic and vascular surgical patients . PARTICIPANTS All patients admitted to the ICU requiring crystalloid fluid therapy were eligible for inclusion . Patients with established AKI requiring renal replacement therapy ( RRT ) were excluded . All 2278 eligible patients were enrolled ; 1152 of 1162 patients ( 99.1 % ) receiving buffered crystalloid and 1110 of 1116 patients ( 99.5 % ) receiving saline were analyzed . INTERVENTIONS Participating ICUs were assigned a masked study fluid , either saline or a buffered crystalloid , for alternating 7-week treatment blocks . Two ICUs commenced using 1 fluid and the other 2 commenced using the alternative fluid . Two crossovers occurred so that each ICU used each fluid twice over the 28 weeks of the study . The treating clinician determined the rate and frequency of fluid administration . MAIN OUTCOMES AND MEASURES The primary outcome was proportion of patients with AKI ( defined as a rise in serum creatinine level of at least 2-fold or a serum creatinine level of ≥3.96 mg/dL with an increase of ≥0.5 mg/dL ) ; main secondary outcomes were incidence of RRT use and in-hospital mortality . RESULTS In the buffered crystalloid group , 102 of 1067 patients ( 9.6 % ) developed AKI within 90 days after enrollment compared with 94 of 1025 patients ( 9.2 % ) in the saline group ( absolute difference , 0.4 % [ 95 % CI , -2.1 % to 2.9 % ] ; relative risk [ RR ] , 1.04 [ 95 % CI , 0.80 to 1.36 ] ; P = .77 ) . In the buffered crystalloid group , RRT was used in 38 of 1152 patients ( 3.3 % ) compared with 38 of 1110 patients ( 3.4 % ) in the saline group ( absolute difference , -0.1 % [ 95 % CI , -1.6 % to 1.4 % ] ; RR , 0.96 [ 95 % CI , 0.62 to 1.50 ] ; P = .91 ) . Overall , 87 of 1152 patients ( 7.6 % ) in the buffered crystalloid group and 95 of 1110 patients ( 8.6 % ) in the saline group died in the hospital ( absolute difference , -1.0 % [ 95 % CI , -3.3 % to 1.2 % ] ; RR , 0.88 [ 95 % CI , 0.67 to 1.17 ] ; P = .40 ) . CONCLUSIONS AND RELEVANCE Among patients receiving crystalloid fluid therapy in the ICU , use of a buffered crystalloid compared with saline did not reduce the risk of AKI . Further large r and omized clinical trials are needed to assess efficacy in higher-risk population s and to measure clinical outcomes such as mortality . TRIAL REGISTRATION clinical trials.gov Identifier : ACTRN12613001370796 Objective : To compare crystalloid and colloid fluids in their effect on pulmonary edema in hypovolemic septic and nonseptic patients with or at risk for acute lung injury/acute respiratory distress syndrome . We hypothesized that 1 ) crystalloid loading results in more edema formation than colloid loading and 2 ) the differences among the types of fluid decreases at high permeability . Design , Setting , and Patients : Prospect i ve r and omized clinical trial on the effect of fluids in 24 septic and 24 nonseptic mechanically ventilated patients with clinical hypovolemia . Interventions : Patients were assigned to NaCl 0.9 % , gelatin 4 % , hydroxyethyl starch 6 % , or albumin 5 % loading for 90 minutes according to changes in filling pressures . Measurements and Main Results : Twenty-three septic and 10 nonseptic patients had acute lung injury/acute respiratory distress syndrome ( p < 0.001 ) . Septic patients had greater pulmonary capillary permeability , edema , and severity of lung injury than nonseptic patients ( p < 0.01 ) , as measured by the pulmonary leak index ( PLI ) for 67Gallium-labeled transferrin , extravascular lung water ( EVLW ) , and lung injury score ( LIS ) , respectively . Colloids increased plasma volume , cardiac index , and central venous pressure ( CVP ) more than crystalloids ( p < 0.05 ) , although more crystalloids were infused ( p < 0.05 ) . Colloid osmotic pressure ( COP ) increased in colloid and decreased in crystalloid groups ( p < 0.001 ) . Irrespective of fluid type or underlying disease , the pulmonary leak index increased by median 5 % ( p < 0.05 ) . Regardless of fluid type or underlying disease , EVLW and LIS did not change during fluid loading and EVLW related to COP-CVP ( rs = −.40 , p < 0.01 ) . Conclusions : Pulmonary edema and LIS are not affected by the type of fluid loading in the steep part of the cardiac function curve in both septic and nonseptic patients . Then , pulmonary capillary permeability may be a smaller determinant of pulmonary edema than COP and CVP . Safety factors may have prevented edema during a small filtration pressure-induced rise in pulmonary protein and thus fluid transport Objectives : This study aim ed to address whether hydroxyethyl starch ( HES ) is beneficial for intra-abdominal pressure ( IAP ) in severe acute pancreatitis ( SAP ) in early stages . Methods : Forty-one patients with SAP were r and omized to HES group ( n = 20 ) and the Ringer 's lactate ( RL ) group ( n = 21 ) . The groups received 6 % HES 130/0.4 for 8 days and RL solution without colloid , respectively . The primary end point was the IAP . The secondary end points were fluid balance , major organ complications , the Acute Physiology and Chronic Heath Evaluation II score , and the serum levels of C-reactive protein , interleukin-6 , and interleukin-8 . Results : The characteristics of baseline data were similar in the 2 groups . In the HES group , the IAP was significantly lower in 2 to 7 days , and fewer patients received mechanical ventilation ( 15.0 % vs 47.6 % ) . A negative fluid balance was observed earlier in the HES group than in the RL group ( 2.5 ± 2.2 vs 4.0 ± 2.5 days ) . Conclusions : Fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation Objective : We sought to compare resuscitation with 0.9 % NaCl versus Plasma-Lyte A , a calcium-free balanced crystalloid solution , hypothesizing that Plasma-Lyte A would better correct the base deficit 24 hours after injury . Background : Sodium chloride ( 0.9 % ) ( 0.9 % NaCl ) , though often used for resuscitation of trauma patients , may exacerbate the metabolic acidosis that occurs with injury , and this acidosis may have detrimental clinical effects . Methods : We conducted a r and omized , double-blind , parallel-group trial ( NCT01270854 ) of adult trauma patients requiring blood transfusion , intubation , or operation within 60 minutes of arrival at the University of California Davis Medical Center . Based on a computer-generated , blocked sequence , subjects received either 0.9 % NaCl or Plasma-Lyte A for resuscitation during the first 24 hours after injury . The primary outcome was mean change in base excess from 0 to 24 hours . Secondary outcomes included 24-hour arterial pH , serum electrolytes , fluid balance , re source utilization , and in-hospital mortality . Results : Of 46 evaluable subjects ( among 65 r and omized ) , 43 % had penetrating injuries , injury severity score was 23 ± 16 , 20 % had admission systolic blood pressure less than 90 mm Hg , and 78 % required an operation within 60 minutes of arrival . The baseline pH was 7.27 ± 0.11 and base excess −5.9 ± 5.0 mmol/L. The mean improvement in base excess from 0 to 24 hours was significantly greater with Plasma-Lyte A than with 0.9 % NaCl { 7.5 ± 4.7 vs 4.4 ± 3.9 mmol/L ; difference : 3.1 [ 95 % confidence interval ( CI ) : 0.5–5.6]}. At 24 hours , arterial pH was greater [ 7.41 ± 0.06 vs 7.37 ± 0.07 ; difference : 0.05 ( 95 % CI : 0.01–0.09 ) ] and serum chloride was lower [ 104 ± 4 vs 111 ± 8 mEq/L ; difference : −7 ( 95 % CI : −10 to −3 ) ] with Plasma-Lyte A than with 0.9 % NaCl . Volumes of study fluid administered , 24-hour urine output , measures of re source utilization , and mortality did not significantly differ between the 2 arms . Conclusions : Compared with 0.9 % NaCl , resuscitation of trauma patients with Plasma-Lyte A result ed in improved acid-base status and less hyperchloremia at 24 hours postinjury . Further studies are warranted to evaluate whether resuscitation with Plasma-Lyte A improves clinical outcomes . R and omized controlled trial , level I. ( Clinical Trials.gov Record UCDIRB-200917793 . BACKGROUND & AIMS Aggressive fluid resuscitation is recommended for initial management of acute pancreatitis . We performed a r and omized controlled trial to evaluate the impact of a goal -directed fluid resuscitation protocol on systemic inflammation in patients with acute pancreatitis . We then determined the impact of resuscitation with lactated Ringer 's solution , compared with normal saline . METHODS We performed a r and omized controlled trial of 40 patients with acute pancreatitis at 3 New Engl and hospitals from May 2009-February 2010 . Patients received goal -directed fluid resuscitation with lactated Ringer 's solution , goal -directed fluid resuscitation with normal saline , st and ard fluid resuscitation with lactated Ringer 's solution , or st and ard fluid resuscitation with normal saline . Systemic inflammation was measured on the basis of levels of systemic inflammatory response syndrome ( SIRS ) and C-reactive protein ( CRP ) level after 24 hours . RESULTS The volumes of fluid administered during a 24-hour period were similar among patients given goal -directed or st and ard fluid resuscitation ( mean , 4300 vs 4600 mL , respectively ; P = .87 ) . Goal -directed resuscitation did not significantly reduce incidence of SIRS , compared with st and ard resuscitation ( 11.8 % vs 13.0 % , respectively ; P = .85 ) or levels of CRP after 24 hours ( 87.1 vs 69.2 mg/dL , respectively ; P = .75 ) . By contrast , there was a significant reduction in SIRS after 24 hours among subjects resuscitated with lactated Ringer 's solution , compared with normal saline ( 84 % reduction vs 0 % , respectively ; P = .035 ) ; administration of lactated Ringer 's solution also reduced levels of CRP , compared with normal saline ( 51.5 vs 104 mg/dL , respectively ; P = .02 ) . CONCLUSIONS Patients with acute pancreatitis who were resuscitated with lactated Ringer 's solution had reduced systemic inflammation compared with those who received saline |
10,884 | 30,480,871 | CONCLUSIONS Vaginal progesterone was the only intervention with consistent effectiveness for preventing preterm birth in singleton at-risk pregnancies overall and in those with a previous preterm birth .
TWEETABLE ABSTRACT In up date d NMA , vaginal progesterone consistently reduced PTB in overall at-risk pregnancies and in women with previous PTB | BACKGROUND Recent progesterone trials call for an up date of previous syntheses of interventions to prevent preterm birth . | Background Neonatal respiratory distress syndrome , as a consequence of preterm birth , is a major cause of early mortality and morbidity . The withdrawal of progesterone , either actual or functional , is thought to be an antecedent to the onset of labour . There remains limited information on clinical ly relevant health outcomes as to whether vaginal progesterone may be of benefit for pregnant women with a history of a previous preterm birth , who are at high risk of a recurrence . Our primary aim was to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth reduced the risk and severity of respiratory distress syndrome in their infants , with secondary aims of examining the effects on other neonatal morbidities and maternal health and assessing the adverse effects of treatment . Methods Women with a live singleton or twin pregnancy between 18 to < 24 weeks ’ gestation and a history of prior preterm birth at less than 37 weeks ’ gestation in the preceding pregnancy , where labour occurred spontaneously or in association with cervical incompetence or following preterm prelabour rupture of the membranes , were eligible . Women were recruited from 39 Australian , New Zeal and , and Canadian maternity hospitals and assigned by r and omisation to vaginal progesterone pessaries ( equivalent to 100 mg vaginal progesterone ) ( n = 398 ) or placebo ( n = 389 ) . Participants and investigators were masked to the treatment allocation . The primary outcome was respiratory distress syndrome and severity . Secondary outcomes were other respiratory morbidities ; other adverse neonatal outcomes ; adverse outcomes for the woman , especially related to preterm birth ; and side effects of progesterone treatment . Data were analysed for all the 787 women ( 100 % ) r and omised and their 799 infants . Findings Most women used their allocated study treatment ( 740 women , 94.0 % ) , with median use similar for both study groups ( 51.0 days , interquartile range [ IQR ] 28.0–69.0 , in the progesterone group versus 52.0 days , IQR 27.0–76.0 , in the placebo group ) . The incidence of respiratory distress syndrome was similar in both study groups—10.5 % ( 42/402 ) in the progesterone group and 10.6 % ( 41/388 ) in the placebo group ( adjusted relative risk [ RR ] 0.98 , 95 % confidence interval [ CI ] 0.64–1.49 , p = 0.912)—as was the severity of any neonatal respiratory disease ( adjusted treatment effect 1.02 , 95 % CI 0.69–1.53 , p = 0.905 ) . No differences were seen between study groups for other respiratory morbidities and adverse infant outcomes , including serious infant composite outcome ( 155/406 [ 38.2 % ] in the progesterone group and 152/393 [ 38.7 % ] in the placebo group , adjusted RR 0.98 , 95 % CI 0.82–1.17 , p = 0.798 ) . The proportion of infants born before 37 weeks ’ gestation was similar in both study groups ( 148/406 [ 36.5 % ] in the progesterone group and 146/393 [ 37.2 % ] in the placebo group , adjusted RR 0.97 , 95 % CI 0.81–1.17 , p = 0.765 ) . A similar proportion of women in both study groups had maternal morbidities , especially those related to preterm birth , or experienced side effects of treatment . In 9.9 % ( 39/394 ) of the women in the progesterone group and 7.3 % ( 28/382 ) of the women in the placebo group , treatment was stopped because of side effects ( adjusted RR 1.35 , 95 % CI 0.85–2.15 , p = 0.204 ) . The main limitation of the study was that almost 9 % of the women did not start the medication or forgot to use it 3 or more times a week . Conclusions Our results do not support the use of vaginal progesterone pessaries in women with a history of a previous spontaneous preterm birth to reduce the risk of neonatal respiratory distress syndrome or other neonatal and maternal morbidities related to preterm birth . Individual participant data meta- analysis of the relevant trials may identify specific women for whom vaginal progesterone might be of benefit . Trial registration Current Clinical Trials IS RCT N20269066 OBJECTIVE The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage . STUDY DESIGN From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks ' gestation were r and omly assigned to receive a McDonald cerclage or no cerclage . Before r and om assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics . After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation . RESULTS Of the 61 patients 31 were r and omly assigned to cerclage and 30 were r and omly assigned to no cerclage . There were no differences between groups with respect to maternal demographic characteristics , risk factors for preterm birth , cervical measurements , rescue procedures , readmission , chorioamnionitis , and abruptio placentae . The mean gestational age at delivery ( 33.5 + /- 6.3 weeks ) and the perinatal death rate ( 12 . 9 % ) in the cerclage group were similar to the mean gestational age at delivery ( 34.7 + /- 4.7 weeks ; P = .4 ) and the perinatal death rate ( 10.0 % ; P = .9 ) in the no-cerclage group . CONCLUSION Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes Objective . To assess efficacy and tolerability of vaginal compared with intramuscular progesterone in reducing the rate of recurrent preterm birth before 34 weeks of gestation . Design . Prospect i ve r and omized study . Setting . Obstetrics and Gynecology Department , Armed Forces Hospital Southern Region , Kingdom of Saudi Arabia . Sample . Five‐hundred and eighteen women with a prior history of preterm birth . Methods . Women were r and omized to receive either 90 mg of vaginal progesterone gel once daily or 250 mg of intramuscular progesterone weekly . Treatment began between 14 and 18 weeks of gestation and continued until 36 complete weeks of gestation , delivery or the occurrence of premature rupture of membranes . Main outcome measures . The primary outcome measure was delivery before 34 weeks of gestation . The secondary outcome measures were PTB between 34 and 37 weeks of gestation and neonatal outcomes including birthweight , neonatal death , and the need for admission to the neonatal intensive care unit . Results . The baseline characteristics of the study participants were similar . Two‐hundred and thirty‐eight ( 94.1 % ) patients in the vaginal group and 226 ( 90.8 % ) patients in the intramuscular group were compliant with their medications . Vaginal progesterone was associated with a lower percentage of deliveries before 34 weeks of gestation than the intramuscular preparation ( p= 0.02 ) . This association was also observed at 28 and 32 weeks of gestation ( p= 0.04 ) . Adverse effects were reported in 14.1 % of patients in the intramuscular group , but in only 7.5 % of patients in the vaginal group ( p= 0.017 ) . Conclusions . Vaginal progesterone was more effective than intramuscular progesterone for the prevention of preterm birth and had fewer adverse effects OBJECTIVE To determine the effectiveness of cerclage pessary in the prevention of preterm birth in asymptomatic Chinese women with a short cervix at 20 to 24 weeks . METHODS Low-risk women carrying singleton pregnancies were screened with transvaginal ultrasound , and those with a cervical length < 25 mm at 20 to 24 weeks were recruited into a r and omized controlled trial , comparing the prophylactic use of cerclage pessary with expectant management . The analysis was by intent-to-treat . The primary outcome measure was preterm delivery before 34 weeks . RESULTS Among 4438 screened women , 203 women ( 4.6 % ) met the inclusion criteria and 108 ( 58 % ) consented for the study . A total of 53 and 55 women were allocated to pessary and control groups , respectively . There was no difference in background demographics , including the mean cervical length ( 19.6 mm versus 20.5 mm ) and the mean gestational age at r and omization ( both 21.9 weeks ) . Delivery before 34 weeks occurred in 9.4 % and 5.5 % ( p = 0.46 ) in the pessary and the control groups , respectively . No differences in major side effects were noted between the groups . CONCLUSION In our population , < 5 % had a cervical length of less than 25 mm at 20 to 24 weeks ' gestation . The prophylactic use of cerclage pessary did not reduce the rate of preterm delivery before 34 weeks Background Preterm birth is a worldwide health concern due to its various negative consequences . Therefore , the prevention of preterm birth is a top priority for healthcare systems in all countries . Objective To compare the effectiveness of vaginal versus intramuscular progesterone in the prevention of preterm delivery . Methods This r and omized clinical trial was conducted at Shahid Sadoughi Hospital in Yazd , Iran , from November 21 , 2012 to January 20 , 2015 . Seventy-eight pregnant women with singleton pregnancy and one risk factor of preterm delivery were included in the study . The subjects were assigned r and omly to two groups , with group one receiving Cyclogest and group two receiving 17-α hydroxyprogesterone caproate . Subsequently , we analyzed drug complications during pregnancy , delivery time , neonatal outcomes , and patients ’ satisfaction among the two groups . The data were analyzed using SPSS version 16 . We used descriptive statistics , chi-squared , t-test , and ANOVA for the analyses of primary and secondary outcomes . Results Among the 39 births in group one , 33.3 % occurred preterm , and , among the 39 births in group two , 30.7 % occurred preterm ( < 37 weeks ) . The mean gestational ages at delivery in groups 1 and 2 were 37.07 ± 2.23 and 36.81 ± 2.77 weeks , respectively ( p = 0.765 ) . Other variables were not significantly different between the two groups , including birth weight ( p = 0.745 ) , Apgar scores for the first and fifth minutes ( p = 0.574 , 0.630 ) , length of stay in the neonatal intensive care unit ( NICU ) when the newborns needed hospitalization ( p = 0.358 ) , and the patients ’ satisfaction with the drugs that were used ( p = 0.615 ) . Conclusions In this study , vaginal progesterone and intramuscular progesterone had the same levels of effectiveness , safety and acceptance by patients in the prevention of preterm delivery . Therefore , both can be used for this purpose in clinical practice s , but more studies are needed Background : Preterm birth is the major cause of neonatal mortality and morbidity . Objective : The aim of this study was to evaluate the effect of prophylactic vaginal progesterone on decreasing preterm birth rate and neonatal complications in a high-risk population . Material s and Methods : A r and omized , double-blind , placebo-controlled study was performed on 100 high-risk singleton pregnancies . Vaginal suppository progesterone ( 400 mg ) or placebo was administered daily between 16 - 22 wks to 36 wks of gestation . Progesterone ( n=50 ) and placebo ( n=50 ) groups were compared for incidence of preterm delivery and neonatal complications . Results : The preterm birth rate was 52 % . Preterm birth rate before the 37 wks of gestation ( 68 % vs. 36 % : RR=1.89 , 95 % CI : 1.25 - 2.86 ) and also before the 34 wks of gestation ( 42 % vs. 18 % : RR=2.33 , 95 % CI : 1.19 - 4.58 ) in placebo group was significantly higher than progesterone group . Our study also showed that the administration of vaginal progesterone was associated with a significant reduction in the risk of birth weight ≤2500 gr , the rates of respiratory distress syndrome ( RDS ) and admission to the Neonatal Intensive Care Unit ( NICU ) in the progesterone group when compared with the placebo group . However , there was no significant difference between the two groups in terms of neonatal death , days of admission in NICU , intraventricular hemorrhage and necrotizing enterocolitis . Conclusion : Prophylactic vaginal progesterone reduced the rate of preterm delivery , the risk of a birth weight ≤2500 gr , the rates of RDS and admission to NICU in women who were at risk of preterm delivery We sought to evaluate the effectiveness of daily oral micronized progesterone ( MP ) in preventing recurrent spontaneous preterm birth ( RSPB ) and whether MP increases maternal serum progesterone . We performed a pilot , single-center , r and omized , double-blind , placebo-controlled trial in women with a prior preterm birth and current singleton gestation at 16 to 20 weeks ( N = 33 ) . The primary outcome was the rate of RSPB . Subjects were given either daily MP ( 400 mg ) or placebo from 16 to 34 weeks . Serum progesterone was obtained at enrollment and in the late second/early third trimester . Pregnancy outcome data were collected . RSPB occurred in 5/19 ( 26.3 % ) in the MP group versus 8/14 ( 57.1 % ) in placebo group ( P = 0.15 ) . The mean age at delivery was 37.0 ± 2.7 weeks for the MP group versus 35.9 ± 2.6 weeks for the placebo ( P = 0.3 ) . Mean serum progesterone at 28 weeks was 122.6 ± 61.8 pg/mL for MP group versus 90.1 ± 38.7 pg/mL for placebo ( P = 0.19 ) . MP was associated with a trend toward a reduction in RSPB and an increase in the maternal serum progesterone . Although the primary outcome in this pilot study did not reach statistical significance , the results suggest a favorable trend meriting further investigation AIM The aim of this study was to compare 17-alpha-hydroxyprogesterone caproate ( 17OHP-C ) with vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix and to evaluate the changes of the cervical length ( CL ) over time . METHODS In this prospect i ve r and omized controlled trial , eligible patients were asymptomatic pregnant women with a sonographically short cervix . The participants in group 1 ( n = 147 ) received vaginal progesterone suppositories at a dose of 400 mg daily and the women in group 2 ( n = 150 ) received an i.m . dose of 250 mg 17OHP-C once a week . Transvaginal sonography was repeated every 3 weeks until 36 gestational weeks or the occurrence of preterm labor . RESULTS A total of 304 singleton pregnant women between 16 and 24 gestational weeks with CL < 25 mm were enrolled in our study . The rates of preterm birth were 10.4 % in the progesterone group and 14 % in the 17OHP-C group : a difference that was not statistically significant ( P = 0.416 ) . Moreover , 264 participants underwent ultrasound examination five times and CL changes were studied for 15 weeks . The results showed that the CL changes over 15 weeks were statistically significant ( P < 0.001 ) , but the method of intervention ( progesterone/17OHP-C ) had no significant effect on CL change ( P = 0.64 ) . CONCLUSION Our findings showed that vaginal progesterone and 17OHP-C had the same effect on the risk of preterm labor in asymptomatic women with a sonographically short cervix . We detected no significant difference between the effect of 17OHP-C and vaginal progesterone on CL changes over time We conducted a double-blind study to determine the efficacy of 17alpha-hydroxyprogesterone caproate in preventing premature delivery in 43 high-risk patients . Premature delivery did not occur in 18 patients receiving the progestational agent , whereas 41 per cent of the 22 receiving the palcebo had premature delivery ( P less than 0.01 ) . The mean duration of pregnancy and the mean birth weight in the former group ( 38.6 weeks + /- 1.6 S.D. , and 2836 g + /- 412 S.D. ) were both significantly greater ( P less than 0.025 ) than that in the latter ( 35.2 weeks + /- 6.7 S.D. ; 2361 g + /- 1085 S.D. ) . The perinatal mortality rate in the group given the progestational agent ( O per cent ) was significantly less than that observed in the placebo group ( 27 per cent ) ( P less than 0.05 ) . Although there were no complications attributable to the progestational drug , the study population was too small for assessment of immediate or long term safety . However , the results indicate a possible obstetric use for this drug OBJECTIVE To compare preterm delivery rates ( before 34 weeks of gestation ) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone . STUDY DESIGN Cervical length was measured in patients with risk factors or symptoms of cervical incompetence . Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence , previous preterm premature rupture of membranes before 32 weeks of gestation , history of cold knife conization , diethylstilbestrol exposure , and uterine anomaly . When a cervical length of < 25 mm was measured before a gestational age of 27 weeks , a r and omization for therapeutic cerclage and bed rest ( cerclage group ) or bed rest alone ( bed rest group ) was performed . The analysis is based on intention to treat . RESULTS Of the 35 women who met the inclusion criteria , 19 were allocated r and omly to the cerclage group and 16 to the bed rest group . Both groups were comparable for mean cervical length and mean gestational age at time of r and omization , mean overall 20 mm and 21 weeks . Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group ( 7 of 16 vs none , respectively ; P = .002 ) . There was no statistically significant difference in neonatal survival between the groups ( 13 neonates survived in the bed rest group vs all in the cerclage group ) . The compound neonatal morbidity , defined as admission to the neonatal intensive care unit or neonatal death , was significantly higher in the bed rest group than in the cerclage group ( 8 of 16 vs 1 of 19 , respectively ; P = .005 ; RR = 9.5 , 95 % CI , 1.3 - 68.1 ) . CONCLUSIONS Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and /or symptoms of cervical incompetence and a cervical length of < 25 mm before 27 weeks of gestation OBJECTIVE The purpose of this study was to determine the efficacy of cerclage and bed rest versus bed rest-only for the prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination . STUDY DESIGN Women with > or = 1 of high-risk factors for preterm birth ( > or = 1 preterm birth at < 35 weeks of gestation , > or = 2 curettages , diethylstilbestrol exposure , cone biopsy , Mullerian anomaly , or twin gestation ) were screened with transvaginal ultrasonography of the cervix every 2 weeks from 14 weeks of gestation to 23 weeks 6 days of gestation . Enrollment was offered to both asymptomatic women who were at high risk and who were identified to have short cervix ( < 25 mm ) or significant funneling ( > 25 % ) and nonscreened women who were at low risk and who were identified incidentally . The women who gave written consent were assigned r and omly to receive either McDonald cerclage or bed rest-only . Both groups received similar counseling and treatment . Primary outcome was preterm birth at < 35 weeks of gestation . RESULTS Sixty-one women were assigned r and omly . Forty-seven pregnancies ( 77 % ) were high-risk singleton gestations . Thirty-one women ( 51 % ) were allocated to cerclage , and 30 women ( 49 % ) were allocated to bed rest . There were no differences between the groups in demographic characteristics , risk factors , and cervical variables . Preterm birth at < 35 weeks of gestation occurred in 14 women ( 45 % ) in the cerclage group and in 14 women ( 47 % ) in the bed rest group ( relative risk , 0.94 ; 95 % CI , 0.34 - 2.58 ) . There was no difference in any obstetric or neonatal outcomes . A sub analysis of singleton pregnancies with previous preterm birth at < 35 weeks of gestation and a short cervix of < 25 mm ( n = 31 women ) also revealed no significant difference in recurrent preterm birth at < 35 weeks of gestation ( 40 % vs 56 % ; relative risk , 0.52 ; 95 % CI , 0.12 - 2.17 ) . CONCLUSION Cerclage did not prevent preterm birth in women with a short cervix . These results should be confirmed by larger trials AIM This is the first report of a r and omized trial of cerclage on pure cervical shortening without vaginosis or cervicitis . The objective of our multicenter r and omized controlled trial was to assess the benefits of ultrasound-indicated cervical cerclage in the mid-trimester to prevent preterm birth in women who have no signs of infection or inflammation of the lower genital tract . MATERIAL AND METHODS Women with a short cervical length < 25 mm between 16 and 26 weeks of gestation were r and omly assigned to receive a Shirodkar cerclage , McDonald cerclage , or bedrest ( no cerclage ) . Before being r and omly assigned to one of the three groups , all women were screened for infection/inflammation of the lower genital tract ; those with positive results were excluded from the study . The ratio of preterm delivery as a primary end-point was evaluated in the groups . RESULTS A total of 106 singleton patients with a short cervical length were assessed for study eligibility ; 106 patients were r and omized to the three treatment options . Ultimately , 98 patients ( in the Shirodkar [ n = 34 ] , McDonald [ n = 34 ] and bedrest [ n = 30 ] groups ) were analyzed . No differences in preterm delivery or perinatal outcomes were found between the three groups . Significantly fewer patients in the Shirodkar group required hospitalization for treatment of threatened preterm labor when compared to patients in the bedrest group . CONCLUSION For women with a short cervical length < 25 mm between 16 and 26 weeks of gestation , Shirodkar cerclage might be considered to reduce the occurrence of threatened preterm labor BACKGROUND Cervical cerclage has been widely used in the past 50 years to prevent early preterm birth and its associated neonatal mortality and morbidity . Results of r and omised trials have not generally lent support to this practice , but this absence of benefit may be due to suboptimum patient selection , which was essentially based on obstetric history . A more effective way of identifying the high-risk group for early preterm delivery might be by transvaginal sonographic measurement of cervical length . We undertook a multicentre r and omised controlled trial to investigate whether , in women with a short cervix identified by routine transvaginal scanning at 22 - 24 weeks ' gestation , the insertion of a Shirodkar suture reduces early preterm delivery . METHODS Cervical length was measured in 47?123 women . The cervix was 15 mm or less in 470 , and 253 ( 54 % ) of these women participated in the study and were r and omised to cervical cerclage ( 127 ) or to expectant management ( 126 ) . Primary outcome was the frequency of delivery before 33 completed weeks ( 231 days ) of pregnancy . FINDINGS The proportion of preterm delivery before 33 weeks was similar in both groups , 22 % ( 28 of 127 ) in the cerclage group versus 26 % ( 33 of 126 ) in the control group ( relative risk=0.84 , 95 % CI 0.54 - 1.31 , p=0.44 ) , with no significant differences in perinatal or maternal morbidity or mortality . INTERPRETATION The insertion of a Shirodkar suture in women with a short cervix does not substantially reduce the risk of early preterm delivery . Routine sonographic measurement of cervical length at 22 - 24 weeks identifies a group at high risk of early preterm birth Purpose The purpose of this study was to evaluate whether the prophylactic administration of vaginal progesterone would reduce the preterm birth rate in high-risk population including singleton and twin pregnancies . Methods This was a r and omized , double blind , placebo-controlled study that included 150 high-risk pregnancies . Risk groups included prior spontaneous preterm birth , twin pregnancy , and uterine malformation . Micronized progesterone or placebo ( 100 mg ) was administered daily by vaginal suppository between 24 and 34 weeks of gestation . We compared progesterone and placebo groups for incidence of preterm labor and preterm delivery . Data were compared by χ² analysis and Fisher exact test . Results There was a statistically significant difference in the rate of preterm labor between placebo and progesterone groups ( 45.7 vs. 25 % , respectively ; p < 0.05 ) . More women delivered before 37 weeks in placebo group ( 57.2 % ) than in progesterone group ( 40 % ; p < 0.05 ) . Administering progesterone also reduced the preterm birth before 34 weeks of gestation . The difference between placebo and progesterone group was statistically significant ( 24.3 vs. 8.8 % ; p < 0.05 ) . However , there was no significant difference in neonatal death between placebo and progesterone groups . Conclusion Prophylactic vaginal progesterone reduced the rate of preterm labor and preterm delivery in high-risk pregnancies OBJECTIVES Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery . This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix ( 10 - 20 mm ) at 19 + 0 to 23 + 6 weeks of gestation . Women were allocated r and omly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks , rupture of membranes or delivery , whichever occurred first . R and omization sequence was stratified by center and history of a previous preterm birth . The primary endpoint was preterm birth before 33 weeks of gestation . Analysis was by intention to treat . RESULTS Of 465 women r and omized , seven were lost to follow-up and 458 ( vaginal progesterone gel , n=235 ; placebo , n=223 ) were included in the analysis . Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo ( 8.9 % ( n=21 ) vs 16.1 % ( n=36 ) ; relative risk ( RR ) , 0.55 ; 95 % CI , 0.33 - 0.92 ; P=0.02 ) . The effect remained significant after adjustment for covariables ( adjusted RR , 0.52 ; 95 % CI , 0.31 - 0.91 ; P=0.02 ) . Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks ( 5.1 % vs 10.3 % ; RR , 0.50 ; 95 % CI , 0.25 - 0.97 ; P=0.04 ) and 35 weeks ( 14.5 % vs 23.3 % ; RR , 0.62 ; 95 % CI , 0.42 - 0.92 ; P=0.02 ) , respiratory distress syndrome ( 3.0 % vs 7.6 % ; RR , 0.39 ; 95 % CI , 0.17 - 0.92 ; P=0.03 ) , any neonatal morbidity or mortality event ( 7.7 % vs 13.5 % ; RR , 0.57 ; 95 % CI , 0.33 - 0.99 ; P=0.04 ) and birth weight < 1500 g ( 6.4 % ( 15/234 ) vs 13.6 % ( 30/220 ) ; RR , 0.47 ; 95 % CI , 0.26 - 0.85 ; P=0.01 ) . There were no differences in the incidence of treatment-related adverse events between the groups . CONCLUSIONS The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45 % reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome OBJECTIVE The purpose of this study was to identify the risk factors that are associated with increased neonatal morbidity in patients who were treated for sonographic evidence of internal os dilation and distal cervical shortening during the second trimester . STUDY DESIGN From May 1998 to June 2000 patients between 16 and 24 weeks of gestation with the following sonographic criteria were r and omly assigned to McDonald cerclage or no cerclage : internal os dilation and either membrane prolapse into the endocervical canal at least 25 % of the total cervical length but not beyond the external os or a shortened distal cervix < 2.5 cm . Before r and omization , all patients were treated identically with an amniocentesis , multiple urogenital cultures , and therapy with indomethacin and clindamycin for 48 to 72 hours . Except for the cerclage , all patients were treated identically after r and omization . Multiple variables of perinatal outcome were analyzed . A regression model with gestational age at delivery as the dependent variable was constructed and repeated with neonatal morbidity as the dependent variable . This model was applied to 3 population s : the cerclage group , the no cerclage group , and both groups combined . RESULTS Of the 135 patients , 20 patients declined r and omization , and 2 patients were diagnosed with acute chorioamnionitis . Of the 113 patients remaining , 55 patients were r and omly assigned to the cerclage group , and 58 patients were r and omly assigned to the no cerclage group . There were 8 rescue cerclage procedures ( 4 in each group ) . Regression analysis showed that readmission for preterm labor , chorioamnionitis , and abruption were consistently associated with early gestational age at delivery and increased morbidity . Cerclage did not affect perinatal outcome . CONCLUSION The sonographic findings of second trimester internal os dilation , membrane prolapse , and distal cervical shortening likely represent a common pathway of several pathophysiologic processes . Use of cerclage does not alter any perinatal outcome variables . Increased neonatal morbidity in these patients appears to be associated with sub clinical infection , preterm labor , and abruption AIM Preterm delivery is defined as a birth before 37 weeks ' gestation and is the cause of two-thirds of perinatal mortality and thus one of the major problems in obstetrics . Its etiology is unknown , but hormonal factors have been reported to play a part . Progesterone is a placental hormone and effective in maintaining pregnancy . The aim of this study is to evaluate the efficacy of 17α-hydroxyprogesterone caproate in the prevention of preterm delivery . METHODS This interventional study was performed with 100 pregnant women who had been referred to the Obstetrics Clinic of Ghaem Hospital ( related to Mashhad University of Medical Sciences ) during 2007 to 2008 . They were r and omly divided into two groups of 50 cases and 50 controls . The case group received 250 mg of intramuscular 17α-hydroxyprogesterone caproate weekly from 16 weeks ' gestation up to a maximum of 37 weeks ' gestation . In the control group , routine perinatal care was performed and the pregnancy outcomes were compared in both groups . RESULTS The mean gestational age was 36 weeks in the case group and 34 weeks in the control group . The mean birth weight was 2695 g in the case group and 2399 g in the control group . A significant difference was observed between the two groups in terms of gestational age and birth weight ( P < 0.05 ) . CONCLUSION Weekly administration of 17α-hydroxyprogesterone caproate to pregnant women with a history of preterm delivery was associated with a decrease in preterm delivery and improvement in birth weight OBJECTIVE Preterm birth is the leading cause of perinatal morbidity and mortality worldwide . Treatment of preterm labor with tocolysis has not been successful in improving infant outcome . The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth . The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth . METHODS This r and omized , double-blind , placebo- controlled , multinational trial enrolled and r and omized 659 pregnant women with a history of spontaneous preterm birth . Between 18 + 0 and 22 + 6 weeks of gestation , patients were assigned r and omly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery , 37 weeks ' gestation or development of preterm rupture of membranes . The primary outcome was preterm birth at < /= 32 weeks of gestation . The trial was analyzed using an intent-to-treat strategy . RESULTS Baseline characteristics were similar in the two treatment groups . Progesterone did not decrease the frequency of preterm birth at < /= 32 weeks . There was no difference between the groups with respect to the mean gestational age at delivery , infant morbidity or mortality or other maternal or neonatal outcome measures . Adverse events during the course of treatment were similar for the two groups . CONCLUSION Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth ( < /= 32 weeks ) in women with a history of spontaneous preterm birth . The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone ( e.g. sonographic cervical length ) requires further investigation OBJECTIVE To compare the efficacy of intramuscular hydroxyprogesterone caproate with that of vaginal progesterone for prevention of recurrent preterm birth . METHODS A prospect i ve r and omized controlled trial was conducted at a US tertiary care center between June 1 , 2007 , and April 30 , 2010 . Women with singleton pregnancies ( 16 - 20 weeks ) and a history of spontaneous preterm birth were r and omly allocated using a computer-generated r and omization sequence to receive either a weekly intramuscular injection of hydroxyprogesterone caproate ( 250 mg ) or a daily vaginal progesterone suppository ( 100 mg ) . Participants , investigators , and assessors were not masked to group assignment . The primary outcome was birth before 37 weeks of pregnancy . Per- protocol analyses were performed : participants who completed follow-up were included . RESULTS Analyses included 66 women given intramuscular progesterone and 79 given vaginal progesterone . Delivery before 37 weeks was recorded among 29 ( 43.9 % ) women in the intramuscular progesterone group and 30 ( 37.9 % ) in the vaginal progesterone group ( P=0.50 ) . CONCLUSION Weekly intramuscular administration of hydroxyprogesterone caproate and daily vaginal administration of a progesterone suppository exhibited similar efficacy in reducing the rate of recurrent preterm birth . Clinical Trials.gov : NCT00579553 OBJECTIVE The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth ( PTB ) in low-risk pregnant women with a short cervical length ( CL ) . STUDY DESIGN Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks . Women with a CL ≤ 30 mm received vaginal progesterone or placebo . Primary outcome was adverse neonatal outcome , defined as a composite of respiratory distress syndrome , bronchopulmonary dysplasia , intracerebral hemorrhage > grade II , necrotizing enterocolitis > stage 1 , proven sepsis , or death before discharge . Secondary outcomes included time to delivery , PTB before 32 , 34 , and 37 weeks of gestation . Analysis was by intention to treat . RESULTS Between 2009 and 2013 , 20,234 women were screened . A CL of 30 mm or less was seen in 375 women ( 1.8 % ) . In 151 women , a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial . We r and omly allocated 41 women to progesterone and 39 to placebo . Adverse neonatal outcomes occurred in two ( 5.0 % ) women in the progesterone and in four ( 11 % ) women in the control group ( relative risk [ RR ] , 0.47 ; 95 % confidence interval [ CI ] , 0.09 - 2.4 ) . The use of progesterone result ed in a nonsignificant reduction of PTB < 32 weeks ( 2.0 vs. 8.0 % ; RR , 0.33 ; 95 % CI , 0.04 - 3.0 ) and < 34 weeks ( 7.0 vs. 10 % ; RR , 0.73 ; 95 % CI , 0.18 - 3.1 ) but not on PTB < 37 weeks ( 15 vs. 13 % ; RR , 1.2 ; 95 % CI , 0.39 - 3.5 ) . CONCLUSION In women with a short cervix , who are otherwise low risk , we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB OBJECTIVE To evaluate oral micronized progesterone ( OMP ) to prevent preterm birth ( PTB ) . METHODS A r and omized , double-blind , placebo-controlled trial of 150 women with at least one PTB who received 100 mg of OMP or placebo twice a day from recruitment ( 18 - 24 weeks ) until 36 weeks or delivery . RESULTS PTB occurred in 29 ( 39.2 % ) women in the OMP group ( n=74 ) compared with 44 ( 59.5 % ) in the control group ( n=74 , P=0.002 ) . Mean gestational age at delivery was higher in the OMP group ( 36.1 vs 34.0 weeks , P<0.001 ) . Fewer preterm births occurred between 28 and 31 weeks plus 6 days in the OMP group ( RR 0.20 ; 95 % CI , 0.05 - 0.73 , P<0.001 ) . Neonatal age at delivery ( 34 vs 32 weeks , P<0.001 ) , birth weight ( 2400 vs 1890 g , P<0.001 ) , NICU stay ( > 24 h , P<0.001 ) , and Apgar scores ( P<0.001 ) were more favorable in the OMP group , and fewer neonatal deaths occurred ( 3 vs 7 , P=0.190 ) . CONCLUSION OMP reduced the risk of PTB between 28 and 31 weeks plus 6 days , NICU admissions , and neonatal morbidity and mortality in high risk patients Summary In a prospect i ve , r and omised trial , 100 pregnant women with ≥ one prior spontaneous pre-term birth were r and omised into two groups . Group 1 women received 100 mg natural micronised progesterone intravaginally once daily from 20–24 weeks ' gestation until 36 weeks . Group 2 women did not receive progesterone . Both groups were regularly supervised until delivery . Pre-term birth ( < 37 and < 34 weeks ) and other maternal , neonatal outcomes were primary and secondary outcomes , respectively . Chi-square test and Fisher exact test were used to compare categorical variables . Independent sample t-test and one-way ANOVA were used to compare continuous variables and multiple comparisons , respectively . Pre-term births < 37 weeks were significantly lower in Group 1 ( 12 % vs 38 % , p = 0.002 ) , but pre-term births < 34 weeks were similar . The mean birth weight of neonates born to women in Group 1 was significantly higher ( 2800 vs 2,500 g , p = 0.023 ) . We concluded intravaginal administration of 100 mg of natural micronised progesterone significantly reduced the incidence of pre-term birth < 37 weeks in women with ≥ one prior pre-term birth . Future research is warranted to assess the long-term safety and efficacy of progesterone Abstract Objective : To determine pregnancy outcome in patients with short cervix on transvaginal ultrasound between 16 and 24 weeks ' gestation treated with McDonald cerclage compared to weekly intramuscular injections of 17 α-hydroxyprogesterone caproate ( 17OHP-C ) . Methods : From November 2003 through December 2006 , asymptomatic , singleton pregnancies were screened with transvaginal ultrasound between 16–24 weeks ' gestation . Patients with a cervical length ( CL ) ≤25 mm were offered enrollment . Patients were r and omly assigned to treatment with McDonald cerclage or weekly intramuscular injections of 17OHP-C. The primary outcome was spontaneous preterm birth ( PTB ) prior to 35 weeks ' gestation . Results : Seventy-nine patients met inclusion criteria ; 42 were r and omly assigned to the cerclage and 37 to 17OHP-C. Spontaneous PTB prior to 35 weeks ' gestation occurred in 16/42 ( 38.1 % ) of the cerclage group and in 16/37 ( 43.2 % ) of the 17OHP-C group ( relative risk , 1.14 95 % CI , 0.67 , 1.93 ) . A post hoc analysis of patients with a prior PTB showed no difference in spontaneous PTB < 35 weeks between groups . A similar analysis of patients with a CL≤15 mm showed a reduction in spontaneous PTB < 35 weeks in the cerclage group ( relative risk 0.48 , 0.24–0.97 ) . Conclusion : Women with CL ≤25 mm in the second-trimester appear to have similar risks of delivering prior to 35 weeks ' gestation when treated with 17OHP-C or McDonald cerclage . However , cerclage may be more effective in preventing spontaneous PTB in women with CL≤15 mm Abstract Objectives : To compare vaginal with intramuscular progesterone administration to prevent preterm labor in women with singleton pregnancies and at increased risk of preterm birth . Study design : Prospect i ve comparative clinical trial . Population : One hundred and sixty pregnant women at 20–24 weeks gestation at the risk of preterm labor were classified into : 80 women who received micronized progesterone tablets 200 mg vaginally daily ( Group A ) and 80 women who received 100 mg progesterone in the form of intramuscular every third day ( Group B ) . Methods : Estimation of gestational age , assessment of fetal growth and fetal biophysical profile by trans-abdominal ultrasonographic examination was done every 4 weeks till delivery . Measurement of cervical length was achieved by transvaginal ultrasonography , done every 4 weeks till delivery . Main outcome measures : Incidence of preterm delivery , mean gestational age and the incidence of adverse events of intramuscular versus vaginal route of progesterone administration . Results : The incidence of preterm delivery in Group A was 20 % and in Group B was 27.5 % . The difference between both groups was statistically insignificant . In addition , the rate of adverse events reported in women received injectable progesterone was significantly higher than the rate of adverse events reported in women who received vaginal progesterone therapy . Conclusion : Vaginally administrated progesterone was nearly as equally effective as intramuscular progesterone in the prevention of preterm labor in women at risk and in the meantime has less undesirable events Summary . A total of 506 women at moderate risk of preterm delivery were r and omly allocated to either cervical cerclage or a control group . Significantly more women in the group allocated to cerclage were admitted to hospital for reasons other than the operation and more received oral toco‐lytic drugs . There were also more caesarean sections and more preterm deliveries in the women allocated to cerclage although the differences between the two groups were small and not statistically significant OBJECTIVE We sought to evaluate whether 17 alpha-hydroxyprogesterone caproate ( 17-OHP ) reduces preterm birth ( PTB ) in nulliparous women with a midtrimester cervical length ( CL ) < 30 mm . STUDY DESIGN In this multicenter r and omized controlled trial , nulliparous women with a singleton gestation between 16 and 22 3/7 weeks with an endovaginal CL < 30 mm ( < 10th percentile in this population ) were r and omized to weekly intramuscular 17-OHP ( 250 mg ) or placebo through 36 weeks . The primary outcome was PTB < 37 weeks . RESULTS The frequency of PTB did not differ between the 17-OHP ( n = 327 ) and placebo ( n = 330 ) groups ( 25.1 % vs 24.2 % ; relative risk , 1.03 ; 95 % confidence interval , 0.79 - 1.35 ) . There also was no difference in the composite adverse neonatal outcome ( 7.0 % vs 9.1 % ; relative risk , 0.77 ; 95 % confidence interval , 0.46 - 1.30 ) . CONCLUSION Weekly 17-OHP does not reduce the frequency of PTB in nulliparous women with a midtrimester CL < 30 mm |
10,885 | 19,160,206 | Studies of nursing care planning systems and total nurse records demonstrated uncertain or equivocal results .
We found some limited evidence of effects on practice attributable to changes in record systems .
It is clear from the literature that it is possible to set up the r and omised trials or other quasi-experimental design s needed to produce evidence for practice . | BACKGROUND A nursing record system is the record of care that was planned or given to individual patients and clients by qualified nurses or other caregivers under the direction of a qualified nurse .
Nursing record systems may be an effective way of influencing nurse practice .
OBJECTIVES To assess the effects of nursing record systems on nursing practice and patient outcomes . | Nursing documentation is an important part of clinical documentation . However , documentation of the nursing process is frequently lacking quality . There are high expectations that computer support in nursing documentation will help improve documentation quality . This study aim ed to examine whether the introduction of a computer based nursing documentation system can improve documentation quality . A prospect i ve intervention study was conducted on 4 wards of the University Medical Center Heidelberg over a period of 18 months . Two wards in the Psychiatric University Medical Center Heidelberg were involved in the research study , as well as a dermatological and a pediatric ward . The results of the study show a significant improvement of documentation quantity and quality on three of the four wards . Positive aspects include completeness of documentation on the nursing process , formal aspects and subjective quality improvement by the nurses . Negative aspects were mainly associated with the contents of the care plans 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 Despite the widespread use of home based child health records of varying complexity in Engl and , there is a notable absence of their evaluation . Such a record booklet developed in the West Lambeth Health Authority has been used by parents , doctors , and community nurses to build up an independent chronological record of a child 's birth statistics , health , growth , immunisation , development checks , and contacts with health services . A r and omised controlled evaluation of the record , analyses of entries in it , and a survey of the views of mothers and health professionals using the record have been carried out . The need for such a record was confirmed by those question ed and analyses of entries in the booklet helped to modify and improve it . The evaluation was unable to show , however , any effect of the record on immunisation and developmental assessment service uptake . Its value in improving communication between the numerous health and other care agencies was dependent on its proper use OBJECTIVE In intensive care units ( ICUs ) , patient outcome depends on quality of nutritional support . We investigated the effect of computerized information systems ( CISs ) on quality of nutritional support by comparing two ICUs with or without CIS and burned patients before and after CIS implementation . METHODS Part 1 was a 2-wk prospect i ve survey in two units of a surgical ICU : unit A ( 11 beds ) without CIS and unit B ( four beds ) with CIS . Part 2 consisted of two 18-mo periods in burn patients before and after CIS implementation . Nurses and doctors belonged to the same team ; procedures were identical . A computer page was configured to retrieve data related to nutritional support . RESULTS A total of 1313 ICU days were analyzed in 109 patients . Patients ' characteristics were similar in parts 1 and 2 . In part 1 , nutritional support was required 38 % of days . Nutritional route was similar but data were more frequently missing in unit A. Energy delivery was higher with CIS but below target values in both units ( 31+/-11 % of target in unit A , 77+/-4 % in unit B ) . Computations were incomplete and time consuming for unit A versus B ( 11+/-2 versus 2+/-1 min/patient , P<0.0001 ) . In part 2 , in the 54 burn patients , use of postpyloric feeding tubes and energy delivery increased with CIS , result ing in less weight loss . CONCLUSION Computerized information systems favored st and ardization of nutritional care and monitoring , thus decreasing time required for writing and computations . Follow-up was improved and nutrient delivery was closer to target values , thus increasing quality of care . In burn patients , the better data visibility was associated with a significant improvement in nutrient delivery A two-month r and omized , controlled trial based on 60 patients has been performed on a ward of the Department of Psychiatry at Heidelberg University Medical Center , Germany , to investigate the influence of computer-based nursing documentation on time investment for documentation , quality of documentation and user acceptance . Time measurements , question naires , documentation analysis and interviews were used to compare patients documented with the computer-based system ( PIK group ) with the control group ( patients documented with the paper-based system ) . The results showed the advantages and disadvantages of computer-based nursing documentation . Time needed for nursing care planning was lower in the PIK group . Some formal aspects of quality were considerably better in the PIK group . On the other h and , time required for documentation of tasks and for report writing was greater in the PIK group . User acceptance increased significantly during the study . The interviews indicated a positive influence of PIK on the cooperation between nurses and physicians Abstract Objective . Nowadays , registration of patient data on paper is gradually being replaced by registration using an intensive care information system ( ICIS ) . The aim of this study was to evaluate the effect of the use of an ICIS on nursing activity . Design . R and omized controlled trial with a crossover design . Setting . An 18-bed medical-surgical ICU in a teaching hospital . Patients , nurses and interventions . During a 6week period 145 consecutive adult patients admitted to the ICU after uncomplicated cardiothoracic surgery were r and omized into two groups : for one group the documentation was carried out using a paper-based registration ( Paper ) , in the second group an ICIS was used for documentation . Measurements and results . The nursing activities for these patients were studied during two separate periods : the admission period and the registration phase ( the period directly following the admission procedure ) . The duration of the admission procedure was measured by time-motion analysis and the nursing activities in the registration phase were studied by work sampling methodology . All nursing activities during the registration phase were grouped in four main categories : patient care , documentation , unit-related and personal time . The duration of the admission procedure was longer in the ICIS group ( 18.1±4.1 versus 16.8±3.1 min , p<0.05 ) . In the registration phase , a 30 % reduction in documentation time ( Paper 20.5 % of total nursing time versus ICIS 14.4 % , p<0.001 ) , corresponding to 29 min ( per 8h nursing shift ) was achieved . This time was completely re-allocated to patient care . Conclusions . The use of the present ICIS in patients after cardiothoracic surgery alters nursing activity ; it reduces the time for documentation and increases the time devoted to patient care . Electronic Supplementary Material is available if you access this article at http://dx.org/10.1007/s00134-002-1542-9 . On that page ( frame on the left side ) , a link takes you directly to the supplementary material The purpose of this study was to determine how use of a st and ardized nomenclature for nursing diagnosis and intervention statements on the computerized nursing care plan in a long-term care ( LTC ) facility would affect patient outcomes , as well as organizational processes and outcomes . An experimental design was used to compare the effects of two methods of documentation : Computer care plan and paper care plan . Twenty participants ( 10 in each group ) were r and omly assigned to either group . No statistically significant differences were found by group for demographic data . Repeated measures ANOVA was computed for each of the study variables with type of care plan , written or computerized , as the independent variable . There were no statistically significant differences between participants , group ( care plan ) , within subjects ( across time ) , or interaction ( group and time ) effects for the dependent variables : Level of care , activities of daily living , perception of pain , cognitive abilities , number of medications , number of bowel medications , number of constipation episodes , weight , percent of meals eaten , and incidence of alteration in skin integrity . There were significantly more nursing interventions and activities on the computerized care plan , although this care plan took longer to develop at each of the three time periods . Results from this study suggest that use of a computerized plan of care increases the number of documented nursing activities and interventions , but further research is warranted to determine if this potential advantage can be translated into improved patient and organizational outcomes in the long-term care setting 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 AIM To investigate whether a comprehensive strategy involving both patients and professionals , with the introduction of a diabetes passport as a key component , improves diabetes care . METHODS The first 150 consecutive patients who visited their internist for a diabetes check up at the internal medicine outpatient departments at each of nine Dutch general hospitals were included in this 1 year clustered , r and omised , controlled trial . Health care professionals attended an educational meeting about the use and dissemination of the diabetes passport which is a patient held record . They also received aggregated feedback on baseline data and personal feedback . Educational meetings were also organised for patients . Patient files were used in conjunction with question naires to determine adherence rates . Data were analysed using multilevel regression analysis . RESULTS Small but significant changes were found in mean HbA1c levels . In the intervention group , positive health changes for patients were found ( -0.3 % ) when compared to those in the control group ( + 0.2 % ) . Diastolic blood pressure improved slightly , but no changes were found in systolic blood pressure or cholesterol . Improvements were found with regard to levels of examination of patients ' feet and in patient education . CONCLUSIONS Efforts to improve professional practice involving both professionals and patients led to small improvements in HbA1c and diastolic blood pressure levels . Further study is needed to establish whether a better structured health care delivery , operating in a more supportive environment can enhance these effects Physicians were much less likely than other primary care team members to use a Web-based application to counsel patients with diabetes about behavior change 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 AIM AND OBJECTIVES The aim of this paper is to present a study describing nurses ' adherence to the VIPS model by evaluating the quality of nursing assessment , and the quantity of completed nursing care plans . BACKGROUND Numerous efforts have been made over the years to improve nursing documentation in Denmark . Hospitals have traditionally based nurses ' charting on a rudimentary version of the nursing process and on Virginia Henderson 's theory of human needs . In 2002 - 2004 the Copenhagen University Hospital , Rigshospitalet , introduced the Swedish VIPS model for nursing documentation . VIPS is an acronym for well being , integrity , prevention and safety , all of which are seen as major goals for nursing care . The model organizes nursing data according to a system of keywords , which facilitates storage and retrieval of data . DESIGN AND METHODS The design in this part of the study was retrospective , wherein 50 journals from each of the departments of cardiology , neurology , oncology and urology were audited annually for three years using the Cat-ch-Ing instrument ( n=600 ) . All nursing journals were r and omly selected by including the first 50 journals at each site given a specific date . RESULTS The nursing documentation significantly improved during the course of the study . After the second year the participants used the keywords appropriately and correctly according to the VIPS model . Application of primary nursing increased during the study . Initial , ongoing and discharge patient status improved . The nurses ' familiarity with nursing diagnoses , goals and interventions increased . CONCLUSIONS The structured implementation programme significantly improved nursing documentation , and the simultaneous training of the entire nursing staff shows promise . The VIPS model has prepared the nurses for more complex computerized taxonomies and classification systems in the future by improving the nurses ' analytical skills . Relevance to clinical practice . New strategies for improving nursing documentation have been demonstrated Summary : We report the introduction of a woman‐held record into an antenatal clinic in a NSW teaching hospital using a r and omized controlled trial . In 1997 , 150 women were r and omized to either retaining their entire antenatal record through pregnancy ( women‐held group ) or to holding a small , abbreviated card , as was st and ard practice ( control group ) . A question naire was distributed to women to measure sense of control , involvement in care and levels of communication . Availability of records at antenatal visits was also measured . Women in both groups were satisfied with their allocated method of record keeping , however , those in the women‐held group were significantly more likely to report feeling in ‘ control ’ during pregnancy . Women in the control group were more likely to feel anxious and helpless and less likely to have information on their records explained to them by their caregiver . The number of records available at each clinic was similar in both groups The Copenhagen University Hospital decided to adhere to the st and ards of the Joint Commission of International Accreditation in 2000 . These st and ards require systematic assessment of patient care needs and include the use of written nursing care plans . In order to meet these st and ards , the hospital management decided to introduce the Swedish VIPS model , which is a model design ed to structure nursing documentation ( VIPS is an acronym for well-being , integrity , prevention and safety ) . The present study explores the nurses ' knowledge and attitudes towards documentation and addresses the research questions : ( a ) what are the nurses ' attitudes towards documentation of nursing care ? and ( b ) do nurses have sufficient knowledge of the documentation system to systematic ally document their patient assessment and clinical decisions ? The research design was prospect i ve , comparative , and quasi-experimental ( nonr and omized ) , including a study group ( n=72 ) and a control group ( n=57 ) . A question naire was used to compare nurses ' self-evaluated attitudes towards documentation , and a multiple-choice test was given in order to assess nurses ' knowledge of the documentation system . The study group participated in a special implementation programme ( response rate 82 % ) , while the control group attended the regular 3-day documentation course at the hospital ( response rate 79 % ) . The study showed that the two groups responded similarly , but the nurses in the study group were significantly stronger in their conviction that they had the knowledge to make care plans and that they routinely made them . The study group demonstrated slightly less motivation than the control group , while the two groups shared a positive attitude towards nursing documentation . The study group did consistently better on the knowledge tests . The findings show that the implementation programme had a positive impact on nursing documentation , and that the VIPS model increased the nurses ' underst and ing of the nursing process A prospect i ve intervention study with historical control has been performed at Giessen University Hospital , Germany , to investigate the influence of electronic data processing systems on nurses ' working environment . Two wards of the medical department were selected for this study , using the combined approach of work-sampling methods and question naires . In the first intervention a central information system with restricted functions was introduced . For the second intervention an additional nursing information system was installed . The distribution of nurses ' worktime into the fields of general nursing care , specific nursing care and administrative activities was not influenced by electronic data processing . No time saving could be measured . Results of the question naires did , however , indicate a positive influence of the hospital information system on nurses ' working environment |
10,886 | 21,975,742 | For the considered outcomes , it seems that adding any psychosocial support to st and ard maintenance treatments do not add additional benefits .
Data do not show differences also for contingency approaches , contrary to all expectations . | BACKGROUND Maintenance treatments are effective in retaining patients in treatment and suppressing heroin use .
Questions remain regarding the efficacy of additional psychosocial services .
These interventions probably can be measured and evaluated by employing diverse criteria for evaluating treatment outcomes , aim ed to rigorously assess changes in emotional , interpersonal , vocational and physical health areas of life functioning | BACKGROUND Despite its effectiveness , methadone maintenance is rarely provided in American correctional facilities . This study is the first r and omized clinical trial in the US to examine the effectiveness of methadone maintenance treatment provided to prisoners with pre-incarceration heroin addiction . METHODS A three-group r and omized controlled trial was conducted between September 2003 and June 2005 . Two hundred eleven Baltimore pre-release inmates who were heroin dependent during the year prior to incarceration were enrolled in this study . Participants were r and omly assigned to the following : counseling only : counseling in prison , with passive referral to treatment upon release ( n=70 ) ; counseling+transfer : counseling in prison with transfer to methadone maintenance treatment upon release ( n=70 ) ; and counseling+methadone : methadone maintenance and counseling in prison , continued in a community-based methadone maintenance program upon release ( n=71 ) . RESULTS Two hundred participants were located for follow-up interviews and included in the current analysis . The percentages of participants in each condition that entered community-based treatment were , respectively , counseling only 7.8 % , counseling+transfer 50.0 % , and counseling+methadone 68.6 % , p<.05 . All pairwise comparisons were statistically significant ( all ps<.05 ) . The percentage of participants in each condition that tested positive for opioids at 1-month post-release were , respectively , counseling only 62.9 % , counseling+transfer 41.0 % , and counseling+methadone 27.6 % , p<.05 , with the counseling only group significantly more likely to test positive than the counseling+methadone group . CONCLUSIONS Methadone maintenance initiated prior to or immediately after release from prison appears to have beneficial short-term impact on community treatment entry and heroin use . This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories OBJECTIVE Both methadone and buprenorphine are effective therapy for heroin dependence . Efficacy is best documented for methadone maintenance therapy , but safety concerns limit its use . Buprenorphine offers lower overdose risk and improved access , but efficacy may be lower . The authors compared adaptive , buprenorphine-based stepped care to optimal methadone maintenance treatment . METHOD This r and omized controlled trial was undertaken 2004 - 2006 . It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria , for a total of 6 months . Ninety-six self-referred subjects with heroin dependence were r and omly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed . All subjects received intensive behavioral treatment . Primary outcome was retention in treatment . Secondary outcomes were completer analyses of problem severity ( Addiction Severity Index ) and proportion of urine sample s free of illicit drugs . RESULTS Overall , 6-month retention was 78 % . Stepped treatment and methadone maintenance therapy outcomes were virtually identical . Among completers of stepped therapy , 46 % remained on buprenorphine/naloxone . Proportion of urine sample s free of illicit opiates increased over time and ultimately reached approximately 80 % in both arms . Problem severity decreased significantly and uniformly in both arms . CONCLUSIONS A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy . Together with prior data on the advantageous safety of buprenorphine , this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered OBJECTIVE This study examined whether substance abuse patients self- selecting into one of three aftercare groups ( outpatient treatment only , 12-step groups only , and outpatient treatment and 12-step groups ) and patients who did not participate in aftercare differed on 1-year substance use and psychosocial outcomes . METHOD A total of 3,018 male patients filled out a question naire at intake and 1 year following discharge from treatment . Patients were classified into aftercare groups at follow-up using information from VA data bases and self-reports . RESULTS Patients who participated in both outpatient treatment and 12-step groups fared the best on 1-year outcomes . Patients who did not obtain aftercare had the poorest outcomes . In terms of the amount of intervention received , patients who had more outpatient mental health treatment , who more frequently attended 12-step groups or were more involved in 12-step activities had better 1-year outcomes . In addition , patients who kept regular outpatient appointments over a longer time period fared better than those who did not . CONCLUSIONS Encouraging substance abuse patients to regularly attend both outpatient aftercare and self-help groups may improve long-term outcomes Methadone-maintained cocaine abusers ( N = 78 ) were r and omly assigned to 1 of the following 52-week interventions : ( a ) usual care only ( UC ) , ( b ) take-home methadone doses contingent on cocaine- and opiate-negative results ( THM ) , or ( c ) take-home methadone doses for cocaine- and opiate-negative results and monetary-based vouchers contingent on cocaine-negative urinalysis results ( THM + V ) . Cocaine use was assessed by urinalysis on a thrice-weekly schedule . Frequency and enjoyability of non-drug-related activities were assessed with the Pleasant Events Schedule ( PES ) at baseline , midtreatment , and end of treatment . The THM + V condition achieved the greatest abstinence from cocaine and opiate use , followed by the THM and UC conditions . The THM + V condition had the highest PES frequency ratings at midtreatment and at the end of treatment , followed by the THM and UC conditions . There were significant differences between the THM + V and UC conditions on 10 of 12 PES-derived subscales . Analyses revealed that abstinence mediated the effects of treatment condition on frequency ratings . There were no significant differences in enjoyability ratings . These results suggest that when contingency-management interventions increase abstinence from drug abuse , they also increase engagement in non-drug-related activities in naturalistic setting BACKGROUND Contingency management ( CM ) and significant other involvement ( SO ) were evaluated as strategies to enhance treatment retention , medication compliance , and outcome for naltrexone treatment of opioid dependence . METHODS One hundred twenty-seven recently detoxified opioid-dependent individuals were r and omly assigned to 1 of 3 conditions delivered for 12 weeks : ( 1 ) st and ard naltrexone treatment , given 3 times a week ; ( 2 ) naltrexone treatment plus contingency management ( CM ) , with delivery of vouchers contingent on naltrexone compliance and drug-free urine specimens ; or ( 3 ) naltrexone treatment , CM , plus significant other involvement ( SO ) , where a family member was invited to participate in up to 6 family counseling sessions . Principal outcomes were retention in treatment , compliance with naltrexone therapy , and number of drug-free urine specimens . RESULTS First , CM was associated with significant improvements in treatment retention ( 7.4 vs 5.6 weeks ; P = .05 ) and in reduction in opioid use ( 19 vs 14 opioid-free urine specimens ; P = .04 ) compared with st and ard naltrexone treatment . Second , assignment to SO did not significantly improve retention , compliance , or substance abuse outcomes compared with CM . Significant effects for the SO condition over CM on retention , compliance , and drug use outcomes were seen only for the subgroup who attended at least 1 family counseling session . The SO condition was associated with significant ( P = .02 ) improvements in family functioning . CONCLUSION Behavioral therapies , such as CM , can be targeted to address weaknesses of specific pharmacotherapies , such as noncompliance , and thus can play a substantial role in broadening the utility of available pharmacotherapies We examined the effectiveness of a contingency management program in preventing relapse to illicit opiate use and increasing treatment retention during outpatient methadone detoxification treatment . Twenty male opiate addicts were r and omly assigned to an experimental or control group . Following a 3-week methadone stabilization period , men in both groups received identical gradual methadone dose reductions during Weeks 4 through 9 and were maintained on placebo during Weeks 10 through 13 . Beginning in Week 4 , control patients received $ 5.00 for providing a specimen twice weekly . Experimental patients received $ 10.00 and a take home methadone dose for each opiate-free urine specimen but forfeited the incentives and participated in more intensive clinic procedures when specimens were opiate positive . The contingency management procedure slowed the rate of relapse to illicit opiate use . Experimental patients provided significantly more opiate-free urines during the methadone dose reduction in Weeks 4 through 9 than control patients , although the difference between groups was no longer significant during placebo administration in Weeks 10 through 13 . In addition , the contingency management program improved treatment retention and reduced symptom complaints during the detoxification . The usefulness and limitations of contingency management procedures for outpatient methadone detoxification are discussed The number of drugs targeted may have an important influence on the ability of drug abusers to abstain during motivational incentive procedures . The authors investigated outcomes in methadone maintenance patients ( n = 58 ) , who had evidence of both opiate and cocaine use , when continuous abstinence from cocaine only ( single target ) or from both cocaine and heroin ( dual target ) was required to earn US dollars 200 in voucher incentives over a 4-day period . Study patients were equally likely to initiate and sustain abstinence from cocaine under the single- versus the dual-drug target . They were more likely to initiate opiate abstinence under the dual-target condition , demonstrating sensitivity to reinforcer effects . Results suggest that adding a second drug target does not impede short-term cocaine abstinence initiation This article presents the outcomes of an innovative vocational rehabilitation model design ed for methadone-maintained patients —the Customized Employment Supports ( CES ) model . CES counselors work intensively with a small caseload of patients to overcome the vocational as well as non-vocational barriers that hinder employment , with the goal of attaining rapid job placement . A r and omized clinical trial was implemented at two methadone treatment programs in New York City and was funded by the National Institute on Drug Abuse The study tested the hypothesis that patients assigned to the experimental ( CES ) condition would have better employment outcomes than those assigned to a control condition who received st and ard vocational counseling at the programs . The data were collected from May 2001 through April 2005 . The efficacy sample for the analysis consisted of 168 patients who completed follow-up interviews . The sample was 58 % male , 75 % minority group , average age 45 years , and in methadone treatment for an average of five years . The results supported the hypothesis for two measures of employment ; i.e. , the CES group was significantly more likely than the control group to obtain both any paid employment and informal paid employment . However , there were no significant differences for competitive employment or total earnings . The study 's limitations are noted . Implication s of the findings for the improvement of vocational rehabilitation for addiction patients are discussed Abstract The effect of giving methadone maintenance clients the opportunity to regulate their dosage and of offering take-home doses as an incentive for dose reduction was studied . Subjects ( 116 ) were r and omly assigned to one of three conditions : self-regulation ofdose ( SR-1 ) ; self-regulation of dose with incentive for reduction ( SR-2 ) and st and ard treatment ( control ) . Dependent variables were dosage and use of illicit drugs ( measured by urinalyses ) . Results for the first four months show SR-1 subjects increased dose and maintained themselves at dosages significantly greater than the SR-2 or control groups while having significantly less use of illicit opiates during certain time periods . SR-2 subjects were not different from controls . Findings indicate subjects behaved responsibly under self-regulation and that this regimen is clinical ly feasible . Nevertheless , an increase in take-home privileges was an insufficient incentive to yield major reductions in dosage in SR-2 as a group Abstract Sixty-nine methadone maintenance patients were r and omly assigned to an immediate contingency for take home or the same contingency 2 months later . The contingency required zero rate drug-seeking as measured by r and omly scheduled and monitored urinalyses once per week and full-time production activity , verified every other week . These were examined two months before and after the contingency . Significant decreases in drug-seeking and increases in productivity were associated with the contingency . Control over drug-seeking was evidence d by increased consecutive “ clean urines ” although there was little change in overall percent “ clean urines ” . Although no diversion incidents were observed , experimenters felt unrecorded diversion occurred and discuss implication s of this and other results , concluding take-home methadone can be a powerful reinforcer of rehabilitation behaviors in methadone programs AIMS The aim of this study was to examine the effect of a case management intervention on retention in opiate agonist therapy among injection drug users ( IDUs ) referred from a needle exchange program ( NEP ) . DESIGN , INTERVENTION , PARTICIPANTS , AND SETTING : A r and omized trial of a strengths-based case management intervention versus passive referral ( control ) was conducted among NEP attendees requesting and receiving referrals to subsidized , publicly funded opiate agonist treatment programs in Baltimore , MD . MEASUREMENTS Multivariable Cox regression models were used to identify predictors of treatment retention using an ecological model approach , taking into account factors at the individual , social , and environmental level . FINDINGS Of 245 IDUs , 127 ( 51.8 % ) entered opiate agonist treatment , for whom median retention was 7.9 months . The intervention was not associated with longer retention ( p = .91 ) . Individual-level factors predictive of shorter retention included being employed and greater levels of psychiatric distress . Participants who had prior treatment experience and multiple treatment requests were retained significantly longer . Social factors adversely affecting treatment retention included unstable housing and buying drugs for others . Living further away from the treatment site was an environmental barrier that negatively affected treatment retention . CONCLUSIONS Multilevel interventions that address individual , social , and environmental factors are necessary to improve substance abuse treatment retention and treatment outcomes among IDUs referred from NEP AIM Contingency management ( CM ) is efficacious in reducing drug use . This study examined whether CM also reduces human immunodeficiency virus ( HIV ) risk behaviors and if these effects are mediated by longest duration of abstinence achieved during treatment . DESIGN Data were analyzed from a subset of participants in a combined data set of three published r and omized controlled trials of CM treatments . SETTING A community-based methadone maintenance clinic . PARTICIPANTS One-hundred and sixty-five cocaine-abusing methadone maintenance patients . INTERVENTION Participants received either st and ard methadone treatment or st and ard methadone treatment with CM for 3 months . MEASUREMENTS The HIV Risk Behavior Scale ( HRBS ) was administered prior to r and omization to a study condition and 3 months after the study treatments ended . The primary objective indicator of drug use was longest duration of cocaine and opioid abstinence achieved during treatment . FINDINGS Relative to those assigned to st and ard care , participants receiving CM significantly decreased overall HIV risk behaviors and injection drug use risk behaviors . CM participants also achieved longer duration s of consecutive cocaine and opioid abstinence during treatment . Duration of abstinence achieved mediated the relationship between treatment condition and HRBS difference scores . CONCLUSIONS These results suggest that CM treatment reduces HIV drug use risk behaviors in cocaine-abusing methadone maintenance patients This study examined contingent methadone take-home privileges for effectiveness in reducing on-going supplemental drug use of methadone maintenance patients . Fifty-three new intakes were r and omly assigned to begin receiving take-home privileges after 2 consecutive weeks of drug-free urines or to a noncontingent procedure in which take-homes were delivered independently of urine test results . The contingent procedure produced more individuals with at least 4 consecutive weeks of abstinence ( 32 % vs. 8 % ) ; 28 % of noncontingent subjects also achieved abstinence after shifting to the contingent procedure . Lower baseline rate of drug-free urines was strongly associated with successful outcome , whereas the type of drug abused ( cocaine vs. benzodiazepines ) did not influence outcomes . Findings support a recommendation for using contingent take-home incentives to motivate abstinence during methadone maintenance treatment Drug abuse counseling was enhanced by node-link mapping , a visual representation technique , and evaluated in a posttreatment follow-up study . Clients r and omly assigned to receive mapping counseling reported less criminal activity 12 months after treatment than did clients in the st and ard counseling condition . It was also found that among clients staying less than 6 months in treatment , those in the mapping group had fewer urine sample s that tested positive for opiates at follow-up . Thus , mapping-enhanced counseling may be especially beneficial for clients who leave treatment prematurely Human subjects protection policies developed for pharmaceutical trials are now being widely applied to psychosocial intervention studies . This study examined occurrences of serious adverse events ( SAEs ) reported in multicenter psychosocial trials of the National Institute on Drug Abuse Clinical Trials Network . Substance-abusing participants ( N = 1,687 ) were r and omized to st and ard care or st and ard care plus either contingency management or motivational enhancement . Twelve percent of participants experienced 1 or more SAEs during the 27,198 person-weeks of follow-up . Of the 260 SAEs recorded , none were judged by the data safety monitoring board to be study related , and there were no significant differences between experimental and control conditions in SAE incidence rates . These data underscore the need to reconsider the rationale behind , and appropriate methods for , monitoring safety during psychosocial therapy trials This pilot clinical trial evaluated whether the efficacy of methadone maintenance treatment ( MMT ) provided with limited psychosocial services is improved by the addition of manual-guided behavioral drug and HIV risk reduction counseling ( BDRC ) . Heroin dependent individuals ( n=37 ) enrolling in two MMT clinics in Wuhan , China , received st and ard MMT services , consisting of daily medication at the clinics and infrequent additional services on dem and , and were r and omly assigned to MMT only ( n=17 ) or MMT with weekly individual BDRC ( n=20 ) for 3 months . Participants were followed for six months from the time of enrollment ( 3 months active counseling phase and 3 months follow-up while treated with st and ard MMT ) . Primary outcome measures included reductions of HIV risk behaviors and illicit opiate use and treatment retention . Participants were 81 % male ; mean ( SD ) age 36.7 ( 7.2 ) years ; there were no significant baseline differences between the two groups . Participants in MMT+BDRC achieved both greater reductions of HIV risk behaviors ( p<0.01 ) , as indicated by the scores on a short version of the AIDS Risk Inventory , and of illicit opiate use , as indicated by the proportions of opiate negative test results during the active phase of the study and the follow-up ( p<0.001 ) . 83.3 % in the MMT+BDRC group and 76.2 % in the st and ard MMT group were still actively participating in MMT at 6 months . Manual-guided behavioral drug and HIV risk reduction counseling is feasible to deliver by the trained MMT nursing personnel and appears to be a promising approach for improving the efficacy of st and ard MMT services in China During a 12-week intervention , opioid dependent participants ( N = 120 ) maintained on thrice-a-week ( M , W , F ) buprenorphine plus therapist and computer-based counseling were r and omized to receive : ( a ) medication contingencies ( MC = thrice weekly dosing schedule vs. daily attendance and single-day 50 % dose reduction imposed upon su bmi ssion of an opioid and /or cocaine positive urine sample ) ; ( b ) voucher contingency ( VC = escalating schedule for opioid and /or cocaine negative sample s with reset for drug-positive sample s ) ; or ( c ) st and ard care ( SC ) , with no programmed consequences for urinalysis results . VC result ed in better 12-week retention ( 85 % ) compared to MC ( 58 % ; p = 0.009 ) , but neither differed from SC ( 76 % retained ) . After adjusting for baseline differences in employment , and compared to SC , the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence ( p = 0.030 ) , while the VC group had 2 more total weeks of abstinence ( p = 0.048 ) . Drug use results suggest that both the interventions were efficacious , with effects primarily in opioid rather than cocaine test results . Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies This study tested whether coordinated care management ( CCM ) , a continuity of care intervention for substance use disorders ( SUD ) , improved rates of abstinence when compared with usual welfare management for substance-using single adults and adults with dependent children applying for public assistance . The study was design ed as a practical clinical trial and was implemented in partnership with a large city welfare agency . Participants were 421 welfare applicants identified via SUD screening and assigned via an unbiased computerized allocation program to a site that provided either CCM ( n = 232 ) or usual care ( UC ; n = 189 ) . Outcomes were assessed for 1 year postbaseline with self-reports and biological measures of substance use . As hypothesized , for participants not enrolled in methadone maintenance programs ( n = 313 ) , CCM clients received significantly more services than did UC clients . Nonmethadone CCM also showed significantly higher abstinence rates ( odds ratio = 1.75 ; 95 % confidence interval = 1.12 , 2.76 ; d = 0.31 ) that emerged early in treatment and were sustained throughout follow-up . In contrast , no treatment services or outcome effects were found for methadone maintenance clients ( n = 108 ) . Findings suggest that CCM is promising as a wraparound to SUD treatment for welfare recipients BACKGROUND Our initial attempts to " match " substance-abuse patients from an employee assistance program to an optimal setting or program failed . Scientifically , we found no differential predictors of better outcomes by setting or program . From a practical perspective , it was impossible to place patients in the intended programs . This led to a second study , design ed to identify specific patient problems and match professional services to those problems within each of the 4 programs . METHODS Ninety-four new patients admitted to 4 substance-abuse treatment programs were r and omly assigned to st and ard treatment and treated in the usual manner or were assigned to " matched " services , in which patients received at least 3 professional sessions directed at their important employment , family , or psychiatric problems . RESULTS Matched patients stayed in treatment longer , were more likely to complete treatment , and had better posttreatment outcomes than did the st and ard patients treated in the same programs . CONCLUSIONS For logistical , financial , and clinical reasons , it is improbable that patients will be matched to specific types of programs . However , within any program , it is possible and practical to match appropriate services to patients ' specific treatment problems . This strategy was clinical ly and administratively practical , attractive to patients , and responsible for a 20 % to 30 % increase in the effectiveness of this substance-abuse treatment system Abstract Treating cocaine use by opiate-dependent clients in methadone programs is a well-documented challenge . Both behavioral ( contingency management ) and cognitive ( relapse prevention ) interventions have shown promise in helping engage these clients in treatment . In this study , the effectiveness of combining contingency management with a cocaine-specific relapse prevention counseling module was examined . Sixty-one cocaine-using methadone clients were r and omly assigned to one of four treatment conditions to participate in the eight-week intervention and eight-week follow-up period . Using analysis of variance ( ANOVA ) , differences in cocaine use and treatment retention were examined . Contingency management was significantly related to reductions in cocaine use and the counseling module was positively related to six-month retention rates . Both interventions were associated with positive treatment response but the effects were reflected in different behavioral outcomes Data from 2 contingency management trials , targeting opiate or cocaine use , were used to investigate whether noncontingent vouchers inadvertently reinforce drug use . The control group in each trial received noncontingent vouchers matched in value and frequency to those received by experimental groups , but independent of urinalysis . Vouchers were offered thrice weekly for 8 weeks ( opiates ) or 12 weeks ( cocaine ) . Both dose-response and temporal associations of noncontingent voucher receipt with drug-positive urines were assessed . Drug use was unrelated to frequency of noncontingent voucher delivery and noncontingent voucher receipt when being drug positive was unassociated with risk of subsequent drug use , with one exception : cocaine use in the cocaine study ( relative risk = 1.05 , 95 % confidence interval : 1.01 - 1.09 ) . Overall , results do not indicate a causal relationship between noncontingent voucher receipt and increased drug use This study evaluated the short-term effectiveness of cognitive-behavioral treatment ( CBT ) for substance abuse delivered in a community setting . At entry into outpatient community substance abuse treatment , participants ( N = 252 ) were r and omly assigned to 3 conditions : high-st and ardization CBT , low-st and ardization CBT , and treatment as usual . Treatment consisted of 12 weekly individual therapy sessions . There was a significant decrease in substance use from baseline , with participants reporting being abstinent on 90 % of within-treatment days and 85 % of days during the 6 months posttreatment . However , there were no significant differences in outcomes across conditions . Findings do not support the hypothesis that disseminating CBT to community setting s will improve outcomes and suggest that st and ard substance abuse counseling may be more effective than previously thought Despite recent emphasis on integrating empirically vali date d treatment into clinical practice , there are little data on whether manual-guided behavioral therapies can be implemented in st and ard clinical practice and whether incorporation of such techniques is associated with improved outcomes . The effectiveness of integrating motivational interviewing ( MI ) techniques into the initial contact and evaluation session was evaluated in a multisite r and omized clinical trial . Participants were 423 substance users entering outpatient treatment in five community-based treatment setting s , who were r and omized to receive either the st and ard intake/evaluation session at each site or the same session in which MI techniques and strategies were integrated . Clinicians were drawn from the staff of the participating programs and were r and omized either to learn and implement MI or to deliver the st and ard intake/evaluation session . Independent analyses of 315 session audiotapes suggested the two forms of treatment were highly discriminable and that clinicians trained to implement MI tended to have higher skill ratings . Regarding outcomes , for the sample as a whole , participants assigned to MI had significantly better retention through the 28-day follow-up than those assigned to the st and ard intervention . There were no significant effects of MI on substance use outcomes at either the 28-day or 84-day follow-up . Results suggest that community-based clinicians can effectively implement MI when provided training and supervision , and that integrating MI techniques in the earliest phases of treatment may have positive effects on retention early in the course of treatment We evaluated 3-month outcomes for reinforcement-based intensive outpatient treatment ( RBT ) , a new relapse prevention behavior therapy for inner city opiate abusers . The therapy provides abstinence-contingent partial support of housing , food and recreational activities , abstinence-contingent access to social skills and job finding group therapy and non-contingent individual counseling , all in the context of a day treatment program . Heroin abusers ( n = 52 ) , contacted at a 3-day detoxification unit , were r and omly assigned to RBT ( n = 28 ) or referred to community treatment re sources ( n = 24 ) after a staff escort from the detoxification unit . For RBT patients , treatment began on the day of discharge ; 61 % received partial rent support in a recovery house based on the need for drug-free housing ; the remainder were eligible for partial support of utility payments where they lived . Abstinence-based contingencies were in effect for 1 month with three times per week counseling available for an additional 2 months . One month after detoxification , 61 % of RBT versus 17 % of referral patients were enrolled in outpatient treatment ( P < 0.01 ) ; RBT patients were significantly less likely than controls to have returned to any drug use ; and 50 % of RBT versus 21 % of controls reported 30 days of abstinence from heroin and cocaine with confirmatory negative urine ( P < 0.05 ) . RBT patients had significantly lower scores on the Beck Depression Inventory at 1 month ( M = 9.0 versus 17.6 for controls ; P < 0.05 ) and showed evidence of less alcohol use and higher rates of employment . These results establish the short-term efficacy for RBT and support continued development and evaluation of this new outpatient behavioral treatment AIM The present study evaluated the effectiveness of an intervention combining motivational enhancement and treatment readiness groups , with and without monetary incentives for attendance and treatment enrollment , on enhancing rates of substance abuse treatment entry among new registrants at the Baltimore Needle Exchange Program ( BNEP ) . DESIGN Opioid-dependent study participants ( n = 281 ) referred by the BNEP were assigned r and omly to one of three referral interventions : ( i ) eight individual motivational enhancement sessions and 16 treatment readiness group sessions ( motivated referral condition -- MRC ) ; ( ii ) the MRC intervention with monetary incentives for attending sessions and enrolling in treatment -- MRC+I ) ; or ( iii ) a st and ard referral condition which directed participants back to the BNEP for referral ( st and ard referral-SRC ) . Participants were followed for 4 months . FINDINGS MRC+I participants were more likely to enroll in any type of treatment than MRC or SRC participants ( 52.1 % versus 31.9 % versus 35.5 % ; chi(2 ) = 9.12 , P = 0.01 ) , and more likely to enroll in treatment including methadone than MRC or SRC participants ( 40.4 % versus 20.2 % versus 16.1 % ; chi(2 ) = 16.65 , P < 0.001 ) . MRC+I participants also reported less heroin and injection use than MRC and SRC participants . CONCLUSIONS Syringe exchange sites can be effective platforms to motivate opioid users to enroll in substance abuse treatment and ultimately reduce drug use and number of drug injections Abstract The current study examined the relationship between need for cognition ( i.e. , cognitive motivation or “ will ” ) and educational experience ( i.e. , cognitive ability or “ skill ” ) to perceived improvements during treatment of probationers receiving residential treatment within the criminal justice system . Probationers were r and omly assigned to either receive motivational activities developed by the authors ( the “ enhanced ” condition ) , or treatment as usual ( but with access to general reading material s in lieu of the motivational activities ) . Need for cognition and educational experience were assessed and used as blocking variables , and ratings of progress were assessed midway and toward the end of treatment . The results indicate that both need for cognition and educational experience are important predictors of improvement during treatment , and that the motivational activities developed by the authors were particularly valuable for clients with lower levels of need for cognition This study determined whether abstinence engendered by intermittent reinforcement might generalize to nonreinforced periods and enhance overall rates of cocaine abstinence among methadone maintenance patients . Participants were r and omized to 1 of 3 groups . The quantitative group ( n = 14 ) earned incentives for a 50 % decrease in urine benzoylecgonine concentrations ; the qualitative group ( n = 13 ) earned incentives for providing urines with concentrations < 300 ng/ml . Both reinforced groups received 12 r and om opportunities to earn 100 US dollars in vouchers for abstinence . The control group ( n = 15 ) was encouraged to abstain on 12 occasions under the same schedule . Incentive participants achieved significantly more cocaine abstinence on earning than on nonearning days , with no difference between quantitative and qualitative groups . The study supports brief abstinence test efficacy but did not find that unpredictable opportunities to earn incentives generalized to nonreinforced days This study examined the effects of contingent vs. non-contingent delivery of a methadone dose supplement on relapse to illicit opiate use in the context of a methadone outpatient detoxification program . Following a 3-week methadone stabilization period on 30 mg , patients ( N = 39 ) were r and omly assigned to a contingent , a non-contingent , or a control treatment group . All patients received identical gradual reductions in their assigned methadone dose . During the dose reduction period ( weeks 4 - 11 ) , members of the contingent ( N = 13 ) and non-contingent groups ( N = 13 ) could obtain daily methadone-dose supplements up to 20 mg , but contingent group members could obtain supplements only if their most recent urinalysis results were opiate negative . Control subjects ( N = 13 ) did not have dose increases available . The contingent group presented significantly lower opiate-positive urines during weeks 8 - 11 ( 14 % positive ) of the detox than the non-contingent ( 38 % positive ) or control ( 50 % positive ) groups . Additionally , the availability of extra methadone improved treatment retention and increased clinic attendance above levels observed in the control group . The potential for further use of methadone 's reinforcing properties in the treatment of opiate dependence is discussed Poor patient adherence remains a serious obstacle to improving the effectiveness of many drug abuse therapies and the overall quality of care delivered in programs . The present study evaluated the utility and efficacy of incorporating behavioral contingencies in a stepped care treatment approach to motivate patient attendance to the varying amounts of prescribed weekly counseling . Study participants were opioid-dependent patients ( n = 127 ) newly admitted to an ambulatory treatment program that provides methadone . Participants were r and omly assigned to a Motivated Stepped Care condition ( MSC ; n = 65 ) with behavioral contingencies to specifically motivate counseling attendance vs. a St and ard Stepped Care condition ( SSC ; n = 62 ) without these contingencies . The MSC vs. SSC condition was associated with a higher rate of counseling attendance ( 83 % vs. 44 % , p < .001 ) and a lower rate of poor treatment response ( 46 % vs. 79 % , p < .001 ) . The behavioral contingencies were well tolerated and strongly associated with excellent attendance across both lower and higher doses of weekly counseling Forty-three residents of a substance abuse treatment center were r and omly assigned to ( a ) Assertiveness Training with Behavioral Practice ( ATBP ) ; ( b ) Assertiveness Training with Journal ( ATJ ) , or ( c ) Waiting List Control ( WLC ) . Using the Behavioral Assertiveness Test and the Gambrill-Richey Assertion Inventory , subjects in the ATBP group showed greater gains than the ATJ group on one behavioral measure , while both the ATBP and ATJ groups changed more than the WLC group on the Gambrill-Richey Response Likelihood scale . Behavioral rehearsal ( homework compliance ) was not consistently related to outcome , calling into question the value of the widespread use of homework assignments in behavioral treatments Homeless adults with both a serious mental illness and substance dependence ( N = 276 ) were r and omly assigned to : ( 1 ) a social model residential program providing integrated mental health and substance abuse treatment ; ( 2 ) a community-based nonresidential program using the same social model approach ; or ( 3 ) a control group receiving no intervention but free to access other community services . Interventions were design ed to provide 3 months of intensive treatment , followed by 3 months of nonresidential maintenance . Subjects completed baseline interviews prior to r and omization and reinterviews 3 , 6 , and 9 months later . Results showed that , while substance use , mental health , and housing outcomes improved from baseline , subjects assigned to treatment conditions differed little from control subjects . Examination of the relationship between length of treatment exposure and outcomes suggested that residential treatment had positive effects on outcomes at 3 months , but that these effects were eroded by 6 months OBJECTIVE This study examined whether enhancing st and ard aftercare with an outreach case management intervention would improve patients ' quality of life . METHODS A sample of 292 patients discharged from an inpatient psychiatry service at an urban general hospital were r and omly assigned either to an intervention group ( N = 147 ) , which received outreach case management services in addition to st and ard aftercare service , or to a control group ( N = 145 ) , which received only st and ard aftercare services . The follow-up period was 15 to 52 months . Individuals in both groups were reinterviewed by an independent research team about 21.6 months after discharge . The groups were compared using 39 measures of quality of life . The interviews elicited information about patients ' physical well-being and competence in performing activities of daily living ; their emotional well-being as shown in emotional expressiveness , sadness , suicidal thoughts , and substance abuse ; and their interpersonal relationships , living arrangements , friendships , income maintenance , and employment . RESULTS No difference was found between the groups on any of the quality -of-life variables . CONCLUSIONS Outreach case management was not associated with improved quality of life Intravenous drug use is a major vector of HIV transmission . We assessed whether contingency management ( CM ) , in which participants earn reinforcers for drug abstinence , reduces HIV risk behaviors in methadone-maintained opiate- and cocaine-using out patients . Participants ( n=116 ) were r and omly assigned to prize-based CM or to receipt of prize draws noncontingently on a schedule yoked to the CM group . Both groups received methadone and individual counseling throughout treatment . The HIV-Risk Taking Behaviour Scale was administered in written question naire form at 2-week intervals ( HRBS ; [ Darke , S. , Hall , W. , Heather , N. , Ward , J. , & Wodak , A. ( 1991 ) . The reliability and validity of a scale to measure HIV risk-taking behaviour among intravenous drug users . AIDS , 5 , 181 - 185 ] ) . A mediation analysis was conducted to determine whether abstinence from opiates and cocaine mediated the effect of CM on HRBS scores . Changes in HRBS scores over time differed significantly by treatment ( F(9,334)=2.4 , p<0.05 ) , with HRBS scores decreasing over time in the CM group to a greater extent than in the noncontingent control group . Participants in the CM group had significantly lower rates of simultaneous cocaine/opiate-positive urine specimens than those in the noncontingent control group during CM treatment ( F(1,111)=6.8 , p=0.01 ) . The relationship between treatment condition and HRBS scores was mediated by abstinence . CM targeted toward cocaine and heroin use produces significant reductions in injection-related drug-taking behaviors associated with heightened risk for getting or transmitting HIV To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine , we conducted a r and omized controlled trial using a 2 x 3 ( dosexcontingency ) factorial design in which dose assignment was double-blind . Participants were 252 heroin- and cocaine-abusing out patients on methadone maintenance . They were r and omly assigned to methadone dose ( 70 or 100mg/day , double-blind ) and voucher condition ( noncontingent , contingent on cocaine-negative urines , or " split " ) . The " split " contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both : the total value of incentives was " split " between drugs to contain costs . The main outcome measures were percentages of urine specimens negative for heroin , cocaine , and both simultaneously ; these were monitored during a 5-week baseline of st and ard treatment ( to determine study eligibility ) , a 12-week intervention , and a 10-week maintenance phase ( to examine intervention effects in return-to-baseline conditions ) . DSM-IV criteria for ongoing drug dependence were assessed at study exit . Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use . The split 100 mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose noncontingent control group . The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups . For a split contingency to promote simultaneous abstinence from cocaine and heroin , a relatively high dose of methadone appears necessary but not sufficient ; an increase in overall incentive amount may also be required To examine the effect of reinforcer density in prize-based abstinence reinforcement , heroin/cocaine users ( N = 116 ) in methadone maintenance ( 100 mg/day ) were r and omly assigned to a noncontingent control group ( NonC ) or to 1 of 3 groups that earned prize draws for abstinence : manual drawing with st and ard prize density ( MS ) or computerized drawing with st and ard ( CS ) or high ( CH ) density . Probabilities ( prizes/draw ) were st and ard ( 50 % ) and high ( 78 % ) ; prize density was double blind . Mean prize values were CH , $ 286 ; CS , $ 167 ; MS , $ 139 ; and NonC , $ 171 . Outcomes were % opioid/cocaine-negative urines during the 12-week intervention and then 8 weeks postintervention as well as diagnosis of dependence up to 6 months post study . CH had significantly more negative specimens than did NonC during intervention and had more than all groups during postintervention treatment : Mean % negative ( 95 % confidence interval ) during postintervention treatment adjusted for baseline drug use and dropout were CH , 55 % ( 14%-90 % ) ; CS , 7 % ( 1%-27 % ) ; MS , 4 % ( 1%-12 % ) ; and NonC , 3 % ( 1%-10 % ) . Current cocaine dependence diagnoses after treatment were significantly lower in contingent compared with noncontingent groups . Computerized drawing with higher-density prizes enhanced reduction of cocaine use ; abstinence reinforcement had long-term therapeutic benefits We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually ( cocaine and heroin ) dependent out patients who completed 70 days of a controlled clinical trial of sublingual buprenorphine ( 16 mg , 8 mg , or 2 mg daily , or 16 mg every other day ) plus weekly individual st and ardized interpersonal cognitive psychotherapy . Treatment outcome was evaluated by quantitative urine benzoylecgonine ( BZE ) and morphine levels ( log-transformed ) , performed three times per week . Repeated- measures linear regression was used to assess the effects of psychotherapy attendance ( percent of visits kept ) , medication group , and study week on urine drug metabolite levels . Mean psychotherapy attendance was 71 % of scheduled visits . Higher psychotherapy attendance was associated with lower urine BZE levels , and this association grew more pronounced as the study progressed ( p=0.04 ) . The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group , being most pronounced for subjects receiving 16 mg every other day ( p=0.02 ) . These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual ( cocaine and opioid ) dependence Although improvement in psychosocial functioning is a common goal in substance-abuse treatment , the primary outcome measure in most cocaine trials is urinalysis-verified cocaine use . However , the relationship between cocaine use and psychosocial outcomes is not well documented . To investigate this relationship and identify the optimal urine-screen method , we retrospectively analyzed data from two 25-week r and omized controlled trials of abstinence reinforcement ( AR ) in 368 cocaine/heroin users maintained on methadone . Cocaine use was measured thrice weekly by qualitative urinalysis , benzoylecgonine concentration ( BE ) , and an estimate of New Uses of cocaine by application of an algorithm to BE . Social adjustment ( SAS-SR ) , current diagnosis of cocaine dependence ( DSM-IV criteria ) , and depression symptoms ( Beck Depression Inventory ) were determined at study exit . Cocaine use was significantly lower in AR groups than in controls . Across groups , in-treatment cocaine use was significantly associated with worse social adjustment , current cocaine dependence , and depression at exit . Significant differences were detected more frequently with New Uses than qualitative urinalysis or BE . Nevertheless , the amount of variance accounted for by the urine screens was typically < 15 % . Cocaine use during treatment , especially when measured with New Uses criteria , can predict psychosocial functioning , but can not substitute for direct measures of psychosocial functioning High-magnitude and long- duration abstinence reinforcement can promote drug abstinence but can be difficult to finance . Employment may be a vehicle for arranging high-magnitude and long- duration abstinence reinforcement . This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs and use cocaine during methadone treatment . Participants could work 4 hr every weekday in a workplace where they could earn about $ 10.00 per hour in vouchers ; they were required to provide routine urine sample s. Participants who attended the workplace and provided cocaine-positive urine sample s during the initial 4 weeks were invited to work 26 weeks and were r and omly assigned to an abstinence- and -work ( n = 28 ) or work-only ( n = 28 ) group . Abstinence- and -work participants had to provide urine sample s showing cocaine abstinence to work and maintain maximum pay . Work-only participants could work independent of their urinalysis results . Abstinence- and -work participants provided more ( p = .004 ; OR = 5.80 , 95 % CI = 2.03 - 16.56 ) cocaine-negative urine sample s ( 29 % ) than did work-only participants ( 10 % ) . Employment-based abstinence reinforcement can increase cocaine abstinence One hundred ten nonpsychotic opiate addicts were r and omly assigned to receive paraprofessional drug counseling alone or counseling plus professional psychotherapy . The outcomes of patients who received psychotherapy were examined in terms of their DSM-III diagnoses . Four groups were compared : those with opiate dependence alone ( N = 16 ) ; opiate dependence plus depression ( N = 16 ) ; opiate dependence plus depression plus antisocial personality disorder ( N = 17 ) ; and opiate dependence plus antisocial personality disorder ( N = 13 ) . Those with opiate dependence plus antisocial personality disorder alone improved only on ratings of drug use . Patients with opiate dependence alone or with opiate dependence plus depression improved significantly and in many areas . Opiate-dependent patients with antisocial personality plus depression responded almost as well as those with only depression . Antisocial personality disorder alone is a negative predictor of psychotherapy outcome , but the presence of depression appears to be a condition that allows the patient to be amenable to psychotherapy , even though the behavioral manifestations of sociopathy are present This study compares the efficacy of three residential therapeutic communities and an outpatient methadone maintenance program for 585 male veterans addicted to heroin . Subjects were r and omly assigned to the treatment modalities . More than 93 % of the subjects completed both six- and 12-month question naires . In this report , the treatment setting s , characteristics of the sample , assignment protocol , and pattern of treatment entry and first-year follow-up results are outlined . The various clinical dem and s that affected the research protocol , the degree to which the r and omization was compromised , and the implication s for the analysis of outcome are discussed . One year after admission to the study , subjects who had been in a therapeutic community for longer than seven weeks or in methadone treatment were more likely to be employed or attending school , and less likely to be in jail , using heroin , or to have been convicted of a serious crime , than subjects who received no treatment at all beyond a short detoxification period . Those who spent less than seven weeks in a therapeutic community were doing no better than subjects in the no treatment group In a r and omized prospect i ve treatment study , 80 overdose patients ( not requiring intensive psychiatric intervention ) received either brief out-patient counselling or were returned to the care of their general practitioners with advice on management . There was little difference in outcome between the two groups . However , two sub-groups of patients benefited more from out-patient counselling than from general practitioner care , these were : ( a ) women , and ( b ) patients with dyadic problems . Counselling following overdoses should be focused on groups of patients such as these who are most likely to benefit from it . Further work is needed to identify treatment approaches that will help other groups who take overdoses , especially men CONTEXT No effective pharmacotherapies exist for cocaine dependence , although contingency management ( CM ) has demonstrated efficacy . OBJECTIVE To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals . DESIGN This 25-week , placebo-controlled , double-blind trial r and omly assigned participants to 1 of 4 treatment conditions : CM and placebo ( CMP ) , CM and 300 mg/d of bupropion hydrochloride ( CMB ) , voucher control and placebo ( VCP ) , or voucher control and bupropion ( VCB ) . SETTING Outpatient clinic at the Veterans Affairs Connecticut Healthcare System . PARTICIPANTS A total of 106 opiate-dependent , cocaine-abusing individuals . INTERVENTIONS All study participants received methadone hydrochloride ( range , 60 - 120 mg ) . Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3 . In the CM conditions , each urine sample negative for both opioids and cocaine result ed in a monetary-based voucher that increased for consecutively drug-free urine sample s during weeks 1 to 13 . Completion of abstinence-related activities also result ed in a voucher . During weeks 14 to 25 , only completion of activities was reinforced in the CM group , regardless of sample results . The voucher control groups received vouchers for su bmi tting urine sample s , regardless of results , throughout the study . MAIN OUTCOME MEASURE Thrice-weekly urine toxicologic test results for cocaine and heroin . RESULTS Groups did not differ in baseline characteristics or retention rates . Opiate use decreased significantly , with all treatment groups attaining equivalent amounts of opiate use at the end of the study . In the CMB group , the proportion of cocaine-positive sample s significantly decreased during weeks 3 to 13 ( P<.001 ) relative to week 3 and remained low during weeks 14 to 25 . In the CMP group , cocaine use significantly increased during weeks 3 to 13 ( P<.001 ) relative to week 3 , but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 ( P<.001 ) . In contrast , by treatment end , the VCB and VCP groups showed no significant improvement in cocaine use . CONCLUSION These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone Network therapy ( NT ) employs family members and /or friends to support compliance with an addiction treatment carried out in office practice . This study was design ed to ascertain whether NT is a useful psychosocial adjunct , relative to a control treatment , for achieving diminished illicit heroin use for patients on buprenorphine maintenance . Patients agreeing to r and omization to either NT ( N = 33 ) or medication management ( MM , N = 33 ) were inducted onto short-term buprenorphine maintenance and then tapered to zero dose . NT result ed in significantly more urine toxicologies negative for opioids than MM ( 65 % vs. 45 % ) and more NT than MM patients ( 50 % vs. 23 % ) experienced a positive outcome relative to secondary heroin use by the end of treatment . The use of NT in office practice may therefore improve the effectiveness of eliminating secondary heroin use during buprenorphine maintenance . It may also be useful in enhancing compliance with an addiction treatment regimen in other context OBJECTIVE Previous research has suggested that support services supplementing methadone maintenance programs vary in their cost-effectiveness . This study examined the cost-effectiveness of varying levels of supplementary support services to determine whether the relative cost-effectiveness of alternative levels of support is sustained over time . METHOD A group of 100 methadone-maintained opiate users were r and omly assigned to three treatment groups receiving different levels of support services during a 24-week clinical trial . One group received methadone treatment with a minimum of counseling , the second received methadone plus more intensive counseling , and the third received methadone plus enhanced counseling , medical , and psychosocial services . The results at the end of the trial period have been published elsewhere . This article reports the results of an analysis at a 6-month follow-up . RESULTS The follow-up analysis reaffirmed the preliminary findings that the methadone plus counseling level provided the most cost-effective implementation of the treatment program . At 12 months , the annual cost per abstinent client was $ 16,485 , $ 9,804 , and $ 11,818 for the low , intermediate , and high levels of support , respectively . Abstinence rates were highest , but modestly so , for the group receiving the high-intensity , high-cost methadone with enhanced services intervention . CONCLUSIONS This study suggests that large amounts of support to methadone-maintained clients are not cost-effective , but it also demonstrates that moderate amounts of support are better than minimal amounts . As funding for these programs is reduced , these findings suggest a floor below which supplementary support should not fall BACKGROUND Relapse to drug use is often seen when contingencies design ed to reduce drug use are discontinued . This paper reports on a stepdown maintenance contingency and 1-year follow-up in 110 patients who were maintained on methadone ( 50 or 70 mg/day ) and who had completed a contingency management trial targeted to decreasing their opiate use . In the prior study ( induction phase , 8 weeks ) participants received vouchers for each opiate-negative urine screen or noncontingently . METHODS In this study ( maintenance phase , 12 weeks ) , participants were rer and omized to receive vouchers and take-home methadone doses contingent on providing opiate-negative urine specimens ( N=55 ) or noncontingently ( N=55 ) . Since participants had been rer and omized from induction-phase contingencies , most study data were analyzed as if from a 2 x 2 ( inductionxmaintenance ) design . Follow-up interviews were conducted at 3 , 6 , and 12 months after study participation . RESULTS Patients who received the maintenance contingency following an 8-week induction contingency had better outcomes than those who received noncontingent incentives in either the maintenance or induction phases of the trial . Good outcome at follow-up was predicted by enrollment in methadone maintenance after the study . Significantly more participants in the maintenance contingency group transferred directly to another methadone program . CONCLUSION These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance Methadone maintenance programs ( MMP ) have the potential to play an important role in reducing HIV risk , given the appropriate type and level of ancillary treatments . In this study , we investigated the efficacy of a 12-session harm reduction group intervention for injection drug users , based upon the Information-Motivation-Behavioral skills model of behavior change , that focused on reducing both drug and sex risk . Two hundred and twenty patients entering an MMP were r and omized to receive either st and ard care (SC)-2 hours of counseling per month and a single-session risk reduction intervention-or SC plus the harm reduction group ( HRG ) . Results showed that during treatment , patients receiving HRG were more likely to be abstinent from cocaine and to report fewer unsafe sexual practice s. Post-treatment , HRG patients scored higher on a sexual risk quiz and reported increased self-efficacy in high risk sexual situations . Enhancing methadone maintenance with a weekly harm reduction group treatment was somewhat more expensive but can bring about positive changes in behaviors and attitudes that are associated with the transmission of HIV This study examines the effectiveness of using vouchers to reinforce either the provision of urine sample s testing negative for illicit drugs ( UA group ) or the completion of objective , individually defined , treatment-plan-related tasks ( TP group ) . A third group was assigned to the clinic 's st and ard treatment ( STD group ) . Participants were r and omly assigned to groups after a 6-week baseline-stabilization period . Urine specimens were collected thrice weekly throughout the study . In the UA condition , participants earned $ 5 ( U.S. dollars ) in vouchers for each drug-free urine su bmi tted . In the TP condition , participants earned up to $ 15 in vouchers per week for demonstrating completion of treatment plan tasks assigned by their counselors . Contingencies were in effect for 12 weeks , after which all participants received the clinic 's st and ard treatment . Urinalysis results indicate that the TP intervention was significantly more effective in reducing illicit drug use than either the UA or STD interventions . These effects were maintained with a trend toward continuing improvement for the TP groups even after contingencies were discontinued Cocaine use is associated with injecting and sexual HIV risk behaviors . This study was a r and omized controlled trial of behavioral interventions for cocaine dependence and HIV risk behaviors among dually ( cocaine and heroin ) dependent out patients . Methadone maintenance was augmented with cognitive-behavioral therapy ( CBT ) , contingency management ( CM ) , both ( CBT+CM ) , or neither . The study sample ( n=81 ) was 52 % female , 70 % African American , and 37.9+/-7.0 years old . Proportions reporting HIV risk behaviors at intake were : 96.3 % ( 78/81 ) injection drug use , 56.8 % ( 46/81 ) sharing needles , 30.9 % ( 25/81 ) unprotected sex , 28.4 % ( 23/81 ) trading sex for money or drugs . Proportions who no longer reported behaviors at study exit were : 51.3 % ( 40/78 ) injection drug use , 91.3 % ( 42/46 ) sharing needles , 88 % ( 22/25 ) unprotected sex , 91.3 % ( 21/23 ) trading sex for money or drugs . Participants receiving CBT+CM were more likely to report cessation of unprotected sex relative to control ( OR=5.44 , 95 % CI 1.14 - 26.0 , p=0.034 ) but this effect was no longer significant after adjusting for drug-negative urines . These results suggest broad beneficial effects of methadone maintenance augmented with behavioral interventions for reducing HIV risk behaviors BACKGROUND Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence have improved treatment outcomes of substance abusers , but have not been widely implemented in community drug abuse treatment setting s. OBJECTIVE To compare outcomes achieved when a lower-cost prize-based contingency management treatment is added to usual care in community methadone hydrochloride maintenance treatment setting s. DESIGN R and om assignment to usual care with ( n = 198 ) or without ( n = 190 ) abstinence incentives during a 12-week trial . SETTING Six community-based methadone maintenance drug abuse treatment clinics in locations across the United States . PARTICIPANTS Three hundred eighty-eight stimulant-abusing patients enrolled in methadone maintenance programs for at least 1 month and no more than 3 years . INTERVENTION Participants su bmi tting stimulant- and alcohol-negative sample s earned draws for a chance to win prizes ; the number of draws earned increased with continuous abstinence time . MAIN OUTCOME MEASURES Total number of stimulant- and alcohol-negative sample s provided , percentage of stimulant- and alcohol-negative sample s provided , longest duration of abstinence , retention , and counseling attendance . RESULTS Su bmi ssion of stimulant- and alcohol-negative sample s was twice as likely for incentive as for usual care group participants ( odds ratio , 1.98 ; 95 % confidence interval , 1.42 - 2.77 ) . Achieving 4 or more , 8 or more , and 12 weeks of continuous abstinence was approximately 3 , 9 , and 11 times more likely , respectively , for incentive vs usual care participants . Groups did not differ on study retention or counseling attendance . The average cost of prizes was 120 dollars per participant . CONCLUSION An abstinence incentive approach that paid 120 dollars in prizes per participant effectively increased stimulant abstinence in community-based methadone maintenance treatment clinics OBJECTIVE Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs , but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available . This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence . METHOD Subjects with cocaine and opioid dependence ( N=162 ) were provided manual-guided counseling and r and omly assigned in a double-blind design to receive daily sublingual buprenorphine ( 12 - 16 mg ) or methadone ( 65 - 85 mg p.o . ) and to contingency management or performance feedback . Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests , which were conducted three times a week ; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13 - 24 . Performance feedback subjects received slips of paper indicating the urine test results . The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests . Analytic models included two-by-two analysis of variance and mixed-model repeated- measures analysis of variance . RESULTS Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests , compared with subjects who received buprenorphine . Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value , compared with those who received performance feedback , but there were no significant differences between groups in these variables during the entire 24-week study . CONCLUSIONS Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence . Combining methadone or buprenorphine with contingency management may improve treatment outcome This study evaluated rates of cannabis use and the effectiveness of an adaptive stepped care intervention for reducing cannabis use in methadone maintenance patients . Patients testing cannabis positive during a 6-month baseline were advanced to more weekly counseling ( up to 9 hours per week ) until producing four consecutive weeks of cannabis- and other drug-negative urine sample s. Patients were followed up for 1 year . Continued access to uninterrupted methadone delivery was ultimately contingent upon attending scheduled counseling and achieving abstinence from all drug use . The results showed that 18 % of the clinic census ( n = 57 ) tested positive for cannabis . The effectiveness of the intervention was assessed for 15 patients testing positive for cannabis exclusively . Ten of these patients ( 67 % ) discontinued cannabis use prior to the intervention and remained at reduced care . Four of the five patients who were advanced to higher steps of care ultimately discontinued cannabis use ; one left treatment against medical advice . The results suggest that motivated stepped care is an effective intervention for reducing cannabis use This clinical trial evaluated a contingency management intervention design ed to improve medication adherence among HIV-positive methadone maintenance patients . After a 4-week baseline observation phase , eligible participants ( N=66 ) were r and omly assigned to : ( a ) medication coaching sessions every other week to assist with adherence strategies ( comparison group ) or ( b ) medication coaching plus voucher reinforcement for opening electronic medication caps on time ( voucher group ) . Baseline adherence ( percent doses taken/percent total possible doses ) was 51 % using electronic measurement , 75 % using self-report and 75 % using pill count . The intervention was provided for 12 weeks , with a 4-week follow-up . The primary outcome results of the clinical trial indicated effectiveness during the intervention , with significant mean adherence differences between voucher and comparison groups using electronic measurement ( 78 % versus 56 % ) , pill count ( 86 % versus 75 % ) , and self-report ( 87 % versus 69 % ) . Differences between groups faded after vouchers were discontinued . Contingency management shows promise as a strategy to promote antiretroviral medication adherence in this population This study examined the impact of a treatment readiness program on probationers receiving drug abuse treatment in a modified therapeutic community ( TC ) . The program we developed was design ed to increase motivation and improve skills needed for treatment progress . Probationers ( N = 500 ) were assigned r and omly to receive either the treatment readiness training or the st and ard approach used at the facility . Probationers responded to newly developed and established measures of community characteristics . Probationers receiving the readiness training rated their communities as more engaged and helpful than did those receiving the st and ard program . As predicted , probationers who had higher levels of treatment experience prior to entry into the current program ( and who may have thus perceived treatment as having more limitations ) gave more reserved estimates of community engagement . The current study suggests that the readiness training is having its intended impact on probationers . In addition , the study supports the usefulness of a newly developed measure in evaluating treatment effectiveness Co-dependence on opiates and cocaine occurs in about 60 % of patients entering methadone treatment and has a poor prognosis . However , we recently found that desipramine ( DMI ) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients . Furthermore , contingency management ( CM ) has been quite potent in reducing cocaine abuse during methadone maintenance . To test the efficacy of combining CM with these medications we design ed a 12-week , r and omized , double blind , four cell trial evaluating DMI ( 150 mg/day ) or placebo plus CM or a non-contingent voucher control in 160 cocaine abusers maintained on buprenorphine ( median 16 mg daily ) . Cocaine-free and combined opiate and cocaine-free urines increased more rapidly over time in those treated with either DMI or CM , and those receiving both interventions had more drug-free urines ( 50 % ) than the other three treatment groups ( 25 - 29 % ) . Self reported opiate and cocaine use and depressive and opioid withdrawal symptoms showed no differences among the groups and symptom levels did not correlate with urine toxicology results . Lower DMI plasma levels ( average 125 ng/ml ) were associated with greater cocaine-free urines . DMI and CM had independent and additive effects in facilitating cocaine-free urines in buprenorphine maintained patients . The antidepressant appeared to enhance responsiveness to CM reinforcement Employment enhances the outcomes of substance dependency treatment . Unfortunately , although unemployed methadone treatment patients frequently state they are interested in a job , many fail to participate in vocational services when available . Unless patients become engaged , vocational services do not have an opportunity to be effective . This is the first study to explore a broad array of factors that may be associated with differential engagement in vocational services among methadone patients . The study was conducted in two methadone programs in New York City during 2001–2004 . Unemployed methadone patients ( n = 211 ) were voluntarily r and omly assigned to either of two vocational counseling programs ( st and ard vs. experimental ) and followed for 6 months . The sample was 59 % male , 75 % minority group , aged 45 years on average , and in methadone treatment for 5 years on average . Being engaged in the vocational counseling programs was defined as five or more sessions with the counselor in the first 6 months after study entry . In multivariate analysis , the factors associated with higher engagement in vocational counseling were being non-Hispanic , having more education , a drug injection history , a crack use history , having chronic emotional/mental problems , better work attitudes , and assignment to the experimental vocational program . The results indicate that it is often the most “ needy ” unemployed methadone patients who become more engaged in vocational counseling . A vocational counseling model which emphasizes assertive outreach and attends to nonvocational clinical issues as well is more likely to engage patients Although substantial evidence favors the efficacy of contingency management ( CM ) for substance use disorders , few studies have examined the effect of CM on one 's motivation to change substance use . One way of conceptualizing motivation to change is by using the stages of change model [ Prochaska , J.O. , DiClemente , C.C. , 1983 . Stages and processes of self-change of smoking : toward an integrative model of change . J. Consult . Clin . Psychol . 51 , 390 - 395 ] . We assessed motivation to change substance use as conceptualized by the stages of change model using the University of Rhode Isl and Change Assessment ( URICA [ McConnaughy , E.A. , Prochaska , J.O. , Velicer , W.F. , 1983 . Stages of change in psychotherapy : measurement and sample profiles . Psychother . Theor . Res . 20 , 368 - 375 ] ) in 115 patients in community treatment clinics before they were r and omized to receive st and ard treatment or st and ard treatment plus CM . Motivation was also assessed 3 months later . Patients in both conditions evidence d significant decreases in their motivation scores from pre- to post-treatment . CM neither increased nor decreased motivation relative to the st and ard treatment condition . Pre-treatment motivation scores were also not related to treatment outcome . Assignment to the CM condition was associated with better treatment outcome as defined by longest duration of abstinence during treatment ( LDA ) . Higher post-treatment motivation was also modestly associated with LDA , but not in all analyses . These findings suggest that CM neither increases nor decreases motivation to change substance use in out patients receiving treatment at community-based drug-free clinics . Future studies should further examine motivation change in CM treatment using different assessment tools and conceptualizations of motivation , extending these effects to other treatment setting s and population A controlled trial studied whether cue exposure prevented relapse in opiate addiction . Subjects were r and omly allocated to one of two inpatient treatment setting s : a drug dependence unit with a special 10 week program and 4 weeks in a behavioural/general treatment unit without such a program . In each setting , following drug-withdrawal , subjects had either cue exposure for at least six sessions over 3 weeks , or a control condition . Subjects were followed up twice , at about 6 weeks and 6 months post-treatment . 186 subjects were r and omly allocated ; 69 were assessed post-detoxification , and of these 43 completed cue exposure or control treatments . Cue exposure and control subjects did not differ in cue reactivity . This was evaluated post-treatment for cue exposure subjects and at a comparable time point for controls . All groups showed a significant decrement in cue-elicited craving , withdrawal responses and negative mood . Cue exposure and control subjects did not differ at either of the two follow up interviews AIMS During 3 months where contingency management ( CM ) had an escalating value for each consecutive drug-free urine ( escalating CM ) , cocaine- and heroin-abusing patients significantly increased drug-free urines . The ' escalating CM ' was eliminated during months 4 - 6 to assess any reduction in drug-free urines . DESIGN Patients who completed a 3-month , r and omized , double-blind , trial evaluating CM versus non-CM and desipramine ( DMI ) versus placebo , had an ' escalating CM ' eliminated during months 4 - 6 . The CM and non-CM groups were compared using thrice-weekly urine sample s. SETTING Out-patient buprenorphine maintenance for 6 months . PARTICIPANTS All 75 of the 160 original study patients who completed month 3 of the clinical trial . INTERVENTION The ' escalating CM ' was eliminated for all 3 months and during months 5 and 6 the response requirement was also increased to two and then three consecutive drug-free urines in order to obtain a voucher . MEASUREMENTS Urine toxicology for opiates and cocaine . FINDINGS After eliminating the ' escalating CM ' , the CM group showed a decline in combined opioid- and cocaine-free urines . This decline within the CM group was greater in those treated with DMI than placebo . CONCLUSIONS Buprenorphine with DMI maintained drug abstinence after eliminating the ' escalating CM ' , but not after increasing the response requirement , suggesting the need for more intensive psychosocial interventions during CM A controlled trial was conducted evaluating cognitive-behavioural group psychotherapy as a measure to reduce concomitant drug use in methadone maintenance treatment ( MMT ) . 73 opiate addicts were r and omly assigned to local routine MMT or to routine MMT plus group psychotherapy ( 20 sessions over 20 weeks ) . Psychotherapy was delivered by therapists according to a manual . Drug use ( urine screen ) was compared at onset of psychotherapy , end of intervention period ( 6 months after study onset ) , and 6 months later . Data analysis was done according to intention-to-treat principles . Results indicated that patients in the psychotherapy group ( n = 41 ) showed less drug use than control subjects ( n = 32 ) . This group difference was statistically significant at 6-month follow-up ( p = 0.02 ) . These findings underscore the usefulness of group psychotherapy in MMT . The delayed effect is comparable to other studies evaluating cognitive-behavioural psychotherapy This study assesses the relationship between the patient-counselor helping alliance ( HA ) and progress in methadone maintenance treatment . Question naire measures of HA were administered to 57 patients 1 and 3 months after admission . Three-month HA measures ( especially counselors ' ratings ) predicted reductions in drug use as measured by weekly urinalysis results and 6-month self-report data . HA was unrelated to treatment retention or improvement in psychiatric symptomatology . Moreover , controlling for urinalysis results in the previous month rendered insignificant the correlations between 3-month HA and subsequent drug use . Thus , this evaluation of the HA 's unique contribution to the prediction of outcome suggests that the development of a positive HA may be more a marker of treatment progress than a necessary precursor of positive outcomes in the methadone maintenance treatment setting OBJECTIVE To evaluate the cost-effectiveness of using prize-based and voucher-based contingency management ( CM ) as additions to st and ard treatment for cocaine- or heroin-dependent out patients in community treatment centers . METHODS This cost-effectiveness analysis is based on a r and omized clinical trial conducted at three community-based outpatient psychosocial substance abuse treatment clinics . A total of 142 cocaine- or heroin-dependent out patients were r and omly assigned to one of three treatment conditions : st and ard treatment ( ST ) , ST with prizes ( prize CM ) , or ST with vouchers ( voucher CM ) for 12 weeks . The primary patient outcome was the longest duration of confirmed abstinence ( LDA ) from cocaine , opioids and alcohol during treatment . Unit costs were collected from the three participating clinics . Re source utilizations and patient outcomes were obtained from the clinical trial . Incremental cost-effectiveness ratios ( ICERs ) and acceptability curves were used to evaluate the relative cost-effectiveness of the interventions . RESULTS Based on the ICERs and acceptability curves , ST is likely to be the most cost-effective intervention when the threshold value to decision makers of lengthening the LDA during treatment by 1 week is less than approximately $ 166 , and prize CM is likely to be the most cost-effective intervention when the threshold value is greater than approximately $ 166 . CONCLUSIONS Prize CM was found likely to be the most cost-effective intervention over a comparatively wide range of threshold values for lengthening the LDA during treatment by 1 week . However , additional studies with alternative incentive parameters are required to determine the generalizability of our results This study compared the relative efficacy of low-magnitude , contingent monetary vouchers , contingent buprenorphine medication , and st and ard counseling in promoting abstinence from illicit opioids and cocaine among opioid-dependent adults . Following an 8-week baseline period during which participants received buprenorphine maintenance treatment with no contingencies in place , 60 participants were r and omly assigned to one of 3 treatment groups for 12 weeks : ( a ) Participants in the voucher group earned vouchers for each opioid- and cocaine-negative urine sample , in accordance with an escalating schedule . Continuous abstinence result ed in voucher earnings equivalent to a total of 269 US dollars , which participants could exchange for material reinforcers of their choice . ( b ) Participants in the medication contingency group received half their scheduled buprenorphine dose for clinic attendance and the other half for remaining abstinent from opiates and cocaine . Thus , they received only half of their scheduled dose on su bmi ssion of an opioid- and /or cocaine-positive urine sample . ( c ) Participants in st and ard treatment did not receive programmed consequences contingent on urinalysis results . All participants were maintained with buprenorphine according to a 3-times-per-week dosing regimen and participated in behavioral drug counseling . Retention rate did not significantly differ across the groups ; however , participants in the medication contingency group achieved significantly more weeks of continuous abstinence from opiates and cocaine compared with participants in the voucher group ( Ms = 5.95 and 2.90 , respectively ) . Results suggest that the use of medication-based contingencies in combination with behavioral therapy in promoting drug abstinence may have clinical utility . Limitations of the study are discussed Female substance abusers recruited from the community were r and omly assigned to receive 1 of 3 brief interventions that differentially targeted their personality and reasons for drug use . The 90-min interventions were : ( a ) a motivation-matched intervention involving personality-specific motivational and coping skills training , ( b ) a motivational control intervention involving a motivational film and a supportive discussion with a therapist , and ( c ) a motivation-mismatched intervention targeting a theoretically different personality profile . Assessment 6 months later ( N = 198 ) indicated that only the matched intervention proved to be more effective than the motivational control intervention in reducing frequency and severity of problematic alcohol and drug use and preventing use of multiple medical services . These findings indicate promise for a client-treatment matching strategy that focuses on personality-specific motives for substance abuse Two studies were conducted to investigate the effectiveness of contingency management techniques in promoting punctual counseling attendance among methadone maintenance patients . In Study 1 , 50 participants were recruited from an inner‐city methadone maintenance program . Study 1 used an A – B – A design with baseline , intervention , and return‐to‐baseline phases . On‐time attendance was reinforced during the intervention phase with a voucher that was redeemable for a draw out of a box containing 100 tokens with values varying from $ 0.00 to $ 100.00 . Methadone maintenance patients who exhibited poor attendance during baseline showed a significant positive response during the contingency management intervention phase . Study 2 used the same design as Study 1 except that the 52 participants were r and omized into reinforcement groups that received either the variable rate of reinforcement as in Study 1 or a fixed value reinforcer of $ 3.25 . As in Study 1 , Poor Attenders significantly improved counseling attendance during the intervention . There were no differences between the variable and fixed reinforcement groups . Overall , results suggest that targeting Poor Attenders with contingency management techniques may be a cost‐effective method of improving counseling attendance . Targeting Poor Attenders early in treatment may be especially important for improving treatment outcomes INTRODUCTION Retention in a Methadone Maintenance Treatment Program ( MMTP ) is predictive of abstaining from heroin and has other benefits . Many individuals leave treatment before they experience these positive outcomes . OBJECTIVE This research project targeted MMTP drop-outs with an intervention design ed to assist them in returning to drug treatment . METHODS Subjects who had left MMTP within the prior 12 months were r and omly assigned to intervention or comparison groups . The 3-month long intervention consisted of street outreach , cognitive behavioral groups , and individual counseling . Data were analyzed for 175 subjects who were out of treatment at baseline and who returned for a 6-month follow-up interview ( Intervention group , N=111 ; Comparison group , N=64 ) . RESULTS A total of 87 % of subjects assigned to the intervention condition participated in at least one component . Intervention subjects who attended two or more cognitive behavioral group sessions were more likely than those who attended 0 - 1 sessions or those in the comparison group to have returned to treatment during the 6 month follow up time period ( 72 vs. 53 vs. 50 % , respectively , P<0.05 , chi square test ) . CONCLUSION MMTP drop-outs need not be lost to the drug treatment system if special efforts are made to engage them in interventions developed to encourage treatment re-entry OBJECTIVE This study examined the differential effectiveness and costs of three weeks of treatment for patients with moderately severe substance dependence assigned to inpatient treatment or to a supportive housing setting . Supportive housing is temporary housing that allows a patient to participate in an intensive hospital-based treatment program . Type and intensity of treatment were generally equivalent for the two groups . METHODS Patients were consecutive voluntary admissions to the substance abuse treatment program of a large metropolitan Veterans Affairs medical center . Patients with serious medical conditions or highly unstable psychiatric disorders were excluded . Patients in supportive housing attended the inpatient program on weekdays from 7:30 a.m. to 5 p.m. They were assessed at baseline and at two-month follow-up . RESULTS Baseline analyses of clinical , personality , and demographic characteristics revealed no substantive differences between the 62 patients assigned to inpatient treatment and the 36 assigned to supportive housing . The degree of treatment involvement and dropout rates did not differ between groups . Of the 55 in patients completing treatment , 29 were known to be abstinent at follow-up , and of the 35 supportive housing patients completing treatment , 22 were abstinent . The proportion was similar for both groups , about 70 percent . The cost of a successful treatment for the inpatient group was $ 9,524 . For the supportive housing group , it was $ 4,291 . CONCLUSIONS Given the absence of differential treatment effects between inpatient and supportive housing setting s , the use of supportive housing alternatives appears to provide an opportunity for substantial cost savings for VA patients with substance dependence disorders OBJECTIVE Because discharged methadone maintenance patients represent a population at particularly high public health risk , the authors studied such patients 1 year after their discharge from a methadone program . METHOD The locations of 94 of 110 discharged patients were successfully determined 1 year after discharge . Nine ( 10 % ) of these patients had died , 37 ( 39 % ) were already reenrolled in treatment , and 7 ( 7 % ) did not require treatment . The 41 remaining subjects were r and omly assigned to either the enhanced outreach counseling condition ( N = 27 ) or a st and ard referral condition ( N = 14 ) . RESULTS Within 2 weeks following this intervention , 17 ( 63 % ) of the 27 patients in the enhanced outreach counseling program and one ( 7 % ) of the 14 patients not in the program had reenrolled in treatment . CONCLUSIONS These data suggest that enhanced outreach counseling may be an effective outreach strategy as well as a risk-reduction for discharged methadone maintenance patients Opiate addicts beginning a new treatment episode on a methadone maintenance program were offered r and om assignment to drug counseling alone or to counseling plus six months of either supportive-expressive psychotherapy or cognitive-behavioral psychotherapy . Sixty percent of patients meeting the study criteria expressed an interest and 60 % of these actually became engaged . One hundred ten subjects completed the study intake procedure and kept three or more appointments within the first six weeks of the project . Measures including st and ardized psychological tests , independent observer ratings , and continuous records of licit and illicit drug use were done at baseline and seven-month follow-up . All three treatment groups showed significant improvement , but patients receiving the additional psychotherapies showed improvement in more areas and to a greater degree than those who received counseling alone , and with less use of medication . More than a third of opiate addicts in our treatment program thus both were interested in professional psychotherapy and apparently benefitted from it . Certain administrative procedures appear necessary to maximize the chances that psychotherapy can be used effectively with drug-addicted patients OBJECTIVES The effectiveness of case-managed residential care ( CMRC ) in reducing substance abuse , increasing employment , decreasing homelessness , and improving health was examined . METHODS A five-year prospect i ve experiment included 358 homeless addicted male veterans 3 , 6 , and 9 months during their enrollment and at 12 , 18 , and 24 months after the completion of the experimental case-managed residential care program . The customary control condition was a 21-day hospital program with referral to community services . RESULTS The experimental group averaged 3.4 months in transitional residential care with ongoing and follow-up case management for a total of up to 1 year of treatment . The experimental group showed significant improvement compared with the control group on the Medical , Alcohol , Employment , and Housing measures during the 2-year period . An examination of the time trends indicated that these group differences tended to occur during the treatment year , however , and to diminish during the follow-up year . CONCLUSIONS Within groups , significant improvements were observed with time from baseline to all posttests on the four major outcomes . We learned , however , that veterans had access to and used significant amounts of services even without the special case-managed residential care program . This partially may account for improvements in the control group and may have muted the differences between groups The effectiveness of motivational enhancement therapy ( MET ) in comparison with counseling as usual ( CAU ) for increasing retention and reducing substance use was evaluated in a multisite r and omized clinical trial . Participants were 461 out patients treated by 31 therapists within 1 of 5 outpatient substance abuse programs . There were no retention differences between the 2 brief intervention conditions . Although both 3-session interventions result ed in reductions in substance use during the 4-week therapy phase , MET result ed in sustained reductions during the subsequent 12 weeks whereas CAU was associated with significant increases in substance use over this follow-up period . This finding was complicated by program site main effects and higher level interactions . MET result ed in more sustained substance use reductions than CAU among primary alcohol users , but no difference was found for primary drug users . An independent evaluation of session audiotapes indicated that MET and CAU were highly and comparably discriminable across sites One hundred ten nonpsychotic opiate addicts were r and omly assigned to receive paraprofessional drug counseling alone , counseling plus cognitive-behavioral psychotherapy , or counseling plus supportive-expressive psychotherapy . Patients were classified low-severity , mid-severity , or high-severity on the basis of the number and severity of their psychiatric symptoms . Overall , the addition of professional psychotherapy was associated with greater benefits than was drug counseling alone . Low-severity patients made considerable and approximately equal progress with added psychotherapy or with counseling alone . Mid-severity patients had better outcomes with additional psychotherapy than with counseling alone , but counseling did effect numerous significant improvements . High-severity patients made little progress with counseling alone , but with added psychotherapy made considerable progress and used both prescribed and illicit drugs less often Abstract This is a report on the double-blind study on EMG biofeedback for 37 narcotic addicts in an outpatient methadone clinic . Patients were r and omly assigned to either the experimental group ( N = 24 ) receiving a contingent EMG biofeedback or a control group ( N = 13 ) receiving non-contingent preaped “ pseudo-biofeedback ” . All patients were stabilized on a study dose of methadone and the mean daily amount did not differ between groups . All were experiencing a significant degree of anxiety at the time of evaluation . The evaluation consisted of the patient 's self-report , which comprised the Beck Depression Inventory , anxiety checklist , withdrawal sickness rating , drug references , and the psychiatrist 's rating of depression , namely the Hamilton Depression Scale , Hamilton Anxiety Scale , and BPRS . In addition , an evaluation of progress was obtained from the patient and his counselor which included the current job or school status and brief ratings of drug use , psychiatric symptoms , social adjustment , and illegal activity . All patients had at least one urine sample analyzed weekly for illicit drug use . Evaluation was done at the beginning , and at the end of the treatment and at a follow-up one month later . Termination status was assessed only for subjects who completed the course of 15 biofeedback sessions ( N = 19 ) . Patients attended five sessions per week for thirty minutes just prior to receiving the methadone . Fifteen sessions were scheduled over a three-week period . The results indicated that the two study groups did not differ and there was a significant improvement ( Contingency management ( CM ) interventions frequently utilize vouchers as reinforcers , but a prize-based system is also efficacious . This study compared these approaches . Seventy-four cocaine-dependent methadone out patients were r and omly assigned to st and ard treatment ( ST ) , ST plus a maximum of $ 585 in contingent vouchers , or ST plus an expected average maximum of $ 300 in contingent prizes for 12 weeks . CM participants achieved longer duration s of abstinence ( LDA ) than ST participants , and CM conditions did not differ significantly in outcomes or amount of reinforcement earned . Although long-term abstinence did not differ by group , LDA during treatment was the best predictor of abstinence at 9 months . Thus , reinforcement with prizes was similar to voucher CM in promoting LDA , which is associated with posttreatment benefits This 6-month r and omized clinical trial ( with 3-month follow-up ) used a 2x2 design to compare the independent and combined effectiveness of two interventions design ed to improve outcomes in treatment-seeking opioid dependent patients ( n=236 ) : motivated stepped care ( MSC ) and contingent voucher incentives ( CVI ) . MSC is an adaptive treatment strategy that uses principles of negative reinforcement and avoidance to motivate both attendance to varying levels of counseling services and brief periods of abstinence [ Brooner , R.K. , Kidorf , M. , 2002 . Using behavioral reinforcement to improve methadone treatment participation . Sci . Pract . Perspect . 1 , 38 - 46 ; Brooner , R.K. , Kidorf , M.S. , King , V.L. , Peirce , J.M. , Bigelow , G.E. , Kolodner , K. , 2004 . A modified " stepped care " approach to improve attendance behavior in treatment seeking opioid abusers . J. Subst . Abuse Treat . 27 , 223 - 232 ] . In contrast , CVI [ Higgins , S. , Delaney , D.D. , Budney , A.J. , Bickel , W.K. , Hughes , J.R. , Foerg , B.A. , Fenwick , J.W. , 1991 . A behavioral approach to achieving initial cocaine abstinence . Am . Psychiatr . 148 , 1218 - 1224 ] relies on positive reinforcement to motivate drug abstinence . The results showed that the combined approach ( MSC+CVI ) was associated with the highest proportion of drug-negative urine sample s during both the r and omized and 3-month follow-up arms of the evaluation . The CVI-only and the MSC-only conditions evidence d similar proportions of drug-negative urine sample s that were both significantly greater than the st and ard care ( SC ) comparison group . Voucher-based reinforcement was associated with better retention , while adaptive stepped-based care was associated with better adherence to scheduled counseling sessions . These results suggest that both CVI and MSC are more effective than routine care for reducing drug use in opioid dependent out patients , and that the overall benefits of MSC are enhanced further by adding positive reinforcement This study was design ed to assess the effect of client characteristics and community interventions on treatment entry and retention , and to evaluate the relative effectiveness of treatment , compared to other interventions , in reducing drug use and crime among out-of-treatment opiate injectors . Subjects ( N = 2973 ) from 15 cities were r and omly assigned to : st and ard intervention (SI)-HIV testing and counseling ; or enhanced intervention (EI)-SI plus additional educational sessions stressing responsible drug use . EI in some cities included staff assistance with treatment admission ( i.e. " active ' referral ) . All locations provided intervention by community outreach workers . Factors positively associated with treatment entry included : prior treatment , intervention by community workers , assignment to the EI , not injecting cocaine , injecting opiates , and fewer program interventions received . Sites where the EI included active referral achieved significantly higher treatment entry rates than sites where the EI did not . Findings supported the efficacy of treatment over other interventions in reducing drug use and arrests , the addition of staff assistance to facilitate clients ' entry into treatment , and the involvement of community outreach workers in achieving treatment entry Abstract To examine the effectiveness of two visual representation counseling techniques for reducing illicit drug use , participants were r and omly assigned to receive st and ard treatment “ as usual ” or st and ard treatment supplemented with free mapping or free plus guide mapping . Each counselor delivered all types of treatment to participants to control for differences in counselor characteristics ( e.g. , experience , empathy ) . Eighty-two participants who had received one year of methadone maintenance treatment and had urinalysis and self-report data for illicit drug use six months after treatment were examined . Compared to participants receiving st and ard treatment , participants r and omly assigned to the free plus guide mapping condition had significantly lower opiate use based on urinalysis and self-report data . These results support the use of the free plus guide visual representation strategy and provide evidence for the concurrent validity of self-report measures of illicit drug use Abstract After drug use stabilization , employment has long been considered an important goal for clients enrolled in Methadone Maintenance Treatment Programs ( MMTPs ) . The integrated counseling and employment intervention described here is a manualized treatment based on interpersonal cognitive problem solving ( ICPS ) theory . The six-month intervention utilized a problem-solving framework to help methadone clients obtain a job and manage employment within the context of drug treatment . In this pilot study , 23 subjects were r and omly assigned to either integrated ICPS drug and employment counseling ( n = 12 ) or to an ICPS drug counseling control condition ( n = 11 ) . While there were no differences between the integrated and control conditions , both groups showed a significant improvement in employment outcomes and reduction in HIV risk behaviors at the six-month follow-up . Although there may be concerns regarding the generalizability of the findings , overall , the problem solving framework may be an improvement over st and ard methadone counseling . The intervention may be beneficial when implemented with a larger group of motivated ex-offenders who are m and ated to drug treatment as a condition of their parole This study assessed the impact on supplemental heroin use by seven methadone maintenance patients of providing extrinsic reinforcement contingent upon morphine-free urinalysis results . Reinforcement was available for morphine-free urine sample s during r and omly selected weeks . Reinforcement consisted of a choice between $ 15 , two methadone take- home privileges , and two opportunities to self-regulate methadone dosage . The monetary reinforcer was chosen on 95 % of reinforcement occasions . During contingent reinforcement the rate of morphine-positive urinalyses declined significantly below pre- study levels ( Wilcoxon Test , P<0.01 ) . The morphine-positive rate during the r and omly intermixed non-reinforcement weeks also declined , and did not differ significantly from that during reinforcement weeks . The post- study morphine-positive rate increased to a level not significantly different from the pre study level . These data suggest generalization of the reinforcement effect to the non-reinforcement weeks , and indicate the need for further studies to determine the specific impact of the reinforcement procedure . Clinical ly , these data support the utility of contingent reinforcement for drug-free biological sample s as a treatment modality for substance abuse In a 3 x 2 factorial design , 360 new admissions to methadone maintenance were r and omly assigned to one of three levels of counseling : ( 1 ) " medication only , " ( 2 ) " st and ard " counseling , and ( 3 ) " enhanced " services ; and one of two contingency contracting conditions : ( 1 ) no contingencies ( NC ) , and ( 2 ) contingency contracting ( CC ) . Contingency contracting included discharge for continuous positive urines ; subsequently CC subjects were discharged at a greater rate than the NC group . However , CC subjects were more likely to be readmitted . NC subjects provided more urines positive for any illicit drug use than did CC subjects . For opiate positives a significant level of counseling by contingency contracting interaction was found with medication only/CC subjects obtaining fewer opiate positives than medication only/NC subjects . The impact of reduced or enhanced services and of contingency contracting will not be fully understood until longer term follow-up ( 18 and 24 month ) is completed . Results suggest that contingency management procedures could be utilized in setting s offering minimum services ( e.g. , " interim methadone " ) to achieve treatment outcomes similar to programs offering st and ard counseling services BACKGROUND The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care , office-based buprenorphine-naloxone treatment of opioid dependence . METHODS We conducted a 24-week r and omized , controlled clinical trial with 166 patients assigned to one of three treatments : st and ard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing . St and ard medical management was brief , manual-guided , medically focused counseling ; enhanced management was similar , but each session was extended . The primary outcomes were the self-reported frequency of illicit opioid use , the percentage of opioid-negative urine specimens , and the maximum number of consecutive weeks of abstinence from illicit opioids . RESULTS The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens ( st and ard medical management and once-weekly medication dispensing , 44 percent ; st and ard medical management and thrice-weekly medication dispensing , 40 percent ; and enhanced medical management and thrice-weekly medication dispensing , 40 percent ; P=0.82 ) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids . All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use , but there were no significant differences among the treatments . The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving st and ard medical management and once-weekly medication dispensing ( 48 percent ) or thrice-weekly medication dispensing ( 43 percent ) or enhanced medical management and thrice-weekly medication dispensing ( 39 percent ) ( P=0.64 ) . Adherence to buprenorphine-naloxone treatment varied ; increased adherence was associated with improved treatment outcomes . CONCLUSIONS Among patients receiving buprenorphine-naloxone in primary care for opioid dependence , the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing . Strategies to improve buprenorphine-naloxone adherence are needed . ( Clinical Trials.gov number , NCT00023283 [ Clinical Trials.gov ] . ) A clinical trial was used to evaluate short-term interpersonal psychotherapy ( IPT ) as treatment for psychiatric disorders in opiate addicts who were also participating in a full-service methadone hydrochloride maintenance program . Seventy-two opiate addicts were r and omly assigned to one of two treatment conditions for six months : ( 1 ) IPT , consisting of weekly individual psychotherapy , and ( 2 ) low-contact treatment , consisting of one brief meeting per month . Recruitment was a problem , as only 5 % of eligible clients agreed to participate and only around half of the subjects completed the study treatment . The outcome was similar for the two study groups . However , in many of the outcome areas , subjects in both treatment conditions attained significant clinical improvement . Several factors limited the generalizability of findings and may have biased against showing a psychotherapy effect The efficacy of three different residential therapeutic communities for male veterans addicted to heroin was studied , comparing 181 subjects who were r and omly assigned to one of the communities with 166 subjects briefly hospitalized only for the treatment of withdrawal symptoms . At two-year follow-up , subjects from both a professionally staffed community and a peer confrontation community were found significantly more likely than the withdrawal-only group to be working or attending school and less likely to have been convicted of a crime . An eclectic program employing both professionals and paraprofessionals was not found to exceed the withdrawal-only group on any of the major outcome variables . The two relatively successful communities , although different in structure and style , were both perceived by their residents to have greater program clarity , order , staff control , and orientation to personal problems than the unsuccessful program Antisocial personality disorder ( APD ) is associated with increased problem severity in treatment-seeking opioid-dependent patients . Treatment studies have reported mixed results but generally show that patients with APD make progress that is often comparable to drug-dependent patients without the personality disorder . Much of this work is based on secondary analyses of studies evaluating responses to a variety of drug abuse treatment interventions . This study reports on a r and omized prospect i ve trial evaluating a behavioral approach for managing opioid-dependent patients with APD . Subjects ( N = 100 ) met Diagnostic and Statistical Manual of Mental Disorders criteria for opioid dependence and APD using a structured clinical interview and were r and omly assigned to either an experimental condition ( n = 51 ) , which used a highly structured contingency management intervention , or a control condition ( n = 49 ) , which reflected st and ard methadone treatment . Subjects in the experimental group had significantly better counseling attendance and some indication of lower psychosocial impairment compared to the control group . The experimental intervention increased attendance in subjects with low and high levels of psychopathy and with and without other psychiatric comorbidity . These findings support the development of interventions more tailored to drug-dependent patients with APD This study examined the impact of prison-initiated methadone maintenance at 12 months postrelease . Males with pre-incarceration heroin dependence ( N = 204 ) were r and omly assigned to ( a ) Counseling Only : counseling in prison , with passive referral to treatment upon release ; ( b ) Counseling + Transfer : counseling in prison with transfer to methadone maintenance treatment upon release ; and ( c ) Counseling + Methadone : counseling and methadone maintenance in prison , continued in the community upon release . The mean number of days in community-based drug abuse treatment were , respectively , Counseling Only , 23.1 ; Counseling + Transfer , 91.3 ; and Counseling + Methadone , 166.0 ( p < .01 ) ; all pairwise comparisons were statistically significant ( all ps < .01 ) . Counseling + Methadone participants were also significantly less likely than participants in each of the other two groups to be opioid-positive or cocaine-positive according to urine drug testing . These results support the effectiveness of prison-initiated methadone for males in the United States . Further study is required to confirm the findings for women BACKGROUND Although methadone maintenance is an effective therapy for heroin dependence , some patients continue to use heroin and may benefit from therapeutic modifications . This study evaluated a behavioral intervention , a pharmacological intervention , and a combination of both interventions . METHODS Throughout the study all patients received daily methadone hydrochloride maintenance ( initially 50 mg/d orally ) and weekly counseling . Following baseline treatment patients who continued to use heroin were r and omly assigned to 1 of 4 interventions : ( 1 ) contingent vouchers for opiate-negative urine specimens ( n = 29 patients ) ; ( 2 ) methadone hydrochloride dose increase to 70 mg/d ( n = 31 patients ) ; ( 3 ) combined contingent vouchers and methadone dose increase ( n = 32 patients ) ; and ( 4 ) neither intervention ( comparison st and ard ; n = 28 patients ) . Methadone dose increases were double blind . Vouchers had monetary value and were exchangeable for goods and services . Groups not receiving contingent vouchers received matching vouchers independent of urine test results . Primary outcome measure was opiate-negative urine specimens ( thrice weekly urinalysis ) . RESULTS Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention . Contingent vouchers , with or without a methadone dose increase , increased the duration of sustained abstinence as assessed by urine screenings . Methadone dose increase , with or without contingent vouchers , reduced self-reported frequency of use and self-reported craving . CONCLUSIONS In patients enrolled in a methadone-maintainence program who continued to use heroin , abstinence reinforcement and a methadone dose increase were each effective in reducing use . When combined , they did not dramatically enhance each other 's effects on any 1 outcome measure , but they did seem to have complementary benefits This study investigated the effects of marathon group counseling on the attitudes of imprisoned male illicit drug users . Residents selected r and omly into a control and an experimental group responded to a semantic differential which included the following concepts : Kindness , Anger , Guilt , Reality , My Real Self , The Future , Drug Treatment Programs , Counselors , Counseling , and Group Counseling . The scores of the control and marathon group participants were compared on posttests by t-tests . The posttest scores of the marathon group participants were significantly higher than the scores of the control group participants on the following scales : Counselor ( E ) , Group Counseling ( E ) , and Drug Treatment Programs ( P ) The authors studied the efficacy of the community reinforcement approach ( CRA ) as compared to st and ard counseling in opiate-dependent patients on methadone maintenance . One hundred eighty subjects were r and omized to three treatment conditions : st and ard , CRA , and CRA with relapse prevention ( CRA/RP ) . Of these , 151 subjects were followed up 6 months after intake . Since few of the RP sessions had been concluded at the 6-month follow-up , the two CRA groups were combined for analyses . Weekly urinalysis drug screens and Addiction Severity Index ( ASI ) scores at intake and 6 months were compared . The combined CRA groups did significantly better than the st and ard group in the following areas : consecutive opiate-negative urinalysis ( 3 weeks ) , and the 6-month ASI drug composite score . These results support the benefit of adding CRA strategies to the treatment of patients who are opiate dependent and on methadone maintenance . Because of insufficient treatment exposure to RP at the 6-month follow-up , the additive effect of RP could not be adequately evaluated ; further follow-up will be required Forty-seven heroin addicts being treated at the New York VA Methadone Clinic were divided into an experimental and a control group . In addition to the regular methadone treatment program , both groups received subliminal exposures to a verbal message for 24 sessions ( 4 times a week for 6 weeks ) . The messages were MOMMY AND I ARE ONE ( experimental ) and PEOPLE ARE WALKING ( control ) , administered under double-blind conditions . In keeping with the main hypothesis , the experimental subjects , when compared with controls , showed a greater decrease in their use of heroin and other illicit drugs during the postintervention period . Additionally , on a follow-up question naire , the experimental subjects reported being more in control of their drug habits and more effective in their work than did those in the control group . Also , analysis of the patients ' reported dreams revealed that the experimental group had more dreams containing positive interactions with a significant woman or son than did the control group We compared two strategies of prize-based contingency management ( CM ) in methadone-maintained out patients . Urine was tested thrice weekly for 5 weeks pre-CM , 12 weeks CM , and 8 weeks post-CM . Participants were r and omly assigned to a cocaine contingency ( four prize draws for each cocaine-negative urine , N=29 ) or an opiate-cocaine contingency ( one draw for each urine negative for opiates or cocaine , four draws if negative for both , N=38 ) . There were no group differences in cocaine abstinence during CM or post-CM and no differences in opiate abstinence during CM . Opiate abstinence was greater in the opiate-cocaine group post-CM , and heroin craving was reduced in this group during and post-CM . Draws earned per cocaine-negative urine ( four vs. one ) did not affect cocaine use In this study , the authors evaluated a low-cost contingency management ( CM ) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients . Patients were r and omly assigned to 12 weeks of st and ard treatment or st and ard treatment with CM , in which patients earned the opportunity to win prizes ranging from $ 1 to $ 100 for su bmi tting cocainenegative sample s and attending therapy . Patients in the CM condition su bmi tted more cocaine-negative sample s and attended more groups than patients in st and ard treatment . The best predictor of cocaine abstinence at follow-up was duration of abstinence during treatment . On average , patients in the CM condition earned $ 117 in prizes . Data from this study suggest that some aspects of reinforcement can be implemented in group therapy in community-based clinics During the 1980s Motivational Interviewing emerged as one of the memes of the addictions field . This occurred despite the lack of scientific evidence supporting its utility . In this paper findings of a controlled trial of a brief motivational intervention with illicit drug users ( n = 122 ) attending a methadone clinic are reported . Clients who met the study 's inclusion criteria were r and omly allocated to either a motivational ( experimental , n = 57 ) or educational ( control , n = 65 ) procedure . Over the 6-month follow-up period the motivational subjects demonstrated a greater , immediate , commitment to abstention , reported more positive expected outcomes for abstention , reported fewer opiate-related problems , were initially more contemplative of change , complied with the methadone programme longer and relapsed less quickly than the control group . There was , however , no difference in terms of the severity of reported opiate dependence and the control group fared better on reported self-efficacy . It was concluded that motivational interventions of the type investigated are useful adjuncts to methadone programmes R and omized controlled trials were conducted at two residential drug abuse treatment facilities to compare programs that differed in planned duration . One trial compared a 6-month and a 12-month therapeutic community program ( n = 184 ) , and the second compared a 3-month and a 6-month relapse prevention program ( n = 444 ) . Retention rates over comparable time periods differed minimally by planned treatment duration , and the longer programs had lower completion rates . There was no effect in either trial of planned treatment duration on changes in psychosocial variables between admission and exit or on rates or patterns of drug use at follow-up between 2 and 6 months after exit OBJECTIVE The authors tested the efficacy of individual psychotherapy in the rehabilitation counseling of psychiatrically symptomatic opiate-dependent patients during methadone maintenance treatment in community programs . METHOD Volunteers in three community programs were r and omly assigned to 24 weeks of counseling plus supplemental drug counseling or to counseling plus supportive-expressive psychotherapy . Follow-ups were done 1 and 6 months after treatment ended . A total of 84 subjects were evaluated at both follow-up points . RESULTS During the study the patients receiving supportive-expressive psychotherapy and those receiving drug counseling had similar proportions of opiate-positive urine sample s , but the patients receiving supportive-expressive psychotherapy had fewer cocaine-positive urine sample s and required lower doses of methadone . One month after the extra therapy ended both groups had made significant gains , but there were no significant differences between groups . By 6-month follow-up many of the gains made by the drug counseling patients had diminished , whereas most of the gains made by the patients who received supportive-expressive psychotherapy remained or were still evident ; many significant differences emerged , all favoring supportive-expressive psychotherapy . CONCLUSIONS Psychotherapy can be delivered to psychiatrically impaired patients in community methadone programs . Additional counseling is associated with early benefits comparable to those from psychotherapy , but these gains are not sustained . The gains associated with psychotherapy persist and in some cases strengthen for at least 6 months after the end of therapy Clients of a methadone-maintenance clinic in Brooklyn , New York participating in a clinical ly-guided self-help ( CGSH ) program plus st and ard treatment ( methadone maintenance plus individual counseling ) demonstrated statistically significant changes in locus-of-control beliefs , from external to internal causation , about personal responsibility for drug misuse . Members of two control groups -- one participating in a didactic lecture program plus st and ard treatment and the other receiving only st and ard treatment -- failed to demonstrate similar changes . This increase in internal locus of control in the CGSH group suggests the potential efficacy of CGSH as a relapse-prevention therapeutic technique The authors evaluated the efficacy of an interactive , computer-based behavioral therapy intervention , grounded in the community reinforcement approach ( CRA ) plus voucher-based contingency management model of behavior therapy . Our r and omized , controlled trial was conducted at a university-based research clinic . Participants comprised 135 volunteer adult out patients who met DSM-IV criteria for opioid dependence . All participants received maintenance treatment with buprenorphine and were r and omly assigned to one of three treatments : ( a ) therapist-delivered CRA treatment with vouchers , ( b ) computer-assisted CRA treatment with vouchers , or ( c ) st and ard treatment . The therapist-delivered and computer-assisted CRA plus vouchers interventions produced comparable weeks of continuous opioid and cocaine abstinence ( M = 7.98 and 7.78 , respectively ) and significantly greater weeks of abstinence than the st and ard intervention ( M = 4.69 ; p < .05 ) , yet participants in the computer-assisted CRA condition had over 80 % of their intervention delivered by an interactive computer program . The comparable efficacy obtained with computer-assisted and therapist-delivered therapy may enable more widespread dissemination of the evidence -based CRA plus vouchers intervention in a manner that is cost-effective and ensures treatment fidelity This study determined whether long-term abstinence reinforcement could maintain cocaine abstinence throughout a year long period . Patients who injected drugs and used cocaine during methadone treatment ( n = 78 ) were r and omly assigned to 1 of 2 abstinence-reinforcement groups or to a usual care control group . Participants in the 2 abstinence-reinforcement groups could earn take-home methadone doses for providing opiate- and cocaine-free urine sample s ; participants in 1 of those groups also could earn 5,800 US dollars in vouchers for providing cocaine-free urine sample s over 52 weeks . Both abstinence-reinforcement interventions increased cocaine abstinence , but the addition of the voucher intervention result ed in the largest and most sustained abstinence . Therefore , voucher-based reinforcement of cocaine abstinence in methadone patients can be a highly effective maintenance intervention BACKGROUND The potential benefits of anti-retroviral therapy for HIV is not fully realized because of difficulties in adherence with dem and ing treatment regimens , especially among injection drug users . METHODS HIV-positive methadone patients who were less than 80 % adherent with their primary anti-retroviral therapy were r and omized to a trial of incentives for on-time adherence . Adherence was rewarded with an escalating scale of vouchers redeemable for goods . Both intervention and control group visited a medication coach twice a month . The cost of the intervention was determined by micro-costing . Other costs were obtained from administrative data and patient report of out-of-system care . RESULTS During the 12-week intervention period , the incremental direct cost of the intervention , including treatment vouchers , was $ 942 . The voucher group incurred $ 2572 in anti-retroviral drug cost , significantly more than the $ 1973 incurred by the comparison group ( p<.01 ) . Adherence , as measured by on-time openings of an electronically monitored vial , was 78 % in the intervention group and 56 % in the control group . CONCLUSIONS The incremental direct cost of voucher incentives was $ 292 per month . If the observed increase in adherence from voucher incentives can be sustained in the long-term , the literature suggests that disease progression will be slowed . Further research is needed to evaluate if the improvement can be sustained or achieved at lower cost . Mitigation of treatment resistance and reduction in HIV transmission are additional benefits that favor adoption OBJECTIVE To determine whether longer duration s of voucher-based reinforcement therapy ( VBRT ) increase long-term abstinence compared to st and ard duration s. METHODS Cocaine-abusing or dependent methadone-maintenance patients ( N = 130 ) were r and omized to receive either St and ard ( 12-week ; n = 62 ) or Extended ( 36-week ; n = 68 ) VBRT . Participants provided 3 urine sample s weekly during VBRT , and each cocaine-negative sample produced a voucher exchangeable for goods and services . RESULTS Extended VBRT produced longer duration s of self-reported continuous abstinence during study Year 1 ( M = 74 vs. 46 days ; F(1,128 ) = 5.23 , P = 0.024 ) , but not during Year 2 . However , each week of abstinence during Year 1 was associated with an increase of 9.19 days of abstinence during Year 2 , regardless of study condition ( t(1 ) = 4.92 , P < 0.001 ) . CONCLUSIONS Longer- duration VBRT can increase abstinence during VBRT , but may not maintain it afterwards . However , longer during-treatment abstinence begets later abstinence suggesting that further research regarding this relationship is needed To provide information on the long-debated issue of the value of psychotherapy as an addition to paraprofessional counseling services for opiate addicts receiving methadone maintenance , the authors obtained 12-month follow-up data on 93 such patients r and omly assigned to a 6-month course of either paraprofessional drug counseling or counseling plus professional psychotherapy . The psychotherapy patients had a significantly better overall status at 7-month follow-up and also at 12-month follow-up , 6 months after the psychotherapy ended . The authors conclude that psychotherapy can be evaluated by using scientific methods and that it can have measurable and sustained benefits in the treatment of opiate addiction AIMS To evaluate the effectiveness of a motivational intervention to reduce attrition from a waiting list for substance abusers seeking publicly funded treatment . DESIGN R and omized clinical trial comparing an " attrition prevention " condition to st and ard care while awaiting treatment admission . SETTING A central ized substance abuse assessment and referral center in Seattle , Washington . PARTICIPANTS Substance abusers ( n = 654 ) eligible for publicly funded drug abuse treatment . MEASUREMENTS Alcohol and drug use , substance-related negative consequences , areas in need of help , perceived need for help , emotional status , readiness to change , reasons for seeking and perceived barriers to entering treatment . FINDINGS Overall , approximately 70 % of clients entered treatment , and of these approximately 70 % completed their assigned treatment . Those who entered treatment showed significant reductions in substance use and improved psychosocial function at a short-term 3-month follow-up . However , the attrition prevention intervention had no differential effect on treatment entry , completion or outcome compared to the st and ard waiting list . Further , there were no differences across therapists on these outcome measures . CONCLUSIONS A motivational attrition prevention intervention did not enhance treatment entry , completion or outcome among treatment-seeking substance abusers . It is suggested that alternative strategies , such as contingency management and case management , may help facilitate treatment entry for individuals seeking publicly funded treatment Methadone detoxification is often used in the treatment of opiate dependence . This procedure , however , is frequently associated with continued opiate use , and high rates of attrition and relapse . In this study , a 90-day methadone detoxification was enhanced by adding voucher-based reinforcement of opiate abstinence before , during and after the dose tapering schedule . After 4 weeks of st and ard methadone maintenance ( baseline ) , subjects were r and omized to either the abstinence ( n=26 ) , or attendance reinforcement ( n=22 ) condition . During the remaining 22 weeks of the study , the abstinence reinforcement group could receive vouchers with monetary value three times per week for providing opiate-negative urine specimens , while subjects in the attendance reinforcement group received vouchers of equal value for attending the clinic , regardless of urinalysis results . Methadone maintenance continued during weeks 5 - 10 , dose tapering was implemented during weeks 11 - 23 , and during weeks 24 - 26 the voucher schedule remained in effect but no medication was provided . Fifty percent of clients in both groups completed dose tapering , and 40 % completed the vouchers-only phase . Subjects in the abstinence as compared with the attendance reinforcement group had lower rates of opiate use during the maintenance and detoxification phases , and longer periods of opiate abstinence during the detoxification phase . Cocaine use was also lower in the abstinence than the attendance reinforcement group during the maintenance and detoxification phases . In addition , abstinence as compared with attendance reinforcement subjects reported significantly fewer intravenous injections during the detoxification phase . Voucher-based reinforcement procedures could be useful for successfully transitioning patients into opiate antagonist therapy , or drug-free treatments Contingency management ( CM ) interventions usually use vouchers as reinforcers , but a new technique awards chances of winning prizes . This study compares these approaches . In community treatment centers , 142 cocaine- or heroin-dependent out patients were r and omly assigned to st and ard treatment ( ST ) , ST with vouchers , or ST with prizes for 12 weeks . CM patients remained in treatment longer and achieved greater duration s of objective ly confirmed abstinence than did ST patients ; CM conditions did not differ significantly . Although abstinence at 6- and 9-month follow-ups did not differ by group , the best predictor of abstinence was longest duration of abstinence achieved during treatment . Thus , prize and voucher CM systems are equally efficacious in promoting long duration s of abstinence , which in turn are associated with benefits posttreatment Opioid- and cocaine-dependent participants ( N=140 ) were r and omly assigned to one of the following in a 12-week clinical trial : LAAM ( 30 , 30 , 39 mg/MWF ) with contingency management ( CM ) procedures ( LC ) ; LAAM ( 30 , 30 , 39 mg/MWF ) without CM ( LY ) ; LAAM ( 100 , 100 , 130 mg/MWF ) with CM ( HC ) ; LAAM ( 100 , 100 , 130 mg/MWF ) without CM ( HY ) . Urine sample s were collected thrice-weekly . In CM , each urine negative for both opioids and cocaine result ed in a voucher worth a certain monetary value that increased for consecutively drug-free urines . Subjects not assigned to CM received vouchers according to a yoked schedule . Vouchers were exchanged for mutually agreed upon goods and services . Groups generally did not differ on retention and baseline characteristics . Overall opioid use was least in the HC and HY groups ; opioid use decreased most rapidly over time in the HC group relative to the HY , LC and LY groups . Overall cocaine use was least in the HC group relative to the HY , LC , and LY groups ; cocaine use decreased over time most rapidly in the HC and LY groups . Abstinence from both was greatest in the HC group . Opioid withdrawal symptoms decreased most rapidly in the high-dose groups relative to the low-dose groups . These results suggest that an efficacious maintenance dose is necessary for contingencies to be effective in facilitating both opioid and cocaine abstinence This pilot r and omized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment ( BMT ) , provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine . After a 2-week buprenorphine and stabilization period , heroin dependent individuals ( n=24 ) in Muar , Malaysia were r and omly assigned to St and ard Services BMT ( physician administered advice and support , and weekly , non-contingent medication pick-up ) or Enhanced Services ( nurse-delivered manual-guided behavioral drug and HIV risk reduction counseling ( BDRC ) and abstinence-contingent take-home buprenorphine ( ACB ) , 7 day supply maximum ) . Outcomes included retention , proportion of opioid-negative urine tests , self-reported drug use , and self-reported HIV risk behaviors . 12/12 ( 100 % ) of Enhanced Services and 11/12 ( 92 % ) of St and ard Services participants completed the entire protocol . The proportion of opioid-negative urine tests increased significantly over time for both groups ( p<0.001 ) , and the reductions were significantly greater in the Enhanced Services group ( p<0.05 ) ; Enhanced Services group achieved higher overall proportions of opiate negative urine toxicology tests ( 87 % vs. 69 % , p=0.04 ) and longer periods of consecutive abstinence from opiates ( 10.3 weeks vs. 7.8 weeks , p=0.154 ) . Both groups significantly reduced HIV risk behaviors during treatment ( p<0.05 ) , but the difference between Enhanced and St and ard Services ( 26 % vs. 17 % reductions from the baseline levels , respectively ) was not statistically significant ( p=0.9 ) . Manual-guided behavioral drug and HIV risk reduction counseling and abstinence-contingent take-home buprenorphine appear promising for adding to the efficacy of office-based BMT provided with limited drug counseling and medication oversight |
10,887 | 29,953,167 | Effects were generally consistent across the different agents , suggesting class effect .
In people with chronic hyponatraemia , vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3 % increased risk of it being rapid .
To date there is very low certainty evidence for patient-important outcomes ; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm ; there does not appear to be an important effect on cognitive function , but hospital stay may be slightly shorter , although available data are limited . | BACKGROUND Chronic ( present > 48 hours ) non-hypovolaemic hyponatraemia occurs frequently , can be caused by various conditions , and is associated with shorter survival and longer hospital stays .
Many treatments , such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia , but whether that translates into improved patient-important outcomes is less certain .
OBJECTIVES This review aim ed to 1 ) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo , no treatment or head-to-head ; and 2 ) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class , on the dosage used , or the underlying disorder causing the hyponatraemia . | Background : In most cases of hyponatremia , arginine vasopressin secretion is inappropriately high . This placebo-controlled , r and omized , double-blind multicenter study evaluated the efficacy and safety of oral conivaptan , a V1A/V2-receptor antagonist , in patients with euvolemic or hypervolemic hyponatremia . Methods : Eighty-three patients with serum [ Na+ ] less than 130 mEq/L were stratified by volume status and r and omly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days . Results : Conivaptan increased the baseline-adjusted area under the serum [Na+]-time curve significantly more than placebo ( P = 0.0001 ) . Patients given either dose of conivaptan demonstrated a serum [ Na+ ] of 4 mEq/L or greater above baseline significantly faster than those given placebo ( P < 0.001 ) and maintained that increase for a greater total time ( P = 0.0001 ) . The least squares mean change in serum [ Na+ ] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d ( 6.8 and 8.8 mEq/L , respectively ) ( P = 0.0001 ) than that with placebo ( 1.2 mEq/L ) . The percentage of patients who obtained an increase from baseline in serum [ Na+ ] of 6 mEq/L or greater or normal serum [ Na+ ] was significantly higher among patients given conivaptan 40 and 80 mg/d ( 67 % and 88 % , respectively ) than among those given placebo ( 20 % ; P < 0.001 ) . Conivaptan was well tolerated ; the most frequent adverse events were urinary tract infection , anemia , pyrexia , cardiac failure , hypotension , and hypokalemia . Conclusion : Oral conivaptan was effective in increasing serum [ Na+ ] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile Hyponatremia is the most common electrolyte disorder in clinical practice . Its incidence increases with age and it is associated with increased morbidity and mortality . Recently , the vaptans , antagonists of the arginine vasopressin pathway , have shown promise for safe treatment of hyponatremia . Here we evaluated the efficacy , safety , and tolerability of oral lixivaptan , a selective vasopressin V2-receptor antagonist , for treatment of nonhospitalized individuals with euvolemic hyponatremia ( sodium less than 135 mmol/l ) in a multicenter , r and omized , double-blind , placebo-controlled , phase III study . About half of the 206 patients were elderly in a chronic care setting . Of these patients , 52 were given a placebo and 154 were given 25 - 100 mg per day lixivaptan , titrated based on the daily serum sodium measurements . Compared with placebo ( 0.8 mmol/l ) , the serum sodium concentration significantly increased by 3.2 mmol/l from baseline to day 7 ( primary efficacy endpoint ) with lixivaptan treatment . A significantly greater proportion of patients that received lixivaptan achieved normal serum sodium ( 39.4 % ) by day 7 relative to placebo ( 12.2 % ) . Overall , lixivaptan was considered safe and well-tolerated . Thus , oral lixivaptan can be safely initiated in the outpatient setting and effectively increases serum sodium concentrations in out patients with euvolemic hyponatremia Purpose Tolvaptan may reduce the signs of volume overload in heart failure ( HF ) patients who experience volume overload despite using conventional diuretics . In this study , we evaluated the dose-response effects of tolvaptan on weight loss , urine volume and electrolyte excretion in furosemide-treated Japanese HF patients exhibiting volume overload . Methods In the study , 117 HF patients with volume overload on stable doses of furosemide ( ≥40 mg/day ) were treated with tolvaptan ( 15 , 30 or 45 mg ) or placebo once-daily for 7 days . Results The decrease in body weight from baseline to the day after the final dose with 15 , 30 or 45 mg tolvaptan ( –1.62 ± 1.55 , –1.35 ± 1.54 and –1.85 ± 1.10 kg , respectively ) , was significantly greater compared with that in the placebo group ( –0.53 ± 0.96 kg ) ( p < 0.05 ) . However , the decrease in body weight with tolvaptan was not significantly dose-dependent . Signs of volume overload improved at all doses of tolvaptan . Tolvaptan elicited a dose-dependent increase in urine volume and a decrease in urine osmolality , but did not affect urinary sodium or potassium excretion . Adverse reactions associated with diuresis were most frequently observed at the higher doses of tolvaptan . Conclusions Once-daily tolvaptan ( 15 , 30 or 45 mg ) was effective and tolerable as an add-on treatment to furosemide therapy in Japanese HF patients with volume overload OBJECTIVES Hyponatremia ( serum sodium [ Na+ ] concentration < 136 mmol/L ) is a prevalent and potentially life-threatening medical comorbidity for schizophrenic patients . No definitive pharmacological treatments have been established . Tolvaptan ( OPC-41061 ) , an oral non-peptide V2-receptor antagonist , was recently shown to correct hyponatremia in a diverse population of 448 hyponatremic patients . Efficacy in a sub-set of 19 schizophrenic patients with idiopathic hyponatremia included in that sample is specifically examined . METHODS Nineteen subjects were r and omly assigned to receive placebo ( n = 12 ) or tolvaptan ( n = 7 ) once daily for 30 days . Dosage adjustment was based on serum Na+ changes , initially 15 mg , titratable to 30 or 60 mg . The average daily area under the curve ( AUC ) changes in serum Na+ from baseline to Day 4 and Day 30 were co- primary end points . RESULTS Increases in serum Na+ concentrations were significantly greater with tolvaptan than placebo at Day 4 ( p = .0055 ) and at Day 30 ( p < .0001 ) . Two subjects receiving tolvaptan ( 28.6 % ) became dehydrated and experienced hypotension , and five subjects receiving placebo ( 41.7 % ) experienced symptoms associated with dilutional hyponatremia . CONCLUSIONS These results suggest that tolvaptan effectively normalizes idiopathic hyponatremia in schizophrenic patients . Clinicians are advised to carefully monitor fluid status especially at the beginning of treatment to prevent dehydration The rate of hyponatremia is higher in hospitalized cancer patients than in hospitalized patients without cancer and is associated with poor clinical outcomes . The availability of V2 receptor antagonists has been a major breakthrough in the management of hyponatremia , but its efficacy and safety in treating hyponatremia in patients with cancer is not known Hyponatremia is common and is associated with a poor prognosis . Traditional management with fluid restriction is difficult to maintain , and it is often ineffective . The objective of this study was to determine the effect of tolvaptan versus fluid restriction on serum sodium concentration . The study was a prospect i ve , multicenter , r and omized , active-controlled , open-label trial . Twenty-eight hospitalized subjects with serum sodium < 135 mmol/L were enrolled in the study . After a 2-day run-in period , subjects were r and omized 2:1 to tolvaptan alone ( n = 17 ) or fluid restriction ( 1,200 ml/day ) plus placebo ( n = 11 ) . Oral tolvaptan was started at 10 mg/day and increased to 60 mg/day as needed . Treatment was continued for up to 27 days , and follow-up continued for up to 65 days . The primary end point was the normalization of serum sodium , defined as > 135 mmol/L or a > or = 10 % increase from baseline . At the last inpatient visit , serum sodium had increased by 5.7 + /- 3.2 mmol/L in the tolvaptan group and 1.0 + /- 4.7 mmol/L in the fluid restriction group ( p = 0.0065 ) . No differences in adverse events were observed between the groups . In conclusion , tolvaptan appears to be more effective than fluid restriction at correcting hyponatremia in hospitalized subjects , without an increase in adverse events OBJECTIVE Tolvaptan , an oral antagonist of the vasopressin V(2 ) receptor , has been found to improve hyponatremia in patients with mixed etiologies . This study analyzed a subgroup of patients with the syndrome of inappropriate antidiuretic hormone secretion ( SIADH ) to evaluate the efficacy and safety of tolvaptan in this group . DESIGN AND PATIENTS Hyponatremic patients in the SALT-1 and SALT-2 studies with a diagnosis of SIADH were identified based on clinical diagnosis by individual study investigators . Subjects were r and omized to receive oral placebo ( n=52 ) or tolvaptan 15 mg daily , with further titration to 30 and 60 mg daily , if necessary , based on the response of serum [ Na(+ ) ] ( n=58 ) . RESULTS In patients with SIADH , improvement in serum [ Na(+ ) ] was significantly greater ( P<0.0001 ) with tolvaptan than placebo over the first 4 days of therapy as well as the entire 30-day study , with minimal side effects of increased thirst , dry mouth , and urination . Only 5.9 % of tolvaptan-treated patients had overly rapid correction of hyponatremia as defined by current guidelines . After discontinuation of tolvaptan , serum [ Na(+ ) ] declined to values similar to placebo . A significant positive treatment effect favoring tolvaptan on the physical component , and a near-significant trend on the mental component , was found using the SF-12 Health Survey . Tolvaptan was associated with a significantly reduced incidence of fluid restriction . CONCLUSIONS Results for the SIADH subgroup were analogous to those of the combined SALT population regarding efficacy and safety but demonstrated a greater improvement in the physical component of the SF-12 Health Survey than in the full mixed etiology SALT patient group Water retention and dilutional hyponatremia , mainly attributable to an impairment of free water excretion and increased vasopressin activity , are well-documented complications in cirrhotic patients with ascites . VPA-985 is a selective , nonpeptide , orally active , vasopressin-2-receptor antagonist . The aim of this study was to determine the pharmacodynamics , safety , and pharmacokinetics of ascending single doses ( 25 , 50 , 100 , 200 , and 300 mg ) in cirrhotic patients with ascites in a r and omized , double-blind , placebo-controlled trial . Each dose level was studied in 5 patients ( 4 active and 1 placebo ) . After an overnight fast and fluid restriction ( continued for 4 hours after dose administration ) , all patients were given placebo on baseline day and an oral suspension of VPA or placebo on the following day . VPA produced a significant dose-related increase in daily urine output ( 1,454 + /- 858 mL to 4,568 + /- 4,385 mL with VPA 300 mg ) and a dose-related decrease in urine osmolality . The free water clearance reached greater than 3 mL/min for doses 100 mg or greater . Simultaneously , significant increases in serum osmolality , sodium , and vasopressin levels were found . There was a significant increase in sodium urine excretion . VPA was rapidly absorbed and maximum serum concentrations were achieved within 1 hour after administration . Elimination half-life ranged from 9.0 hours after 100 mg to 22.6 hours after 200 mg . In conclusion , VPA induced a dose-related aquaretic response , suggesting a therapeutic potential in managing water retention in patients with liver cirrhosis with ascites PURPOSE The effect of serum sodium concentration and tolvaptan treatment on length of stay ( LOS ) in patients hospitalized with heart failure ( HF ) was evaluated . METHODS Data for this study were derived from a large , international , Phase III trial of patients hospitalized for HF . Two distinct post hoc analyses were performed , analyzing the association between serum sodium concentration and index hospitalization LOS in normonatremic patients and hyponatremic patients treated with placebo plus st and ard of care versus tolvaptan . Analysis of covariance models were constructed to adjust for potential variation in care delivery and adjusted for hyponatremia status or treatment . RESULTS Patients with a baseline serum sodium concentration of < 135 meq/L who received placebo had an adjusted mean LOS that was 3.06 days longer than did normonatremic patients ( p < 0.001 ) . More severely hyponatremic patients had an adjusted mean LOS 5.18 days longer than did normonatremic patients ( p < 0.001 ) . In an analysis of all hyponatremic patients , those receiving tolvaptan had an adjusted mean LOS that was 1.72 days shorter than patients receiving placebo , though this difference was not significant . In more severely hyponatremic patients ( serum sodium concentration of < 130 meq/L ) , patients treated with tolvaptan had an adjusted mean LOS 2.12 days shorter than those receiving placebo , but this difference was not significant . CONCLUSION A secondary analysis of a large , international , Phase III trial of patients hospitalized for HF demonstrated that comorbid hyponatremia was associated with a significant increase in hospital LOS . Treatment of hyponatremia with tolvaptan was associated with reductions in LOS that were not significant CONTEXT Hyponatremia [ serum sodium concentration ( [ Na(+ ) ] ) , < 135 mEq/liter ] is the most common fluid and electrolyte abnormality among hospitalized patients . It is frequently caused by the inappropriate release of arginine vasopressin . OBJECTIVE The objective of this study was to evaluate the efficacy and safety of oral conivaptan , a vasopressin V(1A)/V(2 ) receptor antagonist , in patients with euvolemic or hypervolemic hyponatremia . DESIGN The study design was a 5-d placebo-controlled , r and omized , double-blind study . SETTING The study was performed at a hospital . INTERVENTION Oral conivaptan ( 40 or 80 mg/d ) or placebo was given in two divided doses . PATIENTS Seventy-four patients ( average baseline serum [ Na(+ ) ] , 115 to < 130 mEq/liter ) were studied . MAIN OUTCOME MEASURE The main outcome measure was the change from baseline in serum [ Na(+ ) ] area under the curve . RESULTS The least-squares mean change from baseline in the serum [ Na(+ ) ] area under the curve with conivaptan ( 40 and 80 mg/d ) was 2.0-fold ( P = 0.03 ) and 2.5-fold ( P < 0.001 ) greater , respectively , than that with placebo . The median time to achieve a confirmed increase in serum [ Na(+ ) ] of 4 mEq/liter or more from baseline was 71.7 h for placebo , 27.5 h for 40 mg/d conivaptan ( P = 0.044 ) , and 12.1 h for 80 mg/d conivaptan ( P = 0.002 ) . The mean total times during which patients had a serum [ Na(+ ) ] level of 4 mEq/liter or more above baseline were 46.5 , 69.8 , and 88.8 h ( P = 0.001 ) , respectively . The least-squares mean change in serum [ Na(+ ) ] from baseline to end of treatment was 3.4 mEq/liter for placebo , 6.4 mEq/liter for 40 mg/d conivaptan , and 8.2 mEq/liter for 80 mg/d conivaptan ( P = 0.002 ) . A confirmed normal serum [ Na(+ ) ] ( > /=135 mEq/liter ) or increase of 6 mEq/liter or more was observed in 48 % of patients given placebo , 71 % given 40 mg/d conivaptan , and 82 % given 80 mg/d conivaptan ( P = 0.014 ) . Headache , hypotension , nausea , constipation , and postural hypotension were the most common adverse events . CONCLUSION Oral conivaptan ( 40 and 80 mg/d ) was well tolerated and efficacious in correcting serum [ Na(+ ) ] in hyponatremia BACKGROUND In chronic kidney disease ( CKD ) , loop diuretics correct volume-dependent hypertension , but their effect on left ventricular mass index ( LVMI ) is unknown . METHODS Forty hypertensive CKD patients ( estimated creatinine clearance 60 - 15 mL/min/1.73 m² ) , treated with renin-angiotensin system ( RAS ) inhibitors , were r and omized to receive furosemide or non-diuretic antihypertensive treatment ( control group ) . Office blood pressure ( BP ) < 130/80 mmHg was pursued in both groups . Primary end point was the reduction of LVMI after 52 weeks . Secondary aims were to verify safety related to furosemide treatment and its effects on ambulatory and clinic BP and body fluid volumes . RESULTS Office BP similarly declined in the furosemide group ( from 161 ± 14/80 ± 10 to 139 ± 14/74 ± 8 mmHg ) and in controls ( from 159 ± 16/81 ± 10 to 137 ± 16/75 ± 10 mmHg ) . We detected a greater reduction ( P = 0.013 ) of LVMI in patients receiving furosemide ( -7.9 , IQR from -15.8 to -1.4 g/h(2.7 ) ) than in controls ( 0.0 , IQR from -6.2 to + 9.5 g/h(2.7 ) , P = 0.013 ) . Bio-impedance analysis -derived extracellular water ( ECW ) significantly decreased in furosemide-treated patients ( from 18.7 ± 3.9 to 17.7 ± 3.3 L ) while remained unchanged in the control group ( from 19.5 ± 2.2 to 19.6 ± 1.9 L ) . Absolute change of LVMI correlated with changes of ECW in furosemide-treated patients ( r = 0.458 , P = 0.042 ) but not in controls . In the furosemide group , no patient experienced side effects requiring drug withdrawal . CONCLUSIONS In hypertensive CKD patients treated with RAS inhibitors , add-on furosemide efficaciously reduces LVMI independently from BP changes . The effect is possibly mediated by better control of volume expansion AIMS Arginine vasopressin ( AVP ) V(2 ) receptor antagonism is a new approach to the management of hyponatraemia in congestive heart failure ( CHF ) . The aim of this study was to investigate the efficacy and safety of satavaptan , an oral AVP V(2)-receptor antagonist , in patients with dilutional hyponatraemia . METHODS AND RESULTS A total of 118 patients ( 90 with CHF ) with dilutional hyponatraemia ( serum sodium 115 - 132 mmol/L ) were r and omized to double-blind treatment with placebo or to 25 or 50 mg/day of satavaptan for 4 days , followed by non-comparative open-label satavaptan therapy for up to 343 days . The response rate ( sodium ≥ 135 mmol/L and /or an increase in ≥ 5 mmol/L above baseline ) was significantly higher with satavaptan 50 mg than with placebo ( 61.0 vs. 26.8 % ; P= 0.0035 ) , with a trend towards significance with satavaptan 25 mg ( 48.6 % , P= 0.0599 ) . Median times to response were 3.30 and 2.79 days with satavaptan 25 and 50 mg/day , respectively , both shorter than placebo ( > 4 days ; P= 0.0278 and P= 0.0004 , respectively ) . Satavaptan therapy was effective in CHF patients , with response rates higher with both satavaptan 25 mg/day ( 53.6 % ) and 50 mg/day ( 57.1 % ) than with placebo ( 23.5 % ; P= 0.019 and P= 0.009 , respectively ) . Sodium responses were maintained during open-label therapy after a temporary study drug discontinuation period . Higher rates of adverse events occurred with the 50 mg/day dose , including rapid correction of hyponatraemia . CONCLUSIONS In patients with dilutional hyponatraemia , V(2 ) receptor antagonism with satavaptan was effective in increasing serum sodium concentrations . The long-term open-label treatment results demonstrate sustained efficacy of satavaptan in maintaining normal sodium levels . Trial Registration clinical trials.gov Identifier : NCT00274326 Background —Communicating prognosis to enable shared decision-making is strongly endorsed by heart failure ( HF ) guidelines . Patients are concerned with both their quantity and quality of life ( QoL ) . To facilitate the recognition of patients at high risk for unfavorable future QoL or death , we created a simple prognostic tool to estimate this combined outcome . Methods and Results —We identified factors associated with 6-month mortality or persistently unfavorable QoL , defined by Kansas City Cardiomyopathy Question naire ( KCCQ ) scores < 45 at 1 and 24 weeks after hospital discharge , among 1458 patients from the Efficacy of Vasopressin Antagonism in HF Outcome Study with Tolvaptan ( EVEREST ) . Within 24 weeks of discharge , 478 ( 32.8 % ) patients had died and 192 ( 13.2 % ) patients had serial KCCQ scores < 45 . After adjusting for 23 predischarge covariates , independent predictors of the combined end point included low admission KCCQ score , high B-type natriuretic peptide , hyponatremia , tachycardia , hypotension , absence of & bgr;-blocker therapy , and history of diabetes mellitus and arrhythmia . A simplified predischarge HF score for subsequent death or unfavorable QoL had moderate discrimination ( c-statistic 0.72 ) . Predischarge clinical covariates were substantially different in predicting the QoL end point as compared with traditional death or rehospitalization end points . Conclusions —At the time of hospital discharge , readily available clinical characteristics are associated with HF patients at high risk for persistently unfavorable QoL or death over the next 6 months . Such information can target patients for whom aggressive treatment options ( eg , devices or transplantation ) and /or end-of-life discussion s should be strongly considered before hospital discharge . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00071331 Backgroud Acute decompensated heart failure ( ADHF ) is a common and highly morbid cardiovascular disorder . Diuresis is a major therapy for the reduction of congestive symptoms . However , most diuretics cause hyponatremia , which is a worsening factor of ADHF patients prognosis . The purpose of this study was to examine the efficacy and safety of tolvaptan , which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion , compared with carperitide . Methods and Results One hundred and nine hospitalized ADHF patients were enrolled and r and omly assigned to tolvaptan or carperitide treatment groups . Subjective symptoms and plasma BNP level were similarly improved by treatment in both groups . Urine volume was significantly higher in the tolvaptan group ( P < .05 ) , but volume of water intake was also higher in the tolvaptan group ( P < .05 ) . Blood pressure was significantly lower in the carperitide group than in the tolvaptan group after treatment ( P < .05 ) . Less adverse events such as worsening heart failure and hypotension requiring drug discontinuation were observed in the tolvaptan group ( P = .027 ) . The average drug cost of tolvaptan was lower than that of carperitide ( P < .001 ) . Conclusions Tolvaptan might be a novel promising agent for ADHF in terms of efficacy and safety compared to carperitide Recent studies suggest that mild hyponatremia is associated with fractures , but prospect i ve studies are lacking . We studied whether hyponatremia is associated with fractures , falls , and /or bone mineral density ( BMD ) . A total of 5208 elderly subjects with serum sodium assessed at baseline were included from the prospect i ve population -based Rotterdam Study . The following data were analyzed : BMD , vertebral fractures ( mean follow-up 6.4 years ) , nonvertebral fractures ( 7.4 years ) , recent falls , comorbidity , medication , and mortality . Hyponatremia was detected in 399 subjects ( 7.7 % , 133.4 ± 2.0 mmol/L ) . Subjects with hyponatremia were older ( 73.5 ± 10.3 years versus 70.0 ± 9.0 years , p < .001 ) , had more recent falls ( 23.8 % versus 16.4 % , p < .01 ) , higher type 2 diabetes mellitus prevalence ( 22.2 % versus 10.3 % , p < .001 ) , and more often used diuretics ( 31.1 % versus 15.0 % , p < .001 ) . Hyponatremia was not associated with lower BMD but was associated with increased risk of incident nonvertebral fractures [ hazard ratio ( HR ) = 1.39 , 95 % confidence interval ( CI ) 1.11 - 1.73 , p = .004 ] after adjustment for age , sex , and body mass index . Further adjustments for disability index , use of diuretics , use of psycholeptics , recent falls , and diabetes did not modify results . In the fully adjusted model , subjects with hyponatremia also had increased risk of vertebral fractures at baseline [ odds ratio ( OR ) = 1.78 , 95 % CI 1.04 - 3.06 , p = .037 ] but not at follow-up . Finally , all-cause mortality was higher in subjects with hyponatremia ( HR = 1.21 , 95 % CI 1.03 - 1.43 , p = .022 ) . It is concluded that mild hyponatremia in the elderly is associated with an increased risk of vertebral fractures and incident nonvertebral fractures but not with BMD . Increased fracture risk in hyponatremia also was independent of recent falls , pointing toward a possible effect on bone quality BACKGROUND A rapid and sustained relief of heart failure ( HF ) symptoms and signs is an important goal of management in patients hospitalized for acute HF syndromes ( AHFS ) . To date , no novel therapy in AHFS have been shown to improve signs and symptoms throughout hospitalization . This study explores the clinical effects of tolvaptan , a vasopressin-2-receptor antagonist , in addition to st and ard medical therapies on physician-assessed signs and symptoms in hospitalized AHFS patients . METHODS The EVEREST trial r and omized 4,133 patients admitted with worsening HF and reduced ejection fraction ( ≤ 40 % ) within 48 hours after hospital admission . On each inpatient day , investigators assessed dyspnea , orthopnea , fatigue , jugular venous distension ( JVD ) , rales , and pedal edema by predefined ordinal scales . Responder analyses were performed for each sign and symptom , with significant clinical response defined as a change in one point on the measurement scale . RESULTS Post hoc analysis demonstrated greater likelihood of clinical improvement in physician-assessed dyspnea , edema , orthopnea , and JVD among tolvaptan-treated subjects ( P < .05 ) as early as inpatient day 1 . This difference was observed throughout hospitalization only for JVD and orthopnea through day 3 . CONCLUSION The addition of tolvaptan to st and ard therapy for AHFS improves physician-assessed signs and symptoms during hospitalization without serious adverse short- or long-term effects Purpose Diuretics are recommended to treat volume overload with heart failure ( HF ) , however , they may cause serum electrolyte imbalance , limiting their use . Moreover , patients with advanced HF could poorly respond to these diuretics . In this study , we evaluated the efficacy and safety of Tolvaptan , a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients . Methods A phase III , multicenter , r and omized , double-blind , placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics . One hundred and ten patients were r and omly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days . Results Compared with placebo , tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload . The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects . Conclusion Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis ( aquaresis ) BACKGROUND Hyponatremia ( serum sodium concentration , < 135 mmol per liter ) is a predictor of death among patients with chronic heart failure and cirrhosis . At present , therapy for acute and chronic hyponatremia is often ineffective and poorly tolerated . We investigated whether tolvaptan , an orally active vasopressin V(2)-receptor antagonist that promotes aquaresis -- excretion of electrolyte-free water -- might be of benefit in hyponatremia . METHODS In two multicenter , r and omized , double-blind , placebo-controlled trials , the efficacy of tolvaptan was evaluated in patients with euvolemic or hypervolemic hyponatremia . Patients were r and omly assigned to oral placebo ( 223 patients ) or oral tolvaptan ( 225 ) at a dose of 15 mg daily . The dose of tolvaptan was increased to 30 mg daily and then to 60 mg daily , if necessary , on the basis of serum sodium concentrations . The two primary end points for all patients were the change in the average daily area under the curve for the serum sodium concentration from baseline to day 4 and the change from baseline to day 30 . RESULTS Serum sodium concentrations increased more in the tolvaptan group than in the placebo group during the first 4 days ( P<0.001 ) and after the full 30 days of therapy ( P<0.001 ) . The condition of patients with mild or marked hyponatremia improved ( P<0.001 for all comparisons ) . During the week after discontinuation of tolvaptan on day 30 , hyponatremia recurred . Side effects associated with tolvaptan included increased thirst , dry mouth , and increased urination . A planned analysis that combined the two trials showed significant improvement from baseline to day 30 in the tolvaptan group according to scores on the Mental Component of the Medical Outcomes Study 12-item Short-Form General Health Survey . CONCLUSIONS In patients with euvolemic or hypervolemic hyponatremia , tolvaptan , an oral vasopressin V2-receptor antagonist , was effective in increasing serum sodium concentrations at day 4 and day 30 . ( Clinical Trials.gov numbers , NCT00072683 [ Clinical Trials.gov ] [ SALT-1 ] and NCT00201994 [ Clinical Trials.gov ] [ SALT-2 ] . ) The objective of this prospect i ve study was to examine the effect of fluid restriction on body water and the outcome of children with acute meningitis . Fifty consecutively hospitalized children with acute meningitis , divided into two groups ( A , without hyponatremia ; and B , with hyponatremia ) , were r and omly assigned to receive either normal maintenance ( M ) or restricted ( R subgroup ) ( 65 to 70 % of M subgroup ) fluids during the first 48 hours . Total body water , extracellular water ( ECW ) , serum and urinary sodium and plasma and urinary osmolality were measured at admission and after 48 hours . In both groups children receiving restricted fluids showed a significant decrease in the mean total body water and ECW whereas body water remained unchanged in those on maintenance fluids . Children having an ECW reduction of 10 ml/kg or more in 48 hours had a significantly lower intact survival ( 10 of 28 , 36 % ) than those with < 10 ml/kg or no reduction of ECW ( 15 of 22 , 64 % ) ( P < 0.05 ) . The mortality was also higher in the former ( 7 of 28 , 25 % ) than in the latter ( 2 of 22 , 9 % ) . On multiple stepwise regression analysis , ECW volume at admission ( partial r2 0.20 ) , ECW loss in 48 hours ( partial r2 0.13 ) and plasma osmolality at admission ( partial r2 0.22 ) were significantly related to outcome . We conclude that fluid restriction does not improve the outcome of acute meningitis . Indeed a decrease in ECW volume at 48 hours increases the likelihood of adverse outcome BACKGROUND & AIMS Dilutional hyponatremia is a frequent complication of cirrhosis partly because of nonosmotic vasopressin release . No effective therapy exists for this complication . Therefore , we investigated the effects of VPA-985 , an orally active vasopressin V2 receptor antagonist , in patients with cirrhosis and dilutional hyponatremia . Primary endpoint was normalization of serum sodium ( serum sodium > or=136 mmol/L ) . METHODS Sixty patients with cirrhosis and dilutional hyponatremia were r and omly assigned to 100 or 200 mg/day of VPA-985 or placebo in a double-blind study . Treatment was given with fluid restriction ( 1000 mL/day ) until normalization of serum sodium or for 7 days . RESULTS Normalization of serum sodium concentration was achieved in 27 % and 50 % of patients in the VPA-985 100 mg/day and 200 mg/day groups , respectively , but in none of the patients in the placebo group ( P < 0.05 and P < 0.001 , respectively ) . Treatment with VPA-985 was associated with a significant reduction in urine osmolality and body weight . Thirst sensation increased significantly in the VPA 200 mg group but not in the VPA 100 mg or placebo group . Serious adverse events were similar among the 3 groups . CONCLUSIONS An orally active vasopressin receptor antagonist can correct hyponatremia in patients with cirrhosis and ascites . This represents a novel therapy of water retention in cirrhosis OBJECTIVES To determine more conclusively whether intravenous ( IV ) administration of 3 % saline is more efficacious than oral administration in reversing below normal blood sodium concentrations in runners with biochemical hyponatremia . DESIGN R and omized controlled trial . METHODS 26 hyponatremic race finishers participating in the 161-km Western States Endurance Run were r and omized to receive either an oral ( n=11 ) or IV ( n=15 ) 100mL bolus of 3 % saline . Blood sodium concentration ( Na(+ ) ) , plasma protein ( to assess % plasma volume change ) , arginine vasopressin ( AVP ) , blood urea nitrogen ( BUN ) and urine ( Na(+ ) ) were measured before and 60 min following the 3 % saline intervention . RESULTS No significant differences were noted with respect to pre- to post-intervention blood [ Na(+ ) ] change between intervention groups , although blood [ Na(+ ) ] increased over time in both intervention groups ( + 2 mmol/L ; p<0.0001 ) . Subjects receiving the IV bolus had a greater mean ( ± SD ) plasma volume increase ( + 8.6 ± 4.5 % versus 1.4 % ± 5.7 % ; p<0.01 ) without significant change in [ AVP ] ( -0.2 ± 2.6 versus 0.0 ± 0.5 pg/mL ; p=0.49 ) . 69 % of subjects completing the intervention trial were able to produce urine at race finish with a mean ( ± SD ) pre-intervention urine [ Na(+ ) ] of 15.2 ± 8.5 mmol/L ( range 0 - 35 ; NS between groups ) . [ BUN ] of the entire cohort pre-intervention was 30.7 ± 10.5mg/dL ( range 13 - 50 ) . CONCLUSIONS No group difference was noted in the primary outcome measure of change in blood [ Na(+ ) ] over 60 min of observation following a 100mL bolus of either oral or IV 3 % saline . Administration of an oral hypertonic saline solution can be efficacious in reversing low blood sodium levels in runners with mild EAH BACKGROUND & AIMS Cirrhotic patients with recurrent ascites frequently require paracentesis despite diuretic therapy . Vasopressin receptor antagonists , by increasing free water clearance , may reduce the recurrence of ascites . To investigate the effects of the addition of a vasopressin V(2 ) receptor antagonist , satavaptan , to 100 mg spironolactone on ascites recurrence after a large volume paracentesis in patients with liver cirrhosis irrespective of the presence of hyponatraemia . METHODS One hundred and fifty one cirrhotic patients with recurrent ascites with or without hyponatraemia , and normal to mildly abnormal renal function were r and omised in a double-blind study to receive either 5 mg ( n=39 ) , 12.5 mg ( n=36 ) , 25 mg ( n=40 ) of satavaptan or placebo ( n=36 ) for 12 weeks . Their Child-Pugh scores were 9.2+/-1.3 , 8.7+/-1.7 , 8.8+/-1.3 , and 9.0+/-1.5 , respectively . RESULTS Median time to first paracentesis was 23 , 26 , and 17 days with satavaptan 5 , 12.5 , and 25 mg , respectively , versus 14 days with placebo ( ns for all doses ) . The frequency of paracenteses was decreased significantly ( p<0.05 ) in all satavaptan groups versus placebo . Mean increase in ascites was 2.82+/-0.48 L/week for placebo versus 2.12+/-0.40 , 2.14+/-0.33 , and 2.06+/-0.40 L/week for the 5 , 12.5 , and 25 mg of satavaptan , respectively ( ns for all doses ) . Similar numbers of patients experienced major adverse events in all groups . Increases in serum creatinine , orthostatic changes in systolic pressure and thirst were more common with satavaptan . CONCLUSIONS Satavaptan has the potential to reduce recurrence of ascites after a large volume paracentesis at doses from 5 to 25 mg in cirrhotic patients with ascites To assess the effect of furosemide and captopril on renal function and hyponatremia in patients with severe heart failure , we studied two groups of patients with hyponatremia who were receiving digoxin therapy and whose sodium intake was 40 meq/d . One group received captopril and furosemide , the second received captopril . The first group responded to combination therapy with a brisk natriuresis and diuresis , weight reduction , and an increase in serum sodium concentration . Patients who received captopril alone did not respond , despite a similar increase in renal plasma flow and glomerular filtration rate . When furosemide was then administered to patients who had received captopril alone , a brisk natriuresis , weight loss , and correction of hyponatremia followed . Treatment with furosemide is necessary to promote natriuresis and correction of hyponatremia in patients with severe heart failure treated with captopril ; the renal vascular action of captopril enhances the effectiveness of furosemide OBJECTIVE The study objective was to determine the eventual consequences ( falls , unsteadiness , and cognitive impairment ) of mild chronic hyponatremia , which is generally considered as asymptomatic . METHODS In a case-control study , we focused on the incidence of falls among 122 patients ( mean age 72+/-13 years ) with asymptomatic chronic hyponatremia ( mean serum sodium concentration [ SNa ] 126+/-5 mEq/L ) , who were admitted to the medical emergency department , compared with 244 matched controls . To explore the mechanisms of the excess of falls , we prospect ively asked 16 comparable patients ( mean age 63+/-15 years ; SNa+/-2 mEq/L ) to perform 8 attention tests and a gait test consisting of 3 steps " in t and em , " in which we measured the " total traveled way " by the center of pressure or total traveled way . Thereafter , the patients were treated and tested again ( 50 % of the patients were tested first with normal SNa to avoid learning biases ) . RESULTS Epidemiology of falls : Twenty-six patients ( 21.3 % ) of 122 were admitted for falls , compared with only 5.3 % of the control patients ( adjusted odds ratio : 67 ; 95 % confidence : 7.5 - 607 ; P < .001 ) . The frequency of falls was the same regardless of the level of hyponatremia . Gait : The total traveled way by the center of pressure significantly increased in hyponatremia ( 1336+/-320 mm vs 1047+/-172 mm with normal SNa ; P=.003 ) . Attention tests : The mean response time was 673+/-182 milliseconds in hyponatremia and 615+/-184 milliseconds in patients with normal SNa ( difference : 58 milliseconds , P < .001 ) . The total error number in hyponatremia increased 1.2-fold ( P=.001 ) . These modifications were comparable to those observed after alcohol intake in 10 volunteers . CONCLUSIONS Mild chronic hyponatremia induces a high incidence of falls possibly as the result of marked gait and attention impairments . Treating these patients might prevent a considerable number of hospitalizations BACKGROUND The postdischarge rehospitalization and death rates are high in patients with acute heart failure ( HF ) syndromes despite optimization of st and ard therapy for chronic HF . To the best of our knowledge , there has been no systematic analysis of the causes of death and rehospitalization in this patient population . METHODS This was a prespecified analysis of adjudicated cause-specific all-cause mortality and cardiovascular ( CV ) hospitalization in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan ( EVEREST ) trial , a r and omized , double-blind , placebo-controlled study in patients hospitalized with worsening HF and left ventricular ejection fraction < or = 40 % comparing tolvaptan , an oral vasopressin receptor antagonist to placebo , in addition to st and ard care . RESULTS Of the 4,133 r and omized , there were 5,239 rehospitalizations and 1,080 deaths during a median of 9.9 months . Of all deaths , 41.0 % were due to HF , 26.0 % due to sudden cardiac death ( SCD ) , 2.6 % due to acute myocardial infa rct ion ( MI ) , 2.2 % due to stroke , and 13.2 % due to non-CV causes . Of all hospitalizations , 39.2 % were non-CV , whereas 46.3 % were for HF , and a minority of hospitalizations was due to stroke , MI , arrhythmia , or other CV causes . CONCLUSIONS Despite close follow-up and evidence -based therapy within a clinical trial , rehospitalization and death remain high . Although most deaths were from HF , one quarter of patients had SCD . In addition , there were almost as many non-CV hospitalizations as HF hospitalizations . Knowledge of the causes of death and rehospitalization may be essential for proper management and early initiation of therapy Aims Although congestion is the main reason for admission in patients with worsening acute heart failure syndromes , patients presenting with low SBP and renal impairment often do not respond adequately to and may not tolerate traditional diuretic therapy . We sought to determine the short-term hemodynamic effects of tolvaptan in this high-risk population . Methods In a subset analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial , 759 patients ( 18 % of total ) had elevated blood urea nitrogen ( BUN ) ( > 20 mg/dl ) and low SBP ( < 105 mmHg ) at admission . Of these , 386 were r and omized to tolvaptan and 373 to placebo . Results Demographics and baseline characteristics were similar in both groups . Greater reductions from baseline in body weight were observed for tolvaptan ( 1.63 ± 2.00 vs. 0.76 ± 1.75 kg , P < 0.0001 at day 1 and 3.23 ± 3.36 vs. 2.10 ± 3.47 kg , P < 0.0001 at day 7 or discharge ) . Greater increases in serum sodium concentration were also observed in the tolvaptan group as early as day 1 ( 4.41 ± 3.67 vs. 1.32 ± 3.93 mEq/l , P < 0.0001 ) and persisted through day 7 or discharge ( 4.79 ± 4.89 vs. 1.25 ± 5.00 mEq/l , P < 0.0001 ) . Similarly , improvements in patient-reported dyspnea and investigator-assessed orthopnea were significantly greater in the tolvaptan group as early as day 1 of treatment . These changes were not associated with significant differences in heart rate , SBP , DBP or serum creatinine between patients in the two treatment groups during hospitalization . In-hospital mortality rates ( total and cause-specific ) were comparable to patients who had presented with SBP more than 105 mmHg and BUN less than 20 mg/dl . Conclusion In this subgroup analysis of patients with hypotension and renal impairment , tolvaptan improved symptoms , reduced body weight and increased serum sodium as early as inpatient day 1 without adversely affecting blood pressure or renal function Abstract Background : Two r and omized clinical trials , the Study of Ascending Levels of Tolvaptan in Hyponatremia 1 and 2 ( SALT-1 and SALT-2 ) , showed that tolvaptan was an efficacious and safe therapy for the treatment of hyponatremic patients with the syndrome of inappropriate antidiuretic hormone secretion ( SIADH ) . Hypothesis : This study evaluated the potential cost savings associated with tolvaptan usage based on the SALT-1 and SALT-2 trials . Methods : Hospital length of stay ( LOS ) reduction associated with tolvaptan versus placebo was evaluated among hyponatremic patients with the SIADH ( serum sodium < 135 mEq/L ) from the combined data of the SALT-1 and SALT-2 trials . The Healthcare Cost and Utilization Project 2009 Nationwide Inpatient Sample data base was used to estimate hospital cost and LOS for hospitalizations of adult ( age ≥ 18 years ) patients with the SIADH . A cost-offset model was constructed to evaluate the impact of tolvaptan on hospital cost and LOS , with univariate and multivariate Monte Carlo sensitivity analyses . Results : In the SALT-1 and SALT-2 trials , patients with the SIADH receiving tolvaptan had a shorter hospital LOS than patients receiving placebo ( 4.98 vs 6.19 days , respectively ) . There were 21 718 hospitalizations for the SIADH identified from the Healthcare Cost and Utilization Project Nationwide 2009 Inpatient Sample data base , with a mean LOS of 5.7 days and mean total hospital costs of $ 8667 . Using an inpatient tolvaptan treatment duration of 4 days , with a daily wholesale acquisition cost of $ 250 , the cost-offset model estimated an LOS reduction among SIADH hospitalizations of 1.11 days . The total cost offset , including tolvaptan drug cost , was estimated to be $ 694 per admission . The cost-neutral break-even duration of tolvaptan therapy is 6.78 days . Univariate and multivariate sensitivity analyses demonstrated consistent cost reduction associated with tolvaptan usage . Ten thous and cycles of Monte Carlo simulation showed the 95 % CI for cost offset to be $ 73 to $ 1405 . Conclusion : Based on the SALT-1 and SALT-2 trials , tolvaptan usage is associated with a shorter hospital LOS than placebo among patients with the SIADH . Including the drug cost for 4 days of inpatient tolvaptan therapy , tolvaptan is associated with an estimated mean hospital cost reduction of $ 694 per admission in the United States The effects of satavaptan ( SR121463B ) , a novel long-acting orally active vasopressin V(2)-receptor antagonist , were investigated in patients with the syndrome of inappropriate antidiuretic hormone secretion ( SIADH ) . In the first part of this r and omized , double-blind study , 34 patients first were treated with satavaptan ( versus placebo ) for up to 5 d and then during 23 d of open-label dosage-adjustment period . In the second part of the study , long-term efficacy and safety of satavaptan was assessed in an open-label trial during at least 12 mo . Mean ( + /-SD ) serum sodium ( SNa ) levels before treatment were 127 + /- 2 mmol/L ( placebo , n = 8) , 125 + /- 6 mmol/L ( 25 mg , n = 14 ) , and 127 + /- 5 mmol/L ( 50 mg , n = 12 ) . Responders ( patients SNa levels normalized or increased by at least 5 mmol/L from baseline during the double-blind period ) were 79 % in the 25-mg group ( SNa 136 + /- 3 mmol/L ; P = 0.006 ) , 83 % in the 50-mg group ( SNa 140 + /- 6 mmol/L ; P = 0.005 ) , and 13 % in the placebo group ( SNa 130 + /- 5 mmol/L ) . No drug-related serious adverse events were recorded . During the long-term treatment , 15 of 18 enrolled patients achieved 6 mo and 10 achieved 12 mo of treatment . The SNa response was maintained during this time with a good tolerance . The new oral vasopressin V(2)-receptor antagonist satavaptan adequately corrects mild or moderate hyponatremia in patients with SIADH and has a good safety profile PURPOSE The efficacy and safety of conivaptan administered via 30-minute i.v . infusion to patients with euvolemic or hypervolemic hyponatremia were evaluated . METHODS Hospitalized adults with a baseline serum sodium concentration ( SSC ) of 115 - 130 meq/L and euvolemia or hypervolemia on clinical evaluation were r and omized to receive conivaptan hydrochloride 20 mg once or twice daily or placebo via 30-minute i.v . infusion . The primary efficacy measure was the change in SSC from baseline to 48 hours . RESULTS A total of 49 patients received one of the three treatment regimens . Conivaptan once and twice daily produced significant least-squares mean changes from baseline in SSC at 48 hours of 3.46 meq/L ( 95 % confidence interval [ CI ] , 1.75 - 5.18 meq/L ) and 6.22 meq/L ( 95 % CI , 4.34 - 8.10 meq/L ) , respectively ( p = 0.028 between conivaptan-treated groups ) . These changes were significantly greater compared with those in the placebo group at hour 4 ( p = 0.049 ) and at all time points onward of hour 28 ( p ≤ 0.019 ) for the once-daily regimen and at all time points for the twice-daily regimen ( p = 0.045 at hour 4 , then p ≤ 0.010 ) . Both conivaptan regimens were more efficacious than placebo in all secondary efficacy outcomes . Conivaptan was generally well tolerated , with infusion-site reactions being the most common adverse effects ( AEs ) . CONCLUSION Conivaptan hydrochloride 20 mg , administered once or twice daily via 30-minute i.v . infusion , significantly increased SSCs over 48 hours in patients with euvolemic or hypervolemic hyponatremia when compared with placebo . Common AEs were similar to those seen with continuous conivaptan infusions In order to clarify debated issues of the medical treatment of ascites in cirrhosis -- the usefulness of a low sodium diet and washout period preceding diuretic administration , maximal dosage of antimineralocorticoid to be reached before the addition of a loop diuretic , identification s of factors influencing treatment efficacy--115 hospitalized patients with non-azotemic cirrhosis and ascites were recruited and r and omized to receive a diet providing either 40 or 120 mmol of sodium daily . After a washout period from the outpatient diuretic regimen for 7 days ( Step 1 ) , increasing dosages of K-canrenoate ( 200 mg/day every 4th day up to 600 mg ) were administered to patients not undergoing spontaneous diuresis ( Step 2 ) . Upon the failure of Step 2 , K-canrenoate ( 400 mg/day ) and furosemide at increasing dosage ( 25 - 50 - 100 mg every other day ) were given ( Step 3 ) . Nine percent of patients underwent spontaneous diuresis , and 77 % developed a negative sodium balance by the end of Step 2 ( 69 % with a dosage of K-canrenoate < or = 400 mg/day ) and 93 % by the end of Step 3 . Two patients were withdrawn from the protocol due to diuretic side-effects . Univariate analysis showed that the type of diet did not influence the response to treatment . The washout period led to a significant increase in endogenous creatinine clearance ; natremia significantly rose in hyponatremic patients . Multivariate analysis showed that creatinine clearance and plasma aldosterone were independent predictive factors of the response to treatment . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Currently , fluid restriction recommendations in heart failure ( HF ) are based on expert opinion . After implementing a 1,000-mL/d fluid restriction for 60 days after discharge , outcomes were examined . METHODS AND RESULTS In a r and omized controlled design , hyponatremic patients ( serum sodium ≤137 mg/dL ) received usual care ( UC ; n = 26 ) or 1,000 mL/d fluid restriction ( n = 20 ) at discharge . Quality of life ( QoL ) , thirst , difficulty following fluid recommendations , adherence to fluid restriction , HF emergency care , HF rehospitalization , and all-cause death were examined . Mean age was 62.8 ± 12.8 years ; 46 % were white . There were no differences by group in baseline demographics , comorbidities , and QoL , except that more UC patients had New York Heart Association ( NYHA ) functional class III/IV status ( P = .019 ) . Median [ interquartile range ] QoL scores were better in the 1,000 mL/d group for symptom burden ( 83.3 [ 68.8 - 91.7 ] vs 50 [ 29.2 - 79.2 ] ; P = .018 ) , total symptoms ( 77.1 [ 58.1 - 91.7 ] vs 54.2 [ 30.2 - 73.9 ] ; P = .022 ) , overall QoL summary ( 72.6 [ 52.2 - 86.3 ] vs 51.0 [ 37.7 - 68.5 ] ; P = .038 ) , and clinical QoL summary ( 75.5 [ 57.8 - 92.9 ] vs 59.1 [ 35.7 - 77.3 ] ; P = .039 ) . There were no group differences in thirst , difficulty adhering to fluid recommendations , adherence to fluid restriction , or health care consumption . CONCLUSIONS The 1,000 mL/d fluid restriction led to improved QoL at 60 days after discharge . Future research in a larger more heterogeneous sample is needed CONTEXT Vasopressin mediates fluid retention in heart failure . Tolvaptan , a vasopressin V2 receptor blocker , shows promise for management of heart failure . OBJECTIVE To investigate the effects of tolvaptan initiated in patients hospitalized with heart failure . DESIGN , SETTING , AND PARTICIPANTS The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan ( EVEREST ) , an event-driven , r and omized , double-blind , placebo-controlled study . The outcome trial comprised 4133 patients within 2 short-term clinical status studies , who were hospitalized with heart failure , r and omized at 359 North American , South American , and European sites between October 7 , 2003 , and February 3 , 2006 , and followed up during long-term treatment . INTERVENTION Within 48 hours of admission , patients were r and omly assigned to receive oral tolvaptan , 30 mg once per day ( n = 2072 ) , or placebo ( n = 2061 ) for a minimum of 60 days , in addition to st and ard therapy . MAIN OUTCOME MEASURES Dual primary end points were all-cause mortality ( superiority and noninferiority ) and cardiovascular death or hospitalization for heart failure ( superiority only ) . Secondary end points included changes in dyspnea , body weight , and edema . RESULTS During a median follow-up of 9.9 months , 537 patients ( 25.9 % ) in the tolvaptan group and 543 ( 26.3 % ) in the placebo group died ( hazard ratio , 0.98 ; 95 % confidence interval [ CI ] , 0.87 - 1.11 ; P = .68 ) . The upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 ( P<.001 ) . The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients ( 42.0 % ) and 829 placebo group patients ( 40.2 % ; hazard ratio , 1.04 ; 95 % CI , 0.95 - 1.14 ; P = .55 ) . Secondary end points of cardiovascular mortality , cardiovascular death or hospitalization , and worsening heart failure were also not different . Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea , day 1 body weight , and day 7 edema . In patients with hyponatremia , serum sodium levels significantly increased . The Kansas City Cardiomyopathy Question naire overall summary score was not improved at outpatient week 1 , but body weight and serum sodium effects persisted long after discharge . Tolvaptan caused increased thirst and dry mouth , but frequencies of major adverse events were similar in the 2 groups . CONCLUSION Tolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure-related morbidity . TRIAL REGISTRATION clinical trials.gov Identifier : Vasopressin antagonists increase the serum sodium concentration in patients who have euvolemia and hypervolemia with hyponatremia in the short term ( < /=30 days ) , but their safety and efficacy with longer term administration is unknown . SALTWATER was a multicenter , open-label extension of the Study of Ascending Levels of Tolvaptan in Hyponatremia ( SALT-1 and SALT-2 ) . In total , 111 patients with hyponatremia received oral tolvaptan for a mean follow-up of 701 days , providing 77,369 patient-days of exposure . All patients had hyponatremia at r and omization in SALT-1 and SALT-2 , and 85 % continued to have hyponatremia at entry in SALTWATER . The most common adverse effects attributed to tolvaptan were pollakiuria , thirst , fatigue , dry mouth , polydipsia , and polyuria . Six drug-related adverse effects led to study discontinuation . The increase in serum sodium exceeded the desired 1 mmol/L per h at initiation in five patients . Hypernatremia ( > 145 mmol/L ) led to discontinuation in one patient . Mean serum sodium increased from 130.8 mmol/L at baseline to > 135 mmol/L throughout the observation period ( P < 0.001 versus baseline at most points ) . Responses were comparable between patients with euvolemia and those with heart failure but more modest in patients with cirrhosis . In conclusion , prolonged administration of tolvaptan maintains an increased serum sodium with an acceptable margin of safety Hyponatremia is a common electrolyte disorder in patients with heart failure ( HF ) associated with cognitive dysfunction and increased mortality and rehospitalization rates . Loop diuretics worsen renal function , produce neurohormonal activation , and induce electrolyte imbalances . Lixivaptan is a selective , oral vasopressin V2‐receptor antagonist that improves hyponatremia by promoting electrolyte‐free aquaresis without significant side effects . The Treatment of Hyponatremia Based on Lixivaptan in NYHA Class III/IV Cardiac Patient Evaluation ( BALANCE ) study is a r and omized , double‐blind , placebo‐controlled , phase 3 trial design ed to evaluate the effects of lixivaptan on serum sodium in patients hospitalized with worsening heart failure ( target N= 650 ) , signs of congestion and serum sodium concentrations < 135 mEq/L. Other endpoints include assessment of dyspnea , body weight , cognitive function , and days of hospital‐free survival . Patients are r and omized 1:1 to lixivaptan or matching placebo for 60 days , with a 30‐day safety follow‐up . Doses of lixivaptan or placebo are adjusted based on serum sodium and volume status . Lixivaptan was shown to increase serum sodium and reduce body weight , without renal dysfunction or hypokalemia . BALANCE seeks to address unmet questions regarding the use of vasopressin antagonists including their effects on cognitive function and clinical outcomes in patients with hyponatremia and worsening heart failure . Clin Trans Sci 2010 ; Volume 3 : 249–253 Background Conivaptan is an arginine-vasopressin-receptor antagonist approved for the treatment of hyponatremia . We hypothesized that administration of conivaptan to normonatremic patients with traumatic brain injury ( TBI ) is safe and could reduce intracranial pressure ( ICP ) . Methods Open-label , r and omized , controlled trial enrolling 10 subjects within 24 h of severe TBI to receive a single 20 mg dose of conivaptan ( n = 5 ) or usual care ( n = 5 ) . The primary endpoint was the evaluation of the safety profile defined by serum sodium increases averaging > 1 mEq/h when measured every 4 h and any adverse events . Secondary endpoints were 48-h serum sodium , sodium load , change in ICP , and urine output . Results Ten patients were included in the intention-to-treat analysis . Three patients ( 2 conivaptan , 1 usual care group ) experienced brief sodium increases averaging > 1 mEq/h , with no patients achieving Na > 160 mEq/l . There were no drug-related serious adverse events . At 48 h , the mean sodium was 142 ± 6 mEq/l ( conivaptan ) and 144 ± 10 mEq/l ( usual care , P = 0.71 ) . 48-h sodium load was 819 ± 724 mEq in the conivaptan and 1,137 ± 1,165 mEq in the usual care group ( P = 0.62 ) . At 4 h , serum sodium was higher ( P = 0.02 ) and ICP was lower ( P = 0.046 ) in the conivaptan compared with usual care group . 24-h but not 48-h urine output was different between the two groups ( P < 0.01 and P = 0.20 , respectively ) . Conclusions These data suggest that a single dose conivaptan is safe in non-hyponatremic patients with severe TBI and may reduce ICP . Further studies are needed to establish the effect of conivaptan on clinical ly relevant endpoints , and its role in the management of intracranial hypertension Objective Clonidine is an α2-adrenoceptor agonist which , by coupling with G-protein , has been proposed as an alternative treatment for refractory ascites of patients with cirrhosis for several years . Genetic polymorphisms of β-adrenoceptor and angiotensin II type 1 receptor blockers have been reported to affect drug response in patients with cirrhosis . This study evaluated the clonidine – diuretic response rate , favourable predictors and genetic components of the clonidine – diuretic response in patients with cirrhosis with refractory ascites . Methods 270 patients with cirrhosis with refractory ascites were r and omised equally into two treatment groups to receive diuretics alone or the clonidine – diuretics association . The primary end point was clonidine – diuretic response rate . Secondary end points were mean daily dose of diuretics , times of paracentesis , ascites-related readmission and 1-year survival rate . Results Good clonidine responders had better natriuresis and diuresis as well as a significant decrease in abdominal circumference , plasma renin , aldosterone and norepinephrine levels . The overall clonidine – diuretics response rate was 55–60 % . In patients with cirrhosis , the prevalence of ARDA2C WD/DD and GNB3 CT/TT genotypes was 71 % and 77 % , respectively . Among the responders , 71 % of patients with cirrhosis had the ARDA2C WD/DD genotype and 67 % has the GNB3 CT/TT genotype . Besides higher baseline norepinephrine levels , the presence of both ARDA2C WD/DD and GNB3 CT/TT genotypes showed a positive predictive value of 82 % and a negative predictive value of 79 % for good clonidine response . Conclusions These results suggest that neurohormonal and genetic testing may be used as predictive factors for the additive effects of clonidine on the diuresis and natriuresis effects of diuretics in patients with cirrhosis with refractory ascites Hyponatremia in advanced cirrhosis and ascites or congestive heart failure ( CHF ) is the result of an inappropriate increase in vasopressin secretion , which acts through activation of specific V(2 ) receptors in the distal renal nephron to increase water reabsorption . This study investigates the efficacy and safety of 3 different doses of the V(2 ) receptor antagonist , VPA-985 , in correcting hyponatremia over a 7-day inpatient study period . Forty-four hospitalized patients ( 33 patients with cirrhosis , 6 with CHF , and 5 with syndrome of inappropriate antidiuretic hormone ( SIADH ) were studied on a constant sodium intake , with VPA doses of 25 , 125 , and 250 mg twice daily or placebo . Serum sodium measurements were repeated after every daily dose , and the next dose withheld for excessive serum sodium rises . Fluid intake was adjusted according to previous 24-hour urinary outputs . Adverse events were based on clinical signs of dehydration or encephalopathy . VPA-985 produced a significant overall aquaretic response compared with placebo , with significant dose related increases in free water clearance ( P < .05 ) and serum sodium ( P < .05 ) , without significant changes in orthostatic blood pressure or serum creatinine levels . Five patients ( 50 % ) on 250 mg twice daily had to have medication withheld on multiple occasions . End-of- study plasma vasopressin levels increased significantly in the 2 larger dose groups . In conclusion , VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water h and ling and hyponatremia in conditions associated with water retention . Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use Objective Satavaptan , a vasopressin V2 receptor antagonist , has been shown to improve the control of ascites in cirrhosis in short-term phase II studies . The aim of this study was to evaluate the efficacy and safety of satavaptan in three different population s of patients with cirrhosis and ascites . Methods 1200 patients were included in three r and omised double-blind studies comparing satavaptan with placebo in uncomplicated ascites ( study 1 : n=463 patients ) and difficult-to-treat ascites , with and without concomitant diuretic treatment ( studies 2 and 3 : n=497 and n=240 patients , respectively ) . Results Satavaptan was not more effective than placebo in the control of ascites in any of the population s studied as estimated by the primary efficacy endpoints : worsening of ascites ( study 1 ) and the cumulative number of large-volume paracenteses during 12 weeks ( studies 2 and 3 ) . Nevertheless , some of the secondary efficacy endpoints related to the treatment of ascites were met in the three studies , suggesting a slight advantage of satavaptan over placebo in delaying ascites formation . Moreover , satavaptan was more effective than placebo in improving the serum sodium concentration in patients with hyponatraemia . The incidence of major complications of cirrhosis during follow-up did not differ significantly between the satavaptan and placebo groups in the three studies . Overall , the rate of any treatment-related adverse events , serious treatment-related events and treatment-related events leading to permanent discontinuation of treatment did not differ significantly between the treatment groups . However , in study 2 mortality was higher in patients treated with satavaptan compared with placebo ( HR 1.47 ; 95 % CI 1.01 to 2.15 ) ; no significant differences in mortality between the two groups were observed in the other two studies . No specific cause for the increased mortality was identified . Most deaths were associated with known complications of liver cirrhosis . Conclusion Satavaptan , alone or in combination with diuretics , is not clinical ly beneficial in the long-term management of ascites in cirrhosis Background —In this study , we evaluated the effects of tolvaptan ( OPC-41061 ) , a novel , oral , nonpeptide vasopressin V2-receptor antagonist in patients with chronic heart failure ( CHF ) . Methods and Results —This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF . After a run-in period , 254 patients were r and omly assigned to placebo ( n=63 ) or tolvaptan [ 30 mg ( n=64 ) , 45 mg ( n=64 ) , or 60 mg ( n=63 ) ] once daily for 25 days . Patients were not fluid-restricted and were maintained on stable doses of furosemide . At day 1 , when compared with baseline , a decrease in body weight of −0.79±0.99 , −0.96±0.93 , and −0.84±0.02 kg was observed in the 30- , 45- , and 60-mg tolvaptan groups , respectively , and a body weight increase of + 0.32±0.46 kg in the placebo group ( P < 0.001 for all treatment groups versus placebo ) . Although the initial decrease in body weight was maintained during the study , no further reduction was observed beyond the first day . An increase in urine volume was observed with tolvaptan when compared with placebo ( 3.9±0.6 , 4.2±0.9 , 4.6±0.4 , and 2.3±0.2 L/24 hours at day 1 for 30- , 45- , and 60-mg tolvaptan groups , and placebo , respectively;P < 0.001 ) . A decrease in edema and a normalization of serum sodium in patients with hyponatremia were observed in the tolvaptan group but not in the placebo group . No significant changes in heart rate , blood pressure , serum potassium , or renal function were observed . Conclusions —In patients with CHF , tolvaptan was well tolerated ; it reduced body weight and edema and normalized serum sodium in the hyponatremic patients Background and Aims : Conivaptan , a vasopressin receptor antagonist , is commonly used for the treatment of euvolaemic , hypervolaemic hyponatraemia . Usually , an intravenous ( IV ) bolus followed by infusion is administered for many days . We decided to assess the effectiveness of single dose conivaptan for correction of hyponatraemia in post-operative patients . Methods : This was a prospect i ve , r and omised trial conducted in 40 symptomatic post-operative Intensive Care Unit ( ICU ) patients with a serum sodium level of ≤130 mEq/L. Group A patients received IV conivaptan 20 mg over 30 min , whereas in group B infusion of 3 % hypertonic saline was started as an infusion at the rate of 20 - 30 ml/h . Serum sodium levels were measured at 12 , 24 , 48 and 72 h and the daily fluid balance was measured for 3 days . The Chi-square test , Wilcoxon signed rank test and Mann-Whitney tests were used as applicable . Results : The serum sodium levels before initiating treatment were comparable between groups . However , subsequent sodium levels at 12 , 24 and 48 h showed significantly high values in group A. Though at 72 h the mean sodium value was high in group A , it was not statistically significant . Group A showed a significantly high fluid loss on day 1 , 2 and 3 . The mean volume of hypertonic saline required in group B showed a steady decline from day 1 to 3 and only 13 patients required hypertonic saline on the 3 rd day . Conclusion : Single dose conivaptan is effective in increasing serum sodium levels in post-operative ICU patients up to 72 h associated with a significant negative fluid balance PURPOSE The effect of loading dose and formulation on the safety and efficacy of conivaptan in the treatment of euvolemic and hypervolemic hyponatremia was studied . METHODS This parallel-group study r and omized 121 hospitalized patients with euvolemic or hypervolemic hyponatremia to one of four treatment regimens : placebo loading dose followed by conivaptan continuous i.v . infusion using the ampul formulation ( regimen 1 ) , conivaptan loading dose followed by continuous i.v . infusion using the ampul formulation ( regimen 2 ) , placebo loading dose followed by conivaptan continuous i.v . infusion using the premixed formulation ( regimen 3 ) , or conivaptan loading dose followed by continuous i.v . infusion using the premixed formulation ( regimen 4 ) . The primary variable was the incidence and severity of injection-site reactions ( ISRs ) , as evaluated using the ISR modified 5-point scale ( ISRMS ) . Secondary outcomes included effects on serum sodium concentration ( SSC ) , duration of effect , and safety and tolerability . RESULTS All four dosing regimens were efficacious , safe , and well tolerated . No significant differences in ISRMS scores or differences in changes from baseline SSC or in the duration of effects on SSC were observed between the regimens . Overly rapid SSC increases occurred in 7 % , 7 % , 3 % , and 21 % of patients treated with regimens 1 , 2 , 3 , and 4 , respectively . Overall , adverse events related to general disorders and ISRs occurred in 39 % , 43 % , 53 % , and 55 % of patients receiving regimens 1 , 2 , 3 , and 4 , respectively . CONCLUSION Intravenous conivaptan regimens with or without a loading dose , whether using the ampul or a premixed formulation , had similar safety , tolerability , and efficacy in patients with euvolemic or hypervolemic hyponatremia . The pre-mixed formulation used with a loading dose may be associated with an increased frequency of overly rapid increase in SSC compared with the other regimens studied BACKGROUND & AIMS Tolvaptan is a vasopressin V2-receptor antagonist that improves serum sodium concentration by increasing renal solute-free water excretion . Specific data on the safety and efficacy of tolvaptan in patients with cirrhosis and hyponatremia has not been exclusively evaluated . METHODS This sub- analysis of the Study of Ascending Levels of Tolvaptan trials examined cirrhotic patients with hyponatremia who received 15 mg oral tolvaptan ( n=63 ; increased to 30 or 60 mg if needed ) or placebo ( n=57 ) once-daily for 30 days . At baseline , 44 % had mild hyponatremia ( serum sodium 130 - 134 mmol/L ) , 56 % had marked hyponatremia ( serum sodium < 130 mmol/L ) , 85 % had cirrhosis due to alcohol and /or hepatitis B/C , and 80 % were Child-Pugh class B/C. RESULTS Tolvaptan was effective in raising serum sodium . Average daily area under the curve for serum sodium was significantly greater in the tolvaptan group from baseline to day 4 ( p<0.0001 ) and day 30 ( p<0.0001 ) . This superiority was maintained after stratification by baseline hyponatremia ( mild and marked ) , estimated glomerular filtration rate ( ≤ 60 ml/min and > 60 ml/min ) , or serum creatinine levels ( < 1.5mg/dl and ≥ 1.5mg/dl ) . Hyponatremia recurred 7 days after discontinuation of tolvaptan . Mean mental component summary scores of the SF-12 health survey improved from baseline to day 30 in the tolvaptan group but not the placebo group ( 4.68 vs. 0.08 , p=0.02 ) . Major side effects due to tolvaptan were dry mouth and thirst . Gastrointestinal bleeding occurred in 10 % and 2 % of patients in the tolvaptan and placebo group , respectively ( p=0.11 ) . Adverse event rates , withdrawals , and deaths were similar in both groups . CONCLUSIONS One month of tolvaptan therapy improved serum sodium levels and patient-reported health status in cirrhotic patients with hyponatremia . Hyponatremia recurred in tolvaptan-treated patients after discontinuation OBJECTIVE To conduct a long-term , prospect i ve , r and omized controlled trial evaluating rituximab ( RTX ) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis ( CV ) . METHODS Fifty-nine patients with CV and related skin ulcers , active glomerulonephritis , or refractory peripheral neuropathy were enrolled . In CV patients who also had hepatitis C virus ( HCV ) infection , treatment of the HCV infection with antiviral agents had previously failed or was not indicated . Patients were r and omized to the non-RTX group ( to receive conventional treatment , consisting of 1 of the following 3 : glucocorticoids ; azathioprine or cyclophosphamide ; or plasmapheresis ) or the RTX group ( to receive 2 infusions of 1 gm each , with a lowering of the glucocorticoid dosage when possible , and with a second course of RTX at relapse ) . Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group . Study duration was 24 months . RESULTS Survival of treatment at 12 months ( i.e. , the proportion of patients who continued taking their initial therapy ) , the primary end point , was statistically higher in the RTX group ( 64.3 % versus 3.5 % [ P < 0.0001 ] ) , as well as at 3 months ( 92.9 % versus 13.8 % [ P < 0.0001 ] ) , 6 months ( 71.4 % versus 3.5 % [ P < 0.0001 ] ) , and 24 months ( 60.7 % versus 3.5 % [ P < 0.0001 ] ) . The Birmingham Vasculitis Activity Score decreased only after treatment with RTX ( from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2 ; P < 0.001 ) up to month 24 ( 4.4 ± 4.6 ; P < 0.0001 ) . RTX appeared to be superior therapy for all 3 target organ manifestations , and it was as effective as conventional therapy . The median duration of response to RTX was 18 months . Overall , RTX treatment was well tolerated . CONCLUSION RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients Excessive fluid intake ( polydipsia ) and accompanying polyuria occur frequently in chronically ill psychiatric patients 0ose and Perez-Cruet 1979 ; Vieweg et al 1988 , 1989 ) . A significant subgroup Gf these polydipsic patients experience episodes of symptomatic dilutional hyponatremia , that is , water intoxication ( Jose and Perez-Cruet 1979 ) . The symptoms of water intoxication , thought to be due to serum hyponatremia and hypo-osmolality , include lethargy , confusion , seizures , coma , and death . Common strategies for the treatment of chronic psychiatric patients with polydipsia-hyponatremia involve restriction of fluid intake and /or attempts to promote free water excretion . One of the most promising potential treatments is demeclocycline , an antibiotic in the tetracycline family . Demeclocyc!ine blocks the action of antidiuretic hormone ( ADH ) at the kidney and can induce a reversible nephrogenic diabetes insipidus ( Feldman and Singer 1974 ) . It has been used to treat the syndrome of inappropriate OBJECTIVES Our aim was to examine continental and regional differences in baseline characteristics and post-discharge clinical outcomes in the EVEREST ( Efficacy of Vasopressin Antagonism in Heart Failure : Outcome Study with Tolvaptan ) trial . BACKGROUND Continental and regional differences in clinical trials of acute heart failure syndromes ( AHFS ) have not been well studied . METHODS We analyzed data from the EVEREST trial , which r and omized 4,133 patients hospitalized for worsening ( HF ) and left ventricular ejection fraction < or = 40 % to oral tolvaptan , a vasopressin antagonist , or placebo and followed for a median of 9.9 months . Baseline characteristics , mortality , and outcomes were analyzed across North America ( n = 1,251 ) , South America ( n = 688 ) , Western Europe ( 564 patients ) , and Eastern Europe ( n = 1,619 ) . RESULTS There were major differences between the 4 groups in the severity , etiology , and management of HF . Unadjusted 1-year mortality and cardiovascular mortality/HF hospitalization were 30.4 % and 52.5 % in North America , 27.2 % and 41.6 % in South America , 27.1 % and 47.3 % in Western Europe , and 20.5 % and 35.3 % in Eastern Europe . After adjustment , South American patients had the highest overall mortality ( hazard ratio : 1.42 , 95 % confidence interval : 1.15 to 1.76 ) , while Eastern European patients had the lowest cardiovascular death and HF hospitalization rate ( hazard ratio : 0.84 , 95 % confidence interval : 0.73 to 0.97 ) , compared with patients in North America . CONCLUSIONS Major continental and regional differences in HF severity , etiology , and management exist among AHFS patients , result ing in varied post-discharge outcomes , despite pre-defined selection criteria . These differences should be taken into account when planning global trials in AHFS . ( Efficacy of Vasopressin Antagonism in Heart Failure : Outcome Study with Tolvaptan [ EVEREST ] ; NCT00071331 ) r and omized , double-blind , placebo-controlled study of the effects of tolvaptan on the acute and chronic outcomes of patients hospitalized with worsening congestive heart failure Mihai Gheorghiade , MD , Wendy A. Gattis , PharmD , Alej and ro Barbagelata , MD , Kirkwood F. Adams , Jr , MD , Uri Elkayam , MD , Cesare Orl and i , MD , and Christopher M. O’Connor , MD , for the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure ( ACTIV in CHF ) Investigators Chicago , Ill , Durham and Chapel Hill , NC , Los Angeles , Calif , Buenos Aires , Argentina , and Baltimore , BACKGROUND Hospitalizations for worsening heart failure due to fluid overload ( congestion ) are common . Agents that treat congestion without causing electrolyte abnormalities or worsening renal function are needed . Tolvaptan is an oral vasopressin ( V 2 ) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia . The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan ( EVEREST ) trial is evaluating mortality , morbidity , and patient-assessed global clinical status in patients treated with tolvaptan compared with st and ard care . METHODS AND RESULTS Patients are eligible for inclusion if they have a reduced left ventricular ejection fraction and are hospitalized for worsening heart failure with evidence of systemic congestion . Patients are r and omized 1:1 to tolvaptan 30 mg/day or matching placebo for a minimum of 60 days . Time to all-cause mortality and time to cardiovascular mortality or heart failure hospitalization are the co primary end points . Patient-assessed global clinical status and quality of life are also evaluated . EVEREST will be continued until 1065 deaths occur . As of April 18 , 2005 , 2260 patients have been enrolled . CONCLUSION Tolvaptan has been shown to reduce body weight in patients with worsening heart failure without inducing renal dysfunction or causing hypokalemia . The results of EVEREST will determine whether these effects translate into improved clinical outcomes Background : Most cases of hyponatremia – serum sodium concentration ( [ Na+ ] ) < 135 mEq/l ( < 135 mM ) – are associated with an elevated plasma arginine vasopressin level . This study investigated the efficacy and tolerability of intravenous conivaptan ( YM087 ) , a vasopressin V1A/V2-receptor antagonist , in treating euvolemic and hypervolemic hyponatremia . Methods : Eighty-four hospitalized patients with euvolemic or hypervolemic hyponatremia ( serum [ Na+ ] 115 to < 130 mEq/l ) were r and omly assigned to receive intravenous placebo or conivaptan administered as a 30-min , 20-mg loading dose followed by a 96-hour infusion of either 40 or 80 mg/day . The primary efficacy measure was change in serum [ Na+ ] , measured by the baseline-adjusted area under the [Na+]-time curve . The secondary measures included time from first dose to a confirmed ≧4 mEq/l serum [ Na+ ] increase , total time patients had serum [ Na+ ] ≧4 mEq/l higher than baseline , change in serum [ Na+ ] from baseline to the end of treatment , and number of patients with a confirmed ≧6 mEq/l increase in serum [ Na+ ] or normal [ Na+ ] ( ≧135 mEq/l ) . Results : Both conivaptan doses increased area under the [Na+]-time curve during the 4-day treatment ( p < 0.0001 vs. placebo ) . From baseline to the end of treatment , the least-squares mean ± st and ard error serum [ Na+ ] increase associated with placebo was 0.8 ± 0.8 mEq/l ; with conivaptan 40 mg/day , 6.3 ± 0.7 mEq/l ; and with conivaptan 80 mg/day , 9.4 ± 0.8 mEq/l . Conivaptan significantly improved all secondary efficacy measures ( p < 0.001 vs. placebo , both doses ) . Conivaptan was generally well tolerated , although infusion-site reactions led to the withdrawal of 1 ( 3 % ) and 4 ( 15 % ) of patients given conivaptan 40 and 80 mg/day , respectively . Conclusion : Among patients with euvolemic or hypervolemic hyponatremia , 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [ Na+ ] and was well tolerated UNLABELLED Hyponatremia in cirrhosis is associated with significant morbidity and mortality and complicates ascites management . Vasopressin receptor antagonists improve serum sodium concentration by increasing renal solute-free water excretion , but their effects on the management of ascites have not been assessed . Our aim was to investigate the effects of satavaptan , a highly selective vasopressin V(2 ) receptor antagonist , on ascites management and serum sodium in hyponatremic patients with cirrhosis . A total of 110 patients with cirrhosis , ascites , and hyponatremia ( serum sodium < or = 130 mmol/L ) were included in a multicenter , double-blind , r and omized , controlled study comparing three fixed doses of satavaptan ( 5 mg , 12.5 mg , or 25 mg once daily ) versus placebo . Duration of treatment was 14 days and all patients received spironolactone at 100 mg/day . Satavaptan treatment was associated with improved control of ascites , as indicated by a reduction in body weight ( mean change at Day 14 was + 0.49 kg [ + /-4.99 ] for placebo versus + 0.15 kg [ + /-4.23 ] , -1.59 kg [ + /-4.60 ] and -1.68 kg [ + /-4.98 ] for the 5 mg , 12.5 mg , and 25 mg doses , respectively ; P = 0.05 for a dose-effect relationship overall ) and a parallel reduction in abdominal girth . This beneficial effect on ascites was associated with improvements in serum sodium ( mean change from baseline to day 5 was 1.3 + /- 4.2 , 4.5 + /- 3.5 , 4.5 + /- 4.8 , and 6.6 + /- 4.3 mmol/L for the placebo group and the groups on satavaptan at 5 mg , 12.5 mg , and 25 mg/day , respectively ; P < 0.01 for all compared to placebo ) . Thirst was significantly more common in patients treated with satavaptan compared to those treated with placebo , whereas the frequency of other adverse events was similar among groups . CONCLUSION The V(2 ) receptor antagonist satavaptan improves the control of ascites and increases serum sodium in patients with cirrhosis , ascites , and hyponatremia under diuretic treatment Objective : The aim of the study was to compare sequential versus combined diuretic therapy in patients with cirrhosis , moderate ascites and without renal failure . Design : One hundred patients were r and omly assigned to the two diuretic treatments . The sequential treatment provided potassium canrenoate at the initial dose of 200 mg/day , then increased to 400 mg/day . Non-responders were treated with 400 mg/day of potassium canrenoate and furosemide at an initial dose of 50 mg/day , then increased to 150 mg/day . The combined treatment provided the initial dose of 200 mg/day of potassium canrenoate and 50 mg/day of furosemide , then increased to 400 mg/day and 150 mg/day , respectively . Results : Most patients who received sequential treatment responded to potassium canrenoate alone ( 19 % to 200 mg/day and 52.63 % to 400 mg/day , respectively ) . Most patients who received the combined treatment responded to the first two steps ( 40 % to the first step and 50 % to the second , ie , 400 mg/day of potassium canrenoate plus 100 mg/day of furosemide ) . Adverse effects ( 38 % vs 20 % , p<0.05 ) , in particular , hyperkalaemia ( 18 % vs 4 % , p<0.05 ) , were more frequent in patients who received sequential therapy . As a consequence , the per cent of patients who resolved ascites without changing the effective diuretic step was higher in those who received the combined treatment ( 56 % vs 76 % , p<0.05 ) . Conclusions : The combined diuretic treatment is preferable to the sequential one in the treatment of moderate ascites in patients with cirrhosis and without renal failure . NCT00741663 . This work is an open r and omised clinical trial Background Hyponatremia is common in neurocritical care and is associated with poor outcome , but the optimal treatment is not known . We wished to test the hypothesis that for neurocritical care patients with severe hyponatremia ( Na < 130 mmol/l ) or hyponatremia ( Na < 135 mmol/l ) with depressed Glasgow Coma Scale ( GCS ) that conivaptan use would lead to increased serum sodium compared to usual care . Methods We prospect ively screened 249 neurocritical care patients with hyponatremia for a prospect i ve , r and omized pilot ( goal N = 20 ) trial . Study interventions were usual care , or usual care plus conivaptan 20 mg IV as a bolus followed by 20 mg IV over 24 h , the lower FDA -approved dose . Patients were prospect ively followed for changes in serum and urine electrolytes and clinical examinations with a blinded examiner . This study is registered at www . clinical trials.gov ( NCT00727090 ) . Results Despite the prevalence of hyponatremia , recruitment was difficult , and the study was terminated after six patients were enrolled , three in each group . Most hyponatremia in screened but non-r and omized patients was transient or not associated with depressed GCS . Conivaptan led to higher serum sodium compared to usual care . The change in serum sodium from baseline , the pre-specified endpoint , was significantly different between groups at six ( 7.0 ± 1.7 vs. −0.6 ± 2.1 mmol/l , P = 0.008 ) , 24 ( 9.7 ± 3.2 vs. 0 ± 1.0 mmol/l ) , and 36 h ( 8.0 ± 5.6 vs. −1.7 ± 2.1 mmol/l , P = 0.05 ) . There were no apparent differences in clinical examination as a result of treatment . Adverse events were similar , and all r and omized patients completed the protocol . Conclusions Despite an inclusive protocol , most patients were not c and i date s for conivaptan therapy for hyponatremia . The role of conivaptan in the Neuro-ICU remains to be defined Objective : To determine whether asymptomatic exercise-associated hyponatremia ( EAH ) in ultramarathon runners can be corrected with either oral or intravenous ( IV ) 3 % hypertonic saline ( HTS ) . Design : Prospect i ve with r and omization into 1 of 2 intervention arms . Setting : Western States ( 161 km ) Endurance Run , California . Participants : Forty-seven finishers in the event consented to be screened to identify those with EAH , defined as plasma sodium ( [Na+]p ) < 135 mmol/L at race end . Interventions : Participants with EAH but without symptoms were r and omized to receive a single 100 mL dose of either oral or IV 3 % HTS . Blood was drawn before intervention and at 60 minutes postintervention to measure [Na+]p , and concentrations of plasma potassium , proteins , and arginine vasopressin ( AVP ) . Body mass , percent total body water , and percent body fat were measured prerace and postrace using impedance scales . Main Outcome Measures : Change in [Na+]p . Results : Fourteen of 47 consenting finishers ( 30 % ) had EAH . Eight agreed to be r and omized into the intervention protocol . Only in the IV group did [Na+]p change significantly ( from 130.8 to 134.6 mmol/L ) over the 60 minutes post-HTS administration . Elevated AVP concentrations were seen at race finish in both the groups and remained so after HTS treatment . Conclusions : In this preliminary trial , prompt administration of a 100 mL bolus of IV 3 % HTS was associated with normalization of [Na+]p in asymptomatic EAH , but a similar effect was not demonstrated for the same dose orally . Elevated AVP levels were observed and may play a part in the development of EAH but were not suppressed significantly by either intervention Diuretics , have been accepted as first‐line treatment in refractory heart failure , but a lack of response is a frequent event . A r and omised 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 NYHA class IV congestive heart failure ( CHF ) OBJECTIVE Hyponatremia is a complication of diuretic treatment and has been recently identified as a novel factor associated with osteoporosis and fractures . The impact of diuretic-associated electrolyte disorders on osteoporotic fractures ( OF ) has rarely been studied systematic ally . DESIGN AND SETTING We conducted a study in patients presenting to the emergency department at the University Hospital Bern . In this retrospective case series analysis of prospect ively gathered data , over a 2-year period we identified 10,823 adult ( ≥50 years ) out patients with a measured baseline serum sodium , at admission to the hospital . OF patients were compared to a control group without fractures using st and ard statistical methods . RESULTS Four hundred and eighty ( 5 % ) patients had 547 OF . The OF group had a higher mean age ( 73 vs. 68 years , p<0.0001 ) , smaller proportion of men ( 37 % vs. 58 % , p<0.0001 ) , higher hospitalisation rate ( 83 % vs. 62 % , p<0.0001 ) and longer hospital stay ( 8 vs. 6 days , p<0.0001 ) . Any diuretic agent ( p<0.0001 ) , loop diurietics ( p=0.02 ) , spironolactone ( p=0.02 ) and amiloride ( p<0.01 ) were used significantly more in OF patients , but not thiazides ( p=0.68 ) . The prevalence of hyponatremia increased significantly ( p<0.0001 ) with the number of diuretics taken . Advanced age ( odds ratio [ OR ] 1.04 , p<0.0001 ) , hyponatremia ( OR 1.46 , p=0.011 ) higher serum creatinine ( OR 1.53 , p=0.0001 ) , furosemide use alone ( OR 1.40 , p=0.01 ) and co-treatment with amiloride ( OR 2.22 , p=0.02 ) were associated with a higher risk for OF . CONCLUSIONS This study highlights the clinical association of hyponatremia during the use of certain diuretics ( i.e. furosemide or in combination , i.e. amiloride ) with an increased risk of osteoporosis associated fractures . Although evidence -based data is currently lacking a pragmatic approach concerning hyponatremia monitoring and correction appears reasonable in selected groups of patients Objective and design Most cases of euvolaemic hyponatraemia are associated with elevated plasma levels of AVP . Conivaptan is a high‐affinity , nonpeptide vasopressin V1A/V2‐receptor antagonist . We performed a subgroup analysis of a multicentre , r and omized , placebo‐controlled , double‐blind , parallel‐group study to evaluate the efficacy and safety of intravenous ( i.v . ) conivaptan for the treatment of euvolaemic hyponatraemia OBJECTIVES The purpose of this study was to examine the renal effects of a V2 receptor arginine vasopressin ( AVP ) antagonist in heart failure . BACKGROUND Arginine vasopressin has been implicated in the renal water retention and dilutional hyponatremia associated with chronic heart failure . METHODS We examined the effects of the oral , non-peptide , selective V2 receptor antagonist lixivaptan in 42 diuretic-requiring patients with mild-to-moderate heart failure in a r and omized , double-blind , placebo-controlled , ascending single-dose study . After overnight fluid deprivation , patients received single-blind placebo on day -1 ( baseline ) and double-blind study medication ( placebo [ n = 12 ] or lixivaptan 10 , 30 , 75 , 150 , 250 , or 400 mg [ n = 5 per dose group ] ) on day 1 , followed by 4 h of continued fluid restriction and additional 20 h with ad libitum fluid intake . RESULTS At all but the 10-mg dose , lixivaptan produced a significant and dose-related increase in urine volume over 4 h , compared with placebo . During 24 h , increases in urine volume ranged from 1.8 l with placebo to 3.9 l after the 400-mg lixivaptan dose ( p < 0.01 ) . These increases in urine volumes were accompanied by significant increases in solute-free water excretion . At higher doses , serum sodium was significantly increased ; AVP antagonism was well tolerated in these patients . CONCLUSIONS These observations confirm a role for AVP in the renal water retention associated with heart failure and suggest that the V2 receptor antagonist lixivaptan may be a promising therapeutic agent for the treatment of heart failure Background : Hyponatremia predicts poor outcome in patients with acute heart failure syndromes . This study evaluated the relationship between baseline serum sodium , change in serum sodium , and 60‐day mortality in hospitalized heart failure patients . Methods : A post‐hoc analysis of the ACTIV in CHF trial was performed . ACTIV in CHF r and omized 319 patients hospitalized for worsening heart failure to placebo or one of three tolvaptan doses . Cox proportional hazards regression‐ analysis was used to explore the relationship between baseline hyponatremia , sodium change during the hospitalization , and 60‐day mortality . Results : Hyponatremia was observed in 69 patients ( 21.6 % ) . After covariate adjustment , baseline hyponatremia was a statistically significant predictor of 60‐day mortality ( P = 0.0016 ) . Follow‐up serum sodium data were available in 68 patients . At hospital discharge , 45 of 68 ( 66.2 % ) hyponatremic patients had improvements in serum sodium levels ( ⩾2 mmol/l ) . Hyponatremic patients with a serum sodium improvement had a mortality rate of 11.1 % at 60 days post discharge , compared with a 21.7 % mortality rate in those showing no improvement . After covariate adjustment , change in serum sodium was a statistically significant predictor of 60‐day mortality ( HR : 0.736 , 95 % CI : 0.569–0.952 for each 1‐mmol/l increase in serum sodium from baseline ) . Conclusions : Serum sodium improvements during hospitalization for heart failure were associated with improved survival at 60 days Hyponatremia is a common electrolyte disorder associated with increased morbidity and mortality , particularly in the elderly . Lixivaptan , a new selective vasopressin V2-receptor antagonist , safely corrected serum sodium concentrations in phase II studies of patients with euvolemic hyponatremia . Here our multinational , double-blind , placebo-controlled , phase III study assessed the effect of lixivaptan on serum sodium concentrations in 106 initially hospitalized patients with euvolemic hyponatremia ( serum sodium less than 130 mmol/l ) . Of them , 52 were r and omized to receive placebo and 54 received 50 mg lixivaptan once daily and were then titrated to receive 25 - 100 mg once daily depending on serum sodium concentration . Fluid restriction was at the investigator 's discretion . Initial titration occurred in a monitored inpatient setting ; patients were then treated as out patients for a total of 30 days . The primary end point was the change in serum sodium concentration from baseline to day 7 . Lixivaptan significantly increased the serum sodium concentration from baseline to day 7 ( the primary end point ) by 6.7 mmol/l compared with placebo ( 4.5 mmol/l ; P=0.034 ) . Importantly , the serum sodium concentration was normalized safely and more rapidly in patients receiving lixivaptan than placebo ( P=0.004 ) and was well tolerated . After drug discontinuation , serum sodium concentrations decreased to near-baseline levels within 7 days . Thus , lixivaptan safely and effectively corrects serum sodium concentrations in patients with euvolemic hyponatremia 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 CONTEXT Heart failure causes more than 1 million US hospitalizations yearly , mostly related to congestion . Tolvaptan , an oral , nonpeptide , selective vasopressin V2-receptor antagonist , shows promise in this condition . OBJECTIVE To evaluate short-term effects of tolvaptan when added to st and ard therapy in patients hospitalized with heart failure . DESIGN , SETTING , AND PATIENTS Two identical prospect i ve , r and omized , double-blind , placebo-controlled trials at 359 sites in North America , South America , and Europe were conducted during the inpatient period of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan ( EVEREST ) between October 7 , 2003 , and February 3 , 2006 . A total of 2048 ( trial A ) and 2085 ( trial B ) patients hospitalized with heart failure and congestion were studied . INTERVENTION Patients were r and omized to receive either tolvaptan ( 30 mg/d ) or matching placebo , within 48 hours of admission . MAIN OUTCOME MEASURES Primary end point was a composite of changes in global clinical status based on a visual analog scale and body weight at day 7 or discharge if earlier . Secondary end points included dyspnea ( day 1 ) , global clinical status ( day 7 or discharge ) , body weight ( days 1 and 7 or discharge ) , and peripheral edema ( day 7 or discharge ) . RESULTS Rank sum analysis of the composite primary end point showed greater improvement with tolvaptan vs placebo ( trial A , mean [ SD ] , 1.06 [ 0.43 ] vs 0.99 [ 0.44 ] ; and trial B , 1.07 [ 0.42 ] vs 0.97 [ 0.43 ] ; both trials P<.001 ) . Mean ( SD ) body weight reduction was greater with tolvaptan on day 1 ( trial A , 1.71 [ 1.80 ] vs 0.99 [ 1.83 ] kg ; P<.001 ; and trial B , 1.82 [ 2.01 ] vs 0.95 [ 1.85 ] kg ; P<.001 ) and day 7 or discharge ( trial A , 3.35 [ 3.27 ] vs 2.73 [ 3.34 ] kg ; P<.001 ; and trial B , 3.77 [ 3.59 ] vs 2.79 [ 3.46 ] kg ; P<.001 ) , whereas improvements in global clinical status were not different between groups . More patients receiving tolvaptan ( 684 [ 76.7 % ] and 678 [ 72.1 % ] for trial A and trial B , respectively ) vs patients receiving placebo ( 646 [ 70.6 % ] and 597 [ 65.3 % ] , respectively ) reported improvement in dyspnea at day 1 ( both trials P<.001 ) . Edema at day 7 or discharge improved significantly with tolvaptan in trial B ( P = .02 ) but did not reach significance in trial A ( P = .07 ) . Serious adverse event frequencies were similar between groups , without excess renal failure or hypotension . CONCLUSION In patients hospitalized with heart failure , oral tolvaptan in addition to st and ard therapy including diuretics improved many , though not all , heart failure signs and symptoms , without serious adverse events . TRIAL REGISTRATION clinical trials.gov Identifier : To study the effect of tolvaptan on non-acute , non-hypovolemic hyponatremia in inappropriate secretion of antidiuretic hormone ( SIADH ) syndrome in Chinese patients . Hyponatremic SIADH patients received placebo ( N = 18 ) or tolvaptan ( N = 19 ) at an initial dose of 15 mg/day with further titration to 30 mg/day and 60 mg/day based on serum sodium concentrations . R and omized , double-blind , placebo-controlled trial . Primary endpoint was the change of the serum sodium from baseline to days 4 and 7 . Analysis of covariance ( ANCOVA ) was used for statistical analysis . At day 4 , average daily changes in serum sodium levels from baseline was 1.9 ± 2.9 mmol/L ( 1.9 ± 2.9 mEq/L ) in the placebo group and 8.1 ± 3.6 mmol/L ( 8.1 ± 3.6 mEq/L ) in the tolvaptan group ; at day 7 , the values were 2.5 ± 3.9 mmol/L ( 2.5 ± 3.9 mEq/L ) and 8.6 ± 3.9 mmol/L ( 8.6 ± 3.9 mmEq/L ) for the placebo and tolvaptan groups ( ANCOVA , P < 0.001 ) . At days 4 and 7 , daily urine output and proportions of patients with normalized serum sodium were significantly superior in the tolvaptan group . The most common adverse events occurring in the tolvaptan group were dry mouth and thirst . Tolvaptan demonstrated superiority to placebo in the treatment of Chinese SIADH patients with hyponatremia by elevating serum sodium concentration with acceptable safety profile |
10,888 | 28,265,822 | Mechanical mitral valve replacement ( MVR ) had the lowest costs per success compared to mitral valve repair and biological MVR . | Objective To review the evidence on the cost-effectiveness of heart valve implantations generated by decision analytic models and to assess their method ological quality . | Background Patients with severe aortic stenosis and coexisting non-cardiac conditions may be at high risk for surgical replacement of the aortic valve or even be no c and i date s for surgery . In these patients , transcatheter aortic valve implantation ( TAVI ) is suggested as an alternative . Results of the PARTNER ( Placement of AoRTic TraNscathetER Valve ) trial comparing the clinical effectiveness of TAVI with surgical valve replacement and st and ard therapy were published . The authors assessed the cost-effectiveness of TAVI in Belgium . Methods A Markov model of incremental costs , effects ( survival and quality of life ) and incremental cost-effectiveness of TAVI was developed . The impact on survival , number of events and quality of life was based on the PARTNER trial . Costs per event were context specific . Results In high-risk operable patients , even if the minor differences in 30-day and 1-year mortality are taken into account , the incremental cost-effectiveness ratio ( ICER ) remains on average above € 750 000 per quality -adjusted life-year ( QALY ) gained ( incremental cost : € 20 400 ; incremental effect : 0.03 QALYs ) . In inoperable patients , an ICER of € 44 900 per QALY ( incremental cost : € 33 200 ; incremental effect : 0.74 QALYs ) is calculated , including a life-long extrapolation of the mortality benefit . This result was sensitive to the assumed time horizon . The subgroup of anatomically inoperable patients had better outcomes than medically inoperable patients , with ICERs decreasing more than € 10 000/QALY . Conclusions It is inappropriate to consider reimbursement of TAVI for high-risk operable patients . Reimbursing TAVI in inoperable patients in essence is a political decision . From an economic perspective , it would be prudent to first target patients that are inoperable because of anatomical prohibitive conditions . In the search for evidence , the authors identified non-published negative results from a r and omised controlled TAVI trial . The study sponsor should be more willing to share this information to allow balanced evaluations and policy recommendations . Payers should require these data before taking reimbursement decisions Objective To determine the cost-effectiveness of transcatheter aortic valve implantation ( TAVI ) compared with surgical aortic valve replacement ( SAVR ) in a high-risk aortic stenosis ( AS ) population . Design A cost-utility analysis employing the National Institute of Clinical Excellence ( NICE ) reference case design for technology appraisal s. Setting The perspective of the UK National Health Service . Patients Utility data from a UK high-risk AS population . TAVI and SAVR effectiveness was taken from the PARTNER A r and omised controlled trial . Main outcome measures Costs modelled over a 10 year horizon using a Markov model . Incremental cost-effectiveness ratios and cost-effectiveness acceptability curve were calculated with reference to the NICE willingness to pay per quality adjusted life year ( QALY ) gain threshold . Deterministic and probabilistic sensitivity analyses performed . Results Despite greater procedural costs ( £ 16 500 vs £ 9,256 ) , TAVI was cost-effective compared with SAVR over the 10 year model horizon ( costs £ 52 593 vs £ 53 943 and QALYs 2.81 vs 2.75 ) , indicating that TAVI dominated SAVR . This appeared to be due to greater postsurgical costs , related to the length and cost of hospital stay . The results appeared robust to a number of deterministic sensitivity and probabilistic analyses . The cost-effectiveness acceptability curve indicated that at the NICE £ 20 000 willingness to pay threshold per QALY gained , TAVI had a 64.6 % likelihood of being cost-effective , compared with 35.4 % for SAVR . Conclusions TAVI is likely to be a cost-effective treatment for high-risk patients with AS compared with the reference st and ard of SAVR . However , uncertainty surrounding the long-term outcomes for TAVI patients remains ; this could have a substantive impact on estimates of cost-effectiveness Abstract Objective : The only effective treatment for severe aortic stenosis ( AS ) is valve replacement . However , many patients with co-existing conditions are ineligible for surgical valve replacement , historically leaving medical management ( MM ) as the only option which has a poor prognosis . Transcatheter Aortic Valve Replacement ( TAVR ) is a less invasive replacement method . The objective was to estimate cost-effectiveness of TAVR via transfemoral access vs MM in surgically inoperable patients with severe AS from the Canadian public healthcare system perspective . Methods : A cost-effectiveness analysis of TAVR vs MM was conducted using a deterministic decision analytic model over a 3-year time horizon . The PARTNER r and omized controlled trial results were used to estimate survival , utilities , and some re source utilization . Costs included the valve replacement procedure , complications , hospitalization , outpatient visits/tests , and home/nursing care . Re sources were valued ( 2009 Canadian dollars ) using costs from the Ontario Case Costing Initiative ( OCCI ) , Ontario Ministry of Health and Long-Term Care and Ontario Drug Benefits Formulary , or were estimated using relative costs from a French economic evaluation or clinical experts . Costs and outcomes were discounted 5 % annually . The effect of uncertainty in model parameters was explored in deterministic and probabilistic sensitivity analysis . Results : The incremental cost-effectiveness ratio ( ICER ) was $ 32,170 per quality -adjusted life year ( QALY ) gained for TAVR vs MM . When the time horizon was shortened to 24 and 12 months , the ICER increased to $ 52,848 and $ 157,429 , respectively . All other sensitivity analysis returned an ICER of less than $ 50,000/QALY gained . Limitations : A limitation was lack of availability of Canadian-specific re source and cost data for all re sources , leaving one to rely on clinical experts and data from France to inform certain parameters . Conclusions : Based on the results of this analysis , it can be concluded that TAVR is cost-effective compared to MM for the treatment of severe AS in surgically inoperable patients OBJECTIVE With increased life expectancy and improved technology , valve replacement is being offered to increasing numbers of elderly patients with satisfactory clinical results . By using st and ard econometric techniques , we estimated the relative cost-effectiveness of aortic valve replacement by drawing on a large prospect i ve data base at our institution . By using aortic valve replacement as an example , this introductory report paves the way to more definitive studies of these issues in the future . METHODS From 1961 to 2003 , 4617 adult patients underwent aortic valve replacement at our service . These patients were provided with a prospect i ve lifetime follow-up . As of 2005 , these patients had accumulated 31,671 patient-years of follow-up ( maximum 41 years ) and had returned 22,396 yearly question naires . A statistical model was used to estimate the future life years of patients who are currently alive . In the absence of direct estimates of utility , quality -adjusted life years were estimated from New York Heart Association class . The cost-effectiveness ratio was calculated by the patient 's age at surgery . RESULTS The overall cost-effectiveness ratio was approximately 13,528 dollars per quality -adjusted life year gained . The cost-effectiveness ratio increased according to age at surgery , up to 19,826 dollars per quality -adjusted life year for octogenarians and 27,182 dollars per quality -adjusted life year for nonagenarians . CONCLUSIONS Given the limited scope of this introductory study , aortic valve replacement is cost-effective for all age groups and is very cost-effective for all but the most elderly according to st and ard econometric rules of thumb BACKGROUND Major scores for the evaluation of procedural risk in cardiac surgery are the European system for cardiac operative risk evaluation score ( EuroSCORE ) , the Society of Thoracic Surgeons ( STS ) score , and the Parsonnet score . The aim of our study was to analyze the predictive value of these scores in " high risk " patients undergoing isolated aortic valve replacement ( AVR ) . METHODS Six hundred and fifty-two patients underwent isolated AVR from January 1999 through June 2007 . Emergency and redo operations were included ; acute endocarditis was excluded . Evaluation was performed by logistic regression analysis . Data collection was prospect i ve . RESULTS The mean logistic EuroSCORE of all patients was 8.5 + /- 7.9 % , the mean STS score was 4.4 + /- 3.9 % , and the mean logistic Parsonnet score was 9.8 + /- 8.5 % . In-hospital mortality was 2.5 % ( n = 16 ) . Freedom from all-cause death was 93.4 % at 1 year , 90.2 % at 2 years , and 75.8 % at 5 years , respectively . A total of 182 patients had a logistic EuroSCORE greater than 10 . For the group of patients with a EuroSCORE between 10 % and 20 % ( n = 130 ) the mean EuroSCORE was 13.9 + /- 2.8 % and the STS score was 6.5 + /- 3.8 % . Observed mortality was 4.6 % in this group . For the 52 patients with a logistic EuroSCORE of at least 20 ( mean 28.5 + /- 10.3 % , STS score 10.1 + /- 7.3 % ) the observed mortality was 3.9 % ( n = 2 ) . By stepwise logistic regression , none of the EuroSCORE variables could be identified as an independent predictor in the " high- risk " group . CONCLUSIONS The logistic EuroSCORE was primarily created to allow patient grouping for the total spectrum of cardiac surgery . In patients undergoing isolated AVR , the EuroSCORE highly overestimates mortality , whereas the STS score seems to be actually more suitable in assessing perioperative mortality for these patients BACKGROUND The incremental cost-effectiveness of transapical transcatheter aortic valve implantation ( TAVI ) is ill-defined in high-risk patients where aortic valve replacement ( AVR ) is an option , and has not been ascertained outside a r and omized controlled trial . METHODS We developed a Markov model to examine the progression of patients between health states , defined as peri- and post-procedural , post-complication , and death . The mean and variance of risks , transition probabilities , utilities and cost of transapical TAVI , high-risk AVR , and medical management were derived from analysis of relevant registries . Outcome and cost were derived from 10,000 simulations . Sensitivity analyses further evaluated the impact of mortality , stroke , and other commonly observed outcomes . RESULTS In the reference case , both transapical TAVI and high-risk AVR and TAVI were cost-effective when compared to medical management ( $ 44,384/QALY and $ 42,637/QALY , respectively ) . Transapical TAVI failed to meet accepted criteria for incremental cost-effectiveness relative to AVR , which was the dominant strategy . In sensitivity analyses , the mortality rates related to the two strategies , the utilities post-AVR and post-transapical TAVI , and the cost of transapical TAVI , were the main drivers of model outcome . CONCLUSION Transapical TAVI did not satisfy current metrics of incremental cost-effectiveness relative to high-risk AVR in the reference case . However , it may provide net health benefits at acceptable cost in selected high-risk patients among whom AVR is the st and ard intervention BACKGROUND Many patients with severe aortic stenosis and coexisting conditions are not c and i date s for surgical replacement of the aortic valve . Recently , transcatheter aortic-valve implantation ( TAVI ) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis . METHODS We r and omly assigned patients with severe aortic stenosis , whom surgeons considered not to be suitable c and i date s for surgery , to st and ard therapy ( including balloon aortic valvuloplasty ) or transfemoral transcatheter implantation of a balloon-exp and able bovine pericardial valve . The primary end point was the rate of death from any cause . RESULTS A total of 358 patients with aortic stenosis who were not considered to be suitable c and i date s for surgery underwent r and omization at 21 centers ( 17 in the United States ) . At 1 year , the rate of death from any cause ( Kaplan – Meier analysis ) was 30.7 % with TAVI , as compared with 50.7 % with st and ard therapy ( hazard ratio with TAVI , 0.55 ; 95 % confidence interval [ CI ] , 0.40 to 0.74 ; P<0.001 ) . The rate of the composite end point of death from any cause or repeat hospitalization was 42.5 % with TAVI as compared with 71.6 % with st and ard therapy ( hazard ratio , 0.46 ; 95 % CI , 0.35 to 0.59 ; P<0.001 ) . Among survivors at 1 year , the rate of cardiac symptoms ( New York Heart Association class III or IV ) was lower among patients who had undergone TAVI than among those who had received st and ard therapy ( 25.2 % vs. 58.0 % , P<0.001 ) . At 30 days , TAVI , as compared with st and ard therapy , was associated with a higher incidence of major strokes ( 5.0 % vs. 1.1 % , P=0.06 ) and major vascular complications ( 16.2 % vs. 1.1 % , P<0.001 ) . In the year after TAVI , there was no deterioration in the functioning of the bioprosthetic valve , as assessed by evidence of stenosis or regurgitation on an echocardiogram . CONCLUSIONS In patients with severe aortic stenosis who were not suitable c and i date s for surgery , TAVI , as compared with st and ard therapy , significantly reduced the rates of death from any cause , the composite end point of death from any cause or repeat hospitalization , and cardiac symptoms , despite the higher incidence of major strokes and major vascular events . ( Funded by Edwards Lifesciences ; Clinical Trials.gov number , NCT00530894 . ) OBJECTIVES The aim of this article was to provide practical guidance in setting up patient registries to facilitate real-world data collection for health care decision making . METHODS This guidance was based on our experiences and involvement in setting up patient registries in oncology in the Netherl and s. All aspects were structured according to 1 ) mission and goals ( " the Why " ) , 2 ) stakeholders and funding ( " the Who " ) , 3 ) type and content ( " the What " ) , and 4 ) identification and recruitment of patients , data h and ling , and pharmacovigilance ( " the How " ) . RESULTS The mission of most patient registries is improving patient health by improving the quality of patient care ; monitoring and evaluating patient care is often the primary goal ( " the Why " ) . It is important to align the objectives of the registry and agree on a clear and functional governance structure with all stakeholders ( " the Who " ) . There is often a trade off between reliability , validity , and specificity of data elements and feasibility of data collection ( " the What " ) . Patient privacy should be carefully protected , and address (inter-)national and local regulations . Patient registries can reveal unique safety information , but it can be challenging to comply with pharmacovigilance guidelines ( " the How " ) . CONCLUSIONS It is crucial to set up an efficient patient registry that serves its aims by collecting the right data of the right patient in the right way . It can be expected that patient registries will become the new st and ard alongside r and omized controlled trials due to their unique value OBJECTIVES The aim of this study was to assess the role of transcatheter aortic valve implantation ( TAVI ) compared with medical treatment ( MT ) and surgical aortic valve replacement ( SAVR ) in patients with severe aortic stenosis ( AS ) at increased surgical risk . BACKGROUND Elderly patients with comorbidities are at considerable risk for SAVR . METHODS Since July 2007 , 442 patients with severe AS ( age : 81.7 ± 6.0 years , mean logistic European System for Cardiac Operative Risk Evaluation : 22.3 ± 14.6 % ) underwent treatment allocation to MT ( n = 78 ) , SAVR ( n = 107 ) , or TAVI ( n = 257 ) on the basis of a comprehensive evaluation protocol as part of a prospect i ve registry . RESULTS Baseline clinical characteristics were similar among patients allocated to MT and TAVI , whereas patients allocated to SAVR were younger ( p < 0.001 ) and had a lower predicted peri-operative risk ( p < 0.001 ) . Unadjusted rates of all-cause mortality at 30 months were lower for SAVR ( 22.4 % ) and TAVI ( 22.6 % ) compared with MT ( 61.5 % , p < 0.001 ) . Adjusted hazard ratios for death were 0.51 ( 95 % confidence interval : 0.30 to 0.87 ) for SAVR compared with MT and 0.38 ( 95 % confidence interval : 0.25 to 0.58 ) for TAVI compared with MT . Medical treatment ( < 0.001 ) , older age ( > 80 years , p = 0.01 ) , peripheral vascular disease ( < 0.001 ) , and atrial fibrillation ( p = 0.04 ) were significantly associated with all-cause mortality at 30 months in the multivariate analysis . At 1 year , more patients undergoing SAVR ( 92.3 % ) or TAVI ( 93.2 % ) had New York Heart Association functional class I/II as compared with patients with MT ( 70.8 % , p = 0.003 ) . CONCLUSIONS Among patients with severe AS with increased surgical risk , SAVR and TAVI improve survival and symptoms compared with MT . Clinical outcomes of TAVI and SAVR seem similar among carefully selected patients with severe symptomatic AS at increased risk OBJECTIVES The aim of this study was to evaluate the cost-effectiveness of transcatheter aortic valve replacement ( TAVR ) compared with surgical aortic valve replacement ( AVR ) for patients with severe aortic stenosis and high surgical risk . BACKGROUND TAVR is an alternative to AVR for patients with severe aortic stenosis and high surgical risk . METHODS We performed a formal economic analysis based on cost , quality of life , and survival data collected in the PARTNER A ( Placement of Aortic Transcatheter Valves ) trial in which patients with severe aortic stenosis and high surgical risk were r and omized to TAVR or AVR . Cumulative 12-month costs ( assessed from a U.S. societal perspective ) and quality -adjusted life-years ( QALYs ) were compared separately for the transfemoral ( TF ) and transapical ( TA ) cohorts . RESULTS Although 12-month costs and QALYs were similar for TAVR and AVR in the overall population , there were important differences when results were stratified by access site . In the TF cohort , total 12-month costs were slightly lower with TAVR and QALYs were slightly higher such that TF-TAVR was economically dominant compared with AVR in the base case and economically attractive ( incremental cost-effectiveness ratio < $ 50,000/QALY ) in 70.9 % of bootstrap replicates . In the TA cohort , 12-month costs remained substantially higher with TAVR , whereas QALYs tended to be lower such that TA-TAVR was economically dominated by AVR in the base case and economically attractive in only 7.1 % of replicates . CONCLUSIONS In the PARTNER trial , TAVR was an economically attractive strategy compared with AVR for patients suitable for TF access . Future studies are necessary to determine whether improved experience and outcomes with TA-TAVR can improve its cost-effectiveness relative to AVR BACKGROUND The U.S. pivotal trial for the self-exp and ing valve found that among patients with severe aortic stenosis at increased risk for surgery , the 1-year survival rate was 4.9 percentage points higher in patients treated with a self-exp and ing transcatheter aortic valve bioprosthesis than in those treated with a surgical bioprosthesis . OBJECTIVES Longer-term clinical outcomes were examined to confirm if this mortality benefit is sustained . METHODS Patients with severe aortic stenosis who were at increased surgical risk were recruited . Eligible patients were r and omly assigned in a 1:1 ratio to transcatheter aortic valve replacement with the self-exp and ing transcatheter valve ( transcatheter aortic valve replacement [ TAVR ] group ) or to aortic valve replacement with a surgical bioprosthesis ( surgical group ) . The 2-year clinical and echocardiographic outcomes were evaluated in these patients . RESULTS A total of 797 patients underwent r and omization at 45 centers in the United States . The rate of 2-year all-cause mortality was significantly lower in the TAVR group ( 22.2 % ) than in the surgical group ( 28.6 % ; log-rank test p < 0.05 ) in the as-treated cohort , with an absolute reduction in risk of 6.5 percentage points . Similar results were found in the intention-to-treat cohort ( log-rank test p < 0.05 ) . The rate of 2-year death or major stroke was significantly lower in the TAVR group ( 24.2 % ) than in the surgical group ( 32.5 % ; log-rank test p = 0.01 ) . CONCLUSIONS In patients with severe aortic stenosis who are at increased surgical risk , the higher rate of survival with a self-exp and ing TAVR compared with surgery was sustained at 2 years . ( Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) Background — In patients with severe aortic stenosis who can not have surgery , transcatheter aortic valve replacement ( TAVR ) has been shown to improve survival and quality of life compared with st and ard therapy , but the costs and cost-effectiveness of this strategy are not yet known . Methods and Results — The PARTNER trial r and omized patients with symptomatic , severe aortic stenosis who were not c and i date s for surgery to TAVR ( n=179 ) or st and ard therapy ( n=179 ) . Empirical data regarding survival , quality of life , medical re source use , and hospital costs were collected during the trial and used to project life expectancy , quality -adjusted life expectancy , and lifetime medical care costs to estimate the incremental cost-effectiveness of TAVR from a US perspective . For patients treated with TAVR , mean costs for the initial procedure and hospitalization were $ 42 806 and $ 78 542 , respectively . Follow-up costs through 12 months were lower with TAVR ( $ 29 289 versus $ 53 621 ) because of reduced hospitalization rates , but cumulative 1-year costs remained higher ( $ 106 076 versus $ 53 621 ) . We projected that over a patient 's lifetime , TAVR would increase discounted life expectancy by 1.6 years ( 1.3 quality -adjusted life-years ) at an incremental cost of $ 79 837 . The incremental cost-effectiveness ratio for TAVR was thus estimated at $ 50 200 per year of life gained or $ 61 889 per quality -adjusted life-year gained . These results were stable across a broad range of uncertainty and sensitivity analyses . Conclusions — For patients with severe aortic stenosis who are not c and i date s for surgery , TAVR increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00530894 |
10,889 | 17,943,778 | It is likely that self-management education is associated with a reduction in hospital admissions with no indications for detrimental effects in other outcome parameters .
This would in itself already be enough reason for recommending self-management education in COPD .
However , because of heterogeneity in interventions , study population s , follow-up time , and outcome measures , data are still insufficient to formulate clear recommendations regarding the form and contents of self-management education programmes in COPD . | BACKGROUND There is great interest in chronic obstructive pulmonary disease ( COPD ) and the associated large burden of disease .
COPD is characterised by frequent day by day fluctuations , and repetitive clinical exacerbations are typical .
Self-management is a term applied to educational programmes aim ed at teaching skills needed to carry out medical regimens specific to the disease , guide health behaviour change , and provide emotional support for patients to control their disease and live functional lives .
In COPD , the value of self-management education is not yet clear .
The first Cochrane review about self-management was published in 2003 .
It was intended to shed light on the effectiveness of self-management programmes in COPD and the relative efficacy of their constitutive elements .
No conclusions about the effectiveness of self-management could be drawn because of the large variation in outcome measures used in the limited number of included studies .
This article describes the first up date of this review .
OBJECTIVES The objective of this review was to assess the setting s , methods and efficacy of COPD self-management education programmes on health outcomes and use of health care services . | Abstract In March 2002 The Northern Clinical Research Centre , Epping implemented a six week outpatient based pulmonary rehabilitation program for people with COPD . This paper outlines the establishment , underlying philosophy , marketing , coordination and personnel necessary for a successful program , as identified by the research centre . Barriers to program participation were identified and steps to minimize these were implemented . The longitudinal evaluation of this program in a prospect i ve manner enables the duration of the effect of this adjunctive therapy to be examined in the Australian population . One hundred and thirty six participants have graduated from the research centre 's pulmonary rehabilitation program since the program commenced in 2002 . This paper review s the process of implementing a pulmonary rehabilitation program in the northern corridor of Melbourne Aims : The main objective of this study was to investigate whether a comprehensive self-management programme , including self-treatment guidelines for exacerbations and a fitness programme , is an efficient treatment option for chronic obstructive pulmonary disease ( COPD ) patients . Method : We r and omly allocated 248 COPD patients to either self-management ( 127 ) or usual care ( 121 ) . Data on preference-based utilities ( EuroQol-5D ) , health-related quality of life ( HRQoL ) , health-care re source use and productivity losses associated with exacerbations were prospect ively collected . Quality -adjusted life years ( QALYs ) were calculated . The economic analysis took the societal perspective and the observation period was one year . Results : As we observed that the groups were equally effective in terms of QALYs and HRQoL ( SGRQ ) , we described a cost minimization analysis only . The self-management programme-specific costs amounted to 6642 per patient . In the base-case cost analysis , the incremental cost difference amounted to 838 per patient per year in favour of usual care . When only direct medical costs were included , the incremental annual cost of self-managementrelative to usual care was 179 per person per year . If time costs for the fitness programme were set to zero , the costs for self-management diminished to 542 . Sensitivity analysis showed that these results were robust to changes in the underlying assumptions . Conclusion : We conclude that the COPE self-management programme is not an efficient treatment option for moderate to severe COPD patients who rate their HRQoL relatively high . The programme was twice as expensive as usual care and had no measurable beneficial effects on QALYs or On the basis of the beneficial health effects of self-management in the treatment of other chronic diseases like asthma it might be expected that the active participation of COPD - patients in the management of their disease may reduce the burden of the disease . Self-management of COPD includes sufficient coping behaviour , compliance with inhaled medication , attention to changes in the severity of the disease , adequate inhalation technique , and self adjustment of the medication in case of exacerbations . The results of a pilot study on the effects of self-management in COPD suggest a reduction of morbidity due to COPD . The definite place of self-management in the treatment of COPD has to established by larger , prospect i ve , controlled trials This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation . In this r and omized , controlled study , 126 patients with chronic obstructive pulmonary disease ( COPD ) were stratified for dyspnoea using the Medical Research Council ( MRC ) dyspnoea score into MRC3/4 ( Moderate ) ( n=66 ) and MRC 5 ( Severe ) dyspnoeic ( n=60 ) groups . The patients were r and omly assigned to an eight week programme of either exercise plus education ( Exercise group ) or education ( Control group ) . Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting . Severely dyspnoeic patients were all treated at home . Those in the Exercise group received an individualized training programme . There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group , who received exercise training ; baseline ( mean+/-SEM ) 191+/-22 m , post-rehabilitation 279+/-22 m ( p<0.001 ) . There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise . Neither group of control patients improved . Health status , assessed by the Total Chronic Respiratory Disease Question naire score , increased in the moderately dyspnoeic patients receiving exercise from 80+/-18 to 95+/-17 ( p<0.0001 ) after rehabilitation . Much smaller changes were seen in the other three groups . Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea The aim of the present study was to assess the long-term impact on hospitalisation of a self-management programme for chronic obstructive pulmonary disease ( COPD ) patients . A multicentre , r and omised clinical trial was carried out involving 191 COPD patients from seven hospitals . Patients who had one or more hospitalisations in the year preceding study enrolment were assigned to a self-management programme “ Living Well with COPD TM ” or to st and ard care . Hospitalisations from all causes were the primary outcome and were documented from the provincial hospitalisation data base ; emergency visits were recorded from the provincial health insurance data base . Most patients were elderly , not highly educated , had advanced COPD ( reflected by a mean forced expiratory volume in one second of 1 L ) , and almost half reported a dyspnoea score of 5/5 ( modified Medical Research Council ) . At 2 years , there was a statistically significant and clinical ly relevant reduction in all-cause hospitalisations of 26.9 % and in all-cause emergency visits of 21.1 % in the intervention group as compared to the st and ard-care group . After adjustment for the self-management intervention effect , the predictive factors for reduced hospitalisations included younger age , sex ( female ) , higher education , increased health status and exercise capacity . In conclusion , in this study , patients with chronic obstructive pulmonary disease who received educational intervention with supervision and support based on disease-specific self-management maintained a significant reduction in hospitalisations after a 2-year period Abstract Objective : To assess whether sharing the uncertainty of the value of antibiotics for acute bronchitis in the form of written and verbal advice affects the likelihood of patients taking antibiotics . Design : Nested , single blind , r and omised controlled trial . Setting : Three suburban general practice s in Nottingham . Participants : 259 previously well adults presenting with acute bronchitis . Intervention : In group A , 212 patients were judged by their general practitioner not to need antibiotics that day but were given a prescription to use if they got worse and st and ard verbal reassurance . Half of them ( 106 ) were also given an information leaflet . All patients in group B ( 47 ) were judged to need antibiotics and were given a prescription and encouraged to use it . Main outcome measures : Antibiotic use in the next two weeks . Reconsultation for the same symptoms in the next month . Results : In group A fewer patients who received the information leaflet took antibiotics compared with those who did not receive the leaflet ( 49 v 63 , risk ratio 0.76 , 95 % confidence interval 0.59 to 0.97 , P=0.04 ) . Numbers reconsulting were similar ( 11 v 14 ) . In group B , 44 patients took the antibiotics . Conclusion : Most previously well adults with acute bronchitis were judged not to need antibiotics . Reassuring these patients and sharing the uncertainty about prescribing in a information leaflet supported by verbal advice is a safe strategy and reduces antibiotic use . What is already known on this topic Most adults with acute bronchitis who consult their general practitioner will receive antibiotics For most patients antibiotics do not modify the natural course of the symptoms The widespread belief among patients that infection is the problem and antibiotics the solution has considerable influence on prescribing by general practitioners , even when they judge that antibiotics are not definitely indicated What this study adds General practitioners judged that about four in five adults with acute bronchitis did not definitely need antibiotics on the day they consulted Antibiotic use was reduced by a quarter in such patients , who received verbal and written information and reassurance in addition to a prescription for antibiotics Sharing with the patient the uncertainty about the decision to prescribe seems safe and The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life ( HRQoL ) , symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease ( COPD ) . This study was part of the overall COPD study of the Dept of Pulmonary Medicine , Enschede , which consisted of an inhaled corticosteroid ( ICS ) trial and a self-management trial . After the ICS trial , all patients were r and omised again to a self-management and a control group . The self-management intervention consisted of askill-oriented patient education programme and a near-home fitness programme , on top of usual care . The control group received usual care by the treating chest physician . HRQoL was measured by the St George ’s Respiratory Question naire ( SGRQ ) and walking distance by the 6‐min walking test . Patients recorded their symptoms in diaries and grade d their health status from 1–10 in a weekly report . Altogether , 248 COPD patients were r and omly allocated to either an intervention ( 127 ) or control ( 121 ) group . No differences in the SGRQ scores within and between both groups were observed over 1 yr . Similarly , no differences in symptom scores and 6‐min walking distance were found within and between groups . The intervention group reported more exacerbations than the control group . The majority ( 69 % ) of the exacerbations in the intervention group were self-treated at home . This study failed to show positive effects of a self-management programme among moderately severe chronic obstructive pulmonary disease patients This study assessed the long-term efficacy of adding self-treatment guidelines to a self-management programme for adults with asthma . In this prospect i ve r and omized controlled trial , 245 patients with stable , moderate to severe asthma were included . They were r and omized into a self-treatment group ( group S ) and a control group ( group C ) . Both groups received self-management education . Additionally , group S received self-treatment guidelines based on peak expiratory flow ( PEF ) and symptoms . Outcome parameters included : asthma symptoms , quality of life , pulmonary function , and exacerbation rate . The 2-yr study was completed by 174 patients . Both groups showed an improvement in the quality of life of 7 % . PEF variability decreased by 32 % and 29 % , and the number of outpatient visits by 25 % and 18 % in groups S and C , respectively . No significant differences in these parameters were found between the two groups . After 1 yr , patients in both groups perceived better control of asthma and had more self-confidence regarding their asthma . The latter improvements were significantly greater in group S as compared to group C. There were no other differences in outcome parameters between the groups . Individual self-treatment guidelines for exacerbations on top of a general self-management programme does not seem to be of additional benefit in terms of improvements in the clinical outcome of asthma . However , patients in the self-treatment group had better scores in subjective outcome measures such as perceived control of asthma and self-confidence than patients in the control group Seventy five patients with chronic respiratory disability were r and omised to a group visited by a respiratory health worker ( 42 ) or control group ( 33 ) . The first group was visited monthly by a respiratory nurse , who gave education and support . The effect of the intervention was assessed in terms of quality of life ( by question naires ) , the number and duration of admissions to hospital , and the number of deaths . The question naires on quality of life showed no changes in either group during the study , but nearly all of the group visited by a respiratory health worker said that they valued the visits and wished them to continue . Their knowledge about their condition also improved compared with that of the controls . The duration of stay in hospital for respiratory reasons in the group visited by a respiratory health worker was longer than that of control patients . This was explained by their being scored as more ill than the controls on admission . Fewer patients died in the group visited by a respiratory health worker than in the control group ( p = 0.11 ) . The patients in the group visited by respiratory health workers may have survived longer because they sought help rather than dying at home . If confirmed this could have implication s for the cost of their care By instructing patients in how to deal with their disease financial dem and s on health services may be reduced . 100 consecutive patients ( aged 48 to 89 ) admitted to a general medical ward in Denmark with chronic obstructive pulmonary disease ( COPD ) were allocated r and omly to receive either " personalized hospital practice " ( PHP ) , which includes training in aspects of their disease , or st and ard hospital practice . Changes in " consumption " of health services per patient from 1 year before until 1 year after the intervention admission were evaluated in 82 ( PHP group 42 , controls 40 ) patients who completed the intervention phase . Each group contained about the same percentage of asthmatics and smokers . The increase in consumption of health services after intervention was on average Kr15,298 per patient per year less in the PHP group than in the control group ( p = 0.048 , Wilcoxon test ) . Consumption of general practitioner services was significantly increased in the control group compared with the PHP group ( mean [ 95 % Cl ] Kr1346 [ 549 to 2143 ] vs -89 [ -423 to 245 ] per patient per year ; p = 0.001 , Wilcoxon test ) . These differences could not be explained by changes in smoking habits . PHP reduces the consumption of health services by patients with COPD , probably by increasing patients ' knowledge of disease and hence their ability to manage themselves Disability associated with chronic obstructive pulmonary disease has led to the development of rehabilitation programmes that aim to increase exercise tolerance and improve quality of life . Many reports of the benefits of rehabilitation have been from uncontrolled trials and unsupervised programmes . In view of the commitment asked of patients , their families , and health-care professionals , rehabilitation should be justified by a demonstration of sustained improvement over conventional treatment . We undertook a prospect i ve r and omised controlled trial of respiratory rehabilitation in 89 subjects ( 44 men , 45 women ) aged 66 ( SD 7 ) years with severe but stable chronic obstructive pulmonary disease who received rehabilitation or conventional community care . The treatment group were rehabilitated as in patients for 8 weeks and supervised as out patients for 16 weeks . Primary outcome measures of exercise tolerance and quality of life were made at baseline and repeated at 12 , 18 , and 24 weeks . The difference between baseline and last follow-up was significant for 6 min walk distance ( 37.9 m [ 95 % CI 10.8 - 65.0 ] , p = 0.0067 ) and submaximal cycle time ( 4.7 min [ 2.1 - 7.3 ] ) . There were also significant differences in question naire assessment of dyspnoea ( p = 0.0061 ) , emotional function ( p = 0.0150 ) , mastery ( p = 0.0002 ) , and dyspnoea index ( p = 0.0053 ) . Improvements in exercise tolerance and quality of life can be achieved and sustained for 6 months in patients undergoing respiratory rehabilitation compared with those receiving conventional care This study compared the effects on self-efficacy of participation by patients with chronic obstructive pulmonary disease ( COPD ) in a pulmonary rehabilitation program that combined education and supervised exercise training with the results demonstrated by participation in a program that provided education alone . Thirty-seven patients participated in the pulmonary rehabilitation program , and 22 patients participated in the education-only program . Self-efficacy , as it effects managing or avoiding breathing difficulty , was measured before and after the programs . Patients ' self-efficacy scores significantly improved after the pulmonary rehabilitation program and remained significantly improved 6 months later . Education alone was also effective in significantly improving self-efficacy scores , but patients ' scores 6 months later were not significantly better than preprogram scores . This study indicates that a rehabilitation program that combines education and exercise training is more effective in improving long-term self-efficacy in patients with COPD We hypothesized that the use of an Action Plan might assist self-management for patients with chronic obstructive pulmonary disease ( COPD ) . A pilot process and r and omized , controlled study were undertaken to evaluate an Action Plan that provided advice on management of usual care and exacerbations , together with a booklet on self-management . Fifty six subjects with COPD recruited through general practitioners ( GPs ) completed the 6 month study , 27 in the control group and 29 in the intervention group . The control group received usual care from their GP , and the intervention group received a booklet and Action Plan from their practice nurse plus a supply of prednisone and antibiotic from their GP . The two groups were demographically similar with a mean age of 68 yrs . The re sources were well received by GPs , practice nurses and intervention group subjects . After 6 months , there were no differences in quality of life scores or pulmonary function . There were significant changes in self-management behaviour in the intervention group compared to controls . In response to deteriorating symptoms , 34 versus 7 % ( p=0.014 ) initiated prednisone treatment and 44 versus 7 % ( p=0.002 ) initiated antibiotics . Subjects in the intervention group readily adopted self-management skills but did not show any difference in quality of life or lung function parameters . A larger , prospect i ve , controlled , clinical trial of this approach is warranted The effects of three versions of a dyspnea self-management program on depressed mood and the moderating effects of baseline depression risk on improvements in dyspnea severity , exercise performance , and physical and social functioning were examined over a 2-month period in 100 patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . All three versions of the dyspnea self-management programs , which differed in the amount of supervised exercise ( no sessions or four or 24 sessions ) , equally and significantly improved depressed mood . Subjects at high risk for depression at study entry who received 24 sessions had greater reduction in dyspnea than those who received four sessions or no sessions . Patients with COPD at high risk for depression are likely to achieve greater relief of dyspnea with self-management programs that include more intensive supervised exercise The chronic obstructive pulmonary diseases are major causes of disability and death [ 1 - 3 ] . Health statistics underestimate the prevalence of these diseases because of difficulties in definition and recognition and because of misclassification [ 4 ] . Although st and ard medical therapy can alleviate symptoms , many patients with these diseases must cope with the distressing symptom of breathlessness that results from a chronic , irreversible , and disabling disease . These patients may use services in physician offices , emergency departments , hospitals , and intensive care units , in part because of a lack of underst and ing and inability to cope with frightening and disabling symptoms . Since a comprehensive care program for patients with chronic obstructive pulmonary disease was first described [ 5 ] , pulmonary rehabilitation has become an established way to enhance st and ard therapy to control symptoms , optimize functional capacity , and reduce the medical and economic burdens of patients with disabling chronic lung diseases [ 6 - 12 ] . Comprehensive programs usually include education , instruction in respiratory and chest physiotherapy techniques , psychosocial support , and exercise training [ 13 ] . The primary goal of rehabilitation is to restore the patient to the highest possible level of independent function . This is accomplished by helping patients to become more knowledgeable about their disease , more actively involved in their own health care , more independent in performing daily activities , and less dependent on others , including health professionals . Previous studies have shown important benefits of pulmonary rehabilitation , including increased exercise tolerance and quality of life and a decreased number of symptoms and use of health care services [ 7 ] . However , many of these findings are based on small numbers of patients and on observational , nonr and omized studies . We compared the effects of comprehensive pulmonary rehabilitation on both physiologic and psychosocial outcomes with the effects of education alone . Our study featured r and om assignment and long-term , 6-year follow-up . Methods Patients For 18 months , 352 patients with chronic obstructive pulmonary disease were screened for the study ; 128 met entry criteria and were r and omly assigned to either the comprehensive pulmonary rehabilitation program or an education program ( control group ) . Patients were recruited through mechanisms similar to those used in regular clinical pulmonary rehabilitation , including written and personal contact with physicians and direct advertisement to the general public for persons with breathlessness . Nine patients who initially agreed to participate ( 6 in the rehabilitation group and 3 in the education group ) but who withdrew from the study before completing 2 weeks of the interventions were considered to be pretreatment drop-outs . Reasons for dropping out included concurrent illness ( four patients ) , a too-large time commitment ( 2 patients ) , and no clear explanation ( 3 patients ) . Patients who dropped out and those who remained in the study did not differ . The remaining 119 patients comprised 32 women and 87 men . The following were the inclusion criteria : 1 . Clinical diagnosis of mild to severe chronic obstructive pulmonary disease that was confirmed by history , physical examination , spirometry , measurement of arterial blood gases , and chest roentgenograms . Patients with diagnoses of emphysema , chronic bronchitis , or asthmatic bronchitis were accepted . Patients with primarily acute , reversible airway disease ( asthma ) but no chronic airflow obstruction were excluded . 2 . Stable condition while the patient was receiving an acceptable medical regimen and was under the care of a primary care provider . Patients without a primary care physician who presented for evaluation were referred for appropriate evaluation and treatment before they enrolled in the study . 3 . No other significant disabling lung disease , serious heart problems , or other medical condition that would interfere with the patient 's participation . Current smokers were not excluded if they showed a commitment to quitting smoking before enrollment . Smoking cessation counseling was incorporated into the rehabilitation program for patients assigned to that group . Experimental Design All eligible patients were r and omly assigned to participate in either the comprehensive pulmonary rehabilitation program ( n = 57 ) or the education program ( n = 62 ) . The r and omization scheme was fixed before the trial with a block size of 8 . Assignment was determined by a table of r and om numbers and was indicated on cards placed in sequentially numbered envelopes that were kept in a central office separate from the study site . Clinical personnel were unaware of the r and omization scheme . After a patient agreed to enroll and signed the consent form approved by the University of California , San Diego , Human Subjects Committee , the central office was contacted by telephone and the next numbered envelope was opened . Interventions Pulmonary Rehabilitation Program The comprehensive rehabilitation program included two phases . Phase I ( core program ) consisted of twelve 4-hour sessions given over 8 weeks . Each session included two periods of classroom or group support and supervised exercise training . The rehabilitation program included four main components : 1 . Education . Groups of three to six patients were taught by experienced pulmonary rehabilitation staff and selected guest speakers . Topics included the following : How Normal Lungs Work , What Is Chronic Obstructive Pulmonary Disease ? , Medications , Nutrition , Oxygen Therapy , Coping with Stress , Energy-saving Techniques , Self-Care Tips , Travel , Pollution and Environmental Hazards , When To Call Your Doctor , Smoking Cessation Techniques , Planning a Daily Schedule , and Breathing Techniques . 2 . Physical and respiratory care instruction . Patients received individual instruction in respiratory care and chest physiotherapy techniques such as postural drainage , pursed lip and diaphragmatic breathing , oxygen therapy , and proper use of respiratory therapy equipment . 3 . Psychosocial support . Patients and staff met in weekly group sessions facilitated by a psychiatrist . Spouses or partners of the patients were encouraged to attend . Sessions focused on difficulties commonly faced by patients , such as depression , anxiety , fear , and family or social problems . Relaxation techniques were introduced to help patients better cope with the emotional stress of dyspnea . 4 . Supervised exercise training . After the baseline exercise test , each patient received an individualized exercise prescription based on the maximum , symptom-limited level [ 14 ] . Patients with severe hypoxemia ( Pao2 < 55 mm Hg at rest or < 50 mm Hg with exercise ) were trained using supplemental oxygen . The primary exercise-training modality was walking . Training emphasized steady-state exercise consisting of continuous walking at the highest tolerated symptom-limited level for as long as 30 minutes . Patients were initially trained to walk on a motor-driven treadmill under supervision . The staff then instructed patients in translating the target treadmill speed to a pace for free walking . Patients were asked to walk at home at least twice daily and to keep a training log of time , distance , pace ( steps per minute ) , and perceived symptoms of breathlessness and muscle fatigue . Patients were also instructed and trained in upper-extremity exercise using an isokinetic upper-body ergometer during supervised sessions and a progressive program of arm lifts with weights for home training [ 15 ] . Patients were asked to do upper-extremity training daily and to keep a daily log . Phase II of the rehabilitation program involved monthly follow-up visits for 1 year . These visits provided reinforcement after the core phase of the program . These sessions included a supervised period of exercise , group sessions to discuss progress and problems , and the introduction of maintenance techniques . Education Control Program The goal of the education program was to conduct a series of health education classes that would provide information similar to that provided in the rehabilitation program , but in a shorter and less intensive program without the behavioral components , individualized instruction , and supervised exercise training . Patients in the education group attended four 2-hour sessions scheduled biweekly for 8 weeks . Each group consisted of approximately 10 to 15 patients . At the beginning of each session , a videotape describing some aspect of chronic obstructive pulmonary disease management was presented [ Pulmonary Self-Care Series , Encyclopedia Britannica , Vision Multimedia Communications , Inc. , Winter Park , Florida ] . The four-part videotape series included the following programs : 1 ) Learning To Live with a Breathing Problem ; 2 ) Building Your Strength and Endurance ; 3 ) You Can Do It : Clearing Your Airways ; and 4 ) Learning To Breathe Better . Patients also completed life events [ 16 ] , social support [ 17 ] , health locus of control [ 18 ] , and sense of coherence [ 19 ] question naires and a semistructured smoking interview . The patients then participated in a group discussion about either the material covered in the videotape or the question naires . The final hour of the session included a lecture followed by a question and answer period presented by professionals in the fields of pulmonary medicine , pharmacology , respiratory therapy , and nutrition . Assessment Each patient had physiologic and psychosocial function evaluation before intervention ( baseline ) , immediately after the program ended ( 2 months ) , and at regular intervals for 72 months . Physiologic measures , including laboratory pulmonary function and maximal treadmill exercise tests , were done 2 , 12 , 24 , 48 , and 72 months after the program began . Psychosocial measures and endurance exercise tests were done more frequently at 2 , 6 , 12 , 18 , 24 , 36 , 48 , 60 , and 72 months . Laboratory tests of A r and omised controlled trial was undertaken to determine whether a respiratory health worker was effective in reducing the respiratory impairment , disability , and h and icap experienced by patients with chronic airflow limitation attending a respiratory outpatient department . The 152 adults ( aged 30 - 75 years ) who participated had a prebronchodilator forced expiratory volume in one second ( FEV1 ) below 60 % predicted and no other disease . They were r and omised to receive the care of a respiratory health worker or the normal services provided by the outpatient department . The respiratory health worker provided health education and symptom and treatment monitoring in liaison with primary care services . After one year there was little difference between the two groups in spirometric values ( FEV1 and forced vital capacity before and after salbutamol 200 micrograms ) , disability ( six minute walking distance and paced step test ) , and h and icap ( sickness impact profile , hospital anxiety and depression scale ) . Patients not looked after by the respiratory health worker were more likely to die ( relative risk 2.9 ( 95 % confidence limits 0.8 , 10.2 ) ; when age and FEV1 were controlled for this risk increased to 5.5 ( 95 % confidence limits 1.2 , 24.5 ) . Patients looked after by the respiratory health worker attended their general practitioner more frequently and were prescribed a greater range of drugs . This is the third study to have found limited measurable benefit in terms of morbidity from the intervention of a respiratory health worker . This may be due to the ability of such workers to keep frail patients alive Group instruction in self care is a widely used adjunct to the medical management of chronic obstructive pulmonary disease ( COPD ) . Such classes are neither convenient nor accessible to all COPD patients , however , especially those in rural areas . A self-teaching module could be a practical means of serving hard-to-reach patients . This study compares the results of a self-teaching module with those of an established group method in teaching 13 self-care skills to COPD patients . On referral from their physicians , patients in eight rural locations were r and omly assigned to receive training through a group or a self-teaching process . Knowledge gain , skill attainment , skill implementation , and beneficial results were measured at the end of instruction and again six months later . The two teaching methods were compared by analyzing the data on 34 patients matched for the variables of smoking , diagnosis , and severity of disease . No statistically significant difference was observed between the two educational methods in any of the parameters measured . The fact that approximately three out of four patients benefited through either process suggests that the self-teaching module is as effective as group instruction BACKGROUND Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease . We undertook a r and omised controlled trial to assess the effect of outpatient pulmonary rehabilitation on use of health care and patients ' wellbeing over 1 year . METHODS 200 patients with disabling chronic lung disease ( the majority with chronic obstructive pulmonary disease ) were r and omly assigned a 6-week multidisciplinary rehabilitation programme ( 18 visits ) or st and ard medical management . Use of health services was assessed from hospital and general- practice records . Analysis was by intention to treat . FINDINGS There was no difference between the rehabilitation ( n=99 ) and control ( n=101 ) groups in the number of patients admitted to hospital ( 40 vs 41 ) but the number of days these patients spent in hospital differed significantly ( mean 10.4 [ SD 9.7 ] vs 21.0 [ 20.7 ] , p=0.022 ) . The rehabilitation group had more primary -care consultations at the general-practitioner 's premises than did the control group ( 8.6 [ 6.8 ] vs 7.3 [ 8.3 ] , p=0.033 ) but fewer primary -care home visits ( 1.5 [ 2.8 ] vs 2.8 [ 4.6 ] , p=0.037 ) . Compared with control , the rehabilitation group also showed greater improvements in walking ability and in general and disease-specific health status . INTERPRETATION For patients chronically disabled by obstructive pulmonary disease , an intensive , multidisciplinary , outpatient programme of rehabilitation is an effective intervention , in the short term and the long term , that decreases use of health services The effect of patient education on steroid inhaler compliance and rescue medication utilization in patients with asthma or chronic obstructive pulmonary disease ( COPD ) has not been previously investigated in a single study . We r and omized 78 asthmatics and 62 patients with COPD after ordinary outpatient management . Intervention consisted of two 2-h group sessions and 1 to 2 individual sessions by a trained nurse and physiotherapist . A self-management plan was developed . We registered for 12 mo medication dispensed from pharmacies according to the Anatomical Therapeutic Chemical ( ATC ) classification index . Steroid inhaler compliance ( SIC ) was defined as ( dispensed/prescribed ) x 100 and being compliant as SIC > 75 % . Among asthmatics 32 % and 57 % were compliant ( p = 0.04 ) with a median ( 25th/75th percentiles ) SIC of 55 % ( 27/96 ) and 82 % ( 44/127 ) ( p = 0.08 ) in the control and intervention groups , respectively . Patient education did not seem to change SIC in the COPD group . Uneducated patients with COPD were dispensed double the amount of short-acting inhaled beta(2)-agonists compared with the educated group ( p = 0.03 ) . We conclude that patient education can change medication habits by reducing the amount of short-acting inhaled beta(2)-agonists being dispensed among patients with COPD . Educated asthmatics showed improved steroid inhaler compliance compared with the uneducated patients , whereas this seemed unaffected by education in the COPD group PURPOSE Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease ( COPD ) . Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease . This r and omized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years . METHODS Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management . Outcomes were assessed using the 6-minute walk test , St George 's respiratory question naire , and Borg score of perceived breathlessness . Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission . RESULTS Complete data for 23 patients in each group were available for analysis . There was no significant difference between groups on baseline measures . Compared with the control group , intervention patients demonstrated a significant improvement in 6-minute walk test ( P = .023 ) , Borg score of perceived breathlessness ( P = .024 ) , St George 's respiratory question naire total score ( P = .020 ) , and impact subscore ( P = .024 ) . At 6 months , the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation ( P = .035 ) . CONCLUSION A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance , perception of breathlessness , and quality of life for housebound COPD patients . To manage COPD in the community more effectively , health services should focus on exp and ing home-based pulmonary rehabilitation Background In light of health disparities and the growing prevalence of chronic disease , there is a need for community-based interventions that improve health behaviors and health status . These interventions should be based on existing theory . Objective This study aim ed to evaluate the health and utilization outcomes of a 6-week community-based program for Spanish speakers with heart disease , lung disease , or type 2 diabetes . Method The treatment participants in this study ( n = 327 ) took a 6-week peer-led program . At 4 months , they were compared with r and omized wait-list control subjects ( n = 224 ) using analyses of covariance . The outcomes for all the treatment participants were assessed at 1 year , as compared with baseline scores ( n = 271 ) using t-tests . Results At 4 months , the participants , as compared with usual-care control subjects , demonstrated improved health status , health behavior , and self-efficacy , as well as fewer emergency room visits ( p < .05 ) . At 1 year , the improvements were maintained and remained significantly different from baseline condition . Conclusions This community-based program has the potential to improve the lives of Hispanics with chronic illness while reducing emergency room use The principals of rehabilitation medicine are to prevent muscle atrophy and improve mobility . Exacerbations of chronic obstructive pulmonary disease ( COPD ) are associated with muscle atrophy and yet many patients do not undergo pulmonary rehabilitation until they have been in stable health for some time . We investigated the outcome of a supervised home exercise programme initiated immediately after hospitalisation for an exacerbation of COPD . Thirty-one patients were r and omised into an exercise group ( n=16 , FEV(1 ) 0.94+/-0.34 L ) and a control group ( n=15 , FEV(1 ) 1.08+/-0.33 L ) . The exercise group received a twice-weekly supervised exercise programme , in their homes , for 6 weeks . Spirometry , exercise capacity , isometric muscle strength , dyspnea level , quality of life at baseline and 6 weeks as well as subsequent exacerbations were quantified . At 6 weeks , the exercise group , improved the shuttle walk test ( 198 m+/-95 - 304+/-136 m ) and increased 3 min step test capacity ( 119+/-40 - 163+/-26s ) ( both P<0.001 ) . Knee extensor muscle strength and quality of life scores also increased . Neither exercise capacity nor muscle strength altered in the control group . Follow-up at 3 months showed that three of the control group and none of the exercise group had experienced subsequent exacerbations ( P=0.06 ) . Early rehabilitation via a home from hospital programme improved exercise tolerance , muscle strength , dyspnea scores , quality of life in COPD patients and reduced the number of subsequent exacerbations We conducted a r and omized clinical trial to evaluate a limited pulmonary rehabilitation program focused on coping strategies for shortness of breath but without exercise training . Eighty-nine patients with COPD were r and omly assigned to either 6-week treatment or general health education control groups . Treatment consisted of instruction and practice in techniques of progressive muscle relaxation , breathing retraining , pacing , self-talk , and panic control . Tests of 6-min walk distance , quality of well-being , and psychological function as well as six dyspnea measures were administered at baseline , posttreatment , and 6 months after the intervention . Baseline pulmonary function tests also were obtained . At the end of the 6-week treatment , there were no significant differences between the treatment and control groups on any outcome measure . At the 6-month follow-up , a significant group difference was seen on only one variable , Mahler 's transition dyspnea index . The results of this evaluation suggest that a treatment program of dyspnea management strategies , without structured exercise training or other components of a comprehensive pulmonary rehabilitation program , is not sufficient to produce significant improvement in dyspnea , exercise tolerance , health-related quality of well-being , anxiety , or depression PURPOSE The purpose of this study was twofold : ( 1 ) to determine whether exercise training adds to the benefit of a dyspnea self-management ( DM ) program ; and ( 2 ) to determine if there is a " dose response " to supervised exercise training ( 0 , 4 , or 24 sessions ) in dyspnea , exercise performance , and health-related quality of life . METHODS Subjects with chronic obstructive pulmonary disease ( n = 103 , 46 men , 57 women ; age 66 + /- 8 years ; forced expiratory volume in 1 second 44.8 + /- 14 % predicted ) were r and omized to DM , DM-exposure , or DM-training . Dyspnea self-management included individualized education about dyspnea management strategies , a home-walking prescription , and daily logs . Outcomes were measured at baseline and 2 months as part of a 1-year longitudinal r and omized clinical trial . Outcomes included dyspnea during laboratory exercise and with activities of daily living ( Chronic Respiratory Question naire [ CRQ ] ) , Shortness of Breath Question naire , Baseline/Transitional Dyspnea Index ) , exercise performance ( incremental treadmill tests ( ITTs ) and endurance treadmill tests ( ETTs ) , 6-minute walk ( 6MW ) , and health-related quality of life ( SF-36 ) . RESULTS The DM-training group had significantly greater improvements than the DM-exposure and the DM groups in dyspnea at isotime during ITT ( P = .006 ) ; exercise performance during ITT ( P = .005 ) , ETT ( P = .003 ) , and 6MW ( P = .01 ) ; SF-36 Vitality ( P = .031 ) ; and CRQ mastery ( P = .007 ) . There was a dose-dependent improvement in CRQ dyspnea scores ( P < .05 ) with significant improvements only in the DM-training and DM-exposure groups . CONCLUSION Exercise training substantially improved the impact of a dyspnea self-management program with a home walking prescription ( DM ) . This impact tended to be dependent on the " dose " of exercise Abstract Objective : To compare the efficacy of self management of asthma with traditional treatment . Design : 12 month prospect i ve r and omised trial . Setting : Outpatient clinics in Finl and . Subjects : 115 patients with mild to moderately severe asthma . Interventions : Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements . Main outcome measures : Unscheduled admissions to hospital and outpatient visits , days off work , courses of antibiotics and prednisolone , lung function , and quality of life . Results : The mean number of unscheduled visits to ambulatory care facilities ( 0.5 v 1.0 ) , days off work ( 2.8 v 4.8 ) , and courses of antibiotics ( 0.4 v 0.9 ) and prednisolone ( 0.4 v 1.0 ) per patient were lower and the quality of life score ( 16.6 v 8.4 at 12 months ) higher in the self management group than in the traditionally treated group . In both groups admissions for asthma were rare . Conclusions : Self management reduces incidents caused by asthma and improves quality of life . Key messages Key messages This trial of 115 patients with mild to moderately severe disease r and omised half to a traditional care and half to a self management programme consisting of education about asthma and daily peak flow readings Intervention thresholds of < 85 % of the optimal peak flow for doubling the dose of inhaled steroid for two weeks and of < 70 % of the optimal peak flow for starting a course of oral steroids worked well The self management group had fewer incidents ( consultations , days off work , courses of prednisolone or antibiotics ) than the traditionally treated group and better quality of life scores Adherence of patients to the self management instructions was better than Patient satisfaction with general practitioners ( GP ) and pulmonary outpatient clinics has not been previously compared in patients with asthma and chronic obstructive pulmonary disease ( COPD ) in addition to the effect of patient education on this satisfaction . We r and omly allocated 78 asthmatics and 62 patients with COPD after ordinary outpatient management to a control or an intervention group . Intervention consisted of educational group sessions and individual sessions administered by a trained nurse and physiotherapist . A self-management plan was developed . A patient satisfaction question naire was answered at baseline and at the 1-year follow-up . Before r and omization , a higher proportion of asthmatics were satisfied with the overall h and ling of their disease by the outpatient clinic ( 86 % ) compared with their GPs ( 72 % , P=0.027 , chi2-test ) . Equal and high proportions of patients with COPD were satisfied with both their GPs ( 85 % ) and the outpatient clinic ( 87 % ) and in general seemed more satisfied with their GP than asthmatics ( P=0.064 ) . At the 1 year follow-up , 100 % of the educated patients with COPD reported overall satisfaction with GPs compared with 78 % in the control group ( P=0.023 ) , but not for asthmatics ( 75 and 78 % , respectively , P=0.581 ) . We conclude that before being given education , asthmatics are more satisfied with the pulmonary outpatient clinic than with GPs , regarding the overall h and ling of their disease . Patients with COPD seemed more satisfied with GPs than asthmatics . For patients with COPD , patient education seemed to improve overall patient satisfaction with GPs , but this was not true for asthmatics . At baseline , overall satisfaction with the outpatient clinic was so beneficial that we had little chance of detecting any improvement Introduction : Acute exacerbations of chronic obstructive pulmonary disease ( COPD ) are a frequent reason for admission to hospital and are responsible for the majority of the direct economic costs of treating COPD . Aims : To test whether an individualized care plan for patients experiencing acute exacerbations of COPD result in reduced health care utilization and improved quality of life for patients . Methods : Ninety-two patients with confirmed COPD were selected by general practitioners or district nurses , and r and omly assigned to care plan or usual care groups . The care plan was developed in collaboration with general practitioners , secondary care specialists , specialist nurses , ambulance service providers and the after hours clinic . Patients were followed for 12 months , and the primary end-points were frequency of use of primary care services and hospital admissions . Results : There was no significant reduction in hospital admissions or improvement in quality of life in the group of patients who used the care plan compared to controls . The care plan group called out the ambulance service more frequently [ 2.8 ( 1.3 , 4.3 ) versus 1.1 ( 0.7 , 1.5 ) calls per 12 months ; P = 0.03 ] , and there was a trend towards greater use of oral prednisone [ 2.3 ( 1.4 , 3.2 ) versus 1.3 ( 0.8 , 1.8 ) courses per 12 months ; P = 0.06 ] . Conclusion : In contrast to asthma , the provision of individualized self-management plans , whose content was enhanced to provide guidance to carers and health care professionals , did not reduce health care utilization or improve overall quality of life during acute exacerbations of COPD . Other strategies are required Ferrari M , Vangelista A , Vedovi E , Falso M , Segattini C , Brotto E , Brigo B , Lo Cascio V : Minimally supervised home rehabilitation improves exercise capacity and health status in patients with COPD . Am J Phys Med Rehabil 2004;83:337–343 . Objective : The purpose of this study was to investigate the effects on exercise tolerance and quality of life of an outpatient rehabilitation program implemented at home without a physiotherapist 's direct supervision in patients with chronic obstructive lung disease . Design : Patients with moderate chronic obstructive pulmonary disease were studied . The rehabilitation program included lower limb exercise on a stationary bicycle and upper limb exercise and stretching , together with education , and it lasted for 12 wks . Every 2 wks , a physiotherapist contacted patients by phone to evaluate their compliance with the rehabilitation program and any adverse effects . The main measures of outcome were the Health Status Index , cycle ergometer test , forced expiratory volume in 1 sec , and forced vital capacity . Patients were evaluated at the baseline and at 12 wks . Results : A total of 32 patients were recruited and 28 ( mean age , 70.4 yrs ) completed the trial . After pulmonary rehabilitation , a significant improvement was found in seven of the nine Health Status Index quality -of-life subscales . Exercise tolerance also improved significantly , whereas no variation was observed in pulmonary function tests . There was no correlation between the improvement in quality of life and the improvement in exercise tolerance . The improvements in the Health Status Index physical function and general health subscales correlated negatively with forced expiratory volume in 1 sec ( percentage of predicted value ) and positively with residual volume/total lung capacity ratio . The improvement in exercise tolerance ( expressed in watts or as maximum oxygen uptake ) , but not in quality -of-life indexes , was associated negatively with age and positively with weight , cognitive function , and forced expiratory volume in 1 sec/forced vital capacity ratio . Conclusions : We conclude that an inexpensive home rehabilitation program can improve quality of life and exercise tolerance in patients with moderate chronic obstructive pulmonary disease . Furthermore , our results indicate that exercise tolerance evaluated by cycloergometry and quality of life evaluated by the mean of the Health Status Index question naire are independent outcome measures of pulmonary rehabilitation Exercise rehabilitation is recommended increasingly for patients with chronic obstructive pulmonary disease ( COPD ) . This study examined the effect of exercise and education on 79 older adults ( M age = 66.6 + /- 6.5 years ; 53 % female ) with COPD , r and omly assigned to 10 weeks of ( a ) exercise , education , and stress management ( EXESM ; n = 29 ) ; ( b ) education and stress management ( ESM ; n = 25 ) ; or ( c ) waiting list ( WL ; n = 25 ) . EXESM included 37 sessions of exercise , 16 educational lectures , and 10 weekly stress management classes . ESM included only the 16 lectures and 10 stress management classes . Before and after the intervention , assessment s were conducted of physiological functioning ( pulmonary function , exercise endurance ) , psychological well-being ( depression , anxiety , quality of life ) , and cognitive functioning ( attention , motor speed , mental efficiency , verbal processing ) . Repeated measures multivariate analysis of variance indicated that EXESM participants experienced changes not observed among ESM and WL participants , including improved endurance , reduced anxiety , and improved cognitive performance ( verbal fluency ) PURPOSE To evaluate the differences in the long-term outcomes of dyspnea , exercise performance , health-related quality of life , and health re source utilization following a dyspnea self-management program with 3 different " doses " of supervised exercise . PATIENTS AND METHODS In a prospect i ve , r and omized , single-blind , 1-year trial , patients with stable chronic obstructive pulmonary disease ( N = 103 ; age 66 + /- 8 , females 57 ; FEV1 44.8 % + /- 14 % predicted ) were r and omly assigned to either : ( 1 ) Dyspnea self-management program ( DM ) ; ( 2 ) DM plus 4 supervised exercise sessions ( DM-exposure ) ; or ( 3 ) DM plus 24 supervised exercise sessions ( DM-training ) . The dyspnea self-management program included individualized education and demonstration of dyspnea self-management strategies , an individualized home walking prescription , and biweekly nurse telephone calls . Outcomes were measured at baseline and every 2 months for 1 year . RESULTS The DM-training group had significantly greater improvements in dyspnea during incremental treadmill test and in exercise performance on the incremental and endurance treadmill tests at 6 and 12 months compared with the other 2 groups . Dyspnea with activities of daily living and self-reported physical functioning significantly improved for all groups over time . The dose-response relationship between supervised exercise and improvement in dyspnea present at 2 months was not sustained over the year . CONCLUSION Consistent with previous findings from evaluation studies of pulmonary rehabilitation programs , the greater number of supervised exercise training sessions improved laboratory dyspnea and performance more than the other two doses of exercise . In the long term , the improvement in dyspnea with activities of daily living and physical functioning was similar for all 3 groups BACKGROUND A steady increase in chronic obstructive pulmonary disease ( COPD ) admissions was addressed by enhancing primary care to provide intensive chronic disease management . AIM To compare the effect of a disease management programme , including a COPD management guideline , a patient-specific care plan and collaboration between patients , general practitioners , practice nurses , hospital physicians and nurse specialists with conventional care , on hospital admissions and quality of life . METHODS One hundred and thirty-five patients with a clinical diagnosis of moderate to severe COPD were identified from hospital admission data and general practice records . General practice s were r and omized to either conventional care ( CON ) , or the intervention ( INT ) . Pre- and post- study assessment included spirometry , Shuttle Walk Test , Short Form-36 , and the Chronic Respiratory Question naire ( CRQ ) . Admission data were compared for 12 months prior to and during the trial . RESULTS For respiratory conditions , mean hospital bed days per patient per year for the INT group were reduced from 2.8 to 1.1 , whereas those for the CON group increased from 3.5 to 4.0 ( group difference , P = 0.030 ) The INT group also showed an improvement for two dimensions of the CRQ , fatigue ( P = 0.010 ) and mastery ( P = 0.007 ) . CONCLUSIONS A chronic disease management programme for COPD patients that incorporated a variety of interventions , including pulmonary rehabilitation and implemented by primary care , reduced admissions and hospital bed days . Key elements were patient participation and information sharing among healthcare providers The effect of patient education in patients with asthma and Chronic Obstructive Pulmonary Disease ( COPD ) on health-related quality of life ( HRQoL ) is not previously investigated using the St. George 's Respiratory Question naire ( SGRQ ) . We r and omly allocated at our out-patient clinic 78 asthmatics and 62 patients with COPD to either a control or an intervention group . Intervention consisted of two 2-h group sessions and one to two individual sessions each by a nurse and a physiotherapist . A self-management plan was developed . Baseline quality of life assessment showed comparable scores independent of treatment groups among asthmatics and patients with COPD , but statistically significantly better scores ( p < 0.05 ) for the educated asthma group after 12 mo compared with the control group . This aligned with the 12-mo SGRQ assessment , which revealed better symptoms , activity , impact , and total scores by 11 ( p < 0.02 ) , 15 ( p < 0.01 ) , 19 ( p < 0.001 ) , and 16 ( p < 0.001 ) units , respectively . Patient education among asthmatics increased the FEV1 by a mean value of 6.1 % ( SD , 12 ) compared with the control group ( p < 0.05 ) . Education among patients with COPD did not indicate a significant increase in HRQoL as measured by the SGRQ or increased FEV1 . We conclude that patient education increased HRQoL and FEV1 among asthmatics , but not among patients with COPD The effect of patient education on morbidity in asthmatics and COPD patients has not previously been investigated in a single study . We r and omized 78 asthmatics and 62 COPD patients after ordinary outpatient management . Intervention consisted of educational group sessions and individual sessions administered by a trained nurse and physiotherapist . A self-management plan was developed . The utilization of health re sources and absenteeism from work was self-reported monthly . During the 12-month follow-up , approximately two ( P= 0.001 ) and three ( P= 0.001 ) times as many uneducated asthmatics and COPD patients , respectively , visited their general practitioner ( GP ) compared with educated . The mean reduction in GP consultations for the educated were 73 % ( P<0.001 ) and 85 % ( P<0.0001 ) for the asthma and COPD group , respectively , compared with uneducated . Fifty percent of uneducated asthmatics reported absenteeism from work compared with 24 % of the educated ( P = 0.06 ) . The mean reduction in days offwork for the educated was 69 % ( P = 0.03 ) , compared with uneducated . A positive correlation was observed between St George 's Respiratory Question naire total score and number of GP visits for both the asthma and COPD group ( P < 0.001 ) . We conclude that patient education in asthmatics and COPD patients reduced the need for GP visits and kept a greater proportion of patients independent of their GP . Patient education among asthmatics also reduced the number of days off work and appeared to increase the proportion of patients not reporting absenteeism from work at all . Increasing number of GP visits was correlated with decreased health-related quality of life as measured by the SGRQ for both the asthmatics and the COPD patients STUDY OBJECTIVES Whereas pulmonary rehabilitation reduces symptoms and improves the quality of life of patients with COPD and is recommended in management guidelines , few patients have access to rehabilitation services . The purpose of this study was to investigate the effectiveness of increasing access to selected components of pulmonary rehabilitation by providing nurse-assisted home care that was composed of patient education , efforts to improve patient self-management skills , and enhanced follow-up . DESIGN We conducted a 6-month , r and omized , controlled trial . SETTING Primary care clinics associated with an urban academic health system . PATIENTS Patients were > or = 45 years of age with a physician diagnosis of COPD , and had a > or = 20-pack-year smoking history , had experienced at least one respiratory symptom during the past 12 months , and had airflow obstruction ( ie , FEV1/FVC ratio , < 70 % ; FEV1 , < 80 % ) . INTERVENTIONS Four nurses were trained in the use of the Global Initiative for Chronic Obstructive Lung Disease guidelines , and two of the four nurses received additional training in collaborative management . Patients were r and omly assigned to usual care ( UC ) , nurse-assisted medical management ( MM ) , or nurse-assisted collaborative management ( CM ) . MEASUREMENTS The main outcome measures were of generic ( Medical Outcome Study 36-item short form [ SF-36 ] , illness intrusiveness ) and disease-specific ( St. George 's respiratory question naire [ SGRQ ] ) quality of life and self-reported health-care utilization . RESULTS Overall , 151 patients ( UC group , 51 patients ; MM group , 49 patients ; and CM group , 51 patients ) completed the study , their average age was 69 years , and 56.9 % were women . The average change in the SF-36 general health domain for the MM group vs the UC group was 1.1 ( 95 % confidence interval [ CI ] , -7.9 to 11.2 ) , and for the CM group vs the UC group the average change was 2.5 ( 95 % CI , -7.0 to 12.3 ) . The corresponding changes in SGRQ total domain were -2.9 ( 95 % CI , -9.8 to 4.1 ) and -2.6 ( 95 % CI , -9.5 to 4.3 ) . There was no change in the number of self-reported emergency department visits or hospitalizations , but the utilization of these services was infrequent . CONCLUSION The findings of our investigation and those from the published literature suggest that interventions to enhance patient education , self-management skills , and follow-up among patients with COPD do not result in clinical ly meaningful improvements in health status or self-reported health-care utilization . Moreover , future studies of disease management programs for patients with COPD need to evaluate interventions that address associated comorbidities , exercise , and social support |
10,890 | 26,839,640 | However , pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis .
TLR3 has a well-known protective role influencing crucial processes like angiogenesis , cell growth or proliferation .
TLR4 works as an interesting epithelial-mesenchymal transition 's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed .
Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported .
In conclusion , TLRs have been shown to be an interesting influence on the HCC 's microenvironment , with TLR3 clearly determining an anti-tumour influence .
TLR4 and TLR9 are considered to have a positive relationship with tumour development even though , in each of them anti-tumorigenic signals have been described .
TLR2 presents a more ambiguous role , possibly depending on the stage of the inflammation-HCC axis | Hepatocarcinoma ( HCC ) is a highly prevalent cancer worldwide and its inflammatory background was established long ago .
Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis .
An effective innate immunity response relies on the toll-like receptors ( TLR ) found in several different liver cells which , through different lig and s and many signaling pathways can elicit , not only a pro-inflammatory but also an oncogenic or anti-oncogenic response .
Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets .
TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNA-damages and to cell survival .
TLR9 's influence on carcinogenesis is also controversial and despite a potential anti-cancer capacity , a pro-tumorigenic role is more likely . | AIM To establish the extent to which contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of hepatic tumors . METHODS One hundred patients with histologically confirmed malignant or benign hepatic tumor ( maximum size 5 cm ) were analyzed . Contrast-enhanced ultrasound ( bolus injection 2.5 mL SonoVue ) was carried out with intermittent breath-holding technique using a multifrequency transducer ( 2.5 - 4 MHz ) . Native vascularization was analyzed with power Doppler . The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in true detection mode during the arterial , portal venous and late phases . Mechanical index was set at 0.15 . Perfusion analysis was performed by post-processing of the raw data [ time intensity curve ( TIC ) analysis ] . The cut-off of the gray value differences between tumor and normal liver tissue was established using Receiver Operating Characteristic ( ROC ) analysis 64-line multi-slice computed tomography served as reference method in all cases . Magnetic resonance tomography was used additionally in 19 cases . RESULTS One hundred patients with 59 malignant ( 43 colon , 5 breast , 2 endocrine metastases , 7 hepatocellular carcinomas and 2 kidney cancers ) and 41 benign ( 15 hemangiomas , 7 focal nodular hyperplasias , 5 complicated cysts , 2 abscesses and 12 circumscribed fatty changes ) tumors were included . The late venous phase proved to be the most sensitive for classification of the tumor type . Fifty-eight of the 59 malignant tumors were classified as true positive , and one as false negative . This result ed in a sensitivity of 98.3 % . Of the 41 benign tumors , 37 were classified as true negative and 4 as false negative , which corresponds to a specificity of 90.2 % . Altogether , 95.0 % of the diagnoses were classified as correct on the basis of the histological classification . No investigator-dependency ( P = 0.23 ) was noted . CONCLUSION The results show the possibility of accurate prediction of malignancy of hepatic tumors with a positive prognostic value of 93.5 % using advanced contrast-enhanced ultrasound . Contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics is a valuable tool to discriminate hepatic tumors OBJECTIVE To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine . BACKGROUND Frovatriptan is a new , selective serotonin agonist ( triptan ) developed for the acute treatment of migraine . Dose range-finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability . METHODS The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled , acute migraine treatment studies , including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg , as well as a 12-month open-label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24-hour period . Safety and tolerability were assessed through the collection of adverse events , monitoring of heart rate and blood pressure performance of 12-lead electrocardiogram , hematology screen , and blood chemistry studies . RESULTS In the short-term studies , 1554 patients took frovatriptan 2.5 mg and 838 took placebo . In the 12-month study , 496 patients treated 13 878 migraine attacks . Frovatriptan was well tolerated in the short- and long-term studies with 1 % of patients in the short-term studies and 5 % of patients in the long-term study withdrawing due to lack of tolerability . The incidence of adverse events was higher in the frovatriptan-treated patients than in the patients who took placebo ( 47 % versus 34 % ) and the spectrum of adverse events was similar . When compared to sumatriptan 100 mg , significantly fewer patients taking frovatriptan experienced adverse events ( 43 % versus 36 % ; P=.03 ) and the number of adverse events was lower ( 0.62 versus 0.91 ) , there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group . Analysis of the entire clinical data base ( n=2392 ) demonstrated that frovatriptan was well tolerated by the patients regardless of their age , gender , race , concomitant medication , or the presence of cardiovascular risk factors . No effects of frovatriptan on heart rate , blood pressure , 12-lead electrocardiogram , hematology screen , or blood chemistry were observed . No patient suffered any treatment-related serious adverse event . CONCLUSIONS Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients . Frovatriptan treatment produced an adverse events profile similar to that of placebo , and in a direct comparison study was better tolerated than sumatriptan 100 mg |
10,891 | 25,186,777 | CBL around dental implants placed in healed sites using flapped and flapless techniques is comparable | BACKGROUND The aim of the present systematic review is to compare the crestal bone loss ( CBL ) around dental implants placed in healed sites using flapped and flapless surgical techniques .
METHODS The focused question was , " Does flapped and flapless surgical technique influence CBL around dental implants placed in healed sites ? | Guided bone regeneration ( GBR ) is frequently used in oral implantology . It is unclear to what extent GBR affects the periodontium of adjacent teeth . Therefore , the present study quantifies changes in the proximal gingiva and bone levels at these teeth in 30 patients . Staged surgery involved a st and ard GBR treatment , r and omly using resorbable membranes with a bone substitute or non-resorbable membranes with or without a bone substitute , followed by fixture installation at 6 months and abutment connection a further 6 months later . The data were sample d at each surgery and analysed using MANOVA . Twelve months after GBR , there was on average a small but statistically significant amount of proximal gingival recession ( 0.75 mm ) and bone resorption ( 0.34 mm ) observed , of which 50 % was the result of GBR surgery . No significant differences were found between the different GBR treatment modalities . It is concluded that GBR treatment may have a small negative effect on the levels of the free gingival margin and alveolar bone at adjacent teeth , which is in most patients not clinical ly relevant PURPOSE The aim of this study was to report on the rehabilitation of partial edentulism with immediate function implants placed in predominantly soft bone with flap and flapless surgical techniques . MATERIAL S AND METHODS The prospect i ve clinical study comprises 72 implants ( 50 in the maxilla and 22 in the m and ible ) placed in 41 consecutively included patients rehabilitated from partial edentulism , followed for 1 year . An implant specially design ed for immediate function was used . The evaluation included clinical examinations and radiographic assessment of the marginal bone level at 6 months and 1 year . The outcome measure was the implant success , evaluated using the following implant success criteria : clinical stability ( fixed dental prostheses removed and implants individually checked ) ; fulfilled purported function without any discomfort to the patient ; no suppuration or infection present ; no radiolucent areas around the implants at time of evaluation ; and no aesthetic complaints from the patient . RESULTS No dropouts were registered during the follow-up of the study . The overall cumulative survival rate at 1 year was 98.6 % ( 1 implant lost ) , with 100 % for the implants placed with the flap surgical technique , and 96.9 % for the implants placed with the flapless surgical technique . The overall average marginal bone resorption was 1.6 mm ( SD=1.1 mm ) at 1-year follow-up , with 1.4 mm ( SD=0.8 mm ) and 2.0 mm ( SD = 1.4 mm ) for the flap and flapless surgical technique study groups , respectively . The complications registered were : peri-implant pathology ( 3 implants in 3 patients ) ; fracture of the provisional crown/prosthesis ( 2 patients ) ; crown loosening ( 1 patient ) and prosthetic screw loosening ( 1 patient ) . CONCLUSIONS The placement of the specially design ed implant for immediate function in predominantly soft bone is viable , as given by the overall 98.6 % cumulative survival rate , and the rehabilitation using flapless surgery is safe and predictable . However , the flapless technique revealed more marginal bone resorption compared with the flap technique . Extra care should be taken in the flapless approach with respect to the inclusion criteria and difficulty of the surgery Background The association between periodontal conditions , oral yeast colonisation and salivary proteins in subjects with type 2 diabetes ( T2D ) is not yet documented . The present study aim ed to assess the relationship between these variables in type 2 diabetic subjects with reference to gender . Methods Fifty-eight type 2 diabetic subjects ( 23 males and 35 females ) with r and om blood glucose level ≥ 11.1 mmol/L were investigated . Periodontal conditions ( plaque index [ PI ] , bleeding on probing [ BOP ] , probing pocket depth [ PD ] ( 4 to 6 mm and ≥ 6 mm ) , oral yeasts , salivary immunoglobulin ( Ig ) A , IgG and total protein concentrations , and number of present teeth were determined . Results Periodontal conditions ( PI [ p < 0.00001 ] , BOP [ p < 0.01 ] and PD of 4 to 6 mm [ p < 0.001 ] , salivary IgG (μg)/mg protein ( p < 0.001 ) and salivary total protein concentrations ( p < 0.05 ) were higher in type 2 diabetic females with C and ida albicans ( C. albicans ) colonisation compared to males in the same group . Type 2 diabetic females with C. albicans colonisation had more teeth compared to males in the same group ( p < 0.0001 ) . Conclusion Clinical and salivary parameters of periodontal inflammation ( BOP and IgG (μg)/mg protein ) were higher in type 2 diabetic females with oral C. albicans colonisation compared to males in the same group . Further studies are warranted to evaluate the association of gender with these variables in subjects with T2D BACKGROUND The association among periodontal conditions , socioeconomic status ( SES ) , and diabetes has been reported . However , there is a lack of published data comparing periodontal conditions among individuals with poorly controlled type 2 diabetes mellitus ( T2D ) . The aim of the present study was to compare the periodontal conditions and SES between subjects with T2D and non-diabetic controls . METHODS A total of 75 ( 31 males and 44 females ) individuals with T2D ( 62 poorly controlled and 13 well-controlled ) and 99 non-diabetic patients ( healthy controls ; 51 males and 48 females ) participated in the study . Plaque index ( PI ) , bleeding on probing ( BOP ) , and probing depth ( PD ) were investigated . R and om blood glucose level was recorded . Premolar and molar marginal bone loss ( MBL ) was measured digitally on scanned orthopantomograms . RESULTS Individuals with poorly controlled T2D had increased MBL in molars and maxillary premolars ( P<0.05 ) compared to individuals with well-controlled T2D . PI , BOP , and PD of 4 to < 6 mm were increased in individuals with poorly controlled T2D compared to those with well-controlled T2D ( P<0.001 ) . There was no difference between the diabetic groups when PD was > or=6 mm . Individuals with poorly controlled T2D had a lower SES compared to patients with well-controlled T2D ( P<0.05 ) . Illiteracy and the number of missing teeth were not different between the groups . CONCLUSIONS Radiologic and clinical indicators of periodontal destruction were increased in individuals with poorly controlled T2D . Low SES aggravated the periodontal condition in individuals with T2D The purpose of this r and omized controlled clinical study was to compare the survival of a one-piece anodically oxidized surface implant when placed with a flapless or flap protocol . Bone loss measurements on radiographs and changes in clinical probing depths 1 year post-definitive restoration placement were recorded and compared . Fifty-two of 60 patients ( implants ) remained in the study at the 1-year follow-up . At the time of final evaluation , no implant was lost in either group . At the time of placement of the definitive restoration , there was a mean mesial and distal bone gain in both groups compared to bone levels present at the time of implant insertion . There were no significant changes in bone levels between placement of the definitive restoration and those recorded 12 months later , and no significant differences in bone levels between the flap or flapless group at 6 or 12 months were noted . No significant differences were seen either in pocket depth or change in pocket depth at 6 and 12 months in the flapless and flap groups . It was therefore concluded that one-piece anodically oxidized surface implants , 1 year post-definitive restoration insertion , had high survival rates ( 100 % ) and stable marginal bone and probing depth levels whether a flapless or flap protocol was used for implant insertion OBJECTIVES To evaluate and compare the outcome of dental implants placed using a flapless protocol and immediate loading with a conventional protocol and loading after 6 weeks . MATERIAL S AND METHODS Fourteen patients with bilateral maxillary edentulous areas were treated using Straumann SLA-implants . Using a r and omized split-mouth design , implants were placed in one side of the maxilla using a stereolithographic surgical guide for flapless surgery and immediately loaded on temporary abutments with a bridge ( test ) . Implants in the other side were placed using the conventional protocol and loaded after 6 weeks of healing ( control ) . Clinical and radiographic evaluation of peri-implant tissues was performed at time of implant surgery , and after 1 week , 6 weeks , 3 , 6 , 12 and 18 months . RESULTS A total of 70 implants were placed ( 36 test and 34 control ) . One implant ( test ) was lost after 3 months , result ing in a survival rate of 97.3 % for the test implants and 100 % for the control implants . Marginal bone levels were not statistically significantly different between the test and control implants but at baseline the marginal bone level was significantly lower compared to the other evaluation periods ( P < 0.05 ) . The mean bone level for test and control implants was 1.95 mm ± 0.70 and 1.93 mm ± 0.42 after 18 months , respectively . There was a significant change in height of the attached mucosa at implants placed with a conventional flap between post-operative and 1 week and between 1 week and 6 weeks . Statistically significant differences were found between the test side and the control side for opinion about speech , function , aesthetics , self-confidence and overall appreciation the first 6 weeks . CONCLUSION Implants can successfully integrate in the posterior maxilla using a flapless approach with immediate loading similar to a conventional protocol . The mucosal tissues around implants placed with a conventional flap changed significantly compared with flapless placed implants PURPOSE To evaluate and compare the changes in crestal bone height around implants placed with flapless surgery and with-flap surgery . MATERIAL S AND METHODS Ten implants were placed in six patients --five using flapless and five using with-flap techniques . Single-piece root-form implants and a one-stage approach with immediate nonfunctional loading protocol were used . The change in heights of crestal bone was measured on st and ardized digital periapical radiographs taken at 0 , 1 , and 3 months . RESULTS On mesial side , the mean change from months 0 - 1 , months 1 - 3 , and months 0 - 3 for flapless method was significantly lower than with-flap method [ 0.01 - 0.06 mm for flapless and 0.13 - 0.40 mm for with-flap ( P = 0.01 ) ] . On the distal side , the mean change from months 0 - 1 , months 1 - 3 , and months 0 - 3 for flapless method was significantly lower than with-flap method [ 0.02 - 0.05 mm for flapless and 0.09 - 0.30 mm for with-flap ( P = 0.01 ) ] . CONCLUSIONS During the three-month period , reduction of crestal bone height around the implants placed with flapless surgery ( 0.06 mm ) was not statistically significant , while the reduction of crestal bone height around the implants placed using with-flap surgery ( 0.4 mm ) was statistically significant . Comparitively , flapless approach showed lesser crestal bone height reduction , which was statistically significant OBJECTIVE To evaluate how bone-level implants maintain crestal bone stability after thickening of thin mucosal tissues with allogenic membrane . MATERIAL S AND METHODS Ninety-seven bone-level implants of 4.1 mm diameter ( Institute Straumann AG , Switzerl and ) were evaluated in 97 patients ( 28 men and 69 women , mean age 47.3 ± 1.2 years ) . According to vertical gingival thickness , patients were assigned into test T1 ( thin , 2 mm or less , n = 33 ) , test T2 ( thin thickened with allogenic membrane , n = 32 ) and control C groups ( thick , more than 2 mm , n = 32 ) . Implants were placed in posterior m and ible in one-stage approach and after integration were restored with single screw-retained metal-ceramic restorations . Radiographic examination was performed after implant placement , 2 months after healing , after prosthetic restoration and after 1-year follow-up . Crestal bone loss was calculated mesially and distally . Mann-Whitney U-test was applied and significance was set to 0.05 . RESULTS After 2 months , implants in group T1 had 0.75 ± 0.11 mm bone loss mesially and 0.73 ± 0.10 mm distally . Implants in group T2 had 0.16 ± 0.06 mm mesially and 0.20 ± 0.06 mm distally . C group implants lost 0.17 ± 0.05 mm mesially and 0.18 ± 0.03 mm distally . Differences between T1/T2 , and T1/C were statistically significant ( P = 0.000 ) both mesially and distally , while between T2 and C was not significant mesially ( P = 0.861 ) and distally ( P = 0.827 ) . After 1-year follow-up implants in group T1 had 1.22 ± 0.08 mm bone loss mesially and 1.14 ± 0.07 mm distally . Implants in group T2 had 0.24 ± 0.06 mm mesially and 0.19 ± 0.06 mm distally . C group implants lost 0.22 ± 0.06 mm mesially and 0.20 ± 0.06 mm distally . Differences between T1/T2 , and T1/C were statistically significant ( P = 0.000 ) both mesially and distally , while between T2 and C was not significant mesially ( P = 0.909 ) and distally ( P = 0.312 ) . CONCLUSIONS Significantly less bone loss can occur around bone-level implants placed in naturally thick mucosal tissues , in comparison with thin biotype . Augmentation of thin soft tissues with allogenic membrane during implant placement could be way to reduce crestal bone loss UNLABELLED There is evidence suggesting that flapless , or minimally invasive , procedures can preserve bone vascularization because they will not disturb the periosteum of the alveolar bone . The aim of this r and omized , controlled clinical trial study is to compare the effect of flapless ( FL ) and full-thickness flap ( FT ) techniques on crestal bone resorption during healing periods . METHODS Twenty-two implants were placed by FL and FT flap in nine patients in split mouth design ; each patient received two implants , except for two patients who received four implants . A periapical radiograph was taken at implant placement , as well as 6- and 12-week intervals . Crestal bone level was compared between FL and FT during these intervals and compared between intervals for each group . RESULTS Median ( IQR ) crestal bone level at implant placement for the FL was 2.70 ( 0.60 ) and for the FT was 2.60 ( 1.20 ) . At six weeks , median ( IQR ) for the FL was 3.55 ( 0.70 ) and for the FT was 3.40 ( 0.75 ) . At 12 weeks , median ( IQR ) for the FL was 3.60 ( 0.30 ) and for the FT was 3.75 ( 0.85 ) . Statistically insignificant differences were obtained between the two techniques at implant placement , as well as 6- and 12-week intervals , and were p = 0.894 , p = 0.477 , p = 0.755 , respectively . There was a significant difference between the bone level at implant placement and at the 6-week interval for both the FL ( p = 0.006 ) and FT ( p = 0.045 ) , whereas there was no significant difference between the bone level at 6- and 12-week intervals for the FL ( p = 0.722 ) and for the FT ( p = 0.229 ) . Conclusions Based upon this study of nine patients with 22 implants , there was no significant difference in crestal bone resorption between FT and FL techniques during a three-month healing period . The preservation of periosteum in the FL group result ed in early progressive bone resorption BACKGROUND Implant therapy is a highly predictable treatment option ; however , insufficient data exist to show whether flapless implant surgery provides better esthetic outcomes and less bone loss than implant surgery with a flap approach . METHODS In this r and omized , controlled study comparing the flapless and traditional flap protocol for implant placement , 24 patients received a single implant in the anterior maxillary region . A cone beam computed tomography-aided surgical guide was used for implant placement surgery for both groups . Implants were restored using a one-piece , screw-retained ceramic crown at 3 months . Radiographic and clinical measurements were assessed at baseline ( implant placement ) and at 3 ( crown placement ) , 6 , 9 , and 15 months . Clinical parameters evaluated were plaque index , gingival index , papillary index ( PPI ) ( 0 = no papilla , 1 = less than half , 2 = more than half but not complete , 3 = complete fill , and 4 = overfill ) , marginal tissue levels , biotype , width of keratinized tissue , and soft tissue thickness . RESULTS Implant success rate was 92 % in both groups . Mean PPI values for the flap control group and flapless test group were 2.38 ± 0.51 versus 2.31 ± 0.48 at crown placement ( P = 0.68 ) and 2.52 ± 0.52 versus 2.64 ± 0.54 at 15 months ( P = 0.42 ) , respectively . PPI increased over time in both groups , although the flapless group had a significantly larger change in PPI from crown placement to 6 and 9 months ( P < 0.01 ) . Crestal bone levels in the flap group were more apical in relation to the implant platform than those in the flapless group for the duration of the study . No differences among groups were noted for all other measurements . CONCLUSIONS Both flapless and flap implant placement protocol s result ed in high success rates . A flapless protocol may provide a better short-term esthetic result , although there appears to be no long-term advantage The anterior maxilla represents a therapeutic challenge for single-tooth replacement with implants . The surgical trauma delivered to soft and hard tissues during implant placement can influence the future esthetic result . The clinician should use surgical techniques that prevent esthetic complications , such as increased crown length or loss of interdental papillae , without compromising osseointegration . This prospect i ve study investigated the interproximal crestal bone loss occurring after placement of single-tooth implants using 2 different flap design s : a widely mobilized flap design that included papillae , and a limited flap design that protected papillae . The interproximal crestal bone loss was of practical importance and statistically significantly less following the use of a limited flap design versus the widely mobilized flap procedure BACKGROUND Flapless implant surgery has been suggested as one possible treatment option for enhancement of implant esthetics . METHODS Twenty-four patients with a missing tooth in the premaxillary region were r and omly assigned to one of two groups ( 12 each ) : immediate loading ( IL ) or delayed loading ( DL ) ( loading after 4 months ) . An endosseous implant was placed in each patient via a flapless surgery . Clinical measurements including the papillary index ( PPI ) ( 0 , no papilla ; 1 , less than half ; 2 , more than half but not complete fill ; 3 , complete fill ; and 4 , overfill ) , marginal levels of the soft tissue ( ML ) , probing depths ( PDs ) , modified bleeding index ( mBI ) , modified plaque index ( mPI ) , and the width of the keratinized mucosa ( WKM ) were performed at baseline ( at the time of loading ) and at 2 , 4 , and 6 months . RESULTS The soft tissue profile remained stable up to 6 months , without significant differences between the two groups ( mean PPI and ML at 6 months , 2.16 and 0.30 mm , respectively ) . Mean PPI in the IL group significantly increased from 1.50 at baseline to 2.09 at 2 months , and the significance remained up to 6 months ( 2.30 at 6 months ) ( P < 0.05 ) , whereas in the DL group , no significant changes were found from baseline to 6 months in mean PPI ( 2.06 at both time points ) . Mean PPI increased over time when two treatment groups were combined ; however , no statistical significance was found . In ML , the difference at baseline between the two groups ( -0.28 mm for DL versus 0.17 mm for IL ; P < 0.05 ) was no longer significant at 2 months ( 0 versus 0.08 mm for DL and IL , respectively ) and thereafter ( P > 0.05 ) . No significant differences were detected between groups at each time and over time in the other clinical parameters , PD , mBI , mPI , and WKM ( P > 0.05 ) . CONCLUSIONS The results of this study indicate that creeping attachment ( i.e. , soft tissue recovery ) might occur within 2 months after IL . The study suggests that flapless implant surgery provides esthetic soft tissue results in single-tooth implants either immediately or delayed loaded . Other long-term r and omized controlled clinical trials with a large sample size and comparison group ( i.e. , implant surgery with flap ) are recommended to verify the conclusions drawn in this preliminary study OBJECTIVES The objective of this study was to compare the placement of flapped vs. flapless dental implants utilizing clinical , radiographic , microbiological , and immunological parameters . MATERIAL AND METHODS A total of 20 patients received 30 dental implants following a one-stage protocol . The patients were r and omly assigned into two study groups : control group with 15 flapped implants and test group with 15 flapless implants . Follow-up examinations were carried out after 1 , 2 , 6 , and 12 weeks . Clinical recordings , sulcular fluid sampling , microbiological analysis , and digital subtraction radiography were utilized to compare the two surgical approaches . RESULTS Peri-implant sulcus depth was significantly greater in flapped implants at both 6 and 12 postsurgical weeks ( P < 0.001 ) . Flapped implants showed crestal bone loss ( 0.29 ± 0.06 mm ) , whereas no bone resorption was detected around flapless implants . Matrix metalloproteinase-8 values were higher to a statistically significant level in the control group at 1 ( P = 0.003 ) and 6 weeks ( P = 0.007 ) after placement . In the test group , the presence of Porphyromonas gingivalis was significantly higher at the 2nd postoperative week ( P = 0.005 ) , whereas the counts of Tannerella forsythia were significantly elevated at the 1st ( P = 0.005 ) , 2nd ( P = 0.001 ) , and 12th ( P = 0.002 ) postoperative weeks , possibly indicating an earlier formation and maturation of the peri-implant sulcus . Patients reported more pain after flapped implant placement . CONCLUSIONS Flapless implant placement yielded improved clinical , radiographic , and immunological outcomes compared with flapped implantation . In addition , patients seem to better withst and flapless implant placement OBJECTIVES Flapless implant surgery is fast gaining popularity because of several advantages , such as reduced surgical time , postoperative bleeding , and swelling . Studies have shown that flap elevation results in some amount of bone loss . The aim of the current study was to compare the amount of bone loss in procedures using the flapless technique and those where flap elevation was done . Papillary fill was also compared in both techniques , which is unique to this study . STUDY DESIGN Forty patients , selected according to certain inclusion and exclusion criteria , were r and omly assigned to 1 of 2 groups : Flap ( F ) , or Flapless ( FL ) . The amount of crestal bone loss was measured from st and ardized radiographs at baseline , 6 months , 1 year , and 2 years after implant placement . Papillary fill was evaluated using the Papillary presence index , which was measured 6 months after loading . RESULTS The bone loss was greater for the F group during all time periods and the mean papillary fill was greater for the FL group . CONCLUSIONS In conclusion , the results of the current study show that flapless implant surgery results in less crestal bone loss both during the healing period and after loading . In addition , it can produce better papillary fill . The cases selected for this study were ideal cases in terms of bone volume and the operator was well experienced , however . Care should be taken during case selection for flapless implant surgery |
10,892 | 27,013,450 | This includes the finding that less intensive occlusion treatments can be successful in treating amblyopia .
A relationship between adherence to treatment and visual acuity has also been established and has been shown to be influenced by the use of intervention material .
In addition , there is growing evidence of that a period of glasses wearing only can significantly improve visual acuity alone without any other modes of treatment . | The treatment of amblyopia , particularly anisometropic ( difference in refractive correction ) and /or strabismic ( turn of one eye ) amblyopia has long been a challenge for many clinicians .
Achieving optimum outcomes , where the amblyopic eye reaches a visual acuity similar to the fellow eye , is often impossible in many patients .
Part of this challenge has result ed from a previous lack of scientific evidence for amblyopia treatment that was highlight by a systematic review by Snowdon et al. in 1998 . | PURPOSE To investigate the effect of the augmentation of levodopa with part-time and full-time occlusion on visual acuity and to determine its late results in amblyopia . METHODS Seventy-two patients with amblyopia were prospect ively studied and r and omly distributed into groups A , B , and C consisting of 24 patients each . Group A patients received levodopa alone , group B received levodopa and part-time ( 3 hours/day ) occlusion , and group C received levodopa and full-time ( during all waking hours ) occlusion of the dominant eye . Levodopa 0.50 mg/kg body weight , with a 25 % fixed dose combination of carbidopa , was administered orally three times a day for 7 weeks . Snellen visual acuity and its logMAR equivalent were recorded before treatment , at weeks 1 , 3 , 5 , and 7 after starting treatment , and every 6 weeks for 1 year after the completion of treatment . RESULTS Fifty-three ( 74 % ) of the 72 patients had an improvement in visual acuity after treatment . Forty-four of the 53 patients with improved visual acuities completed 1-year post-treatment follow-up . Twenty-three ( 52 % ) of the 44 patients had a regression in visual acuity . CONCLUSION The augmentation of levodopa with part-time or full-time occlusion does not enhance the recovery of vision in amblyopia . Improved visual acuity after levodopa administration persists at least 1 year in almost half of patients after cessation of treatment . Addition of full-time occlusion to levodopa helps maintain improved visual acuity for a longer duration compared to levodopa alone or combined with part-time occlusion PURPOSE To determine the effectiveness of weekend atropine for severe amblyopia from strabismus , anisometropia , or both combined among children 3 to 12 years of age . METHODS We enrolled children into 2 prospect i ve , r and omized multicenter clinical trials of amblyopia therapy . Herein we report the results for severe amblyopia , 20/125 to 20/400 . In Trial 1 , 60 children 3 to 6 years of age ( mean , 4.4 years ) were r and omized to weekend atropine plus a plano lens or weekend atropine plus full spectacle correction for the sound eye . In Trial 2 , 40 children 7 to 12 years of age ( mean , 9.3 years ) were r and omized to weekend atropine or 2 hours of daily patching . The visual acuity outcome was assessed at 18 weeks in Trial 1 and 17 weeks in Trial 2 . RESULTS In Trial 1 , visual acuity improved by an average of 4.5 lines in the atropine plus correction group ( 95 % CI , 3.2 - 5.8 lines ) and 5.1 lines in the atropine plus plano lens group ( 95 % CI , 3.7 - 6.4 lines ) . In Trial 2 , visual acuity improved by an average of 1.5 lines in the atropine group ( 95 % CI , 0.5 - 2.5 lines ) and 1.8 lines in the patching group ( 95 % CI , 1.1 - 2.6 lines ) . CONCLUSIONS Weekend atropine can improve visual acuity in children 3 to 12 years of age with severe amblyopia . Improvement may be greater in younger children The authors previously showed that a single dose of levodopa improves the contrast sensitivity and decreases the size of fixation point scotomas in amblyopic patients . In the present study , they investigated the effect of levodopa after 1 wk of daily administration using a cross-over , double masked design . The decrease of fixation point scotomas was confirmed with automatic static perimetry . An improvement of visual acuity occurred in 70 % of the patients after 1 wk of levodopa administration compared to only 22 % in the authors ' previous study using one single dose . The improvements in visual acuities and visual fields persisted even after the levodopa administration was completed BACKGROUND amblyopia is a major cause of visual impairment in children . Our aim is to compare patching and atropine penalization for treatment of moderate amblyopia in 4 - 10 years old children . METHODS During 2004 - 2007 , in a r and omized clinical trial , 120 patients aged 4 - 10 years old with moderate amblyopia in the range of 20/40 -20/100 were enrolled . Subjects r and omized either to patch therapy or twice weekly atropine penalization in equal groups and were followed for 2 years . The success rate was defined as increment of 2 or more lines of visual acuity or final visual acuity of 20/25 or better . RESULTS The visual acuity in amblyopic eye improved from base line to a mean of 3.8 lines in patching group and mean of 3.7 lines in atropine group at the end of follow up . The average visual acuity in both groups was 0.5 Log MAR acuity that increased to 0.18 in patching group and 0.2 in atropine group . CONCLUSION Twice weekly atropine penalization could improve visual acuity of a magnitude like to improvement provided by patching in treatment of moderate amblyopia in patients aged 4 - 10 years The aim of this study was to investigate the effect of laser acupuncture on cerebral activation . Using functional magnetic imaging ( fMRI ) cortical activations during laser acupuncture at the left foot ( Bladder 67 ) and dummy acupuncture , were compared employing a block design in ten healthy male volunteers . All experiments were done on a 1.5 Tesla magnetic resonance scanner equipped with a circular polarized head coil . During laser acupuncture , we found activation in the cuneus corresponding to Brodmann Area ( BA ) 18 and the medial occipital gyrus ( BA 19 ) of the ipsilateral visual cortex . Placebo stimulation did not show any activation . We could demonstrate that laser acupuncture of a specific acupoint , empirically related to ophthalmic disorders , leads to activation of visual brain areas , whereas placebo acupuncture does not . These results indicate that fMRI has the potential to eluci date effects of acupuncture on brain activity OBJECTIVE To determine the visual acuity outcome at age 10 years for children younger than 7 years when enrolled in a treatment trial for moderate amblyopia . METHODS In a multicenter clinical trial , 419 children with amblyopia ( visual acuity , 20/40 - 20/100 ) were r and omized to patching or atropine eyedrops for 6 months . Two years after enrollment , a subgroup of 188 children entered long-term follow-up . Treatment after 6 months was at the discretion of the investigator ; 89 % of children were treated . MAIN OUTCOME MEASURE Visual acuity at age 10 years with the electronic Early Treatment Diabetic Retinopathy Study test . APPLICATION TO CLINICAL PRACTICE Patching and atropine eyedrops produce comparable improvement in visual acuity that is maintained through age 10 years . RESULTS The mean amblyopic eye acuity , measured in 169 patients , at age 10 years was 0.17 logMAR ( logarithm of the minimum angle of resolution ) ( approximately 20/32 ) , and 46 % of amblyopic eyes had an acuity of 20/25 or better . Age younger than 5 years at entry into the r and omized trial was associated with a better visual acuity outcome ( P < .001 ) . Mean amblyopic and sound eye visual acuities at age 10 years were similar in the original treatment groups ( P = .56 and P = .80 , respectively ) . CONCLUSIONS At age 10 years , the improvement of the amblyopic eye is maintained , although residual amblyopia is common after treatment initiated at age 3 years to younger than 7 years . The outcome is similar regardless of initial treatment with atropine or patching BACKGROUND Although amblyopia can be successfully treated with patching or atropine , there have been few prospect i ve studies of amblyopia recurrence once treatment is discontinued . METHODS We enrolled 156 children with successfully treated anisometropic or strabismic amblyopia ( 145 completed follow-up ) , who were younger than 8 years of age and who received continuous amblyopia treatment for the previous 3 months ( prescribed at least 2 hours of daily patching or prescribed at least one drop of atropine per week ) and who had improved at least 3 logMAR levels during the period of continuous treatment . Patients were followed off treatment for 52 weeks to assess recurrence of amblyopia , defined as a 2 or more logMAR level reduction of visual acuity from enrollment , confirmed by a second examination . Recurrence was also considered to have occurred if treatment was restarted because of a nonreplicated 2 or more logMAR level reduction of visual acuity . RESULTS Recurrence occurred in 35 ( 24 % ) of 145 cases ( 95 % confidence interval 17 % to 32 % ) and was similar in patients who stopped patching ( 25 % ) and in patients who stopped atropine ( 21 % ) . In patients treated with moderately intense patching ( 6 to 8 hours per day ) , recurrence was more common ( 11 of 26 ; 42 % ) when treatment was not reduced prior to cessation than when treatment was reduced to 2 hours per day prior to cessation ( 3 of 22 ; 14 % , odds ratio 4.4 , 95 % confidence interval 1.0 to 18.7 ) . CONCLUSIONS Approximately one fourth of successfully treated amblyopic children experience a recurrence within the first year off treatment . For patients treated with 6 or more hours of daily patching , our data suggest that the risk of recurrence is greater when patching is stopped abruptly rather than when it is reduced to 2 hours per day prior to cessation . A r and omized clinical trial of no weaning versus weaning in successfully-treated amblyopia is warranted to confirm these observational findings Background and purpose : To date , much of the research regarding amblyopia has been focused on which therapeutic modality is the most efficacious in amblyopia management . Unfortunately , there is a lack of research into which method of treatment cessation is the most appropriate once therapy has been completed . The purpose of this study is to investigate if the cessation method affects the recurrence rate of amblyopia . Methods : This study was a prospect i ve r and omized clinical trial of 20 subjects who were wearing full-time occlusion and were at the end point of their therapy . The subjects were r and omized into one of two groups : abrupt cessation or therapy tapering . All subjects were followed for 3 consecutive 4-week intervals , for a total of 12 weeks , to assess the short-term recurrence rate of amblyopia . Subjects who were in the tapered group had their occlusion reduced from full-time occlusion ( all waking hours minus one ) to 50 % of waking hours at study enrollment ( i.e. , from 12 hours/day to 6 hours per day ) ; occlusion was reduced by an additional 50 % at the first 4-week study visit ( i.e. , from 6 hours/day to 3 hours ) , with occlusion being discontinued completely at the week 8 visit . All subjects who were in the abrupt cessation group had their full-time occlusion discontinued completely at the start of the study ( i.e. , from 12 hours/day to none ) . Additional assessment s were also conducted at week 26 and week 52 post – therapy cessation to determine the longer term amblyopia regression rate . For the purpose s of this study , recurrence was defined as a 0.2 ( 10 letters ) or more logarithm of the minimum angle of resolution ( logMAR ) loss of visual acuity . Results : A recurrence of amblyopia occurred in 4 of 17 ( 24 % ; CI 9%–47 % ) participants completing the study by the week 52 study end point . There were 2 subjects from each treatment group who demonstrated a study protocol –defined recurrence . Conclusion : There was a 24 % risk of amblyopia recurrence if therapy was discontinued abruptly or tapered in 8 weeks . In this small sample , the assigned cessation method did not affect the rate of amblyopia recurrence . It is recognized that the smaller sample size in our study prevents us from making definitive conclusions on the potential role that abrupt cessation has on the regression rate of amblyopia . The sample size was too small to reach an acceptable level of statistical power ; therefore the generalizability of the findings to the broad population of all patients with amblyopia requires continuing research . This study therefore could be considered as a pilot study Amblyopia is a developmental abnormality that results in physiological alterations in the visual cortex and impairs form vision . It is often successfully treated by patching the sound eye in infants and young children , but is generally considered to be untreatable in adults . However , a number of recent studies suggest that repetitive practice of a visual task using the amblyopic eye results in improved performance in both children and adults with amblyopia . These perceptual learning studies have used relatively brief periods of practice ; however , clinical studies have shown that the time-constant for successful patching is long . The time-constant for perceptual learning in amblyopia is still unknown . Here we show that the time-constant for perceptual learning depends on the degree of amblyopia . Severe amblyopia requires > 50 h ( ≈35,000 trials ) to reach plateau , yielding as much as a five-fold improvement in performance at a rate of ≈1.5%/h . There is significant transfer of learning from the amblyopic to the dominant eye , suggesting that the learning reflects alterations in higher decision stages of processing . Using a reverse correlation technique , we document , for the first time , a dynamic retuning of the amblyopic perceptual decision template and a substantial reduction in internal spatial distortion . These results show that the mature amblyopic brain is surprisingly malleable , and point to more intensive treatment methods for amblyopia A pilot study suggests that playing video games may enhance a range of spatial vision functions in adults with amblyopia OBJECTIVE To compare full-time patching ( all hours or all but 1 hour per day ) to 6 hours of patching per day , as prescribed treatments for severe amblyopia in children younger than 7 years . DESIGN Prospect i ve , r and omized multicenter clinical trial ( 32 sites ) . PARTICIPANTS One hundred seventy-five children younger than 7 years with amblyopia in the range of 20/100 to 20/400 . INTERVENTION R and omization either to full-time patching or to 6 hours of patching per day , each combined with at least 1 hour of near-visual activities during patching . MAIN OUTCOME MEASURE Visual acuity in the amblyopic eye after 4 months . RESULTS Visual acuity in the amblyopic eye improved a similar amount in both groups . The improvement in the amblyopic eye acuity from baseline to 4 months averaged 4.8 lines in the 6-hour group and 4.7 lines in the full-time group ( P = 0.45 ) . CONCLUSION Six hours of prescribed daily patching produces an improvement in visual acuity that is of similar magnitude to the improvement produced by prescribed full-time patching in treating severe amblyopia in children 3 to less than 7 years of age BACKGROUND To plan a future r and omized clinical trial , we conducted a pilot study to determine whether children r and omized to near or non-near activities would perform prescribed activities . A secondary aim was to obtain a preliminary estimate of the effect of near versus non-near activities on amblyopic eye visual acuity , when combined with 2 hours of daily patching . METHODS Sixty-four children , 3 to less than 7 years of age , with anisometropic , strabismic , or combined amblyopia ( 20/40 to 20/400 ) were r and omly assigned to receive either 2 hours of daily patching with near activities or 2 hours of daily patching without near activities . Parents completed daily calendars for 4 weeks recording the activities performed while patched and received a weekly telephone call in which they were asked to describe the activities performed during the previous 2 hours of patching . Visual acuity was assessed at 4 weeks . RESULTS The children assigned to near visual activities performed more near activities than those assigned to non-near activities ( by calendars , mean 1.6 + /- 0.5 hours versus 0.2 + /- 0.2 hours daily , P < 0.001 ; by telephone interviews , 1.6 + /- 0.4 hours versus 0.4 + /- 0.5 hours daily , P < 0.001 ) . After 4 weeks of treatment , there was a suggestion of greater improvement in amblyopic eye visual acuity in those assigned to near visual activities ( mean 2.6 lines versus 1.6 lines , P = 0.07 ) . The treatment group difference in visual acuity was present for patients with severe amblyopia but not moderate amblyopia . CONCLUSIONS Children patched and instructed to perform near activities for amblyopia spent more time performing those near activities than children who were instructed to perform non-near activities . Our results suggest that performing near activities while patched may be beneficial in treating amblyopia . Based on our data , a formal r and omized amblyopia treatment trial of patching with and without near activities is both feasible and desirable Background We previously demonstrated that compliance with occlusion therapy for amblyopia was improved by the use of an educational programme , especially in children of parents of foreign origin and who spoke Dutch poorly . The programme consisted of : ( i ) a cartoon story for amblyopic children that explained without words why they should patch , ( ii ) a calendar with reward stickers , and ( iii ) an information leaflet for parents . In the current study , we assessed the individual effect of each component on compliance . Methods We recruited 120 3- to 6-year-old children who lived in a low socio-economic status ( SES ) area in The Hague and were starting occlusion therapy for the first time . They were r and omised to receive one of the components ( three intervention groups ) , or a picture to colour ( control group ) . The r and omisation was blinded for treating orthoptist and research er . Compliance was measured electronically using the Occlusion Dose Monitor ( ODM ) . Primary outcome was percentage of compliance ( actual/prescribed occlusion time ) . Secondary outcome was absolute occlusion hours per day . Parental fluency in Dutch was rated on a five-point scale . Results Compliance could be measured electronically in 88 of the 120 children ; in 32 others , it failed for various reasons . Parental fluency in Dutch was moderate or worse in 36.4 % ( p = 0.327 ) . Average compliance was 55 % st and ard deviation ( SD ) 40 ( n = 18 ) in the control group , 89 % SD 25 in the group receiving the educational cartoon ( n = 25 , P = 0.002 compared with control group ) , 67 % SD 33 ( n = 24 , P = 0.301 ) in the reward-calendar group and 73 % SD 40 ( n = 21 , P = 0.119 ) in the parent-information-leaflet group . On average , children in the control group occluded 1:46 SD1:19 hours/day , 2:33 SD 1:18 hours/day in the group receiving the educational cartoon , 1:59 SD 1:13 hours/day in the reward-calendar group and 2:18 SD 1:13 hours/day in the parent-information-leaflet group . No child who received the cartoon story occluded less than 1 hour per day , against seven in the reward-calendar group , five in the parent-information-leaflet group and five in the control group . Conclusions Although all three components of the programme improved compliance with occlusion therapy in children in low-SES areas , the educational cartoon had the strongest effect , as it explained without words to a 4- to 5-year-old child why it should wear the eye patch Objectives To compare visual outcome in response to two prescribed rates of occlusion ( six hours a day and 12 hours a day ) . Design Unmasked r and omised trial . Setting Research clinics in two London hospitals . Participants 97 children with a confirmed diagnosis of amblyopia associated with strabismus , anisometropia , or both . Interventions : 18 week period of wearing glasses ( refractive adaptation ) followed by occlusion prescribed ( “ patching ” ) for six or 12 hours a day . Main outcome measures Visual acuity measured by logMAR letter recognition ; objective ly monitored rate of occlusion ( hours a day ) . Results The mean age of children at study entry was 5.6 ( SD 1.5 ) years . Ninety were eligible for occlusion but 10 dropped out in this phase , leaving 80 children who were r and omised to a prescribed dose rate of six ( n=40 ) or 12 ( n=40 ) hours a day . The mean change in visual acuity of the amblyopic eye was not significantly different ( P=0.64 ) between the two groups ( 0.26 ( 95 % confidence interval 0.21 to 0.31 ) log units in six hour group ; 0.24 ( 0.19 to 0.29 ) log units in 12 hour group ) . The mean dose rates ( hours a day ) actually received , however , were also not significantly different ( 4.2 ( 3.7 to 4.7 ) in six hour group v 6.2 ( 5.1 to 7.3 ) in 12 hour group ; P=0.06 ) . The visual outcome was similar for those children who received three to six hours a day or more than six to 12 hours a day , but significantly better than that in children who received less than three hours a day . Children aged under 4 required significantly less occlusion than older children . Visual outcome was not influenced by type of amblyopia . Conclusions Substantial ( six hours a day ) and maximal ( 12 hours a day ) prescribed occlusion results in similar visual outcome . On average , the occlusion dose received in the maximal group was only 50 % more than in the substantial group and in both groups was much less than that prescribed . Younger children required the least occlusion . Trials registration Clinical Trials NCT00274664 OBJECTIVE To compare 2 hours vs 6 hours of daily patching as treatments for moderate amblyopia in children younger than 7 years . METHODS In a r and omized multicenter ( 35 sites ) clinical trial , 189 children younger than 7 years with amblyopia in the range of 20/40 to 20/80 were assigned to receive either 2 hours or 6 hours of daily patching combined with at least 1 hour per day of near visual activities during patching . Main Outcome Measure Visual acuity in the amblyopic eye after 4 months . RESULTS Visual acuity in the amblyopic eye improved a similar amount in both groups . The improvement in the visual acuity of the amblyopic eye from baseline to 4 months averaged 2.40 lines in each group ( P = .98 ) . The 4-month visual acuity was at least 20/32 and /or improved from baseline by 3 or more lines in 62 % of patients in each group ( P>.99 ) . CONCLUSION When combined with prescribing 1 hour of near visual activities , 2 hours of daily patching produces an improvement in visual acuity that is of similar magnitude to the improvement produced by 6 hours of daily patching in treating moderate amblyopia in children aged 3 to 7 years PURPOSE To evaluate the role of levodopa/carbidopa in the treatment of amblyopia . METHODS Thirty patients with strabismic amblyopia between the ages of 3 and 12 years were part of this double-blind , r and omized study . Patients were divided into two groups . Group A received 0.50 mg + 1.25 mg of levodopa/carbidopa per kilogram body weight three times daily after meals , with a protein rich drink , whereas Group B received placebo . Both groups received full-time conventional occlusion until a visual acuity of 6/6 was achieved or for a maximum of 3 months . RESULTS The authors observed more than two lines improvement in visual acuity that was greater in the levodopa group ( 15 of 15 ) than in the placebo group ( 9 of 15 ) ( P < .005 ) . Furthermore , improvement in visual acuity of more than two lines was greater in patients younger than 8 years ( 100 % ) than in patients older than 8 years of age ( 60 % ) ( P = .0026 ) . There was also no significant reversal of the improved visual acuity in up to 6 months of follow-up . CONCLUSION Levodopa/carbidopa improves visual acuity in patients with amblyopia and maintains improved visual acuity , especially in patients younger than 8 years PURPOSE To investigate compliance with patching therapy and the dose-effect relationship in occlusion therapy in amblyopia by recording the effective patching time using occlusion dose monitors ( ODMs ) . METHODS Fifty-two children with strabismic or mixed amblyopia ( Snellen equivalent , 6/12 - 6/48 ) were given optimal refractive correction and r and omly allocated for 12 weeks into three treatment groups : group 1 , no patching ; group 2 , prescribed patching for 3 hours ; and group 3 , prescribed patching for 6 hours . The effective time of occlusion was monitored with ODMs continuously . Visual acuity ( VA ) was measured every 3 weeks with LogMAR ( logarithm of the minimum angle of resolution ) Crowded Tests . RESULTS In the 3- and 6-hour groups , mean ( SD ) compliance was 57.5 % ( 30.8 % ) and 41.2 % ( 30.9 % ) , respectively , and mean effective patching time per day was 1 hour 43 minutes ( 55 minutes ) and 2 hours 33 minutes ( 1 hour 52 minutes ) , respectively . The mean ( SD ) improvement in logMAR VA of amblyopic eyes was 0.24 ( 0.17 ) , 0.29 ( 0.14 ) , and 0.34 ( 0.19 ) in groups 1 , 2 , and 3 , respectively . There was no significant difference in compliance with the prescribed patching between the 3- and 6-hour groups . VA outcomes in the 3- and 6-hour groups were not significantly better than 0-hour patching . However , the VA of patients with eyes effectively patched for more than 3 hours improved significantly . A dose-effect relationship was observed . Age at treatment did not influence the visual outcome . CONCLUSIONS Poor compliance with prescribed occlusion explains discrepancies in previous studies . No differences in the effect between the different prescribed patching periods were found . The dose-effect relationship observed should encourage development of methods such as educational intervention to improve visual outcome by increasing effective patching time OBJECTIVE To evaluate the effectiveness of treatment of amblyopia in children aged 7 to 17 years . METHODS At 49 clinical sites , 507 patients with amblyopic eye visual acuity ranging from 20/40 to 20/400 were provided with optimal optical correction and then r and omized to a treatment group ( 2 - 6 hours per day of prescribed patching combined with near visual activities for all patients plus atropine sulfate for children aged 7 to 12 years ) or an optical correction group ( optical correction alone ) . Patients whose amblyopic eye acuity improved 10 or more letters ( > or = 2 lines ) by 24 weeks were considered responders . RESULTS In the 7- to 12-year-olds ( n = 404 ) , 53 % of the treatment group were responders compared with 25 % of the optical correction group ( P<.001 ) . In the 13- to 17-year-olds ( n = 103 ) , the responder rates were 25 % and 23 % , respectively , overall ( adjusted P = .22 ) but 47 % and 20 % , respectively , among patients not previously treated with patching and /or atropine for amblyopia ( adjusted P = .03 ) . Most patients , including responders , were left with a residual visual acuity deficit . CONCLUSIONS Amblyopia improves with optical correction alone in about one fourth of patients aged 7 to 17 years , although most patients who are initially treated with optical correction alone will require additional treatment for amblyopia . For patients aged 7 to 12 years , prescribing 2 to 6 hours per day of patching with near visual activities and atropine can improve visual acuity even if the amblyopia has been previously treated . For patients 13 to 17 years , prescribing patching 2 to 6 hours per day with near visual activities may improve visual acuity when amblyopia has not been previously treated but appears to be of little benefit if amblyopia was previously treated with patching . We do not yet know whether visual acuity improvement will be sustained once treatment is discontinued ; therefore , conclusions regarding the long-term benefit of treatment and the development of treatment recommendations for amblyopia in children 7 years and older await the results of a follow-up study we are conducting on the patients who responded to treatment OBJECTIVE To determine whether visual acuity improvement with Bangerter filters is similar to improvement with patching as initial therapy for children with moderate amblyopia . DESIGN R and omized , clinical trial . PARTICIPANTS We enrolled 186 children , 3 to < 10 years old , with moderate amblyopia ( 20/40 - 20/80 ) . METHODS Children were r and omly assigned to receive either daily patching or to use a Bangerter filter on the spectacle lens in front of the fellow eye . Study visits were scheduled at 6 , 12 , 18 , and 24 weeks . MAIN OUTCOME MEASURES Visual acuity in amblyopic eyes at 24 weeks . RESULTS At 24 weeks , amblyopic eye improvement averaged 1.9 lines in the Bangerter group and 2.3 lines in the patching group ( difference in mean visual acuities between groups adjusted for baseline acuity = 0.38 line ) . The upper limit of a 1-sided 95 % confidence interval was 0.76 line , which slightly exceeded a prespecified noninferiority limit of < 0.75 line . Similar percentages of subjects in each group improved > or =3 lines ( Bangerter group 38 % vs patching group 35 % ; P = 0.61 ) or had > or = 20/25 amblyopic eye acuity ( 36 % vs 31 % , respectively ; P = 0.86 ) . There was a lower treatment burden in the Bangerter group as measured with the Amblyopia Treatment Index . With Bangerter filters , neither a fixation switch to the amblyopic eye nor induced blurring in the fellow eye to worse than that of the amblyopic eye was required for visual acuity improvement . CONCLUSIONS Because the average difference in visual acuity improvement between Bangerter filters and patching was less than half a line , and there was lower burden of treatment on the child and family , Bangerter filter treatment is a reasonable option to consider for initial treatment of moderate amblyopia Background Previous reports suggest that adherence to patching is a major issue in amblyopia treatment . We tested with an unmasked r and omised controlled clinical trial whether an intense educational/motivational intervention improves adherence when a high-dose regime is prescribed . Methods 62 children with newly diagnosed amblyopia were r and omly allocated into two treatment arms with and without educational/motivational intervention material . Both were prescribed patching 10 h/day , 6 days/week for a fixed period of 12 weeks . The intervention arm received an educational/motivational intervention before patching which included information booklets , video , a cartoon story book , sticker charts and a dedicated session with a research er . The control arm received the usual clinical information . The primary outcome measure was adherence measured using electronic occlusion dose monitors where a success/failure binary outcome was used to account for participants who dropped out of the study defined as patching > 4 h/day . Visual outcome , expressed as percentage visual deficit , was measured as secondary outcome . Results The intervention increased adherence success rate from 45.2 % in the control group to 80.6 % in the intervention group ( p=0.0027 ) . However , visual outcome was not significantly better in the intervention group ( p=0.190 ) . Conclusions Our study shows that an intense educational/motivational intervention can improve adherence to patching to high prescribed doses although no significant improvement in visual outcome was observed . Trials registration number : IS RCT N05346737 ( International St and ard R and omised Controlled Trial Number Register ) PURPOSE The purpose of the current study was to compare the effects of levodopa-carbidopa with and without part-time occlusion on visual function in older amblyopic children . METHODS Thirteen older amblyopic children were r and omly assigned to receive or not receive part-time occlusion ( 3 h/day ) combined with 7 weeks of oral dosing with levodopa-carbidopa ( 1.02 mg/0.25 mg/kg body weight three times daily ) . Visual acuity , contrast sensitivity , and fusion were measured at baseline ; 1 , 3 , 5 , and 7 weeks during the treatment regimen ; and 4 weeks after termination of all treatment . At these same times health status was assessed with st and ard laboratory blood tests , physical examination , and subjective question naire . RESULTS From baseline to the follow-up test trial , both groups improved in visual acuity in the amblyopic eyes ( occlusion group 20/116 to 20/76 , P < .001 ; no occlusion group 20/90 to 20/73 , P < .01 ) and dominant eyes ( occlusion group 20/18 to 20/15 , P > .05 ; no occlusion group 20/20 to 20/16 , P < .01 ) . The occlusion group exhibited a significant decrease in the difference in acuity between the dominant and amblyopic eyes of 1.3 lines ( P < .02 ) , whereas the no occlusion group revealed no significant effect . A comparison between groups revealed a significantly greater improvement in visual acuity in the amblyopic eye in the occlusion group compared with the no occlusion group ( P = .01 ) . In contrast , there was no significant difference between groups in terms of the change in visual acuity in the dominant eye ( P = .15 ) . Mean log contrast sensitivity in the amblyopic eye significantly improved in the occlusion group and did not significantly change in the no occlusion group . Fusion changed similarly in both groups . The improvements in visual function were maintained 4 weeks after the termination of all treatment . Adverse side effects were minimal in both groups . CONCLUSION The combination of levodopa-carbidopa and occlusion improves visual function more than levodopa-carbidopa alone in older amblyopic children BACKGROUND Deep amblyopia is a recognized cause of monocular visual deficit in children with a high rate of poor compliance with conventional occlusion therapy . This study evaluates a new occlusion technique that can be used for children with failed amblyopia treatment . METHODS In a prospect i ve study , surgical silicone-eyelid closure was done for 15 children ( age : 4 to 6 years ; median age : 5.2 years ) with a history of deep amblyopia and poor compliance with occlusion methods . In this technique , the good eye was closed by passing one limb of a double armed 5 - 0 polypropylene suture from one eyelid margin through a silicone sleeve and through the corresponding eyelid margin . The other polypropylene limb was passed behind the silicone sleeve and then through the opposite eyelid margin to form a barrier between the sleeve and the cornea . After 2 to 4 weeks , the suture was cut and the silicone sleeve was removed . RESULTS Preoperative visual acuity ranged between counting fingers at 1 meter and counting fingers at 4 meters . Following eyelid closure , visual acuity was improved to between 20/40 and 20/200 for 12 patients , whereas three patients did not improve . Complications were seen in 8 patients : marginal eyelid irritation and erythema in 6 and suture break in 2 . CONCLUSION Silicone-eyelid closure can be used safely and effectively for management of deep amblyopia . This technique affords a good option to restore vision in a deeply amblyopic eye and grants the child a lifetime of useful vision Purpose There have been few viable alternatives to patching the better eye as a treatment of amblyopia for more than two centuries . The success of patching depends on compliance , which is problematic for up to 59 % of children and their families . Methods This pilot study trialled the interactive binocular treatment ( I-BiT ) system as an alternative amblyopia treatment in 12 older amblyopes ( 6.1–11.4 years , median 8.2 ) , who had not complied with or responded to occlusion . Virtual reality images were projected to each eye simultaneously via a headset during eight treatment sessions of 25-min duration . Outcome measures were changes in high- ( HCVA ) and low-contrast log MAR acuity ( LCVA ) at 1 week , 4 weeks and a final follow-up ( 3–18 months ) after the final treatment . Results Sustained improvements in HCVA were observed in seven children ( 58 % ) and in LCVA in eight children ( 67 % ) , including two for whom amblyopia was eliminated . Five children had visual acuities equivalent to 6/12 or better at least 6 months after stopping treatment , compared with one child prior to treatment . Significant improvements in HCVA occurred up to the fourth treatment ; in LCVA to the seventh treatment . ConclusionS ustained improvements in visual acuity were observed for 58 % of this small group of children using the I-BiT system , despite prior failure with conventional treatment . This offers hope for a potential time-saving alternative to patching , in which compliance can easily be monitored , but the results need to be vali date d by means of a r and omised controlled trial The neurotransmitter dopamine ( DA ) is involved in several visual functions . Visual deprivation decreases retinal DA concentration in chickens and monkeys . In animals with deprivation amblyopia , several studies suggest that neurotransmitters are involved in visual-cortical plasticity and can restore partial visual acuity in adult cats . We investigated in a cross-over , double-masked study the influence of levodopa on contrast sensitivity and binocular suppression in human adult strabismic and amblyopic patients . After one single administration of levodopa , a significant increase in contrast sensitivity and decrease of the size of the fixation point scotoma was found . No changes could be detected after placebo administration . Levodopa did not induce changes in contrast sensitivity in the dominant eyes of the patients or in normal subjects . In conclusion , we found a short-term effect of levodopa on contrast sensitivity and fixation point scotomas in amblyopic eyes of adult patients OBJECTIVE To determine visual acuity improvement in children with strabismic and combined strabismic-anisometropic ( combined-mechanism ) amblyopia treated with optical correction alone and to explore factors associated with improvement . DESIGN Prospect i ve , multicenter , cohort study . PARTICIPANTS We included 146 children 3 to < 7 years old with previously untreated strabismic amblyopia ( n = 52 ) or combined-mechanism amblyopia ( n = 94 ) . METHODS Optical treatment was provided as spectacles ( prescription based on a cycloplegic refraction ) that were worn for the first time at the baseline visit . Visual acuity with spectacles was measured using the Amblyopia Treatment Study HOTV visual acuity protocol at baseline and every 9 weeks thereafter until no further improvement in visual acuity . Ocular alignment was assessed at each visit . MAIN OUTCOME MEASURES Visual acuity 18 weeks after baseline . RESULTS Overall , amblyopic eye visual acuity improved a mean of 2.6 lines ( 95 % confidence interval [ CI ] , 2.3 - 3.0 ) , with 75 % of children improving ≥ 2 lines and 54 % improving ≥ 3 lines . Resolution of amblyopia occurred in 32 % ( 95 % CI , 24%-41 % ) of the children . The treatment effect was greater for strabismic amblyopia than for combined-mechanism amblyopia ( 3.2 vs 2.3 lines ; adjusted P = 0.003 ) . Visual acuity improved regardless of whether eye alignment improved . CONCLUSIONS Optical treatment alone of strabismic and combined-mechanism amblyopia results in clinical ly meaningful improvement in amblyopic eye visual acuity for most 3- to < 7-year-old children , resolving in at least one quarter without the need for additional treatment . Consideration should be given to prescribing refractive correction as the sole initial treatment for children with strabismic or combined-mechanism amblyopia before initiating other therapies . FINANCIAL DISCLOSURE(S ) The authors have no proprietary or commercial interest in any of the material s discussed in this article PURPOSE To compare conventional patching therapy with atropine penalization in the treatment of anisometropic amblyopia . METHODS Prospect i ve , r and omized , institution-based clinical trial of patching versus atropine penalization in patients aged 8 - 20 years . Patients received either conventional , full-time patching , or atropine penalization . RESULTS Fifty-seven patients were enrolled , with visual acuity ranging from 6/12 to 6/60 in the amblyopic eye . Twenty-nine patients received conventional full-time patching ; 28 received atropine penalization . At 6 months , visual acuity improved by 2.38 lines in the conventional patching group and 2.34 lines in the atropine group ( p = 0.889 ) . The speed of visual recovery was faster in the patching group ( 3.7 months ) than in the atropine group ( 4.7 months ; p = 0.013 ) . There was significant improvement in near vision and contrast sensitivity in both groups , but improvement in the patching group was significantly better than in the atropine group . No patient had reduced visual acuity in the unaffected eye . Redness of eyes was observed more in the atropine group than in the patching group . Treatment tended to be better-accepted by parents and patients in the atropine group , but not significantly more . CONCLUSIONS In patients aged 8 - 20 years with anisometropic amblyopia , both patching and atropine therapy improved visual acuity . Although recovery was faster with patching , the 2 modalities of treatment appeared to be equally effective AIM To explore why emmetropisation fails in children who have strabismus . METHODS 289 hypermetropic infants were r and omly allocated spectacles and followed . Changes in spherical hypermetropia were compared in those who had strabismus and those who did not . The effect of wearing glasses on these changes was assessed using t tests and regression analysis . RESULTS Mean spherical hypermetropia decreased in both eyes of “ normal ” children ( p<0.001 ) . The consistent wearing of glasses impeded this process in both eyes ( p<0.007 ) . In the children with strabismus , there were no significant changes in either eye , irrespective of treatment ( p>0.05 ) . CONCLUSIONS In contrast with normal infants , neither eye of those who had strabismus emmetropised , irrespective of whether the incoming vision was clear or blurred . It is suggested that these eyes did not “ recognise ” the signal of blurred vision , and that they remained long sighted because they were destined to squint . Hence , the children did not squint because they were long sighted , and glasses did not prevent them squinting OBJECTIVE To assess the psychosocial impact on the child and family of patching and atropine as treatments for moderate amblyopia in children younger than 7 years . METHODS In a r and omized , controlled clinical trial , 419 children younger than 7 years with amblyopic eye visual acuity in the range of 20/40 to 20/100 were assigned to receive treatment with either patching or atropine at 47 clinical sites . After 5 weeks of treatment , a parental quality -of-life question naire was completed for 364 ( 87 % ) of the 419 patients . Main Outcome Measure Overall and subscale scores on the Amblyopia Treatment Index . RESULTS High internal validity and reliability were demonstrated for the Amblyopia Treatment Index question naire . The overall Amblyopia Treatment Index scores and the 3 subscale scores were consistently higher ( worse ) in the patching group compared with the atropine-treated group ( overall mean , 2.52 vs 2.02 , P<.001 ; adverse effects of treatment : mean , 2.35 vs 2.11 , P = .002 ; difficulty with compliance : mean , 2.46 vs 1.99 , P<.001 ; and social stigma : mean , 3.09 vs 1.84 , P<.001 , respectively ) . CONCLUSION Although the Amblyopia Treatment Index question naire results indicated that both atropine and patching treatments were well tolerated by the child and family , atropine received more favorable scores overall and on all 3 question naire subscales OBJECTIVES To evaluate the safety and adjunctive effect of acupuncture added to refractive correction for anisometropic amblyopia in younger children . DESIGN Prospect i ve , r and omized , controlled , crossover trial . PARTICIPANTS We included 83 children aged 3 to < 7 years with untreated anisometropic amblyopia and baseline best-corrected visual acuity ( BCVA ) of 20/40 to 20/200 in the amblyopic eye . METHODS Participants were r and omized to receive spectacles alone ( group 1 ; n = 42 ) or spectacles + acupuncture ( group 2 ; n = 41 ) for 15 weeks , and were then crossed over to receive the other regimen for another 15 weeks . The BCVA in both eyes was measured at baseline and every 5 ( ±1 ) weeks for the initial 45 weeks and at 60 ( ±1 ) weeks . MAIN OUTCOME MEASURES BCVA in the amblyopic eye at 15 , 30 , and 60 weeks . RESULTS The mean baseline BCVA in the amblyopic eye was 0.50 and 0.49 logarithm of the minimum angle of resolution ( logMAR ) in groups 1 and 2 , respectively . After 15 weeks of treatment , the BCVA had improved by a mean of 2.2 lines in group 1 and 2.9 lines in group 2 . The mean difference in BCVA between groups was 0.77 lines ( 95 % confidence interval ( CI ) , 0.29 - 1.3 ; P = 0.0020 ) with baseline adjustment . BCVA of ≤0.1 logMAR was achieved in 14.6 % of the patients in group 1 and 57.5 % in group 2 ( P<0.00010 ) . After the regimens were crossed over at 30 weeks , group 1 had a mean of 1.2 ( 95 % CI , 0.98 - 1.48 ; P = 2.0 × 10⁻¹² ) lines additional improvement from the 15-week BCVA , whereas in group 2 the mean improvement was 0.4 ( 95 % CI , 0.19 - 0.63 ; P = 0.0010 ) lines . The proportions of responders , resolution , and participants achieving a BCVA of ≤0.1 logMAR at 30 weeks were similar between groups . After completion of acupuncture , only 1 participant had > 1 line of VA decrease to 60 weeks . Acupuncture was well-tolerated by all children , and no severe adverse effect was encountered . CONCLUSIONS Acupuncture is a potentially useful complementary treatment modality that may provide sustainable adjunctive effect to refractive correction for anisometropic amblyopia in young children . Further large-scale studies seem warranted . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references Introduction : Children presenting with strabismus and mixed ( anisometropic/strabismic ) amblyopia are managed by a local protocol as per guidelines from the Royal College of Ophthalmologists . Decisions regarding intervention for occlusion are currently delayed until a 22 week review allowing for refractive adaptation , with intermediate review s at 6 and 14 weeks . Purpose : The purpose of this audit was to determine adherence to the protocol and the benefit of the 14 week review . Material s and Methods : We performed a prospect i ve data collection of all children attending the orthoptic department with strabismus without pathology , both with and without unequal vision , from October 2007 to July 2008 managed using the protocol . Results : 26 patients were eligible . Mean age at presentation was 3.3 years ( 1.4 to 6.5 ) . Cycloplegic spherical equivalent ( SE ) mean was 2.6 dioptres ( −2.25 to + 7.25 ) . Five patients failed to comply with the protocol ; one patient was listed surgery , four patients commenced premature occlusion . At presentation 8 patients had equal vision ( defined as < 0.1 logMAR difference ) between the two eyes or would only perform BEO vision , by week 14 , over 60 % were found to have a difference in vision between the eyes , despite refraction correction ( mean 0.4 logMAR , range 0 to 1.4 logMAR ) . In a subgroup of patients ( n = 8 at 6 weeks ) with a small discrepancy of vision between the eyes ( 0.1 to 0.5 logMAR ) there was no progressive worsening of vision during the period of observation and 50 % of patients improved spontaneously , although two patients were lost to follow up . In the subgroup ( n = 10 at 6 weeks ) with a large discrepancy between the eyes ( > 0.5 logMAR ) , all patients ultimately required occlusion , and there was minimal improvement in only three patients . Conclusion : Recorded vision at 6 weeks is more informative for making treatment decisions than that recorded at presentation . The 14 week review confers no benefit to those with reliable and improving visual acuity . Those patients presenting with a large discrepancy in visual acuity do not improve after 14 weeks and we feel that these patients could be occluded at 6 weeks . We propose a new algorithm for the treatment of this patient group Two infant vision screening programmes on total population s in the Cambridge Health District have been design ed to identify manifest strabismus and strabismogenic and amblyogenic refractive errors at 7–9 months of age . The first , completed , programme used the isotropic photorefractor with cycloplegia together with a st and ard orthoptic examination . The second , current , programme uses the VRP-1 isotropic videorefractor to identify infants with accommodative lags which are followed up by refraction under cycloplegia . Both programmes show good agreement between infants identified at screening and retinoscopic refractions at follow-up , showing that photo- and videorefraction ( with or without cycloplegia ) can be effective methods for screening for ametropia in infants and young children . In each programme 5–6 % of infants showed abnormal levels of hyperopia ( ≥3.5 D in any meridian ) , less than 1 % showed anisometropia ≥1.5 D ; very few infants ( 0.25 % ) showed −3 D myopia or greater . Less than 1 % showed manifest strabismus . Hyperopic and anisometropic children entered a r and omised controlled trial of partial refractive correction . All children identified at screening , alongside appropriate control groups , are extensively followed up to age 4 years . The first programme has found that children who were hyperopic in infancy were 13 times more likely to become strabismic , and 6 times more likely to show measurable acuity deficits by 4 years , compared with controls . Wearing a partial spectacle correction reduced these risk ratios to 4:1 and 2.5:1 respectively . The impaired acuity can be attributed , in part , to meridional amblyopia result ing from persisting astigmatism . Both hyperopic and myopic infants showed refractive changes in the direction of emmetropia between 9 months and 4 years . Wearing a partial spectacle correction did not affect this process of emmetropisation , but does provide the possibility of reducing the incidence of common pre-school vision problems PURPOSE To evaluate the psychometric properties of the original Parent and new Child Amblyopia Treatment Index ( ATI ) , question naires that assess the burden of amblyopia treatment in children and families , and to compare scores between children treated with atropine or patching . METHODS Parent ATI and Child ATI were administered to 233 children 7 to < 13 years old and their parents as part of a r and omized trial comparing patching and atropine for amblyopia treatment . For each ATI version , construct validity was assessed using factor analysis ; internal consistency reliability was assessed using Cronbach 's alpha . Data from the Parent ATI and Child ATI were correlated and scores for each version were compared between treatment groups . RESULTS We analyzed the 3 subscales found in prior Parent ATI studies in younger children and confirmed subscales for adverse effects and treatment compliance , but not for social stigma , in both parent and child versions . Overall and subscale scores on the Parent ATI and Child ATI were moderately to well correlated except for the social stigma subscale . For both the Parent ATI and the Child ATI , children treated with atropine had better scores than those treated with patching , both overall and on treatment compliance and social stigma subscales ( all p values ≤ 0.01 ) . CONCLUSIONS When used for children 7 to < 13 years old , the Parent ATI and Child ATI have similar factor structures to each other and to the Parent ATI for children 3 to < 7 years old . Atropine treatment was found to have less negative impact than patching PURPOSE Noncompliance is one of the limiting factors in the success of occlusion therapy for amblyopia . Electronic monitoring was used to investigate predictors of noncompliance , and , in a prospect i ve r and omized clinical trial , determined the effectiveness of an educational program . METHODS Compliance was measured electronically during 1 week every 3 months in 310 newly diagnosed amblyopic children . The family 's demographic parameters and the child 's clinical parameters were assessed for their influence on the level of compliance . In addition to st and ard orthoptic care , children were r and omized to receive an educational cartoon story , reward stickers , and an information sheet for the parents ( intervention group ) , or a picture to color ( reference group ) . These and the electronic device were distributed during home visits by research ers . The primary outcome measure was the percentage of compliance ( actual/prescribed occlusion time ) in the two groups . The secondary outcome measure was the influence of demographic and clinical factors on compliance . RESULTS Compliance was associated with parental fluency in the national language , country of origin , level of education , and initial visual acuity of the child . During the first 1-week measurement period children in the intervention group had better compliance than the reference group had ( 78 % + /- 32 % vs. 57 % + /- 40 % ; P < 0.0001 ) , and fewer children were not occluded at all ( 3 vs. 23 in the reference group ; P < 0.0001 ) . This difference remained throughout the study period . CONCLUSIONS Poor parental fluency in the national language , a low level of education , and poor acuity at the start of treatment were predictors of low compliance . An educational program primarily aim ed at the child improved compliance and reduced the number of children who did not comply with occlusion at all OBJECTIVE To compare the effectiveness of 2-hour daily patching with the effectiveness of acupuncture in treating anisometropic amblyopia in children aged 7 to 12 years who have worn optimal spectacles for at least 16 weeks . METHODS In a single-center r and omized controlled trial , 88 eligible children with an amblyopic eye who had a best spectacle-corrected visual acuity ( BSCVA ) of 0.3 to 0.8 logMAR at baseline were r and omly assigned to receive 2 hours of patching of the sound eye daily or 5 sessions of acupuncture weekly . All participants in our study received constant optical correction , plus 1 hour of near-vision activities daily , and were followed up at weeks 5 , 10 , 15 , and 25 . The main outcome measure was BSCVA in the amblyopic eye at 15 weeks . RESULTS The mean BSCVA of the amblyopic eye at 15 weeks improved from baseline by 1.83 and 2.27 lines in the patching and acupuncture groups , respectively . After baseline adjustment , the mean difference of BSCVA between the 2 groups was 0.049 logMAR ( 95 % confidence interval , 0.005 - 0.092 ; P = .03 ) , meeting the definition of equivalence ( difference within 1 line ) . The BSCVA had improved by 2 lines or more in 28 ( 66.7 % ) and 31 ( 75.6 % ) eyes in the patching and acupuncture groups , respectively . Amblyopia was resolved in 7 ( 16.7 % ) and 17 ( 41.5 % ) eyes in the patching and acupuncture groups , respectively . CONCLUSION Acupuncture produced equivalent treatment effect for anisometropic amblyopia , compared with patching , and was statistically superior . Further studies are warranted to investigate its value in the treatment of amblyopia . CLINICAL RELEVANCE Acupuncture could potentially become an alternative treatment to occlusion therapy for amblyopia . TRIAL REGISTRATION Centers for Clinical Trials Registry Identifier : CUHK_CCT00248 Background / aims Several studies have recently provided insights into how amblyopia may be most effectively managed . Despite the new evidence , a US study reported that a recent r and omised controlled trial had made little influence on clinical practice . The aims of this research are to assess current practice of amblyopia management in the UK and to determine the comparability with the evidence -based recommendations . Methods A question naire was constructed to assess current amblyopia management practice , particularly in relation to areas investigated by recent research and emailed to every head orthoptist within the UK . Results There was a great deal of variability in the amount of occlusion that was prescribed for moderate and severe amblyopia . Sixty per cent of clinicians indicated that the maximum they would prescribe was in excess of the 6 h recommended by research . Atropine was rarely recommended as a first-line treatment , with occlusion generally being considered to be more effective . Despite recommendations regarding education as a means of reducing non-compliance , only 39 % of clinicians always gave written information , although various other methods of enhancing compliance were used . A period of refractive adaptation was allowed by most clinicians but often far less than recommended . Conclusion The uptake of recent research evidence into clinical practice is sporadic and incomplete with one-third of respondents indicating that following the studies , they had made no changes whatsoever to their practice . This is similar to other areas of medicine ; the reasons are likely to be varied , and is an area that would benefit from greater attention |
10,893 | 19,943,678 | Indeed these three interventions are predicted to have the same or less effect than what may be expected due purely to reporting bias in unblinded studies With the currently available evidence ceramic filters are the most effective form of HWT in the longterm , disinfection-only interventions including SODIS appear to have poor if any longterm public health benefit | Household water treatment ( HWT ) is being widely promoted as an appropriate intervention for reducing the burden of waterborne disease in poor communities in developing countries .
A recent study has raised concerns about the effectiveness of HWT , in part because of concerns over the lack of blinding and in part because of considerable heterogeneity in the reported effectiveness of r and omized controlled trials .
This study set out to attempt to investigate the causes of this heterogeneity and so identify factors associated with good health gains . | A r and omized , controlled intervention trial of two household-scale drinking water filters was conducted in a rural village in Cambodia . After collecting four weeks of baseline data on household water quality , diarrheal disease , and other data related to water use and h and ling practice s , households were r and omly assigned to one of three groups of 60 households : those receiving a ceramic water purifier ( CWP ) , those receiving a second filter employing an iron-rich ceramic ( CWP-Fe ) , and a control group receiving no intervention . Households were followed for 18 weeks post-baseline with biweekly follow-up . Households using either filter reported significantly less diarrheal disease during the study compared with a control group of households without filters as indicated by longitudinal prevalence ratios CWP : 0.51 ( 95 % confidence interval [ CI ] : 0.41 - 0.63 ) ; CWP-Fe : 0.58 ( 95 % CI : 0.47 - 0.71 ) , an effect that was observed in all age groups and both sexes after controlling for clustering within households and within individuals over time Daniel Maeusezahl and colleagues conducted a cluster-r and omized controlled trial in rural Bolivia of solar drinking water disinfection , and find only moderate compliance with the intervention and no evidence of reduction in diarrhea among children A number of household water treatment and safe storage technologies , such as chlorine disinfection , solar disinfection , and ceramic filtration , have been documented for their ability to reduce diarrheal disease and improve microbial water quality . The bios and filter ( BSF ) is a promising household water treatment technology in use by > 500,000 people globally . The purpose of this research was to document the ability of BSFs to improve water quality and to reduce diarrheal disease in user compared with non-user households in a r and omized controlled trial in Bonao , Dominican Republic , during 2005 - 2006 . During the 6-month intervention period , 75 BSF households had significantly improved drinking water quality on average compared with 79 control households ( P < 0.001 ) . Based on r and om intercepts logistic regression , BSF households had 0.53 times the odds of diarrheal disease as control households , indicating a significant protective effect of the BSF against waterborne diarrheal disease Although the efficacy of chlorine disinfection under controlled laboratory conditions is well known , the effectiveness of chlorine under field point-of-use ( POU ) conditions is still not clearly understood and may be impacted by a variety of factors . This study evaluated the effectiveness of POU chlorine disinfection in rural Ecuador under typical use conditions and compared this effectiveness with the efficacy in controlled laboratory conditions . While reductions of indicator organisms were slightly higher in households that used chlorination , no significant differences were seen between households employing POU chlorination and the households with no chlorination ( 1 - 1.5 log10 median reductions for chlorinating households and 0.31 - 0.55 log10 for nonchlorinating households , depending on the indicator organism ) . In contrast , significant reduction of all test organisms was found when simulating POU conditions in the laboratory . This study demonstrates that POU chlorination can be considerably less effective under actual field conditions than would be predicted based on its laboratory efficacy ( 3 - 5 log10 median reductions for chlorinated and 0 - 0.3 log10 for nonchlorinated sample s ) . Human factors ( including improper storage and chlorine dosing ) and uncontrolled water quality effects are hypothesized to impact significantly the effectiveness of chlorine disinfection Simple , effective and affordable methods are needed to treat and safely store non-piped , gathered household water . This study evaluated point-of-use chlorination and storage in special plastic containers of gathered household water for improving microbial quality and reducing diarrhoeal illness of consumers living under conditions of poor sanitation and hygiene . Community families were recruited and r and omly divided into intervention ( household water chlorination and storage in a special container ) and control ( no intervention ) households . Microbes in stored household water were extensively inactivated by 1 - 5-mg/L doses of hypochlorite . Escherichia coli levels in stored household waters were < 1/100 mL in most intervention households but readily detectable at high levels in control households . Stored water of intervention households was also lower in Clostridium perfringens and heterotrophic plate count bacteria than in control households . The intervention reduced household diarrhoeal illness . In Bolivia , monthly episodes of household diarrhoeal illness were 1.25 and 2.2 in intervention and control families , respectively ( P = < 0.002 ) indicating that 43 % of community diarrhoea was preventable by using the intervention . In Bangladesh , mean episodes of child diarrhoea/1,000 d were 19.6 and 24.8 in intervention and control groups respectively ( P = < 0.03 ) indicating that about 24 % of observed diarrhoea was preventable by using the intervention . Chlorine disinfection and storage in an appropriate container significantly improved the microbiological quality of non-piped household drinking water and reduced community diarrhoeal disease . Widespread use of this simple treatment and storage system for non-piped domestic water has the potential to dramatically reduce the global burden of waterborne diarrhoeal disease To determine the effectiveness of ceramic filters in reducing diarrhea , we conducted a r and omized controlled trial in Zimbabwe and South Africa , in which 61 of 115 households received ceramic filters . Incidence of non-bloody and bloody diarrhea was recorded daily over 6 months using pictorial diaries for children 24 - 36 months of age . Poisson regression was used to compare incidence rates in intervention and control households . Adjusted for source quality , intervention household drinking water showed reduced Escherichia coli counts ( relative risk , 0.67 ; 95 % CI , 0.50 - 0.89 ) . Zero E. coli were obtained for drinking water in 56.9 % of intervention households . The incidence rate ratio for bloody diarrhea was 0.20 ( 95 % CI , 0.09 - 0.43 ; P < 0.001 ) and for non-bloody diarrhea was 0.17 ( 95 % CI , 0.08 - 0.38 ; P < 0.001 ) , indicating much lower diarrhea incidence among filter users . The results suggest that ceramic filters are effective in reducing diarrheal disease incidence |
10,894 | 30,143,702 | Data analysis revealed that UTN reduced the incidence rates of superficial infection and malunion after fixation compared with EF .
However , EF led to a significant reduction in hardware failure .
For postoperative deep infection , delayed union and nonunion , the treatment effects were similar between these two groups . | Controversy exists over whether the use of external fixation ( EF ) or unreamed tibial intramedullary nailing ( UTN ) is optimal for the treatment of open tibial fractures .
The aim of this study was to compare clinical outcomes in terms of postoperative superficial and deep infection , malunion , delayed union , nonunion and hardware failure between these two treatment methods . | 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 Severe open fractures of the tibia have a high incidence of complications and a poor outcome . The most usual method of stabilisation is by external fixation , but the advent of small diameter locking intramedullary nails has introduced a new option . We report the early results of a r and omised , prospect i ve study comparing external fixation with non-reamed locked nails in grade -IIIb open tibial fractures . Of 29 patients , 15 were treated by nails and 14 by external fixation . Both groups had the same initial management , soft-tissue procedures , and early bone grafting . All 29 fractures healed within nine months , but the nailed group had slightly better motion and less final angulation . Complications included one deep infection and two pin-track infections in the external fixator group and one deep infection and one vascular problem in the nailed group . Although the differences in healing and range of motion were not statistically significant , we found that the nailed fractures were consistently easier to manage , especially in terms of soft-tissue procedures and bone grafting . It is the treatment preferred by patients and does not require the same high level of patient compliance as external fixation . The only factors against nailing are the longer operating time and the greater need for fluoroscopy . We consider that locked non-reamed nailing is the treatment of choice for grade -IIIb open tibial fractures OBJECTIVE To compare unreamed intramedullary nailing ( IMN ) with external fixation ( EF ) in patients with Type II , IIIA , and IIIB open fractures of the tibial shaft . DESIGN An inception cohort of consecutive patients with Type II , IIIA , and IIIB tibial fractures incurred between January 1988 and March 1993 were systematic ally allocated into one of two treatment groups . Patients were treated and followed with a prospect ively design ed protocol . PATIENTS AND SETTING All patients were skeletally mature and had incurred a fracture of the tibial diaphysis within twenty-four hours of presentation to the tertiary care hospital , a Level I Trauma Center . One hundred seventy-four fractures in 168 patients were stabilized with either IMN ( 104 ) or half-pin EF ( 70 ) . There were 132 men and thirty-six women , with an average age of thirty-three years ( range , 14 to 77 years ) . INTERVENTION Except for the selection of the fixation device , open fracture care was similar in the two treatment groups . All patients underwent emergent irrigation and debridement with concomitant skeletal stabilization . Cephalosporin antibiotics were administered perioperatively for twenty-four to forty-eight hours . No wounds were closed primarily . Delayed primary closure , skin grafting , and /or myoplasty were performed between three and ten days after injury . MAIN OUTCOME MEASURES The main outcome measures were final fracture alignment , presence of infection or inflammation , hardware failure , time to union , and the number of operative procedures . RESULTS The IMN group had significantly fewer incidences of malalignment than did the EF group [ 8 vs. 31 percent ; p = 0.00005 ; confidence interval ( CI ) = 0.18 , 0.76 ] and had significantly fewer subsequent procedures ( mean of 1.7 vs. mean of 2.7 per fracture ; p = 0.001 ; CI = 0.45 , 1.59 ) . IMN result ed in fewer infections/ inflammatory problems than did EF at the injury site ( 13 vs. 21 percent ; p = 0.73 ; CI = -0.63 , 0.45 ) and significantly fewer at surgical interfaces ( i.e. , pin sites , nail and interlocking screw insertion sites ; 2 vs. 50 percent ; p = 0.000 ; CI = 0.39 , 0.60 ) . No significant difference was found in the healing rates for the two implant groups . The more severe Gustilo injury types had longer healing times regardless of the type of fixation . CONCLUSIONS Results suggest that unreamed interlocking intramedullary nails are more efficacious than half-pin external fixators , in particular with regard to maintenance of limb alignment . However , the severity of soft tissue injury rather than the choice of implant appears to be the predominant factor influencing rapidity of bone healing and rate of injury site infection Although the intramedullary nailing is thought to be the method of choice for treatment of closed tibial shaft , there is ongoing debate on the optimal surgical approach in patients with open types of these fractures . In addition , choosing between the reamed and unreamed intramedullary nailing is still an issue for the orthopedic surgeons . In present study , we aim ed to compare the outcome and consequences of OA tubular external fixation vs. unreamed intramedullary nailing in open grade IIIA-IIIB tibial shaft fractures . In a r and omized clinical trial , 50 patients with open tibial shaft fractures ( grade s IIIA-IIIB ) were recruited in Tabriz Shohada teaching centre in a 2-year period of time . They r and omized in two equal groups underwent either AO tubular external fixation or unreamed intramedullary nailing . These 2 groups were matched for sex , age and fracture- grade . The follow-up time was one year . Union time , surgical outcome , postoperative complications and the ambulation time were compared between the two groups . Twenty five patients , 20 males and 5 females with a mean age of 30.80 + /- 5.24 years were allocated in unreamed intramedullary group and 25 other patients , 22 males and 3 females with a mean age of 28.92 + /- 8.88 years were studied in the external fixation group ( p = 0.70 and 0.37 , respectively ) . The two groups were matched for sex ( p = 0.70 ) and age ( p = 0.37 ) . The time of union was 3 , 4 , 5 and 6 < or = weeks after operation in 28 , 12 , 32 and 28 % of the cases in unreamed intramedullary group vs. 4 , 12 , 48 and 36 % of the cases in external fixation group , respectively ( p = 0.14 ) . Post-operative infection , soft tissue injury , malunion and nonunion were documented in 16 , 8 , 0 and 4 % of the cases in unreamed intramedullary group vs. 32 , 12 , 24 and 8 % of the cases in external fixation group , respectively ( p = 0.19 , 0.50 , 0.02 and 0.50 , respectively ) . The mean ambulation time after operation was 2.92 + /- 2.43 weeks in the unreamed intramedullary nailing group vs. 2.68 + /- 2.14 weeks in the external fixation group ( p = 0.71 ) . Our results are in favor of unreamed intramedullary nailing against external fixation in treatment of open tibial shaft fractures In a prospect i ve study , since March 1989 , 55 tibial shaft fractures have been treated with a new , unreamed solid tibial nail ( UTN ) . This nail was initially design ed as a temporary implant . The first 33 cases with second or third degree soft tissue damage were review ed 6 months or more after the operation . Fractures were classified according to Müller : 6 type A ( 18.2 % ) , 15 type B ( 45.5 % ) , and 12 type C ( 36.7 % ) . In 9 cases ( 27.3 % ) , there was GII ( n = 4 ) or GIII ( n = 5 ) closed soft tissue damage according to Tscherne 's classification . The 24 open fractures ( 72.7 % ) comprised 11 OII , 3 OIIIA and 10 OIIIB fractures ( Gustilo classification ) . 24 patients ( 72.7 % ) were polytraumatized , the mean PTS ( Hannover Polytrauma Score ) was 18 points ( range : 8 - 65 points ) . All fractures were stabilized without reaming . The implant diameter was 8 mm ( n = 14 ) or 9 mm ( n = 19 ) . Static locking was performed in 31 cases . Dermatofasciotomy was necessary because of compartment syndrome in 14 cases . In 1 grade IIIB open fracture soft tissue coverage was performed with a latissimus dorsi myocutaneous free flap 4 days after nailing . In 32 of the 33 cases the use of an additional cast or brace was not necessary during the follow-up treatment ; 1 patient had a cast for 8 weeks for the treatment of accompanying injuries . Full weight-bearing was achieved in 5 cases within 3 weeks , in 16 cases within 12 weeks , and in 30 cases within 26 weeks . In 16 cases ( 48.5 % ) the interlocking screws were removed after 5 - 26 weeks ( mean : 10 weeks ) . ( ABSTRACT TRUNCATED AT 250 WORDS Unreamed intramedullary nailing is an alternative to external fixation in the treatment of open tibial fractures . We compared a prospect i ve series of thirty-one patients managed with a solid nail with static interlocking without intramedullary reaming , with a retrospective series of thirty-one patients managed by external fixation . The protocol for soft tissue treatment was the same throughout the study period . Most fractures were caused by high energy trauma and included Grade I to III B injuries . The fracture wound infection rate was equal in both groups ; there were two deep and three superficial infections in the nail group and three deep and two superficial infections in the external fixation group . In addition , eleven patients in the external fixation group had severe pin track infections . The mean time to union was five months in the nail group and eight months in the external fixation group . The incidence of delayed union was twice as high in the external fixation group as in the nail group . The number of surgical procedures performed to promote union was three times higher in the external fixation group . The malunion rate did not differ between the groups . Although the treatment groups are not fully comparable , the results indicate that intramedullary nailing is superior to external fixation in the treatment of most open tibial fractures We undertook a prospect i ve study comparing the unreamed interlocking nail to Hoffmann external skeletal fixation ( ESF ) in the treatment of 36 consecutive patients with open type IIIA and IIIB tibia fractures . The choice of interlocking nail or Hoffmann ESF was r and omized , ultimately producing four different patient groups : group 1 , type IIIA fractures treated by interlocking nail ; group 2 , type IIIA fractures treated by ESF ; group 3 , type IIIB fractures with interlocking nail ; and group 4 , type IIIB fractures with ESF . The average length of follow-up was 20.5 months . The infection rate was highest in group 3 ( 3 of 8) . The malrotation , malunion , and nonunion rates were highest in group 4 and lowest in group 1 . These results suggest the unreamed interlocking nail is a good choice for the treatment of open type IIIA tibia fractures , but not recommended for the treatment of open type IIIB tibia fractures because of the high infection rate We performed a prospect i ve , r and omised study on 50 patients with Tscherne C1 tibial diaphyseal fractures comparing treatment with reamed and unreamed intramedullary nails . Our results show that reamed nailing is associated with a significantly lower time to union and a reduced requirement for a further operation . Unreamed nailing should not be used in the treatment of the common Tscherne C1 tibial fracture In 673 open fractures of long bones ( tibia and fibula , femur , radius and ulna , and humerus ) treated from 1955 to 1968 at Hennepin County Medical Center , Minneapolis , Minnesota , and analyzed retrospectively , the infection rate was 12 per cent from 1955 to 1960 and 5 per cent from 1961 to 1968 . In a prospect i ve study from 1969 to 1973 , 352 patients were managed as follows : débridement and copious irrigation , primary closure for Type I and II fractures and secondary closure for Type III fractures , no primary internal fixation except in the presence of associated vascular injuries , cultures of all wounds , and oxacillin-ampicillin before surgery and for three days postoperatively . In 158 of the patients in the prospect i ve study the initial wound cultures revealed bacterial growth in 70.3 per cent and the infection rate was 2.5 per cent . Sensitivity studies suggested that cephalosporin is currently the prophylactic antibiotic of choice . For the Type III open fractures ( severe soft-tissue injury , segmental fracture , or traumatic amputation ) , the infection rates were 44 per cent in the retrospective study and 9 per cent in the prospect i ve study Grade III open tibial fractures are known for frequent complications and poor clinical results , yet published series are few and cite conflicting results . To address this dilemma , the authors report a prospect i ve study of 202 consecutive Grade III tibial fractures . All injuries were treated under protocol at the authors ' university with primary external fixation and serial debridement . Equinus deformity was prevented with a new tibiometatarsal frame extension . Severe injuries crossing the ankle or knee were temporarily stabilized with external fixation across these joints . Staged reconstruction of soft tissue and then bone was undertaken for 176 of these tibias in patients who survived their multiple injuries . Reconstructive procedures included skin grafts in 57 % , muscle flaps in 32 % , and bone grafts in 28 % . Gastrosoleus myocutaneous flaps were successful in 92 % of cases versus 66 % for free flaps . Late follow-up data were obtained for 171 ( 97 % ) . Infection occurred in 15 % and led to amputation in 7 % . The infection rate was reduced to 9 % in the second half of the series largely by removal of all necrotic bone prior to wound coverage . Angulation ( greater than 10 degrees ) in 9 % and delayed union were lessened with early posterolateral grafting followed by progressive fracture loading in the fixator . A 9 % incidence of pin tract drainage or loosening was reduced with predrilling and diaphyseal half pins . The time to fixator removal averaged 87 days . Ninety-three percent of the fractures united ( median time , nine months ) but healing times varied widely according to the amount of tissue injury and bone loss . Eighty-nine percent had satisfactory late clinical function . Results from this study , the largest series of open Grade III tibial fractures reported to date , suggest that successful staged reconstruction is now a reasonable expectation for most of these severe injuries The clinical mechanical failures of small diameter intramedullary interlocking nails were evaluated to determine the relationship of failure modes to the type or location of tibial fractures . Methods were developed to duplicate failure modes in vitro in st and ardized tests to simulate the clinical situations . Where st and ard test methods were inadequate , new methods were developed to provide quantifiable , reliable methods of evaluating potential clinical performance . The modes and rates of mechanical failure in the clinical series were consistent among participating centers : ( 1 ) In diaphyseal fractures with secondary trauma , the intramedullary nail bent at the fracture site where the working length was unsupported ; ( 2 ) failures that occurred several weeks after nailing were the result of fatigue fractures of the locking screws , usually at the distal end ; and ( 3 ) nail and screw failures occurred most commonly in proximal and distal tibial fractures . The strength of the 8- and 9-mm sizes of Synthes and Russell-Taylor nails were comparable A r and omized , prospect i ve study comparing Ender nailing with external fixation for open fractures of sixty-three tibiae ( sixty patients ) was undertaken . Ender nailing proved to be at least as effective as external fixation with respect to seven parameters : time to union , tibial alignment , total number of operations , ranges of motion of the knee and ankle , pain , presence of infection , and complications . Ender nailing is a safe alternative to external fixation for grade -I and grade -II open fractures . It should not be used for comminuted fractures , which might shorten about the nails |
10,895 | 30,760,227 | Conclusions This meta- analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases .
It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases | Background The brain is a common site for metastasis in non-small-cell lung cancer ( NSCLC ) .
This study was design ed to evaluate the relationship between the mutational of the epidermal growth factor receptor ( EGFR ) and overall survival ( OS ) in NSCLC patients with brain metastases . | BACKGROUND The results of FASTACT , a r and omised , placebo-controlled , phase 2 study , showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival ( PFS ) in patients with advanced non-small-cell lung cancer . We undertook FASTACT-2 , a phase 3 study in a similar patient population . METHODS In this phase 3 trial , patients with untreated stage IIIB/IV non-small-cell lung cancer were r and omly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm ( stratified by disease stage , tumour histology , smoking status , and chemotherapy regimen ) to receive six cycles of gemcitabine ( 1250 mg/m(2 ) on days 1 and 8 , intravenously ) plus platinum ( carboplatin 5 × area under the curve or cisplatin 75 mg/m(2 ) on day 1 , intravenously ) with intercalated erlotinib ( 150 mg/day on days 15 - 28 , orally ; chemotherapy plus erlotinib ) or placebo orally ( chemotherapy plus placebo ) every 4 weeks . With the exception of an independent group responsible for monitoring data and safety monitoring board , everyone outside the interactive internet response system company was masked to treatment allocation . Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death , and all patients in the placebo group were offered second-line erlotinib at the time of progression . The primary endpoint was PFS in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00883779 . FINDINGS From April 29 , 2009 , to Sept 9 , 2010 , 451 patients were r and omly assigned to chemotherapy plus erlotinib ( n=226 ) or chemotherapy plus placebo ( n=225 ) . PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo ( median PFS 7·6 months [ 95 % CI 7·2 - 8·3 ] , vs 6·0 months [ 5·6 - 7·1 ] , hazard ratio [ HR ] 0·57 [ 0·47 - 0·69 ] ; p<0·0001 ) . Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months ( 16·3 - 20·8 ) and 15·2 months ( 12·7 - 17·5 ) , respectively ( HR 0·79 [ 0·64 - 0·99 ] ; p=0·0420 ) . Treatment benefit was noted only in patients with an activating EGFR gene mutation ( median PFS 16·8 months [ 12·9 - 20·4 ] vs 6·9 months [ 5·3 - 7·6 ] , HR 0·25 [ 0·16 - 0·39 ] ; p<0·0001 ; median overall survival 31·4 months [ 22·2-undefined ] , vs 20·6 months [ 14·2 - 26·9 ] , HR 0·48 [ 0·27 - 0·84 ] ; p=0·0092 ) . Serious adverse events were reported by 76 ( 34 % ) of 222 patients in the chemotherapy plus placebo group and 69 ( 31 % ) of 226 in the chemotherapy plus erlotinib group . The most common grade 3 or greater adverse events were neutropenia ( 65 [ 29 % ] patients and 55 [ 25 % ] , respectively ) , thrombocytopenia ( 32 [ 14 % ] and 31 [ 14 % ] , respectively ) , and anaemia ( 26 [ 12 % ] and 21 [ 9 % ] , respectively ) . INTERPRETATION Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status . FUNDING F Hoffmann-La Roche 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 PURPOSE To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations . PATIENTS AND METHODS In this surgical series , 52 resected lung adenocarcinomas from never-smokers ( < 100 cigarettes in a lifetime ) at a single institution ( Fudan University , Shanghai , China ) were analyzed concurrently for mutations in EGFR , KRAS , NRAS , HRAS , HER2 , BRAF , ALK , PIK3CA , TP53 and LKB1 . RESULTS Forty-one tumors harbored EGFR mutations , three harbored EML4-ALK fusions , two harbored HER2 insertions , and one harbored a KRAS mutation . All mutations were mutually exclusive . Thus , 90 % ( 47 of 52 ; 95 % CI , 0.7896 to 0.9625 ) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes . No BRAF , NRAS , HRAS , or LKB1 mutations were detected , while 15 had TP53 mutations . Four tumors contained PIK3CA mutations , always together with EGFR mutations . CONCLUSION To our knowledge , this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers . Since drugs are now available that target mutant EGFR , HER2 , and ALK , respectively , this result indicates that prospect i ve mutation testing in these patients should successfully assign a targeted therapy in the majority of cases |
10,896 | 30,761,580 | The pooled SMD for the dental plaque index ( n = 10 studies ) was -9.43 ( 95 % CI -14.36 to -4.495 ; I2 = 99 % , p < 0.001 ) , and that of gingival bleeding ( n = 7 studies ) was -8.54 ( 95 % CI -13.16 to -3.91 ; I2 = 99 % , p < 0.001 ) , indicating significant improvement in dental plaque control and gingival bleeding for groups that received the mobile health ( mHealth ) strategy .
CONCLUSION mHealth can be used as an adjunct component in managing gingivitis , acquiring oral health knowledge and improving oral hygiene | AIM To evaluate the effectiveness of mobile applications and text messages , compared with conventional oral hygiene instructions , for improving oral health knowledge and /or reducing gingival inflammation , when delivered to adolescents , adults and mothers of young children . | Background Several studies have recently demonstrated that a post-treatment communication to explain the importance of an oral hygiene can improve the orthodontic patients ’ compliance over a period of 66 days . The main goal of this study is to evaluate the effects of a structured follow-up communication after orthodontic appliance application on oral hygiene compliance after 30–40 days . Methods Eighty-four orthodontic participants enrolled from patients who were beginning fixed orthodontic treatment at the Orthodontic Department , Gaslini Hospital , Genova , between July and October 2014 were r and omly assigned to one of three trial arms . Before the bonding , all patients underwent a session of oral hygiene aim ed at obtaining an plaque index of “ zero . ” At the following orthodontic appointment , the plaque index was calculated for each patient in order to assess oral hygiene compliance . The first group served as control and did not receive any post-procedure communication , the second group received a structured text message giving reassurance , and the third group received a structured telephone call . Participants were blinded to group assignment and were not made aware that the text message or the telephone call was part of the study . ( The research protocol was approved by the Italian Comitato Etico Regionale della Liguria-sezione 3^ c/o IRCCS-Istituto G. Gaslini 845/2014 , and it is not registered in the trial ’s register . ) Results Thirty patients were r and omly assigned to the control group , 28 participants to the text message group , and 26 to the telephone group . Participants who received a post-treatment communication reported higher level of oral hygiene compliance than participants in the control group . The plaque index was 0.3 ( interquartile range ( Iqr ) , 0.60 ) and 0.75 ( Iqr , 1.30 ) , respectively , with a significant difference ( P = 0.0205 ) . Conclusions A follow-up procedure after orthodontic treatment may be an effective tool to increase oral hygiene compliance also over a short period OBJECTIVE Text messaging is useful for promoting numerous health-related behaviors . The Text2Floss Study examines the feasibility and utility of a 7-day text messaging intervention to improve oral health knowledge and behavior in mothers of young children . METHODS Mothers were recruited from a private practice and a community clinic . Of 156 mothers enrolled , 129 r and omized into text ( n = 60 ) and control groups ( n = 69 ) completed the trial . Participants in the text group received text messages for 7 days , asking about flossing and presenting oral health information . Oral health behaviors and knowledge were surveyed pre- and post-intervention . RESULTS At baseline , there were no differences between text and control group mothers in knowledge and behaviors ( P > 0.10 ) . Post-intervention , text group mothers flossed more ( P = 0.01 ) , had higher total ( P = 0.0006 ) and specific ( P < 0.05 ) knowledge , and tried to improve their child 's oral health behaviors ( P = 0.03 ) and decrease their soda and sugary snacks ( P = 0.05 ) more than control mothers . Text messages were accepted and perceived as useful . CONCLUSIONS Mothers receiving text messages improved their own oral health behaviors and knowledge as well as their behaviors regarding their children 's oral health . Text messaging represents a viable method to improve oral health behaviors and knowledge . Its high acceptance may make it useful for preventing oral disease OBJECTIVE To determine if text message reminders regarding oral hygiene compliance have an influence on the level of compliance within an orthodontic population . MATERIAL S AND METHODS In this prospect i ve , r and omized , controlled clinical trial , 42 orthodontic patients were assigned to a text message or control group . Parents of patients assigned to the text message group received a reminder text message one weekday each week . Oral hygiene compliance was measured using bleeding index ( BI ) , modified gingival index ( MGI ) , and plaque index ( PI ) , and visual examination of white spot lesion ( WSL ) development at baseline ( T0 ) , two appointments after baseline ( T1 ) , and four appointments after baseline ( T2 ) . RESULTS BI , MGI , and PI scores were significantly lower in the text message group than in the control group at T2 . CONCLUSION A text message reminder system is effective for improving oral hygiene compliance in orthodontic patients BACKGROUND Rising concern over the poor level of blood-pressure ( BP ) control among hypertensive patients has prompted search es for novel ways of managing hypertension . The objectives of this study were to develop and pilot-test a home BP tele-management system that actively engages patients in the process of care . METHODS Phase 1 involved a series of focus-group meetings with patients and primary care providers to guide the system 's development . In Phase 2 , 33 diabetic patients with uncontrolled ambulatory hypertension were enrolled in a 4-month pilot study , using a before- and -after design to assess its effectiveness in lowering BP , its acceptability to users , and the reliability of home BP measurements . RESULTS The system , developed using commodity hardware , comprised a Bluetooth-enabled home BP monitor , a mobile phone to receive and transmit data , a central server for data processing , a fax-back system to send physicians ' reports , and a BP alerting system . In the pilot study , 24-h ambulatory BP fell by 11/5 ( + /-13/7 SD ) mm Hg ( both P < .001 ) , and BP control improved significantly . Substantially more home readings were received by the server than expected , based on the preset monitoring schedule . Of 42 BP alerts sent to patients , almost half ( n = 20 ) were due to low BP . Physicians received no critical BP alerts . Patients perceived the system as acceptable and effective . CONCLUSIONS The encouraging results of this study provide a strong rationale for a long-term , r and omized , clinical trial to determine whether this home BP tele-management system improves BP control in the community among patients with uncontrolled hypertension Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently AIM The aims of this study were to discover the knowledge of and attitudes towards dental health of a group of regularly attending mothers of young children at high-risk of caries , and to evaluate their toothbrushing techniques . METHOD As part of the baseline examination of a r and omised controlled trial to test the influence of dental health counselling on the caries increment of at-risk pre-school children , 268 mothers of 334 children completed a question naire enquiring about their dental health knowledge and attitudes , and were also observed brushing their children 's teeth . RESULTS Although most mothers ( 71 % ) knew that they should brush their children 's teeth twice a day using a small toothbrush ( 94 % ) only 52 % knew that they should use only a small pea-sized amount of paste , and only 3 % knew the recommended level of fluoride in toothpaste for these at-risk children . 40 % of the children insisted on brushing their own teeth and 40 % of the mothers brushed their children 's teeth inadequately . Although three-quarters of the mothers knew that sugary foods and drinks should be consumed only at mealtimes , only 7 % knew the four foods and drinks supplying most sugar to a child 's diet . Although three-quarters of mothers thought that dental decay in milk teeth was very important , only half wanted their children 's carious teeth restored . CONCLUSION Knowledge , attitudes and behaviour about dental health among these regularly attending mothers of at-risk , pre-school children were superficial . Their attitudes to dental health of primary teeth were equivocal and their demonstrated brushing behaviour on the part of their children was inadequate INTRODUCTION Fixed orthodontic treatment is frequently associated with increased plaque accumulation leading to gingivitis and white spot lesions ( WSLs ) . AIM This study evaluated the role of text message reminder on oral hygiene of orthodontic patients . MATERIAL S AND METHODS A total of 60 patients under fixed orthodontic treatment were r and omly divided into two equal groups as control group and study ( text message ) group . Text message group received reminders about oral hygiene , while the control group did not receive any messages . Oral hygiene of both the groups was evaluated at baseline , 2 , and 3 months using plaque indices ( PIs ) along with WSL status . Data were statistically analyzed using Statistical Package for the Social Sciences ( SPSS ) statistical software , version 19 , with chi-square test and t-test . RESULTS At the baseline , plaque score was higher in the study group over control group ( p > 0.038 ) , whereas it was decreased after 3 months in the test group ( p > 0.001 ) . For WSL , there was no significant difference at baseline , but it was significantly lower in study group ( p > 0.003 ) . CONCLUSION Oral hygiene status improved with text message reminder Objective To investigate the effect of using mobile applications active reminders to improve oral hygiene in comparison to verbal oral hygiene instructions . Design Two-arm parallel r and omised controlled trial . Setting orthodontic clinics at two branches of a university hospitals of the college of dentistry of Riyadh Colleges of Dentistry and Pharmacy , Riyadh , Saudi Arabia . Participants Forty-four 12-year-old and older subjects . Method Subjects undergoing orthodontic treatment with fixed appliances were r and omly assigned to one of two groups using simple r and omisation . Group I : subjects received a mobile application that sends active reminders of oral hygiene three times a day ( n = 22 ) . Group II : subjects received verbal oral hygiene instructions verbally during their routine orthodontic visits ( n = 22 ) . Two primary outcomes were assessed using plaque index ( PI ) and gingival index ( GI ) for Ramfjord teeth to evaluate the level of oral hygiene at baseline and after 4 weeks . Results Mean differences for PI and GI for group I were reduced from T1 to T2 ( P < 0.05 , P < 0.05 ) but did not significantly change for group II ( P > 0.05 , P > 0.05 ) . Both PI and GI significantly reduced for group I compared to group II between T1 and T2 ( P < 0.05 , P < 0.05 ) . Conclusions PI and GI all significantly decreased after 4 weeks of using active reminders of oral hygiene instructions on mobile application compared to verbal oral hygiene instructions . The study was registered at clinical trials.gov with number : NCT03109769 OBJECTIVE To investigate whether text message reminders regarding oral hygiene have an effect on plaque removal in orthodontic patients . MATERIAL S AND METHODS In this r and omized , controlled clinical trial , 50 orthodontic patients were assigned to either a text message or control group . Patients in the text message group received 12 text messages over the course of 4 weeks and one text message for 8 weeks thereafter . Photos were taken at baseline ( T0 ) , at 4 weeks after baseline ( T1 ) , and at 12 weeks after baseline ( T2 ) . For each subject , photos of eight teeth were taken and then the area of the tooth and amount of plaque were measured using planimetry . RESULTS There was a statistically significant difference in plaque coverage between baseline and both T1 and T2 in the text message group as measured using planimetry . This was demonstrated by comparing the average measurements of the control group and the treatment group . CONCLUSION This study demonstrated that the use of automated text message reminders sent from an orthodontic office was effective in improving oral hygiene compliance in orthodontic patients Objectives This study aims to determine the effectiveness of a messaging app ( WeChat ) in improving patients ’ compliance and reducing the duration of orthodontic treatment ( DOT ) . Material s and methods A r and omized controlled trial was performed in a dental hospital and a clinic from August 2012 to May 2015 . Orthodontic patients were included at the beginning of treatment . Patients with multiphase treatment or braceless technique were excluded . Participants were r and omized to WeChat group ( received regular reminders and educational messages ) or control group ( received conventional management ) and were followed up until the treatment was completed . Primary outcome measure was DOT . Others were late and failed attendance , bracket bond failure , and oral hygiene condition . Results One hundred twelve patients in each group participated and completed the trial . DOT in WeChat group were 7.3 weeks shorter ( P = 0.007 ) . There were less failed attendance ( 3.1 vs. 10.9 % , P < 0.001 ) , late attendance ( 20.1 vs. 29.9 % , P < 0.001 ) , and bracket bond failure ( 11.8 vs. 16.1 % , P < 0.001 ) in WeChat group than control . There was no difference in orthodontic plaque index nor modified gingivitis index between the two groups before and after treatment . Number of failed attendances was identified as an independent factor affecting DOT ( P = 0.004 ; HR = 0.89 , 95 % CI 0.84 to 0.95 ) . Conclusions The intervention with WeChat is effective in reducing the treatment duration and bracket bond failure , and improving the attendance in orthodontic patients . Clinical relevance DOT can be reduced by improving patient ’s compliance . The messaging app is useful for outpatient education and management 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 BACKGROUND Oral health education for the mothers of very young children is important in reducing the risk of early childhood caries . This study aim ed to evaluate the impact of an oral health intervention among mothers of 1 - 2 years old children . METHODS This cluster r and omized controlled trial ( 2012 ) was conducted among ninety mothers of 1 - 2 year old children . The setting of study was 10 child day-care centers out of 18 in Hamadan , western Iran . Day-care centers were r and omly allocated into two groups : an intervention group ( 5 day-care centers , 45 mothers ) and a control group ( 5 day-care centers , 45 mothers ) . Intervention consisted of three sessions , a booklet , and mobile phone text-message reminders . The primary outcome was change in cleaning the children ' teeth , while the secondary outcomes were changes in Theory of Planned Behavior ( TPB ) cognitions . Question naires at baseline , 10 days , and 3 months assessed intervention effects . Data were analyzed using SPSS v.16 . T tests , chi- square , and logistic and linear generalized estimating equations ( GEE ) regression were used to test intervention impact . RESULTS At 10-day assessment , mothers in intervention group reported a significant difference in knowledge ( P=0.001 ) , attitude ( P=0.004 ) , perceived behavioral control ( P=0.008 ) , and cleaning of children 's teeth ( P=0.011 ) . Also , at 3-month assessment compared to control group , the mothers in intervention group significantly improved in scores of knowledge ( P=0.001 ) , attitude ( P=0.001 ) , perceived behavioral control ( P=0.001 ) , and cleaning of children 's teeth ( P=0.001 ) . However , the effect sizes were small to medium and ranged from 0.1 to 0.4 for all cognitions except knowledge ( effect size>0.70 ) . Generalized estimating equations ( GEE ) showed that score of attitude and perceived behavioral control of intervention group improved between the two post-test assessment s. CONCLUSIONS A brief multicomponent theory-based intervention among mothers of 1 - 2 years old children was effective moderately in improving cognitions and self-reported cleaning children 's teeth |
10,897 | 31,545,815 | These results indicate that the BPS can be considered a valuable Positive Psychology Intervention to improve clients ' wellbeing , and it seems that it might be more effective for older participants and with shorter practice s ( measured as total minutes of practice ) | The Best Possible Self ( BPS ) exercise promotes a positive view of oneself in the best possible future , after working hard towards it .
Since the first work that attempted to examine the benefits of this intervention in 2001 , studies on the BPS have grown exponentially and , currently , this is one of the most widely used Positive Psychology Interventions .
However , little is yet known about its overall effectiveness in increasing wellbeing outcomes .
Thus , the aim of this meta- analysis is to shed light on this question . | OBJECTIVES Self-criticism and reassurance are important mechanisms for regulating negative emotions but relatively little attention has been paid to interventions aim ed at improving them . DESIGN This study explored the use of an expressive writing task to increase self-reassurance and reduce self-criticism using a r and omized controlled design . METHOD A total of 46 participants wrote either about life goals ( the expressive writing task , n= 23 ) or a control topic ( a review of a recent book or film , n= 23 ) for 15 min , three times within an hour . Measures of self-criticism/self-reassurance , stress , and positive affect were completed at baseline and at 2-week follow-up . The Linguistic Inquiry and Word Count ( LIWC ) was used to analyse the writing of participants in the ' life goals ' condition to identify psychological processes that might differentiate those who improved and those who did not . RESULTS While there were no significant changes in self-reported stress or positive affect , participants writing about life goals decreased in their levels of self-criticism at 2-week follow-up relative to participants writing about control topics . Text analysis showed that experimental participants using words that imply the possibility of doubt or failure , including use of the subjunctive tense ( e.g. , could , would , should ) , were least likely to decrease their self-criticism . CONCLUSION . Expressive writing shows promise as a means by which people may decrease in their self-criticism . Future research should determine whether such experimentally induced changes in self-criticism lead to the improvements in psychological health that is implied by previous cross-sectional research Growing evidence suggests that well-being interventions can be effective . However , it is unclear whether happiness-increasing practice s are equally effective for individuals from different cultural background s. To investigate this question , Anglo Americans and predominantly foreign-born Asian Americans were r and omly assigned to express optimism , convey gratitude , or list their past experiences ( control group ) . Multilevel analyses indicated that participants in the optimism and gratitude conditions reported enhanced life satisfaction relative to those in the control condition . However , Anglo Americans in the treatment conditions demonstrated larger increases in life satisfaction relative to Asian Americans , while both cultural groups in the control condition showed the least improvement . These results are consistent with the idea that the value individualist cultures place on self-improvement and personal agency bolsters the efforts of Anglo Americans to become more satisfied , whereas collectivist cultures ’ de-emphasis of self-focus and individual goals interferes with the efforts of Asian Americans to pursue enhanced well-being This study examined the influence of expressive writing on working memory capacity ( WMC ) , a component of executive function . Japanese undergraduates ( N=104 ) were individually tested across six separate experimental sessions ( baseline , three writing , and two follow-up sessions at 1 and 5 weeks ) . Participants were r and omly assigned to write about a traumatic experience , their best possible future selves ( BPS ) , or a trivial topic for 20 minutes . WMC tests were completed at baseline and follow-ups . Results indicate that expressive writing about traumatic experience can improve WMC at 5 weeks after writing , but that writing about BPS or trivial topics has no effect on WMC 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 |
10,898 | 31,864,398 | Conclusions Compared to MIPPO , IMN had a significantly low risk of wound complications and associated with limited time for reunion .
Although the pooled functional outcomes of the two groups were controversial due to different evaluating scores , IMN was the preferred surgical technique than MIPPO for treating distal tibial fractures | Background The treatment for distal tibial fractures remains controversial to date .
Minimally invasive percutaneous plate osteo synthesis ( MIPPO ) and intramedullary nailing ( IMN ) are well-accepted and effective methods for distal tibial fractures , but these methods were associated with complications .
This study aim ed to assess and compare the clinical and functional outcomes in patients with distal tibial fractures treated with MIPPO or IMN . | BACKGROUND Minimally invasive plate osteo synthesis ( MIPO ) is an established technique for fixation of fractures of the distal third tibia . Our study aim ed to manage intra articular and extraarticular fractures of the distal third tibia by the minimally invasive plate osteo synthesis technique and follow them prospect ively . Clinical and radiological outcomes were studied and clinical indications & efficacy of the procedure review ed . Though many studies on the subject have been done previously , these have been retrospective review s or small series . METHODS From May 2010 to May 2013 , 50 patients of closed distal tibial fractures were operated by MIPO technique with a distal tibial anatomical locking plate having 4.5/5 proximal and 3.5/4 distal screw holes . The follow up duration was for 3 years . RESULTS The mean fracture healing time was 21.4 weeks ( range 16 - 32 weeks ) and average AOFAS score 95.06 was out of a total possible 100 points . At last follow up , superficial infection occurred in 5 patients ( 10 % ) ; deep infection , implant failure and malunion in 1-patient each ( 2 % ) . CONCLUSION MIPO technique provides good , though slightly delayed bone healing and decreases incidence of nonunion and need for bone grafting . This technique should be used in distal tibia fractures where locked nailing can not be done like fractures with small distal metaphyseal fragments , vertical splits , markedly comminuted fractures and in fractures with intra-articular extension BACKGROUND The ideal treatment of distal tibial extra articular fractures remains controversial . Minimally invasive percutaneous plate osteo synthesis and intramedullary nailing are the two most commonly used methods . We did a prospect i ve r and omized controlled study to assess the functional outcome of distal tibial extra articular tibial fractures by comparing these treatment methods . MATERIAL S AND METHODS Sixty patients with distal tibial extra articular fractures were r and omly assigned to an IMN ( intramedullary nailing ) group and a MIPPO ( minimally invasive percutaneous plate osteo synthesis ) group . All patients were followed up for a period of one year . At final follow-up , clinical and radiological outcome was assessed by foot function index . Malunion , infection , implant removal , time to union and secondary interventions were compared between the two groups . The comparison of continuous variables was performed by using the Student t-test or Mann-Whitney U test in accordance with normality testing . A value of p less than 0.05 was considered statistically significant . RESULTS All patients were followed up for a period of one year . Time to callus formation was equal in both groups . There was no non-union in our series . Malunion was more common in the nailing group . The foot function index was similar in both groups . CONCLUSION MIPPO and intramedullary nailing are effective treatment options in the management of distal tibial extra particular fractures , with comparable functional outcomes Objective : To evaluate the clinical , radiographic , and functional outcomes of middle and distal third humeral shaft fractures treated with the minimally invasive percutaneous osteo synthesis ( MIPO ) . Design : Prospect i ve , single-center , nonconsecutive clinical series study . Setting : Skeletal trauma center of a university teaching hospital . Patients : Thirteen patients who were seen from May 2004 to October 2005 with an average age of 38.1 years ( range , 25 to 60 years ) form the basis of this study . Patients were obtained from a surgical data base of 1 surgeon . Intervention : The middle and the distal third humeral shaft fractures were reduced by closed means and fixed with long narrow 4.5-mm dynamic compression plates introduced through 2 small incisions away from the fracture sites and placed on the anterior aspect of the humerus . Main Outcome Measurements : Time to fracture healing and functional assessment s were assessed at an average follow-up of 12.5 months ( range , 7 to 19 months ) for the affected shoulders and elbows using the UCLA and Mayo elbow performance scoring systems , respectively . Results : All fractures united with a mean healing time of 16.2 weeks ( range , 12 to 32 years ) . There were no nonunions , radial nerve palsies , or implant failures . The UCLA scoring system showed excellent results in 7 cases ( 53.8 % ) and good results in 6 cases ( 46.2 % ) . Thirteen patients had excellent results of their elbow function when assessed with the Mayo elbow performance scoring system . Conclusion : Closed reduction and internal fixation of middle or distal third humeral shaft fractures using MIPO is a safe and effective surgical treatment method and an alternative option to open techniques This study compared the results of external fixation combined with limited open reduction and internal fixation ( EF + LORIF ) , minimally invasive percutaneous plate osteo synthesis ( MIPPO ) , and intramedullary nailing ( IMN ) for distal tibia fractures . A total of 84 patients with distal tibia shaft fractures were r and omized to operative stabilization using EF + LORIF ( 28 cases ) , MIPPO ( 28 cases ) , or IMN ( 28 cases ) . The 3 groups were comparable with respect to patient demographics . Data were collected on operative time and radiation time , union time , complications , time of recovery to work , secondary operations , and measured joint function using the American Orthopaedic Foot and Ankle Society ( AOFAS ) score . There was no significant difference in time to union , incidence of union status , time of recovery to work , and AOFAS scores among the 3 groups ( P>.05 ) . Mean operative time and radiation time in the MIPPO group were longer than those in the IMN or EF + LORIF groups ( P<.05 ) . Wound complications after MIPPO were more common compared with IMN or EF + LORIF ( P<.05 ) . Anterior knee pain occurred frequently after IMN ( 32.1 % ) , and irritation symptoms were encountered more frequently after MIPPO ( 46.4 % ) . Although EF + LORIF was associated with fewer secondary procedures vs MIPPO or IMN , it was related with more pin-tract infections ( 14.3 % ) . Findings indicated that EF + LORIF , MIPPO , and IMN all achieved similar good functional results . However , EF + LORIF had some advantages over MIPPO and IMN in reducing operative and radiation times , postoperative complications , and reoperation rate . [ Orthopedics . 2016 ; 39(4):e627-e633 . ] 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 Introduction : The treatment of fractures of proximal and distal tibia is challenging , because of the limited soft tissue envelope and poor vascularity . The best treatment remains controversial and it depends on the fracture morphology , displacement and comminution . Treatment options vary from closed reduction and cast to open reduction and internal fixation with plate . Open reduction and internal fixation with plate can result in extensive dissection and tissue devitalization . We conducted a study on management of these fractures by biological osteo synthesis using Minimally Invasive Plate Osteo synthesis ( MIPO ) technique with preservation of osseous and soft tissue vascularity . Methods : We conducted a prospect i ve study on closed reduction and percutaneous plating in 30 cases ( mean age 42.7 years ; 22 males and 8 females ) of closed fractures of tibia . Among them 24 had proximal tibial fractures and 6 had distal tibial fractures . The mean time from injury to surgery was seven days . Results : The mean operative time was 72.6 minutes ( range : 55 - 90 minutes ) . Mean time for radiological union was 17 weeks ( range : 14 - 22 weeks ) . There was one superficial wound infection which resolved with daily dressings and one week of oral antibiotics . One patient developed a nonunion which required a bone grafting procedure . Conclusions : The satisfactory functional results and lack of soft tissue complications suggest that this method should be considered in periarticular fractures . Biological fixation of complex fractures gives stable as well as optimal internal fixation and complete recovery of limb function at an early stage with minimal risk of complications Purpose The purpose of this r and omized clinical trial is to compare intramedullary nailing ( IMN ) versus minimally invasive plate osteo synthesis ( MIPO ) for the treatment of extra-articular distal tibial shaft fractures . Material s and methods Twenty-five consecutive patients with distal extra-articular tibial fractures which were located between 4 and 12 cm from the tibial plafond ( AO 42A1 and 43A1 ) were r and omly assigned into IMN ( n : 10 ) or MIPO ( n : 15 ) treatment groups . All patients were followed for at least 1 year . Foot function index , time to weight bearing , union time , duration of operation , length of incision , intra-operative blood loss , intra-operative fluoroscopy time , rotational and angular malalignment , rate of infection , secondary interventions and complications were compared between groups . Results All patients completed the trial and were followed with a mean of 23.1 ± 9.4 months ( range 12–52 ) . Foot function index , weight bearing time , union time , rate of malunion , rate of infection and rate of secondary interventions were all similar between groups ( p = 0.807 , p = 0.177 , p = 0.402 , p = 0.358 , p = 0.404 , p = 0.404 , respectively ) . Intra-operative blood loss , length of surgical incision , radiation time and rotational malalignment were higher in the IMN group ( p = 0.012 , p = 0.019 , p = 0.004 and p = 0.027 , respectively ) . Conclusions Results of our study showed that both treatment methods have similar therapeutic efficacy regarding functional outcomes and can be used safely for extra-articular distal tibial shaft fractures , and none of the techniques had a major advantage over the other Purpose A few studies focused on the methods of treatment for displaced distal tibial shaft fractures have been published , all of which compared two different methods . In this r and omized , prospect i ve study , we aim ed to compare minimally invasive plate osteo synthesis , locking intramedullary nail stabilization and external fixation combined with limited open reduction and absorbable internal fixation for distal tibial shaft fractures by assessing complications and secondary procedures . Methods From November 2002 to June 2012 , 137 skeletally mature patients with displaced distal tibial shaft fractures with or without fibula fracture were r and omized to be treated by minimally invasive plate osteo synthesis ( group A , n = 46 ) , locking intramedullary nail ( group B , n = 46 ) or external fixation combined with limited open reduction and absorbable internal fixation ( group C , n = 45 ) . Age , gender , mechanism of injury , fracture pattern and presence of open fracture were equally distributed among the three groups . Indexes for evaluation included hospital stay , operative time , time to radiographic union , union status , infection and the incidence of re-operation . Mazur ankle score was introduced for functional evaluation . Statistics Analysis System ( SAS ) 9.2 was used for analysis . Results A total of 121 patients were included in the final analysis ( group A 42 , group B 40 and group C 39 ) and evaluated after a mean of 14.8 months follow-up . There was no significant difference ( P > 0.05 ) in hospital stay , time to radiographic union and the incidence of union status among the three groups . Although group C was associated with less secondary procedures versus groups A and B , it was related with more pin tract infections ( 15.4 % ) . Anterior knee pain occurred frequently after locking intramedullary nailing ( 37.5 % ) and the irritation symptoms were more frequently encountered in group A ( 59.5 % ) . There was no difference in ankle function between the three methods after operation ( P > 0.05 ) . Conclusions We consider that the minimally invasive plate osteo synthesis , locking intramedullary nail stabilization and external fixation combined with limited open reduction and absorbable internal fixation techniques are all efficient methods for treating distal tibia fractures . With its wide indications , external fixation combined with limited open reduction and absorbable internal fixation leads to minimal soft tissue complication , good functional result and no local soft tissue irritation or implant removal Background : Extraarticular distal tibial fractures are among the most challenging fractures encountered by an orthopedician for treatment because of its subcutaneous location , poor blood supply and decreased muscular cover anteriorly , complications such as delayed union , nonunion , wound infection , and wound dehiscence are often seen as a great challenge to the surgeon . Minimally invasive plate osteo synthesis ( MIPO ) and intramedullary interlocking nail ( IMLN ) are two well-accepted and effective methods , but each has been historically related to complications . This study compares clinical and radiological outcome in extraarticular distal tibia fractures treated by intramedullary interlocking nail ( IMLN ) and minimally invasive plate osteo synthesis ( MIPO ) . Material s and Methods : 42 patients included in this study , 21 underwent IMLN and 21 were treated with MIPO who met the inclusion criteria and operated between June 2014 and May 2015 . Patients were followed up for clinical and radiological evaluation . Results : In IMLN group , average union time was 18.26 weeks compared to 21.70 weeks in plating group which was significant ( P < 0.0001 ) . Average time required for partial and full weight bearing in the nailing group was 4.95 weeks and 10.09 weeks respectively which was significantly less ( P < 0.0001 ) as compared to 6.90 weeks and 13.38 weeks in the plating group . Lesser complications in terms of implant irritation , ankle stiffness , and infection , were seen in interlocking group as compared to plating group . Average functional outcome according to American Orthopedic Foot and Ankle Society score was measured which came out to be 96.67 . Conclusion : IMLN group was associated with lesser duration of surgery , earlier weight bearing and union rate , lesser incidence of infection and implant irritation which makes it a preferable choice for fixation of extra-articular distal tibial fractures . However , larger r and omized controlled trials are required for confirming the results Importance The best treatment for fractures of the distal tibia remains controversial . Most such fractures require surgical fixation but outcomes are unpredictable and complications are common . Objective To assess disability , quality of life , and complications in patients with displaced tibial fracture treated with intramedullary nail fixation vs locking plate fixation . Design , Setting , and Participants A multicenter r and omized trial recruiting 321 patients 16 years or older with an acute , displaced , extra-articular fracture of the distal tibia from April 2013 through April 2016 with final follow-up in February 2017 . Exclusion criteria included open fractures , fractures involving the ankle joint , contraindication to nailing , or inability to complete question naires . Interventions Intramedullary nail fixation ( nail group ; n = 161 ) , a metal rod inserted into the hollow center of the tibia , vs locking plate fixation ( plate group ; n = 160 ) , a plate attached to the surface of the tibia with fixed-angle screws . Main Outcomes and Measures Disability Rating Index ( DRI ; score range , 0 [ no disability ] to 100 [ complete disability ] ) at 6 months was the primary outcome measure , with a minimal clinical ly important difference of 8 points . DRI measurement was also collected at 3 and 12 months . Secondary outcomes were the Olerud-Mol and er Ankle Score ( OMAS ) , quality of life , and complications ( such as infection and further surgery ) . Results Among 321 r and omized patients ( mean age , 45 years [ SD , 16.2 ] ; men , 197 [ 61 % ] ; had experienced traumatic injury after a fall , 223 [ 69 % ] ) , 258 completed the study . There was no statistically significant difference in the DRI score at 6 months between groups ( mean score , 29.8 in the nail group vs 33.8 in the plate group ; adjusted difference , 4.0 [ 95 % CI , −1.0 to 9.0 ] , P = .11 ) . There was a statistically significant difference in the DRI score at 3 months in favor of nail fixation ( mean score , 44.2 in the nail group and 52.6 in the plate group ; adjusted difference , 8.8 [ 95 % CI , 4.3 to 13.2 ] , P < .001 ) , but not at 12 months ( mean score , 23.1 in the nail group and 24.0 in the plate group ; adjusted difference , 1.9 [ 95 % CI , −3.2 to 6.9 ] , P = .47 ) . Secondary outcomes showed the same pattern , including a statistically significant difference in mean OMAS at 3 and 6 months in favor of nail fixation . There were no statistically significant differences in complications , including the number of postoperative infections ( 9 % in the nail group vs 13 % in the plate group ) . Further surgery was more common in the plate group at 12 months ( 8 % in nail group vs 12 % in plate group ) . Conclusions and Relevance Among patients 16 years or older with an acute , displaced , extra-articular fracture of the distal tibia , neither nail fixation nor locking plate fixation result ed in superior disability status at 6 months . Other factors may need to be considered in deciding the optimal approach . Trial Registration clinical trials.gov Identifier : IS RCT Background and purpose Strategies to manage tibial fractures include nonoperative and operative approaches . Strategies to enhance healing include a variety of bone stimulators . It is not known what forms of management for tibial fractures predominate among Canadian orthopedic surgeons . We therefore asked a representative sample of orthopedic trauma surgeons about their management of tibial fracture patients . Methods This was a cross-sectional survey of 450 Canadian orthopedic trauma surgeons . We inquired about demographic variables and current tibial shaft fracture management strategies . Results 268 surgeons completed the survey , a response rate of 60 % . Most respondents ( 80 % ) managed closed tibial shaft fracture operatively ; 47 % preferred reamed intramedullary nailing and 40 % preferred unreamed . For open tibial shaft fractures , 59 % of surgeons preferred reamed intramedullary nailing . Some surgeons ( 16 % ) reported use of bone stimulators for management of uncomplicated open and closed tibial shaft fractures , and almost half ( 45 % ) made use of this adjunctive modality for complicated tibial shaft fractures . Low-intensity pulsed ultrasound and electrical stimulation proved equally popular ( 21 % each ) and 80 % of respondents felt that a reduction in healing time of 6 weeks or more , attributed to a bone stimulator , would be clinical ly important . Interpretation Current practice regarding orthopedic management of tibial shaft fractures in Canada strongly favors operative treatment with intramedullary nailing , although respondents were divided in their preference for reamed and unreamed nailing . Use of bone stimulators is common as an adjunctive modality in this injury population . Large r and omized trials are needed to provide better evidence to guide clinical decision making regarding the choice of reamed or unreamed nailing for tibial shaft fractures , and to inform surgeons about the actual effect of bone stimulators |
10,899 | 23,788,580 | Our review showed that a considerable number of labels has been proposed for trial design s evaluating prognostic and predictive biomarkers which , based on patient flow elements , can be classified into five basic categories . | There is an increasing interest in the evaluation of prognostic and predictive biomarkers for personalizing cancer care .
The literature on the trial design s for evaluation of these markers is diverse and there is no consensus in the classification or nomenclature .
We set this study to review the literature systematic ally , to identify the proposed trial design s , and to develop a classification scheme . | Purpose : A new generation of molecularly targeted agents is entering the definitive stage of clinical evaluation . Many of these drugs benefit only a subset of treated patients and may be overlooked by the traditional , broad- eligibility approach to r and omized clinical trials . Thus , there is a need for development of novel statistical methodology for rapid evaluation of these agents . Experimental Design : We propose a new adaptive design for r and omized clinical trials of targeted agents in setting s where an assay or signature that identifies sensitive patients is not available at the outset of the study . The design combines prospect i ve development of a gene expression – based classifier to select sensitive patients with a properly powered test for overall effect . Results : Performance of the adaptive design , relative to the more traditional design , is evaluated in a simulation study . It is shown that when the proportion of patients sensitive to the new drug is low , the adaptive design substantially reduces the chance of false rejection of effective new treatments . When the new treatment is broadly effective , the adaptive design has power to detect the overall effect similar to the traditional design . Formulas are provided to determine the situations in which the new design is advantageous . Conclusion : Development of a gene expression – based classifier to identify the subset of sensitive patients can be prospect ively incorporated into a r and omized phase III design without compromising the ability to detect an overall effect PURPOSE Biomarkers can add substantial value to current medical practice by providing an integrated approach to prediction using the genetic makeup of the tumor and the genotype of the patient to guide patient-specific treatment selection . We discuss and evaluate various clinical trial design s for the validation of biomarker-guided therapy . METHODS Design s for predictive marker validation are broadly classified as retrospective ( ie , using data from previously well-conducted r and omized controlled trials [ RCTs ] ) versus prospect i ve ( enrichment , unselected , hybrid , or adaptive analysis ) . We discuss the salient features of each design in the context of real trials . RESULTS Well- design ed retrospective analysis from well-conducted prospect i ve RCTs can bring forward effective treatments to marker-defined subgroups of patients in a timely manner ( eg , KRAS and colorectal cancer ) . Enrichment design s are appropriate when preliminary evidence suggest that patients with or without that marker profile do not benefit from the treatments in question ; however , this may sometimes leave questions unanswered ( eg , trastuzumab and breast cancer ) . An unselected design is optimal where preliminary evidence regarding treatment benefit and assay reproducibility is uncertain ( eg , epidermal growth factor receptor and lung cancer ) . Hybrid design s are appropriate when preliminary evidence demonstrate the efficacy of certain treatments for a marker-defined subgroup , making it unethical to r and omly assign patients with that marker status to other treatments ( eg , multigene assay and breast cancer ) . Adaptive analysis design s allow for prespecified marker-defined subgroup analyses of data from an RCT . CONCLUSION The implementation of these design strategies will lead to a more rapid clinical validation of biomarker-guided therapy Purpose : Many anticancer therapies benefit only a subset of treated patients and may be overlooked by the traditional broad eligibility approach to design phase III clinical trials . New biotechnologies such as microarrays can be used to identify the patients that are most likely to benefit from anticancer therapies . However , due to the high-dimensional nature of the genomic data , developing a reliable classifier by the time the definitive phase III trail is design ed may not be feasible . Experimental Design : Previously , Freidlin and Simon ( Clinical Cancer Research , 2005 ) introduced the adaptive signature design that combines a prospect i ve development of a sensitive patient classifier and a properly powered test for overall effect in a single pivotal trial . In this article , we propose a cross-validation extension of the adaptive signature design that optimizes the efficiency of both the classifier development and the validation components of the design . Results : The new design is evaluated through simulations and is applied to data from a r and omized breast cancer trial . Conclusion : The cross-validation approach is shown to considerably improve the performance of the adaptive signature design . We also describe approaches to the estimation of the treatment effect for the identified sensitive sub population . Clin Cancer Res ; 16(2 ) ; Background There is currently much interest in pharmacogenetics : determining variation in genes that regulate drug effects , with a particular emphasis on improving drug safety and efficacy . The ability to determine such variation motivates the application of personalized drug therapies that utilize a patient 's genetic makeup to determine a safe and effective drug at the correct dose . To ascertain whether a genotype-guided drug therapy improves patient care , a personalized medicine intervention may be evaluated within the framework of a r and omized controlled trial . The statistical design of this type of personalized medicine intervention requires special considerations : the distribution of relevant allelic variants in the study population ; and whether the pharmacogenetic intervention is equally effective across sub population s defined by allelic variants . Methods The statistical design of the Clarification of Optimal Anticoagulation through Genetics ( COAG ) trial serves as an illustrative example of a personalized medicine intervention that uses each subject 's genotype information . The COAG trial is a multicenter , double blind , r and omized clinical trial that will compare two approaches to initiation of warfarin therapy : genotype-guided dosing , the initiation of warfarin therapy based on algorithms using clinical information and genotypes for polymorphisms in CYP2C9 and VKORC1 ; and clinical -guided dosing , the initiation of warfarin therapy based on algorithms using only clinical information . Results We determine an absolute minimum detectable difference of 5.49 % based on an assumed 60 % population prevalence of zero or multiple genetic variants in either CYP2C9 or VKORC1 and an assumed 15 % relative effectiveness of genotype-guided warfarin initiation for those with zero or multiple genetic variants . Thus we calculate a sample size of 1238 to achieve a power level of 80 % for the primary outcome . We show that reasonable departures from these assumptions may decrease statistical power to 65 % . Conclusions In a personalized medicine intervention , the minimum detectable difference used in sample size calculations is not a known quantity , but rather an unknown quantity that depends on the genetic makeup of the subjects enrolled . Given the possible sensitivity of sample size and power calculations to these key assumptions , we recommend that they be monitored during the conduct of a personalized medicine intervention . Trial Registration clinical trials.gov : The optimal design of phase II studies continues to be the subject of vigorous debate , especially studies of newer molecularly targeted agents . The observations that many new therapeutics “ fail ” in definitive phase III studies , coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials , further emphasize the critical importance of robust and efficient phase II design . The Clinical Trial Design Task Force ( CTD-TF ) of the National Cancer Institute ( NCI ) Investigational Drug Steering Committee ( IDSC ) has published a series of discussion papers on phase II trial design in Clinical Cancer Research . The IDSC has developed formal recommendations about aspects of phase II trial design that are the subject of frequent debate , such as endpoints ( response versus progression-free survival ) , r and omization ( single-arm design s versus r and omization ) , inclusion of biomarkers , biomarker-based patient enrichment strategies , and statistical design ( e.g. , two-stage design s versus multiple-group adaptive design s ) . Although these recommendations in general encourage the use of progression-free survival as the primary endpoint , r and omization , inclusion of biomarkers , and incorporation of newer design s , we acknowledge that objective response as an endpoint and single-arm design s remain relevant in certain situations . The design of any clinical trial should always be carefully evaluated and justified based on characteristic specific to the situation . Clin Cancer Res ; 16(6 ) ; Pharmacogenomics is the science of determining how the benefits and adverse effects of a drug vary among a target population of patients based on genomic features of the patient 's germ line and diseased tissue . By identifying those patients who are most likely to respond while eliminating serious adverse effects , the therapeutic index of a drug can be substantially increased . This may facilitate demonstrating the effectiveness of the drug and may avoid subsequent problems due to serious adverse events . Our objective here is to provide clinical trial design s and analysis strategies for the utilization of genomic signatures as classifiers for patient stratification or patient selection in therapeutics development . We review methods for the development of genomic signature classifiers of treatment outcome in high-dimensional setting s , where the number of variables available for prediction far exceeds the number of cases . The split- sample and crossvalidation methods for obtaining estimates of prediction accuracy in developmental studies are described . We present clinical trial design s for utilizing genomic signature classifiers in therapeutics development . The purpose of the classifier is to facilitate the identification of groups of patients with a high probability of benefiting from it and avoiding serious adverse events . We distinguish exploratory analysis during the development of the genomic classifier from prospect i ve planning and rigorous testing of therapeutic hypotheses in studies that utilize the genomic classifier in therapeutics development . We discuss a variety of clinical trial design s including those utilizing specimen collection and assay prospect ively for newly accrued patients and those involving a prospect ively planned analysis of archived specimens from a previously conducted clinical trial . Our discussion of the development and use of classifiers of efficacy is mostly focused on applications in oncology using classifiers based on biomarkers measured in tumors . Some of the same considerations apply , however , to development of efficacy and safety classifiers in nononcologic diseases based on single-nucleotide germline polymorphisms Advancements made in molecularly targeted therapeutics have focussed increasing attention on biomarker-adaptive clinical trial design s as a means of improving the efficiency of drug development and advancing medical care . Here , we focus on r and omized clinical trial ( RCT ) design s aim ed at developing/validating clinical ly relevant pharmacogenomic biomarkers capable of identifying patients sensitive to a given therapy(s ) , and thereby , selecting the best therapy for a given patient . The term ‘ biomarker-adaptive ’ refers to biomarker trials that incorporate adaptive clinical trial method ology to modify the trial according to the accumulating outcome data . While some adaptive methods ( e.g. , interim monitoring ) have been an integral part of traditional clinical trial design for decades , these methods can be particularly advantageous in biomarker studies that evaluate molecularly targeted therapies . Here , we briefly review the main clinical trial methods that are used in design ing adaptive trials . We then discuss how these methods can be used to improve the efficiency of biomarker RCT design The decade since the publication of the Human Genome Project draft has ended with the discovery of hundreds of genomic markers related to diseases and phenotypes . However , the project has not yet delivered on its promise to tailor treatments for individuals . The number of genomic markers in clinical practice is very small . The number of markers to guide treatment decisions is even smaller . In order to speed up discovery and validation of genomic treatment selection markers , we call for considering the brilliant potential of r and omized clinical trials . If biomedical research community can collaborate in organizing large-scale consortium of clinical trials associated with well- design ed biobanks , these studies would soon act as huge laboratories for investigating genomic medicine ; a big step forward towards personalizing medicine BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . The developmental pathway from discovery to clinical practice for biomarkers and biomarker-directed therapies is complex . While several issues need careful consideration , two critical issues that surround the validation of biomarkers are the choice of clinical trial design ( which is based on the strength of the preliminary evidence and marker prevalence ) and the biomarker assay related issues surrounding the marker assessment methods such as the reliability and reproducibility of the assay . This review focuses on trial design s for marker validation , both in the setting of early phase trials for initial validation , as well as in the context of larger definitive trials . Design s for biomarker validation are broadly classified as retrospective ( i.e. , using data from previously well-conducted , r and omized , controlled trials ) or prospect i ve ( enrichment , allcomers or adaptive ) . We believe that the systematic evaluation and implementation of these design strategies are essential to accelerate the clinical validation of biomarker-guided therapy , thereby taking us a step closer to the goal of personalized medicine Background Targeted therapies are becoming increasingly important for the treatment of various diseases . Biomarkers are a critical component of a targeted therapy as they can be used to identify patients who are more likely to benefit from a treatment . Targeted therapies , however , have created major challenges in the design , conduct , and analysis of clinical trials . In traditional clinical trials , treatment effects for various biomarkers are typically evaluated in an exploratory fashion and only limited information about the predictive values of biomarkers obtained . Purpose New study design s are required , which effectively evaluate both the diagnostic and the therapeutic implication of biomarkers . Methods The Bayesian approach provides a useful framework for optimizing the clinical trial design by directly integrating information about biomarkers and clinical outcomes as they become available . We propose a Bayesian covariate-adjusted response-adaptive r and omization design , which utilizes individual biomarker profiles and patient ’s clinical outcomes as they become available during the course of the trial , to assign the most efficacious treatment to individual patients . Predictive biomarker subgroups are determined adaptively using a partial least squares regression approach . Results A series of simulation studies were conducted to examine the operating characteristics of the proposed study design . The simulation studies show that the proposed design efficiently identifies patients who benefit most from a targeted therapy and that there are substantial savings in the sample size requirements when compared to alternative design s. Limitations The design does not control for the type I error in the traditional sense and a positive result should be confirmed by conducting an independent phase III study focusing on the selected biomarker profile groups . Conclusions We conclude that the proposed design may serve a useful role in the early efficacy phase of targeted therapy development . Clinical Trials 2010 ; 7 : 546—556 . BACKGROUND Many molecularly targeted anticancer agents entering the definitive stage of clinical development benefit only a subset of treated patients . This may lead to missing effective agents by the traditional broad- eligibility r and omized trials due to the dilution of the overall treatment effect . We propose a statistically rigorous biomarker-adaptive threshold phase III design for setting s in which a putative biomarker to identify patients who are sensitive to the new agent is measured on a continuous or grade d scale . METHODS The design combines a test for overall treatment effect in all r and omly assigned patients with the establishment and validation of a cut point for a prespecified biomarker of the sensitive sub population . The performance of the biomarker-adaptive design , relative to a traditional design that ignores the biomarker , was evaluated in a simulation study . The biomarker-adaptive design was also used to analyze data from a prostate cancer trial . RESULTS In the simulation study , the biomarker-adaptive design preserved the power to detect the overall effect when the new treatment is broadly effective . When the proportion of sensitive patients as identified by the biomarker is low , the proposed design provided a substantial improvement in efficiency compared with the traditional trial design . Recommendations for sample size planning and implementation of the biomarker-adaptive design are provided . CONCLUSIONS A statistically valid test for a biomarker-defined subset effect can be prospect ively incorporated into a r and omized phase III design without compromising the ability to detect an overall effect if the intervention is beneficial in a broad population Biomarkers are critical to targeted therapies , as they may identify patients more likely to benefit from a treatment . Several prospect i ve design s for biomarker-directed therapy have been previously proposed , differing primarily in the study population , r and omization scheme , or both . Recognizing the need for r and omization , yet acknowledging the possibility of promising but inconclusive results after a stage I cohort of r and omized patients , we propose a 2-stage phase II design on marker-positive patients that allows for direct assignment in a stage II cohort . In stage I , marker-positive patients are equally r and omized to receive experimental treatment or control . Stage II has the option to adopt “ direct assignment ” whereby all patients receive experimental treatment . Through simulation , we studied the power and type I error rate of our design compared with a balanced r and omized two-stage design , and conducted sensitivity analyses to study the effect of timing of stage I analysis , population shift effects , and unbalanced r and omization . Our proposed design has minimal loss in power ( < 1.8 % ) and increased type I error rate ( < 2.1 % ) compared with a balanced r and omized design . The maximum increase in type I error rate in the presence of a population shift was between 3.1 % and 5 % , and the loss in power across possible timings of stage I analysis was less than 1.2 % . Our proposed design has desirable statistical properties with potential appeal in practice . The direct assignment option , if adopted , provides for an “ extended confirmation phase ” as an alternative to stopping the trial early for evidence of efficacy in stage I. Clin Cancer Res ; 18(16 ) ; 4225–33 . © 2012 AACR 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 OBJECTIVE To estimate the number of r and omized controlled trials ( RCTs ) published annually that evaluate the impact of diagnostic tests on patient outcomes to gauge the extent of available r and omized evidence assessing the effectiveness of diagnostic tests . STUDY DESIGN AND SETTING Relevant RCTs published in 2004 - 2007 were identified from electronic search es of the Cochrane Central Register of Controlled Trials ( CENTRAL ) . Two search strategies were developed , one using diagnostic method ological terms and one using test names . Potentially relevant RCTs were identified by screening titles and abstract s. Final inclusion decisions were based on full-text review . A r and om 10 % sample of all citations was independently screened by a second review er . Capture-recapture methodology was used to estimate the number of relevant RCTs missed by both search es . RESULTS One hundred thirty-five relevant RCTs were identified from the 23,888 records retrieved . Interobserver agreement was substantial . Capture-recapture methodology estimated that 148 ( 95 % confidence interval : 140 , 160 ) relevant RCTs were published in the 4-year period , an average of only 37 publications per year . CONCLUSION RCTs of diagnostic tests that evaluate patient outcomes are rare . Consequently recommendations on the use of diagnostic tests can rarely be made on the basis of r and omized comparisons , lower grade evidence frequently being the best available Purpose : Cancer therapies with mechanisms of action which are very different from the more conventional chemotherapies are now being developed . In this article , we investigate the performance of several phase III clinical trial design s , both for testing the overall efficacy of a targeted agent and for testing its efficacy in a subgroup of patients with a tumor marker present . We study different design s and different underlying scenarios assuming continuous markers , and assess the trade-off between the number of patients on the study and the effectiveness of treatment in the subgroup of marker-positive patients . Experimental Design : We investigate binary outcomes and use simulation studies to determine sample size and power for the different design s and the various scenarios . We also simulate marker prevalence and marker misclassification and evaluate their effect on power and sample size . Results : In general , a targeted design which r and omizes patients with the appropriate marker status performs the best in all scenarios with an underlying true predictive marker . R and omizing all patients regardless of their marker values performs as well as or better in most cases than a clinical trial that r and omizes the patient to a treatment strategy based on marker value versus st and ard of care . Conclusion : If there is the possibility that the new treatment helps marker-negative patients , or that the cutpoint determining marker status has not been well established and the marker prevalence is large enough , we recommend r and omizing all patients regardless of marker values , but using a design such that both the overall and the targeted subgroup hypothesis can be tested Developments in biotechnology and genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians . The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials . In oncology , treatment of broad population s with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics . The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of r and omized clinical trials as a reliable basis for predictive medicine . We review prospect i ve design s for the development of new therapeutics and predictive biomarkers to inform their use . We cover design s for a wide range of setting s. At one extreme is the development of a new drug with a single c and i date biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug . At the other extreme are Phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier . We have outlined a prediction-based approach to the analysis of r and omized clinical trials that both preserves the Type I error and provides a reliable internally vali date d basis for predicting which patients are most likely or unlikely to benefit from the new regimen Selecting the best treatment for a patient 's disease may be facilitated by evaluating clinical characteristics or biomarker measurements at diagnosis . We consider how to evaluate the potential impact of such measurements on treatment selection algorithms . For example , magnetic resonance neurographic imaging is potentially useful for deciding whether a patient should be treated surgically for Carpal Tunnel Syndrome or should receive less-invasive conservative therapy . We propose a graphical display , the selection impact ( SI ) curve that shows the population response rate as a function of treatment selection criteria based on the marker . The curve can be useful for choosing a treatment policy that incorporates information on the patient 's marker value exceeding a threshold . The SI curve can be estimated using data from a comparative r and omized trial conducted in the population as long as treatment assignment in the trial is independent of the predictive marker . Estimating the SI curve is therefore part of a post hoc analysis to determine whether the marker identifies patients that are more likely to benefit from one treatment over another . Nonparametric and parametric estimates of the SI curve are proposed in this article . Asymptotic distribution theory is used to evaluate the relative efficiencies of the estimators . Simulation studies show that inference is straightforward with realistic sample sizes . We illustrate the SI curve and statistical inference for it with data motivated by an ongoing trial of surgery versus conservative therapy for Carpal Tunnel Syndrome Before medical tests are introduced into practice , they should be properly evaluated . R and omized trials and other comprehensive evaluations of tests and test strategies can best be design ed based on an underst and ing of how tests can benefit or harm patients . Tests primarily affect patients ’ health by guiding clinical decision making and downstream management , such as the decision to order more tests or to start , stop , or modify treatment . In this article , the authors demonstrate that tests can have additional effects on patient outcome , which may be cognitive , emotional , social , or behavioral . They present a framework to help research ers and policy makers consider the cognitive , emotional , social , and behavioral effects of testing . These additional effects may be important themselves and may also influence the clinical outcomes of testing through different pathways . The authors provide examples from test evaluations in the literature to illustrate how these additional effects can be important in the evaluation of testing or indeed any health intervention Pharmacogenetics is one of many evolving sciences that have come to the fore since the formation of the Statisticians in the Pharmaceutical Industry ( PSI ) 30 years ago . Following the completion of the human genome project and the HapMap in the early 21st century , pharmacogenetics has gradually focused on studies of whole-genome single-nucleotide-polymorphisms screening associating disease pathophysiology with potential therapeutic interventions . Around this time , transcription profiling aim ing at similar objectives has also been actively pursued , known as pharmacogenomics . It has become increasingly apparent that treatment effects between different genomic patient subsets can be dissimilar , and the value and need for genomic biomarkers to help predict effects , particularly in cancer clinical studies , have become issues of paramount importance . Pharmacogenomics/pharmacogenetics has thus become intensely focused on the search for genomic biomarkers for use as classifiers to select patients in r and omized-controlled trials . We highlight that the predictive utility of a genomic classifier has tremendous clinical appeal and that there will be growing examples in which use of a companion diagnostic will need to be considered and may become an integral part in the utilization of drugs in medical practice . The credible mechanism to test the clinical utility of a genomic classifier is to employ the study results from a prospect i ve trial that recruits all patients . Such investigations , if well design ed , will allow analysis of all relevant performance factors in the drug and diagnostic combination including the sensitivity , specificity , positive and negative predictive values of the diagnostic test and the efficacy of the drug Background Advances in molecular therapeutics in the past decade have opened up new possibilities for treating cancer patients with personalized therapies , using biomarkers to determine which treatments are most likely to benefit them , but there are difficulties and unresolved issues in the development and validation of biomarker-based personalized therapies . We develop a new clinical trial design to address some of these issues . The goal is to capture the strengths of the frequentist and Bayesian approaches to address this problem in the recent literature and to circumvent their limitations . Methods We use generalized likelihood ratio tests of the intersection null and enriched strategy null hypotheses to derive a novel clinical trial design for the problem of advancing promising biomarker-guided strategies toward eventual validation . We also investigate the usefulness of adaptive r and omization ( AR ) and futility stopping proposed in the recent literature . Results Simulation studies demonstrate the advantages of testing both the narrowly focused enriched strategy null hypothesis related to validating a proposed strategy and the intersection null hypothesis that can accommo date to a potentially successful strategy . AR and early termination of ineffective treatments offer increased probability of receiving the preferred treatment and better response rates for patients in the trial , at the expense of more complicated inference under small-to-moderate total sample sizes and some reduction in power . Limitations The binary response used in the development phase may not be a reliable indicator of treatment benefit on long-term clinical outcomes . In the proposed design , the biomarker-guided strategy ( BGS ) is not compared to ‘ st and ard of care ’ , such as physician ’s choice that may be informed by patient characteristics . Therefore , a positive result does not imply superiority of the BGS to ‘ st and ard of care ’ . The proposed design and tests are valid asymptotically . Simulations are used to examine small-to-moderate sample properties . Conclusion Innovative clinical trial design s are needed to address the difficulties and issues in the development and validation of biomarker-based personalized therapies . The article shows the advantages of using likelihood inference and interim analysis to meet the challenges in the sample size needed and in the constantly evolving biomarker l and scape and genomic and proteomic technologies Background The current practice for seeking genomically favorable patients in r and omized controlled clinical trials using genomic convenience sample s. Purpose To discuss the extent of imbalance , confounding , bias , design efficiency loss , type I error , and type II error that can occur in the evaluation of the convenience sample s , particularly when they are small sample s. To articulate statistical considerations for a reasonable sample size to minimize the chance of imbalance , and , to highlight the importance of replicating the subgroup finding in independent studies . Methods Four case examples reflecting recent regulatory experiences are used to underscore the problems with convenience sample s. Probability of imbalance for a pre-specified subgroup is provided to eluci date sample size needed to minimize the chance of imbalance . We use an example drug development to highlight the level of scientific rigor needed , with evidence replicated for a pre-specified subgroup cl aim . Results The convenience sample s evaluated ranged from 18 % to 38 % of the intent-to-treat sample s with sample size ranging from 100 to 5000 patients per arm . The baseline imbalance can occur with probability higher than 25 % . Mild to moderate multiple confounders yielding the same directional bias in favor of the treated group can make treatment group incomparable at baseline and result in a false positive conclusion that there is a treatment difference . Conversely , if the same directional bias favors the placebo group or there is loss in design efficiency , the type II error can increase substantially . Limitations Pre-specification of a genomic subgroup hypothesis is useful only for some degree of type I error control . Conclusion Complete ascertainment of genomic sample s in a r and omized controlled trial should be the first step to explore if a favorable genomic patient subgroup suggests a treatment effect when there is no clear prior knowledge and underst and ing about how the mechanism of a drug target affects the clinical outcome of interest . When stratified r and omization based on genomic biomarker status can not be implemented in design ing a pharmacogenomics confirmatory clinical trial , if there is one genomic biomarker prognostic for clinical response , as a general rule of thumb , a sample size of at least 100 patients may be needed to be considered for the lower prevalence genomic subgroup to minimize the chance of an imbalance of 20 % or more difference in the prevalence of the genomic marker . The sample size may need to be at least 150 , 350 , and 1350 , respectively , if an imbalance of 15 % , 10 % and 5 % difference is of concern . Clinical Trials 2010 ; 7 : 525—536 . Scientific inquiry into the discovery , development , and application of tumor markers is proceeding rapidly . Despite this explosion in research and interest , the design of studies to formally assess the value of tumor markers in clinical practice is inconsistent and immature . Indeed , few markers have been widely accepted into st and ard clinical practice . Many issues must be prospect ively considered in a method ical , systematic , and scientific fashion if progress is to be made in the development of vali date d tests that will have value in the management of patients with cancer . The purpose of this report is to present a discussion of the issues involved in design ing clinical studies of putative tumor markers which provide sufficient data to result in the incorporation of the marker into clinical practice . We will focus on the design of studies to demonstrate and vali date the clinical utility of both prognostic and predictive markers . Topics to be covered include issues of patient and sample heterogeneity , the prevalence of the marker , the sample capture rate , and the choice of endpoints . This will be followed by explicit consideration of study design , specifically the trial r and omization schema for both prognostic and predictive factor studies BACKGROUND Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient . Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure . OBJECTIVE Clinical trial design s and adaptive analysis plans for the prospect i ve design of pivotal trials of new therapeutics and companion diagnostics are review ed . CONCLUSIONS Effective co-development requires careful prospect i ve planning of the design and analysis strategy for pivotal clinical trials . R and omized clinical trials continue to be important for evaluating the effectiveness of new treatments , but the target population s for analysis should be prospect ively specified based on the companion diagnostic . Post hoc analyses of traditionally design ed r and omized clinical trials are often deeply problematic . Clear separation is generally required of the data used for developing the diagnostic test , including their threshold of positivity , from the data used for evaluating treatment effectiveness in subsets determined by the test . Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospect i ve definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions Background : With the advancement in biomedicine , many biologically targeted therapies have been developed . These targeted agents , however , may not work for everyone . Biomarker profiles can be used to identify effective targeted therapies . Our goals are to characterize the molecular signature of individual tumors , offer the best-fit targeted therapies to patients in a study , and identify promising agents for future development . Methods : We propose an outcome -based adaptive r and omization trial design for patients with advanced stage non-small cell lung cancer . All patients have baseline biopsy sample s taken for biomarker assessment prior to r and omization to treatments . The primary endpoint of this study is the disease control rate at 8 weeks after r and omization . The Bayesian probit model is used to characterize the disease control rate . Patients are adaptively r and omized to one of four treatments with the r and omization rate based on the up date d disease control rate from the accumulated data in the trial . For each biomarker profile , high-performing treatments have higher r and omization rates , and vice versa . An early stopping rule is implemented to suspend low-performing treatments from r and omization . Results : Based on extensive simulation studies , with a total of 200 evaluable patients , our trial has desirable operating characteristics to : ( 1 ) identify effective agents with a high probability ; ( 2 ) suspend ineffective agents ; and ( 3 ) treat more patients with effective agents that correspond to their biomarker profiles . Our trial design continues to up date and refine the estimates as the trial progresses . Limitations : This biomarker-based trial requires biopsible tumors and a two-week turn around time for biomarker profiling before r and omization . Additionally , in order to learn from the interim data and adjust the r and omization rate accordingly , the outcome -based adaptive r and omization design is applicable only for trials when the endpoint can be assessed in a relative short period of time . Conclusion : Bayesian adaptive r and omization trial design is a smart , novel , and ethical design . In conjunction with an early stopping rule , it can be used to efficiently identify effective agents , eliminate ineffective ones , and match effective treatments with patients ' biomarker profiles . The proposed design is suitable for the development of targeted therapies and provides a rational design for personalized medicine . Clinical Trials 2008 ; 5 : 181—193 . Background Developments in biotechnology and genomics have increased the focus of biostatisticians on prediction problems . This has led to many exciting developments for predictive modeling where the number of variables is larger than the number of cases . Heterogeneity of human diseases and new technology for characterizing them presents new opportunities and challenges for the design and analysis of clinical trials . Purpose In oncology , treatment of broad population s with regimens that do not benefit most patients is less economically sustainable with expensive molecularly targeted therapeutics . The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of r and omized clinical trials as a reliable basis for predictive medicine [ Simon R. An agenda for clinical trials : clinical trials in the genomic era . Clin Trials 2004 ; 1:468—70 , Simon R. New challenges for 21st century clinical trials . Clin Trials 2007 ; 4 : 167—9 . ] . Results We have review ed prospect i ve design s for the development of new therapeutics with c and i date predictive biomarkers . We have also outlined a prediction based approach to the analysis of r and omized clinical trials that both preserves the type I error and provides a reliable internally vali date d basis for predicting which patients are most likely or unlikely to benefit from the new regimen . Conclusions Developing new treatments with predictive biomarkers for identifying the patients who are most likely or least likely to benefit makes drug development more complex . But for many new oncology drugs it is the only science based approach and should increase the chance of success . It may also lead to more consistency in results among trials and has obvious benefits for reducing the number of patients who ultimately receive expensive drugs which expose them risks of adverse events but no benefit . This approach also has great potential value for controlling societal expenditures on health care . Development of treatments with predictive biomarkers requires major changes in the st and ard paradigms for the design and analysis of clinical trials . Some of the key assumptions upon which current methods are based are no longer valid . In addition to review ing a variety of new clinical trial design s for co-development of treatments and predictive biomarkers , we have outlined a prediction based approach to the analysis of r and omized clinical trials . This is a very structured approach whose use requires careful prospect i ve planning . It requires further development but may serve as a basis for a new generation of predictive clinical trials which provide the kinds of reliable individualized information which physicians and patients have long sought , but which have not been available from the past use of post-hoc subset analysis . Clinical Trials 2010 ; 7 : 516—524 . Efficient development of targeted therapies that may only benefit a fraction of patients requires clinical trial design s that use biomarkers to identify sensitive sub population s. Various r and omized phase III trial design s have been proposed for definitive evaluation of new targeted treatments and their associated biomarkers ( eg , enrichment design s and biomarker-stratified design s ) . Before proceeding to phase III , r and omized phase II trials are often used to decide whether the new therapy warrants phase III testing . In the presence of a putative biomarker , the phase II trial should also provide information as to what type of biomarker phase III trial is appropriate . A r and omized phase II biomarker trial design is proposed , which , after completion , recommends the type of phase III trial to be used for the definitive testing of the therapy and the biomarker . The recommendations include the possibility of proceeding to a r and omized phase III of the new therapy with or without using the biomarker and also the possibility of not testing the new therapy further . Evaluations of the proposed trial design using simulations and published data demonstrate that it works well in providing recommendations for phase III trial design . Background With better underst and ing of the disease ’s etiology and mechanism , many targeted agents are being developed to tackle the root cause of problems , hoping to offer more effective and less toxic therapies . Targeted agents , however , do not work for everyone . Hence , the development of target agents requires the evaluation of prognostic and predictive markers . In addition , upon the identification of each patient ’s marker profile , it is desirable to treat patients with best available treatments in the clinical trial accordingly . Methods Many design s have recently been proposed for the development of targeted agents . These include the simple r and omization design , marker stratified design , marker strategy design , efficient targeted design , etc . In contrast to the frequentist design s with equal r and omization , we propose novel Bayesian adaptive r and omization design s that allow evaluating treatments and markers simultaneously , while providing more patients with effective treatments according to the patients ’ marker profiles . Early stopping rules can be implemented to increase the efficiency of the design s. Results Through simulations , the operating characteristics of different design s are compared and contrasted . By carefully choosing the design parameters , types I and II errors can be controlled for Bayesian design s. By incorporating adaptive r and omization and early stopping rules , the proposed design s incorporate rational learning from the interim data to make informed decisions . Bayesian design also provides a formal way to incorporate relevant prior information . Compared with previously published design s , the proposed design can be more efficient , more ethical , and is also more flexible in the study conduct . Limitations Response adaptive r and omization requires the response to be assessed in a relatively short time period . The infrastructure must be set up to allow timely and more frequent monitoring of interim results . Conclusion Bayesian adaptive r and omization design s are distinctively suitable for the development of multiple targeted agents with multiple biomarkers . Clinical Trials 2010 ; 7 : 584—596 . Scientific innovation has promoted the rapid discovery and development of cancer-related biomarkers . This has fostered improved mechanistic underst and ings of disease biology , facilitated the development of novel targeted therapies and offers the potential to better define the natural history of a disease and to predict response to specific treatment . Clinical trials are evolving , from the use of exploratory ' correlative studies ' that assist in the underst and ing of disease mechanisms , to the use of vali date d biomarkers that are integral to the design of definitive prospect i ve studies . A rigorous process for biomarker development and validation , followed by evaluation in well- design ed , prospect i ve clinical trials that demonstrate improved patient outcomes is required for new biomarkers to change clinical practice . To date , the number of biomarkers considered clinical ly useful is disappointingly small because of conflicting conclusions generated from trials with practical and method ological limitations . This review will highlight several important aspects related to the design and analysis of clinical trials that incorporate a biomarker as a central component . First , we review biomarker development , how biomarkers may be used as targets and how biomarkers can influence methodology to optimize efficiency of drug development through the use of surrogate outcomes . Second , we focus on issues related to trials evaluating potential prognostic biomarkers and how the predictive properties of biomarkers may be used to determine which patients might optimally benefit from a specific intervention Background With the advent of targeted therapies , biomarkers provide a promising means of individualizing therapy through an integrated approach to prediction using the genetic makeup of the disease and the genotype of the patient . Biomarker validation has therefore become a central topic of discussion in the field of medicine , primarily due to the changing l and scape of therapies for treatment of a disease and these therapies purported mechanism(s ) of action . Purpose In this report , we discuss the merits and limitations of some of the clinical trial design s for predictive biomarker validation using examples from ongoing or completed clinical trials . Methods The design s are broadly classified as retrospective ( i.e. , using data from previously well-conducted r and omized controlled trials ( RCT ) ) versus prospect i ve ( enrichment or targeted , unselected or all-comers , hybrid , and adaptive analysis ) . We discuss some of these design s in the context of real trials . Results Well- design ed retrospective analysis of prospect i ve RCT can bring forward effective treatments to marker defined subgroup of patients in a timely manner . An example is the KRAS gene status in colorectal cancer — the benefit from cetuximab and panitumumab was demonstrated to be restricted to patients with wild type status based on prospect ively specified analyses using data from previously conducted RCTs . Prospect i ve enrichment design s are appropriate when compelling preliminary evidence suggests that not all patients will benefit from the study treatment under consideration ; however , this may sometimes leave questions unanswered . An example is the established benefit of trastuzumab as adjuvant therapy for breast cancer ; a clear definition of HER2-positivity and the assay reproducibility have , however , remained unanswered . An all-comers design is optimal where preliminary evidence regarding treatment benefit and assay reproducibility is uncertain ( e.g. , EGFR expression and tyrosine kinase inhibitors in lung cancer ) , or to identify the most effective therapy from a panel of regimens ( e.g. , chemotherapy options in breast cancer ) . Limitations The design s discussed here rest on the assumption that the technical feasibility , assay performance metrics , and the logistics of specimen collection are well established and that initial results demonstrate promise with regard to the predictive ability of the marker(s ) . Conclusions The choice of a clinical trial design is driven by a combination of scientific , clinical , statistical , and ethical considerations . There is no one size fits all solution to predictive biomarker validation . Clinical Trials 2010 ; 7 : 567—573 . Several advances have been made in our underst and ing of the molecular aberrations in renal cell carcinoma that have led to the identification of novel prognostic and predictive biomarkers . At the same time , several novel agents targeting these molecular aberrations have shown promising efficacy in the therapy of advanced renal cancer . As these agents enter more advancedstage clinical trials , efforts must be made to integrate exploration of these novel prognostic and predictive markers into clinical trial design . These elements then can be combined with more traditional prognostic features to form more robust prognostic models . Finally , predictive markers and prognostic models should be vali date d prospect ively , either as part of clinical trials design ed specifically for that purpose or as part of large phase-3 trials . Once vali date d , these features can be used to best inform prognosis and guide therapy based on individual patient characteristics and the number of r and omised trials with diagnostic tests is rising . R and omised comparisons R and omised comparisons have several advantages over other methods of comparing medical interventions . R and om assignment of patients to the strategies under study should prevent any bias in the selection of patients : differences at baseline between groups of patients have to be attributed to chance . 4,5 This basic principle opens up the application of experimental statistical design , such as testing for significance and calculating confidence intervals . R and omised controlled trials are also attractive from a pragmatic point of view : if r and omisation coincides with a choice between two management strategies , trial design closely mimics existing clinical dilemmas . The precision of the estimates will mainly depend on the number of individuals included . One trial design is said to be more statistically efficient than another if it yields more precise estimates when applied in similarly sized groups . OBJECTIVE To explore design s for evaluating the prognostic and predictive value of medical tests and their effect on patient outcome . STUDY DESIGN Theoretical analysis with examples from the medical literature . RESULTS For evaluating the prognostic value of a test , one can include the test at baseline in prognostic studies . To evaluate the value of test in predicting treatment outcome , the test results can be used as baseline information in r and omized controlled trials of treatment . To compare the prognostic or predictive value of two or more tests , the test result combinations can be used as baseline information . To evaluate the effect on patient outcome , r and omized controlled trials of test strategies are an option . R and omization can apply to all tested or be restricted to specific subgroups , such as those with discordant test results , to increase the efficiency of trials . CONCLUSION The prognostic and predictive value of medical tests can and should be evaluated , to demonstrate the test 's ability to guide clinical decision making and to improve patient outcome . Various r and omized design s can be used to evaluate the effects on testing on patient outcome BACKGROUND First-line chemotherapy for advanced non-small-cell lung cancer ( NSCLC ) is usually limited to four to six cycles . Maintenance therapy can delay progression and prolong survival . The oral epidermal growth factor receptor ( EGFR ) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC . We design ed the phase 3 , placebo-controlled Sequential Tarceva in Unresectable NSCLC ( SATURN ; BO18192 ) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy . METHODS Between December , 2005 , and May , 2008 , 1949 patients were included in the run-in phase ( four cycles of platinum-based chemotherapy ) . At the end of the run-in phase , 889 patients who did not have progressive disease were entered into the main study , and were r and omly allocated using a 1:1 adaptive r and omisation method through a third-party interactive voice response system to receive erlotinib ( 150 mg/day ; n=438 ) or placebo ( n=451 ) until progression or unacceptable toxicity . Patients were stratified by EGFR immunohistochemistry status , stage , Eastern Cooperative Oncology Group performance status , chemotherapy regimen , smoking history , and region . Co- primary endpoints were progression-free survival ( PFS ) in all analysable patients irrespective of EGFR status , and PFS in patients whose tumours had EGFR protein overexpression , as determined by immunohistochemistry . This study is registered with www . Clinical Trials.gov , number NCT00556712 . FINDINGS 884 patients were analysable for PFS ; 437 in the erlotinib group and 447 in the placebo group . After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group , median PFS was significantly longer with erlotinib than with placebo : 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group ( HR 0.71 , 95 % CI 0.62 - 0.82 ; p<0.0001 ) . PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib ( n=307 ) compared with EGFR-positive patients given placebo ( n=311 ; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group ; HR 0.69 , 0.58 - 0.82 ; p<0.0001 ) . The most common grade 3 or higher adverse events were rash ( 37 [ 9 % ] of 443 patients in the erlotinib group vs none of 445 in the placebo group ) and diarrhoea ( seven [ 2 % ] of 443 patients vs none of 445 ) . Serious adverse events were reported in 47 patients ( 11 % ) on erlotinib compared with 34 patients ( 8 % ) on placebo . The most common serious adverse event was pneumonia ( seven cases [ 2 % ] with erlotinib and four [ < 1 % ] with placebo ) . INTERPRETATION Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo . First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy . FUNDING F Hoffmann-La Roche |
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